green tea - cosmetic ingredient reviewfor example, tea-isostearate is the tea salt of isostearic...

GREEN

TEA

CIR EXPERT PANEL MEETING

JUNE 27-28, 2011

Ad

min

istrative

Memorandum

To: CIR Expert Panel Members and Liaisons From: Monice M. Fiume MMF Senior Scientific Analyst/Writer Date: June 3, 2011 Subject: Draft Amended Report of Triethanolamine (TEA) and TEA-containing ingredients In 1983, the Expert Panel published a safety assessment on triethanolamine (TEA), diethanolamine (DEA), and monoethanolamine (MEA) with the conclusion that TEA, DEA, and MEA are safe for use in cosmetic formulations designed for discontinuous, brief use followed by thorough rinsing from the surface of the skin. In products intended for prolonged contact with the skin, the concentration of ethanolamines should not exceed 5%. MEA should only be used in products that do not contain N-nitrosating agents. At the December 2010 Panel meeting, the Panel made the decision to reopen the safety assessment of TEA, DEA, and MEA. That decision was based on the need to incorporate new data, but most impor-tantly, on the benefit of separating the ethanolamines and having each of these ingredients be in its own report, with a family of related ingredients created for each. The Draft Amended Report for TEA, listing 93 TEA-containing ingredients as possible add-ons, is being submitted. We are aware that the list of ingredients is extensive and that many may not be appropriate for inclusion in the re-review of TEA. However, the Panel has indicated that they would like to see a complete list, giving them the opportunity to determine the final grouping. Please be aware that the Council has sub-mitted an opinion on the possible add-ons, and it follows this transmittal memo. The safety of 8 of the ingredients included in this re-review, as currently grouped, has been reviewed previously by the CIR. Summary information from the existing safety assessments is included in the current re-review document, and conclusions from the original CIR reports are provided in Table 1 of the report. In most cases, existing information on these ingredients was not substantial. Some of the ingredients included in this re-review include a “component” that has been reviewed by the CIR. For example, TEA-isostearate is the TEA salt of isostearic acid; isostearic acid has been reviewed by the CIR. Table 1 provides the conclusions from the CIR reports on the component ingredients. The data profile indicates the types of data that were available in those reports. Finally, many of the ingredients are lacking safety data. The Panel should consider whether read-across data from existing reports can be used. To facilitate that determination, full reports on the previously reviewed TEA ingredients are provided at http://www.cir-safety.org/jun11.shtml.

Included in the data tab of this report are:

1. concentration of use data by FDA product category, memo dated May 17, 2011; 2. Council comments on the December version of the TEA document, memo dated Dec 10, 2010; 3. FDA raw data.

Once the Panel finalizes the grouping for TEA, and if there are no additional data needs, the Panel should be prepared to formulate a tentative conclusion on the TEA family of ingredients, with the rationale provided in the Discussion of the report. A Tentative Amended Report would then be issued for public comment. If the data are not complete for making a determination of safety, then an Insufficient Data Announcement should be issued listing the additional data that are needed.

Personal Care Products CouncilCommitted to Safety,Quality & Innovation

Memorandum

TO: F. Alan Andersen, Ph.D.Director - COSMETIC INGREDIENT REVIEW (CIR)

FROM: CIR Science and Support Committee of the Personal Care Products Council

DATE: March 15, 2011

SUBJECT: Comments on the Proposed Ingredient Grouping for the Draft Report onTriethanolamine (TEA) and Related TEA-Containing Ingredients

The CR Science and Support Committee (CIR SSC) is highly supportive of scientifically based grouping ofingredients in CR reports. However, the CR SSC is concerned about the grouping of ingredients in theproposed report on Triethanolamine (TEA) and related TEA-containing ingredients that is posted on the CRwebsite at http://www.cir-safety. org/current. shtml (short list is attached).

It is the Cornniittee’s understanding that for re-review reports the information in the original report shouldsupport the safety of ingredients added to the report. CR reviews of components of ingredients and relatedingredients can also be used to support the safety of ingredients containing the components.

The chemical and toxicological properties of many ingredients in the list of ingredients proposed for inclusionin the TEA report are likely to be driven by the other portion of the compound, not TEA. In addition, there aremany ingredients included in the proposed list for which the other components have not yet been reviewed byCR. Examples of unreviewed components included among ingredients proposed for inclusion in the TEAreview include amino acids (for which the CR SSC has previously requested be reviewed by CR), carrageenanand a number of hydrolyzed proteins.

Because a component other than TEA may drive the chemical and toxicological properties, and because of thelack of review of a component, the CR SSC recommends that the following ingredients not be included in there-review of TEA.TEA-Lauryl PhosphateTEA-C 12-l3Alkyl PhosphateTEA-C12-14 Alkyl PhosphateTEA-Dimethicone PEG-7 PhosphateTEA-Laureth-4 PhosphateTEA-PolyphosphateDi-TEA-Palmitoyl AspartateTEA-Cocoyl AlaninateTEA-Cocoyl GlutamateTEA-Cocoyl GlutaminateTEA-Cocoyl GlycinateTEA-Hydrogenated Tallowoyl Glutamate

1101 17th Street, N.W., Suite 300 Washington, D.C. 20036-4702 202.331.1770 202.331.1969 (fax) www.personalcarecouncil.org

TEA-Lauroyl GlutamateTEA-LauryolfMyristoyl AspartateTEA-AlginateSodium/TEA-Lauroyl Collagen Amino AcidsSodium/TEA-Lauroyl Hydrolyzed KeratinSodium TEA-Lauroyl Keratiri Amino AcidsSodium/TEA-Undecylenoyl AlginateSodium/TEA-Undecylenoyl Collagen Amino AcidsSodium/TEA-Undecylenoyl Hydrolyzed Soy ProteinSodium/TEA-Undecylenoyl Hydrolyzed Wheat ProteinTEA-Cocoyl Hydrolyzed Soy ProteinTEA-Lauroyl Collagen Amino AcidsTEA-Lauroyl Keratin Amino AcidsTEA-Acrylates/Acrylonitrogens CopolymerTEA-Acrylates/Ethylhexyl CopolymerTEA-Diethanolaminoethyl PolyisobutenylsuccinateTEA-Diricinoleate/IPDI CopolymerTriethanolamine Polyoxyethylene Alkylphenylether Phosphate (Japan Trivial Name)

The CW Expert Panel has included a number of TEA-containing ingredients in other reports, suggesting thatTEA may not be driving potential safety concerns of these ingredients. The CIR SSC recommends that thesepreviously reviewed TEA-containing ingredients not be added to this report as they have been moreappropriately reviewed in other reports.

Based on a previous dR review, the CIR SSC recommends that the following ingredients not be included in there-review of TEA.TEA-LaurateTEA-LactateTEA-SalicylateTEA-EDTATEA-Lauryl SulfateTEA-TridecylbenzenesulfonateTEA-DodecylbenzenesulfonateTEA-Cocoyl Hydrolyzed Collagen

The CIR Expert Panel has reviewed the safety of Sodium Lauraminopropionate (report published in 1997) andfound the data insufficient to support safety. The data requested included concentration of use, chemicalcharacterization, chemical and physical properties, method of manufacture, 28-day dermal toxicity, dermalteratogenicity, ocular irritation at concentration of use, dermal irritation and sensitization at concentration ofuse and two different mammalian genotoxicity studies. Based on this conclusion, the CIR SSC recommendsthat TEA-Lauraminopropionate be removed from the re-review of TEA.

2

List of Potential Additional ingredients to TEA (Triethanolamine ) Report

Inorganic Acid SaltsTEA-Hydrochloride TEA-Sulfate

Organic Acid SaltsTEA-U ndecylenateTEA-La urateTEA-La urate/MyristateTEA-MyristateTEA-Pa ImitateTEA-Stea rateTEA-Isostea rate

Hydroxy Acid SaltsTEA-LactateTEA-Diricinoleate

Amine & Amide Acid SaltsTEA-EDTATEA-Myristaminopropion ateTEA-Laura minopropionateDi-TEA Cocamide DiacetateDi-TEA-Palmitoyl AspartateTEA-Cocamide DiacetateTEA-Cocoyl AlaninateTEA-Cocoyl GlutamateTEA-Cocoyl GlutaminateTEA-Cocoyl Glycinate

TEA-SorbateTEA-OleateTEA-Ca nolateTEA-CocoateTEA-Hydrogenated CocoateTEA-RosinateTEA-Ta I late

TEA-Glyceryl DimaleateTEA-Salicylate

TEA-Cocoyl SarcosinateTEA-Hydrogenated Tallowoyl GlutamateTEA-Lauroyl GlutamateTEA-Lauroyl MethylaminopropionateTEA-Lauroyl/Myristoyl AspartateTEA-Lauroyl SarcosinateTEA-Oleoyl SarcosinateTEA-Palm Kernel SarcosinateTEA-PCA

Ester Acid SaltsTEA-Lauroyl Lactylate

Organo-Substituted Inorganic Acid SaltsMagnesium/TEA-Coco-SulfateSodium/TEA C12-13 Pareth-3 SulfateDi-TEA-Oleamido PEG-2 SulfosuccinateTEA-Lauryl SulfateTEA-Laneth-5 SulfateTEA-Laureth SulfateTEA-Oleyl SulfateTEA-C1O-15 Alkyl SulfateTEA-C11-15 Alkyl SulfateTEA-C12-13 Alkyl SulfateTEA-C12-14 Alkyl SulfateTEA-C12-15 Alkyl Sulfate

-Aryl Sulfonate SaltsTEA-Tridecylbenzen esu Ifon ate

Polysaccharide & Protein SaltsTEA-Cocoyl Hydrolyzed CollagenTEA-Algi nate

TEA-PEG-50 Hydrogenated Castor Oil Succinate

TEA C14-17 Alkyl Sec SulfonateTEA-Coco-Su IfateTEA-C11-15 Pareth SulfateTEA-C12-13 Pareth-3 SulfateTEA-PEG-3 Cocamide SulfateTEA-Lauryl PhosphateTEA-C12-13 Alkyl PhosphateTEA-C12-14 Alkyl PhosphateTEA-Dimethicone PEG-7 PhosphateTEA-Laureth-4 PhosphateTEA-Polyphosph ate

TEA- Dodecylenzenesu Ifonate

TEA-Isostearoyl Hydrolyzed CollagenSodium/TEA-Lauroyl Collagen Amino Acids

Sodium/TEA-Lauroyl Hydrolyzed CollagenSodium/TEA-Lauroyl Hydrolyzed KeratinSodium/TEA-Lauroyl Keratin Amino AcidsSodium/TEA-Undecylenoyl AlginateSodium/TEA-Undecylenoyl CarrageenanSodium/TEA-Undecylenoyl Collagen Amino AcidsSodium/TEA-Undecylenoyl Hydrolyzed CollagenSodium/TEA-Undecylenoyl Hydrolyzed Corn ProteinSodium/TEA-Undecylenoyl Hydrolyzed Soy ProteinSodium/TEA-Undecylenoyl Hydrolyzed Wheat Protein

Polymer SaltsTEA-Acrylates/Acrylonitrogens CopolymerTEA-Acrylates/Ethylhexyl Acrylate CopolymerTEA-Ca rbomerTEA-Diethanolaminoethyl PolyisobutenylsuccinateTEA-Diricinoleate/l PDI CopolymerTriethanolamine Polyoxyethylene AlkylphenyletherPhosphate

TEA-Abietoyl Hydrolyzed CollagenTEA-Cocoyl Hydrolyzed Soy ProteinTEA-Dextrin OctenylsuccinateTEA-Lauroyl Collagen Amino AcidsTEA-Lauroyl Hydrolyzed CollagenTEA-Lauroyl Keratin Amino AcidsTEA-Myristoyl Hydrolyzed CollagenTEA-Oleoyl Hydrolyzed CollagenTEA-U ndecylenoyl Hydrolyzed Collagen

Distributed for Comment Only - Do Not Cite or Quote

Panel Book Page 1

History: Triethanolamine

Original Report: In 1983, the Expert Panel determined that these ingredients were safe for use in cosmetic formulations designed for discontinuous, brief use followed by thorough rinsing from the surface of the skin. In products intended for prolonged contact with the skin, the concentration of ethanolamines should not exceed 5%. Ethanolamine (MEA) should be used only in rinse-off products. Triethanolamine (TEA) and diethanolamine (DEA) should not be used in products containing N-nitrosating agents. December 2010: a formal rereview package was presented to the Panel for the report on TEA, DEA, and MEA

- the report was split into 3 separate documents – DEA, TEA, and MEA, - appropriate new ingredients are to be added to each report

June 2011: the Draft Amended Report for TEA was presented to the Panel, including 93 ingredients for review as possible “add-ons”


Panel Book Page 2

TRIETHANOLAMINE: SEARCH STRATEGY

April 21, 2011: SCIFINDER search - All ingredients with CAS Nos. were searched using the Search Substances search engine of SciFinder;

when applicable, the search was limited to only years since the previous CIR review(2095 hits before refining by document type)

- Ingredients without CAS Nos. were searched using the Search References search engine - Combining all search results yielded 1120 hits; 34 references were ordered

KeepMe Posted Results are received weekly

SEARCH STRATEGY – TEA/DEA/MEA

TOXLINE PUBMED EU Jan 17. 2010 DEA not to be used 111-42-2 & choline 13 15 111-42-2 & carcinogen* 83 21

choline & deficiency & human & cancer

38

TEA restrictions 102-71-6 & carcinogen* 55 11 102-71-6 & choline 5 2 MEA restrictions Jan 25, 2010 102-71-6 OR 111-42-2 (1980-current)

1003 (downloaded 58)

UPDATED SEARCH May 31, 2010 (102-71-6 OR 111-42-2 OR 141-43-5) AND (REPRODUCTI* OR TERATOGEN*) – 142 (Toxline); 41 (DART) (102-71-6 OR 111-42-2 OR 141-43-5) AND (DEVELOPMENT* OR FETOTOX*) – 378 (Toxline); 47

(DART) (102-71-6 OR 111-42-2 OR 141-43-5) AND TOX* (102-71-6 OR 111-42-2 OR 141-43-5) AND (GENOTOX* OR MUTAGEN* OR CLASTOGEN*) – 286

Toxline); 7 (DART); 9 (CCRIS) (102-71-6 OR 111-42-2 OR 141-43-5) AND (SENSITIZA* OR SENSITIZE* OR SENSITIS* OR

IRRIT*) – 306 (Toxline); 6 (DART)


Panel Book Page 3

(102-71-6 OR 111-42-2 OR 141-43-5) AND (METBOLI* OR ABSORB* OR ABSORP* OR DISTRIBUT* OR EXCRET*) – 403 (Toxline); 18 (DART)

141-43-5 AND CARCINOGEN* – 193 141-43-4 AND CHOLINE - 0 Total Download (most duplicates removed): 1218 UPDATED SEARCH – Sept 21, 2010 – last 12 mos 102-71-8 OR 111-42-2 OR 141-43-5 128 hits/1 useful


Panel Book Page 4

1

TE

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Dat

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(up

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Previously Reviewed#

Reported Use

Method of Manufacture

Toxicokinetics

Animal Tox – Acute, Dermal

Animal Tox – Acute, Oral

Animal Tox, Acute, Inhalation

Animal Tox – Rptd Dose, Dermal

Animal Tox, Rptd Dose, Oral

Animal Tox – Rptd Dose, Inhalation

Repro/Dev Tox

Genotoxicity

Carcinogenicity

Dermal Irr/Sens

Ocular Irritation

TE

A

1983

X

X

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Panel Book Page 5

2

TE

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Reported Use


Toxicokinetics







Repro/Dev Tox

Genotoxicity

Carcinogenicity

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TE

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Panel Book Page 6

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X

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X

X

X

X

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Panel Book Page 7

4

TE

A, T

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nd

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Dat

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(up

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2011

)


Reported Use


Toxicokinetics







Repro/Dev Tox

Genotoxicity

Carcinogenicity

Dermal Irr/Sens

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PC

A

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Panel Book Page 8

Tran

scripts

DR. BERGFELD: Thank you. So, the

motion's been made to reopen and it's been

seconded. Any further discussion?

DR. MARKS: And with the intent -- and

we'll -- as Paul mentioned earlier, at least for

our team the intent was to add methylene glycol,

but as we work through the report, we'll decide

whether or not we want to continue that.

DR. BERGFELD: All right. Call for the

question, all those in favor, please indicate by

raising your hand?

Thank you. Unanimous. Then moving on

to the second to the last ingredient which is the

MEA/DEA/TEA. Dr. Belsito?

DR. BELSITO: Yes, this is a re-review

of the document and it's gone through a number of

iterations. The initial was 1983, and since that

time there have been a number of discussions

regarding DEA. However, it's really time that we

look at the original report which contained all

three. And when we -- when my team looked at the

data we really felt that perhaps with the

FULL PANEL - December 2010

exception of opening it to reassess MEA and

changing it to our current way of stating that we

had limited it to rinse off products because of

irritation, to the current way of stating, could

be used in leave-ons if formulated not to be

irritating, it was really no reason to open the

document.

However, the reason to open it would be

that there are a number of MEA, DEA, and TEA

compounds that could be tagged onto this quite

easily that we haven't reviewed. So we are

recommending that, A, the report be split into

three different reports: An MEA, a DEA, and a TEA

report; and that all of the related cosmetic MEAs,

DEAs, and TEAs be included in each of those

reports. And that's a motion.

DR. BERGFELD: Motion to reopen and

split it into three different ingredient groups

has been made.

DR. MARKS: Second.

DR. BERGFELD: Second. Any further

discussion about reopening? John?

DR. BAILEY: Yeah, I agree, but I think

that it's really important how these groups are

going to be constituted. And I would like to see

the proposed group as soon as possible and then we

will refer that to our Science and Support

Committee just to make sure that they're

comfortable with the way the group is put

together. You know, there was some, I wouldn't

say concern, but some interest in making sure that

these groups are as rational and logical as

possible, so we would need to get those as soon as

we can.

DR. BERGFELD: Alan?

DR. ANDERSEN: Yeah, we will most

certainly get the potential add-ons out ASAP. I

see a primary focus of the March meeting on

receiving that input from industry, receiving the

input from the panel as the panel gets the

opportunity to look at those groupings, and

negotiating what actually should be done as

add-ons. So, I don't know that we're -- I mean,

unless we hit the nail perfectly on the head,

there's going to be some negotiating in March.

DR. BERGFELD: Call for the question

then to reopen, all those in favor please indicate

by raising your hands?

Thank you. It's reopened. And then

moving to the last ingredient to be considered

this morning, human umbilical extract, Dr. Marks?

DR. MARKS: In 2002, the CIR published

its final safety assessments in the ingredients

derived from human and animal placentas and

umbilical cords with a conclusion that the

available data were insufficient to support the

safety. We recently had correspondence from a

company specifically concerning use of human

umbilical extract in cosmetic products. They

supplied some data, but when you look at our

insufficient data needs from the original safety

assessment, really those data needs were not met

and so our team moves not to reopen this safety

assessment.

DR. BERGFELD: Second? Is that a

second? Comment?


Panel Book Page 9

CIR Meeting day 1 of 2 (Breakout Session) Page: 14

Anderson Court Reporting -- 703-519-7180 -- www.andersonreporting.net

1 the risk assessment pages that you're looking at

2 will substantially make up the summary that you're

3 going to see at the next meeting.

4 DR. BELSITO: Okay, good. Anything else

5 on this? No? Okay. So moving on to the next

6 one, it's the re- review of MEA, DEA, and TEA.

7 And Alan has essentially already stolen my

8 thunder, which is basically how many salts and

9 esters of these can we make into super families?

10 And so I'm thinking we should be reopen it not

11 only to add those in, but I think our conclusion

12 that MEA should not be used in leave-on products

13 is based upon irritation. And we've taken a

14 different step now to say "when formulated not to

15 be irritating," so that conclusion may not be

16 correct either as it stands. So I would say that

17 we reopen the documents and take Alan's, split

18 them into three and add the salts and esters of

19 the MEAs, DEAs, and TEAs so that we get everything

20 that's out there.

21 DR. ANDERSEN: I think with that

22 strategy what you could expect to see at the next

BELSITO TEAM - December 2010CIR Meeting day 1 of 2 (Breakout Session) Page: 15


1 meeting would be three more, three separate and

2 more comprehensive documents that list the Organic

3 Acid Salts that could conceptually be included and

4 then examines the question of going on to, let's

5 see, MEAs, for example, the DEA list. There is

6 yet a second group that takes off on the fact that

7 we've already reviewed cocamide DEA, lauramide

8 DEA, which are not -- may not technically be

9 considered as salts, but we'll look at forming

10 those groups as well. Monice and Bart have

11 already done a great deal of homework on this, and

12 are kind of ready to package that, but we just

13 kind of finished it last week and it seemed

14 disingenuous to dump all of that on the Panel for

15 this meeting. So if for all sorts of reasons, it

16 seems appropriate to reopen these, then we can

17 take the next step at the next meeting.

18 DR. BELSITO: Is everyone in agreement

19 of splitting them into three separate documents

20 when we do that?

21 DR. SNYDER: Yes.

22 DR. LIEBLER: Fine with it.

CIR Meeting day 1 of 2 (Breakout Session) Page: 16


1 DR. BELSITO: Okay, any comments?

2 DR. LIEBLER: I guess I had

3 misinterpreted the cover memo, and I thought that

4 the main reason to discuss these was the

5 appearance of new data on carcinogenicity. So

6 really that's not the main issue here.

7 DR. SNYDER: No.

8 DR. LIEBLER: Okay.

9 MS. FIUME: Originally --

10 DR. ANDERSEN: I think, in fact, it's an

11 old issue at this point in terms of DEA

12 carcinogenesis. At this point in time arguably

13 explained process of choline metabolism in mice,

14 and it's not hugely relevant.

15 DR. LIEBLER: Right, so based on all of

16 that, I said don't reopen these, but I agree with

17 the reason now to reopen.

18 DR. BELSITO: Any other comments? Okay,

19 dicarboxylic acid. Okay, so in August we issued a

20 tentative report for the twelve dicarboxylic

21 acids, 44 diesters, finding them safe in present

22 practice of use and concentration. There was one

CIR Meeting day 1 of 2 ( Main Session) Page: 147


1 HIV, it put together all sorts of stuff, and we

2 started to separate the two boilerplates out, and

3 some time next year, we will be bringing to the

4 panel all of the boilerplates for boilerplate

5 re-review so we can go through and make sure

6 they're currently up to date. We felt there were

7 more than enough agenda items on this meeting to

8 not do it starting with this meeting.

9 DR. MARKS: Thank you. Okay, onto the

10 next ingredient or ingredients. We're in the MEA,

11 DEA, TEA re- review. There's quite a history of

12 these ingredients, and I think where we're at at

13 this point is do we reopen, do we separate it out

14 into three different reports, do we put them

15 together? And I'll open it up for discussion.

16 And then, also, we should talk about if we reopen,

17 do we reopen it to add salts and simple esters,

18 also? And to further comment, and, Tom, I'd asked

19 you about the nitrosamine formulation concern, and

20 Ron's, where DEA has been banned in the EU and

21 Canada, plus it's salts and MEA and TEA has had

22 restrictions. So, let's go ahead and decide

MARKS TEAM - December 2010


Panel Book Page 10



1 whether we're going to reopen and then do we do

2 them together or separate and what do we add?

3 DR. SLAGA: After reading this and

4 trying to compare to three of them, the DEA and

5 TEA and the MEA, so to speak, and with the data

6 related to EU and Canada, it seems to me it would

7 be a good idea to reopen and separate them.

8 In terms of nitrosamines, they all have

9 capabilities, don't they?

10 DR. SHANK: Not MEA.

11 DR. SLAGA: I mean, TEA.

12 DR. SHANK: Yes, TEA.

13 DR. SLAGA: TEA and DEA.

14 DR. HILL: I'm not sure I understand why

15 TEA does actually. I'm a little confused about

16 that.

17 DR. SLAGA: Chemistry.

18 DR. MARKS: So, let's go back. So, I

19 saw nodding of heads, all team members endorse the

20 idea of reopening?

21 DR. SHANK: Yes.

22 DR. MARKS: And to separate into the



1 mono, di, and tri?

2 DR. SHANK: What do you mean by

3 "separate?" Three reports or three sections of

4 one report?

5 DR. MARKS: That's the question.

6 Because my sense was there was a possibility of

7 doing three separate reports, but we can do --

8 MS. BRESLAWEC: We could do it

9 administratively anyway. We just noticed that,

10 over the years, keeping them in one report has led

11 to unnecessary confusion. So, we would like to

12 either keep them separately in the same report or

13 put them in three different reports with cross

14 references.

15 DR. HILL: I guess I'd endorse the idea

16 of putting them in three separate reports on the

17 basis that there doesn't seem to be any

18 significant biotransformation, for example, of TEA

19 to DEA. The only relationships I see are in the

20 choline depletion, the ones that have that

21 activity, and I'm wondering, I mean,

22 monoethanolmine is relatively abundant endogenous



1 molecules.

2 So, until you get to really, really

3 artificial dose levels, I'm not sure -- so, my

4 personal bias, but I hadn't thought about keeping

5 them in the same report and just considering them

6 separately. My personal bias was to separate them

7 out into three individual reports. That is just

8 my personal bias based on everything I saw there.

9 DR. MARKS: Tom and Ron Shank? Together

10 or as separate? I should together in one report,

11 but separated within that report?

12 DR. SLAGA: I don't know. It seems to

13 me it'd be better in separate reports, not

14 confusing them.

15 DR. SHANK: I don't feel strongly about

16 it. If it were strictly up to me, I'd have one

17 report with three sections.

18 DR. MARKS: Okay. Well it sounds like

19 at least at this point we'll go with separate

20 reports, and we'll see what the Belsito Team's

21 feelings are.

22 Any further comments before we --



1 DR. SHANK: Yes, that being the case,

2 then I think TEA and MEA would carry the same

3 conclusion that the report has now, in that the

4 major changes would be in the DEA report.

5 MS. FIUME: Could you clarify what you

6 mean, Dr. Shank?

7 DR. SHANK: Yes, we have a report

8 already with all three ingredients in it. The

9 conclusion for that report would still apply to

10 TEA and MEA, even though you're splitting those

11 reports. And then the major changes would be in

12 the new report on DEA, diethanolamine.

13 MS. BRESLAWEC: Are you suggesting that

14 you would not reopen TEA and MEA?

15 DR. SHANK: You have to reopen it

16 because it's now one report, and now you're going

17 to split it into three. So, I don't see how you

18 can do that without reopening it. And now if

19 you're going to add the other ingredients that

20 pertain to each of those ethanolamines, that's

21 your opportunity to do that.

22 MS. BRESLAWEC: But you can reopen them


Panel Book Page 11



1 just to add ingredients, which makes it a little

2 more expedient. DEA, it seems you're suggesting

3 to reopen to reconsider the conclusion, perhaps?

4 DR. SHANK: Correct.

5 DR. SLAGA: Yes.

6 DR. SHANK: How do you reopen? You're

7 creating three new reports. So, you're not

8 reopening DEA, you're not reopening the current

9 report. You're splitting it.

10 DR. MARKS: Yes --

11 DR. SHANK: How do you do that

12 procedurally? What words you use --

13 MS. BRESLAWEC: I think it's something

14 that we would do administratively.

15 DR. MARKS: No, that's a good point,

16 Ron, because in 1983, these were grouped together.

17 So, you're reopening that report, but if we decide

18 to do three separate reports, we're not reopening

19 them in that; we're reopening to separate it. So,

20 I guess administratively, you have to make sure

21 that that's not a problem with the CIR guidelines.

22 But, if there are, it seems to me just as we've



1 done with other reports; we've had major sections

2 within the report. There will be. Well, the

3 conclusion will just deal with it.

4 DR. BAILEY: And couldn't this also --

5 in splitting these, wouldn't it be logical to

6 include adding the other alkanolamines within that

7 group, like a diethanol. I mean, it would be

8 dialkonalamines because there are some in the

9 dictionary now.

10 MS. BRESLAWEC: We've actually prepared,

11 and, Bart, maybe you'd like to come up here, as

12 well, but we've started looking at possible

13 add-ons for all there, MEA, DEA, and TEA, and we

14 are approaching it very systematically. There are

15 groups that seem to us to be natural add-ons, like

16 organic acid salts, for example, and then there

17 are groups that are related, but may be a little

18 far out or groups that are related, but probably

19 should be considered on their own. We're not

20 ready to present those groups for discussion right

21 now, but we have started the process, and we have

22 quite a bit of information on it, but it's



1 something that warrants more preparation before

2 it's presented to you all for discussion.

3 So, yes, we would like to consider

4 reopening all three reports for the potential of

5 adding new ingredients.

6 DR. MARKS: Halyna, how much do you see

7 in having separate reports that you're now going

8 to have a lot of refer to the other report to

9 support that the safety of the other ingredients.

10 Like Ron says TEA and MEA, the same conclusions.

11 So, does that make sense to separate them out if

12 we're going to be using data from one to support

13 the other? And, I, again, am looking forward in

14 terms of if there's going to be a lot of data

15 that's shared in all three reports, and does it

16 make sense to have there separate reports?

17 DR. BOYER: For each of the three

18 chemicals, there is a lot of chemical-specific

19 information. So, it doesn't need to be a lot of

20 cross-reference and so forth. And DEA actually

21 stands out when you look at that data and the

22 mechanistic information that's been published and



1 so forth. So, I think from that perspective, it

2 certainly makes sense to separate them.

3 DR. HILL: Excuse me. And in regards to

4 potentially expanding the groups, I would just say

5 that I strongly suspect that there's going to be,

6 particularly with DEA, there's some toxicology

7 issues that might pertain to it that might not

8 pertain to anything even related. Now, amides of

9 DEA at some point, but those are really widely,

10 heavily used for cosmetic ingredients, and I think

11 moving in that direction would be right now with

12 great caution in my estimation because I think

13 there might not be that much to worry about.

14 DR. BOYER: Right.

15 DR. HILL: And, so, if you tag related

16 to something where there clearly is a problem --

17 well, I say "clearly is a problem," seems to be a

18 problem. Don't know in humans, but you might be

19 creating a problem where there wasn't one before.

20 DR. MARKS: I think, again, for the

21 stenographers, that was Dr. Boyer who was

22 commenting earlier, correct?


Panel Book Page 12



1 DR. BOYER: Yes.

2 DR. MARKS: As new member of the CIR

3 support staff. Thank you.

4 To kind of reinforce what you said, Ron

5 Hill, for TEA, there's now 2010 -- am I reading

6 this correctly, 4,015 products that it's used in?

7 DR. ANSELL: The group is potentially

8 enormous depending on where you start drawing your

9 lines.

10 DR. MARKS: Yes. Plus it looks like --

11 and, obviously, there are also baby products

12 there, but a huge number of products that contain

13 this ingredient.

14 Okay, so, it looks like I think what

15 we'll find out what the other team moves tomorrow,

16 but, for us, it's to reopen separate reports and

17 to consider add-ons, and we'll see that, I

18 presume, some time in a future meeting. And then

19 we'll start, I suspect, on looking at the add-ons

20 to begin with and then go from there.

21 Does that sound reasonable, team

22 members?



1 TEAM MEMBERS: (Nodding)

2 DR. MARKS: Anything else we need to

3 discuss about these three at this point? And, Ron

4 Shank, you've given us an insight of where the

5 safety assessments are going to go in the TEA and

6 MEA. It sounds like the same conclusion or

7 similar, and DEA, that I will have some

8 significant changes in the conclusion.

9 MR. SHANK: Okay, so, we're not going to

10 discuss this until we see it in three different

11 reports? Is that what you're saying?

12 DR. MARKS: Well, that's what I

13 suggested, but I guess in discussing it --

14 MR. SHANK: Do you want to discuss the

15 mouse carcinogenicity assay?

16 DR. MARKS: Sure.

17 MR. SHANK: Or not? Wait?

18 MS. FIUME: That's fine, because that

19 would be one reason to reopen that portion of the

20 report to separate than just to add.

21 MR. SHANK: Yes.

22 MS. FIUME: So, if there's information



1 you want taken care of there, I'd like to discuss

2 that part now.

3 DR. MARKS: Go ahead, Tom.

4 DR. SLAGA: (Off mike) restriction, too.

5 DR. MARKS: This isn't --

6 DR. SHANK: I think the reason --

7 DR. MARKS: This is the choline.

8 DR. SHANK: The main reason this was

9 coming up for re-review was there was a cancer

10 bioassay in the mouse on DEA that produced tumors,

11 and I think we need to address that mouse

12 bioassay. But if you want to wait until the

13 reports are split, then we can do it at that time.

14 DR. MARKS: I think that's up to you.

15 DR. SHANK: (Off mike) for three

16 different reports.

17 DR. MARKS: Yes, for Ron and Tom and Ron

18 Hill, there is that, and, also, the nitrosamine

19 formulation, we could discus that, also, at this

20 point and give a nice idea of the direction we're

21 going. Yes.

22 DR. SHANK: That's pretty simple. MEA,



1 it's a primary amine, and that's not

2 nitro-satiable. DEA and TEA are, and the

3 nitrosation products are in the literature. So,

4 that's not an issue. The issue is how does one

5 interpret the mouse cancer bioassay?

6 MS. DAHLIN: Dr. Marks, Dr. Shank, the

7 report, although under one cover, is in three

8 separate sections, as you've noted. So, we are

9 certainly prepared to hear a discussion on one of

10 the reports to see if you want any additional

11 scientific or safety information incorporated and

12 considered before considering add-ons.

13 DR. SHANK: No, I don't think there's a

14 data need. It's just how do we interpret that

15 assay?

16 MS. FIUME: And, Dr. Shank, I think it

17 was probably after this report was packaged and

18 sent out. We did find some information from I

19 want to say 1999 or the last time it was reviewed

20 where it was discussed and the panel at that time

21 had decided that the problem was it was the

22 choline deficiency causing the problem. It wasn't


Panel Book Page 13



1 the DEA, it was the choline, and there was a

2 discussion. So, I will capture that, as well, it

3 was just discovered after it came out. But if you

4 don't agree what may have been said at that time,

5 then I'll capture something differently or look

6 for different information.

7 DR. SHANK: Okay, I'd have to read that,

8 but I was on the panel at that time, so, I

9 shouldn't make the same argument all over again.

10 We don't need to discuss that now, and we'll see

11 what we said 11 years ago.

12 DR. MARKS: Well, basically in 2008, the

13 panel agreed that the NTP findings of

14 carcinogenesis in the mouse for DEA and certain

15 DEA fatty acid esters was related to choline

16 (inaudible) and not relevant to human health.

17 Tom, is that your recollection?

18 DR. SLAGA: (Nodding)

19 DR. MARKS: I think that's how we dealt

20 with the mouse carcinogenicity.

21 DR. HILL: But I had a question based on

22 information that was in both presentations at the



1 1999 meeting. Of course, that was long before my

2 participation. Both Dr. Lehman-McKeeman, I don't

3 know if I'm saying her name right, and Dr. Stott

4 mentioned that DEA is incorporated in ceramides

5 and possibly sphingomyelins, and then in the

6 discussion of DEA, that whole possible mechanism

7 is dropped, and because I guess there's a

8 pharmacologist in our department who's working on

9 that and effects on cancer stem cells and

10 apoptosis, I want to know if that thread of

11 biology has continued or people have just ignored

12 those pieces of information which came from

13 industry source presentations. Whether there's

14 been any follow-up whatsoever on that biology.

15 And that's one of the reasons why I was looking to

16 see this split was because there may be an issue

17 with DEA biology that doesn't show up at all that

18 shouldn't be an issue with TEA, that shouldn't be

19 an issue with monoethanolmine, but it very well

20 might be a big issue with DEA and only DEA.

21 DR. BOYER: Well, that mechanism seems

22 to certainly distinguish DEA from the other two.



1 As far as I know, there has been no significant

2 progress in terms of developing information to

3 interpret or to determine the importance of those

4 observations, the observation that DEA seems to be

5 incorporated into possible lipids. And there's a

6 lot of speculation about what could happen and how

7 that mechanism might explain some of the toxic

8 effects not necessarily the carcinogenicity.

9 DR. HILL: Well, ceramides have a strong

10 role to play in regulating apoptotic pathways, as

11 well as proliferative pathways, and these were

12 mentioned in two different presentations by two

13 independent labs. So, I guess I'm raising it now

14 so that in mining the literature, whatever might

15 be out there, you will be attuned to looking for

16 anything.

17 DR. BOYER: Absolutely.

18 DR. HILL: (off mike)

19 DR. BOYER: Right.

20 DR. HILL: And I'm not thinking that

21 this is at all relevant in any of the amides of

22 DEA because I doubt that DEA is significantly



1 generated from those amides. But I think it might

2 be something specific to DEA, which I guess is

3 really not used much at all at this point. I get

4 the sense.

5 DR. BOYER: Right.

6 DR. HILL: But it would be clean if

7 those three were dealt with separately then in

8 going to -- because I can envision language in

9 something that's reviewed that's structurally

10 similar, like the kinds of ingredients you were

11 suggesting to expand to. The panel has previously

12 reviewed DEA. We note the structural similarity,

13 but the specific toxicological issues pertaining

14 to that compound don't pertain to any of these,

15 and here's why.

16 DR. BOYER: Yes.

17 DR. HILL: And, so, it would be very

18 clean to be able to refer to that single report

19 and not give issue with the other two that I don't

20 think have any same issues at all.

21 DR. MARKS: Would you like to, since

22 there are three separate reports within this


Panel Book Page 14



1 document, should we, again, sort of have a preview

2 of what's coming down the road, take a look at

3 them individually? I think that the conclusion in

4 1983 -- it's going to be a little interesting if

5 we keep the same wording. So, his conclusion that

6 TEA, DEA, and MEA are safe for use in cosmetic

7 formulations designed for discontinuous brief use

8 followed by thorough rinsing from the surface of

9 the skin. And products intended for prolonged

10 contact with the skin, the concentration

11 ethanolamines should not exceed 5 percent, MEA

12 should only be used in products that do not

13 contain nitrosating agents.

14 So, I know the TEA and the MEA, Ron, you

15 suggested this same conclusion or something

16 similar is going to be okay. The DEA, there's

17 going to be changes.

18 Do you want to go through these

19 individually now? We dealt with the mouse, I

20 think, where the choline metabolism not relevant

21 to the human. We disused the nitrosamine

22 formulation concern left to deal with the ban in



1 EU and Canada. Or restricted.

2 DR. SLAGA: Wasn't it suggested to have

3 two reports instead of three? I mean, I thought

4 that's what you were thinking, too. No?

5 DR. SHANK: No, my suggestion was one

6 report with three sections. But we all decided

7 three individual reports. I think.

8 DR. SLAGA: I thought you meant that you

9 wanted to have TEA and MEA combined because they

10 all have the same conclusions.

11 DR. ANDERSEN: I wanted all three

12 combined. One single report with three sections.

13 But that's a minority opinion.

14 DR. HILL: Well, if there's nothing to

15 ceramides and if there's nothing to more than

16 choline deficiency in that particular assay then

17 you could keep them combined. I guess in my mind,

18 it's somewhat dependent on the toxicology here.

19 MS. BRESLAWEC: We really would prefer

20 separating them out in one form or another because

21 it's caused a lot of confusion when we've looked

22 at derivatives or components that contain DEA or



1 MEA or TEA. Administratively, it's very difficult

2 to deal with them in the same report. So, whether

3 it's one report with three sections, we're fine

4 with that, or three separate reports, we're fine

5 with that, as long as each of the ingredients are

6 handled separately.

7 DR. MARKS: Well, certainly, if they

8 were all in the same report, we wouldn't be

9 dealing with taking a combined report in 1983 and

10 now re-reviewing it and creating three separate

11 reports.

12 Ron Hill and Tom, does it matter to you

13 whether they all be combined in the one report and

14 three sections or three separate reports?

15 DR. SLAGA: Really, it's the same thing.

16 DR. MARKS: Yes, except we have to know

17 which way we're going to go as we proceed. Should

18 we wait and see what the Belsito Team says? I can

19 see there's not a strong --

20 DR. SLAGA: -- (Off mike) six reports.

21 DR. MARKS: Yes, six. I can see there's

22 not a great strong feeling one way or another, as



1 long as it's separated. So, we'll just say

2 separated in either3 separate reports or within

3 one.

4 Anything more in terms of looking at

5 these individual ones before we come back to this

6 in a future meeting? If there anything else you

7 wanted, Monice, to get any directions?

8 MS. FIUME: I just wanted to make sure

9 so from my understanding, what we will bring back

10 at the next meeting is three reports with what we

11 feel were the proper add-on ingredients that you

12 are more than welcome to take out, but this way,

13 we'd at least have it prepared for you as what we

14 think the next iteration of the reports are.

15 Is that correct?

16 DR. MARKS: Yes. Are there any data

17 needs for these individual ones at this point, and

18 is there enough in this report in terms of the

19 data? Certainly from irritation and

20 sensitization, I thought it was fine. Is there

21 anything else in terms of data needs?

22 Ron, you had mentioned one concern you


Panel Book Page 15



1 had, but --

2 DR. HILL: It was just an information,

3 sort of see if there's anything out there request.

4 Not a data need.

5 DR. MARKS: So, it sounds like the main

6 thing we're going to do next time is clarify the

7 discussion concerning the mouse and concerning the

8 nitrosamine formation for each of these as

9 separate ingredients, and then decide on the

10 add-ons, but in terms of data, it seems like we're

11 okay at this point. Is that --

12 DR. BRESLAWEC: Just to clarify one

13 thing, they'll be draft amended reports that

14 you'll get next time.

15 MS. FIUME: And then the only other

16 thing I was going to say is in Wave 2, you should

17 have received what the original re-review summary

18 was for DEA. So, I will pull from that

19 information, as well, that includes some of your

20 decision-making or conclusion as to why it went

21 the way it did.

22 DR. MARKS: Anything else?


Panel Book Page 16

Rep

ort

Draft Amended Report

Triethanolamine (TEA) and TEA-Containing Ingredients as Used in Cosmetics

June 27, 2011 The 2011 Cosmetic Ingredient Review Expert Panel members are: Chair, Wilma F. Bergfeld, M.D., F.A.C.P.; Donald V. Belsito, M.D.; Ronald A. Hill, Ph.D.; Curtis D. Klaassen, Ph.D.; Daniel C. Liebler, Ph.D.; James G. Marks, Jr., M.D.; Ronald C. Shank, Ph.D.; Thomas J. Slaga, Ph.D.; and Paul W. Snyder, D.V.M., Ph.D. The CIR Director is F. Alan Andersen, Ph.D. This report was prepared by Monice Fiume, Senior Scientific Analyst/Writer.

© Cosmetic Ingredient Review 1101 17th Street, NW, Suite 412 " Washington, DC 20036-4702 " ph 202.331.0651 " fax 202.331.0088 "

[email protected]


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ii

Table of Contents

Introduction ................................................................................................................................................................................. 1 Chemistry ..................................................................................................................................................................................... 2

Definition and Structure .......................................................................................................................................................... 4 Method of Manufacture .......................................................................................................................................................... 4 Stability ................................................................................................................................................................................... 5 Impurities ................................................................................................................................................................................ 5 N-Nitrosodiethanolamine Formation ...................................................................................................................................... 5

Use ............................................................................................................................................................................................... 5 Cosmetic ................................................................................................................................................................................. 5 Non-Cosmetic ......................................................................................................................................................................... 6

Toxicokinetics.............................................................................................................................................................................. 7 Dermal ................................................................................................................................................................................. 7

In Vitro ............................................................................................................................................................................ 7 Non-Human ..................................................................................................................................................................... 7 Human ............................................................................................................................................................................. 8

Oral ...................................................................................................................................................................................... 9 Non-Human ..................................................................................................................................................................... 9

Other .................................................................................................................................................................................... 9 Non-Human ..................................................................................................................................................................... 9

Toxicological Studies .................................................................................................................................................................. 9 Acute (Single) Dose Toxicity ............................................................................................................................................... 10

Dermal ............................................................................................................................................................................... 10 Oral .................................................................................................................................................................................... 10 Other .................................................................................................................................................................................. 10

Repeated Dose Toxicity ........................................................................................................................................................ 10 Dermal ............................................................................................................................................................................... 10 Oral .................................................................................................................................................................................... 11 Inhalation ........................................................................................................................................................................... 11

Reproductive and Developmental Studies ................................................................................................................................. 12 Dermal ............................................................................................................................................................................... 12 Oral .................................................................................................................................................................................... 12

Genotoxicity .............................................................................................................................................................................. 12 In Vitro .................................................................................................................................................................................. 12 In Vivo .................................................................................................................................................................................. 13

Carcinogenicity .......................................................................................................................................................................... 13 Dermal ............................................................................................................................................................................... 13 Oral .................................................................................................................................................................................... 14

Possible Mode of Action for Carcinogenic Effects of TEA .................................................................................................. 14 Carcinogenic Potential in Humans ........................................................................................................................................ 15

Irritation and Sensitization ......................................................................................................................................................... 15 Irritation ................................................................................................................................................................................ 15

Skin .................................................................................................................................................................................... 15 In Vitro .......................................................................................................................................................................... 15 Non-Human ................................................................................................................................................................... 15 Human ........................................................................................................................................................................... 16

Mucosal ............................................................................................................................................................................. 17 In Vitro .......................................................................................................................................................................... 17 Non-Human ................................................................................................................................................................... 17

Sensitization .......................................................................................................................................................................... 17 Non-Human ................................................................................................................................................................... 18 Human ........................................................................................................................................................................... 18

Provocative Testing .............................................................................................................................................................. 18 Phototoxicity/Photoallergenicity ........................................................................................................................................... 19

Non-Human ................................................................................................................................................................... 19 Human ........................................................................................................................................................................... 19


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iii

Clinical Assessment ................................................................................................................................................................... 19 Case Reports ......................................................................................................................................................................... 19

Summary .................................................................................................................................................................................... 20 Tables......................................................................................................................................................................................... 21

Table 1. Conclusions of previously reviewed ingredients and components......................................................................... 21 Table 2. Definitions and structures ...................................................................................................................................... 22 Table 3. Physical and Chemical Properties .......................................................................................................................... 38 Table 4a. Frequency and concentration of use according to duration and type of exposure ................................................ 39 Table 4b. Ingredients not reported to be used ....................................................................................................................... 42

References ................................................................................................................................................................................. 43


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INTRODUCTION

In 1983, the Cosmetic Ingredient Review (CIR) Expert Panel issued a report on the safety of Triethanolamine,

Diethanolamine, and Monoethanolamine. In 2010, the Panel decided to reopen that safety assessment as three separate

reports and to add additional related ingredients included in each of the new reviews. This assessment addresses triethanol-

amine (TEA) and 93 possible add-on cosmetic ingredients containing TEA.

TEA, an ingredient that functions as a surfactant or pH adjuster in cosmetic products, has previously been reviewed

by the CIR Expert Panel. In 1983, the Expert Panel concluded that TEA is safe for use in cosmetic formulations designed for

discontinuous, brief use followed by thorough rinsing from the surface of the skin.1 In products intended for prolonged

contact with the skin, the concentration of TEA should not exceed 5%. TEA should not be used with products containing N-

nitrosating agents. In the 1983 assessment, data demonstrated that TEA was a mild skin and eye irritant, and that irritation

increased with increasing ingredient concentration.

The following 93 ingredients are the potential “add-ons” to the TEA re-review. The ingredients are sorted by chem-

ical class. Most of these ingredients function in cosmetics as surfactants, viscosity increasing agents, skin conditioning

agents, or hair conditioning agents. A few ingredients may function as a chelating agent, binder, film former, or emulsion

stabilizer. TEA-sorbate functions only as a preservative and TEA-salicylate as a light stabilizer or sunscreen agent.

It is almost certain that the Expert Panel will delete some of the ingredients from this list; however, all are being

presented, as requested by the Panel.

Inorganic salts TEA-Hydrochloride TEA-Sulfate Organic acid salts TEA-Laurate TEA-Laurate/ Myristate TEA-Myristate TEA-Palmitate TEA-Stearate* TEA-Isostearate TEA-Undecylenate

TEA-Sorbate TEA-Oleate TEA-Canolate TEA-Cocoate TEA-Hydrogenated Cocoate TEA-Rosinate TEA-Tallate TEA-Glyceryl Dimaleate

Triethanolamine diester TEA-Diricinoleate Hydroxy Acid Salts TEA-Lactate* TEA-Salicylate* Amine & Amide Acid Salts TEA-EDTA* TEA-Myristaminopropionate TEA-Lauraminopropionate Di-TEA-Palmitoyl Aspartate TEA-Cocoyl Glycinate TEA-Cocamide Diacetate TEA-Cocoyl Alaninate TEA-Cocoyl Sarcosinate TEA-Hydrogenated Tallowoyl Glutamate

TEA-Lauroyl Glutamate TEA-Lauroyl Methylaminopropionate TEA-Lauroyl/Myristoyl Aspartate TEA-Lauroyl Sarcosinate TEA-Oleoyl Sarcosinate TEA-PCA Di-TEA Cocamide Diacetate TEA-Cocoyl Glutamate TEA-Cocoyl Glutaminate TEA-Palm Kernel Sarcosinate


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2

Ester Acid Salts TEA-PEG-50 Hydrogenated Castor Oil Succinate TEA-Lauroyl Lactylate Inorganic Acid Salts -Sulfates and Sulfonates Magnesium/TEA-Coco-Sulfate Sodium/TEA C12-13 Pareth-3 Sulfate Di-TEA-Oleamido PEG-2 Sulfosuccinate TEA-Lauryl Sulfate* TEA-Laneth-5 Sulfate TEA-Laureth Sulfate TEA-Oleyl Sulfate TEA-C10-15 Alkyl Sulfate

TEA-C11-15 Alkyl Sulfate TEA-C12-13 Alkyl Sulfate TEA-C12-14 Alkyl Sulfate TEA-C12-15 Alkyl Sulfate TEA C14-17 Alkyl Sec Sulfonate TEA-Coco-Sulfate TEA-C11-15 Pareth Sulfate TEA-C12-13 Pareth-3 Sulfate TEA-PEG-3 Cocamide Sulfate TEA-Dodecylbenzenesulfonate* TEA-Tridecylbenzenesulfonate*

-Phosphates TEA-Lauryl Phosphate TEA-Laureth-4 Phosphate TEA-C12-13 Alkyl Phosphate

TEA-C12-14 Alkyl Phosphate TEA-Dimethicone PEG-7 Phosphate TEA-Polyphosphate

Polysaccharide & Protein Salts TEA-Cocoyl Hydrolyzed Collagen* TEA-Alginate TEA-Isostearoyl Hydrolyzed Collagen Sodium/TEA-Lauroyl Collagen Amino Acids Sodium/TEA-Lauroyl Hydrolyzed Collagen Sodium/TEA-Lauroyl Hydrolyzed Keratin Sodium/TEA-Lauroyl Keratin Amino Acids Sodium/TEA-Undecylenoyl Alginate Sodium/TEA-Undecylenoyl Carrageenan Sodium/TEA-Undecylenoyl Collagen Amino Acids Sodium/TEA-Undecylenoyl Hydrolyzed Collagen

Sodium/TEA-Undecylenoyl Hydrolyzed Corn Protein Sodium/TEA-Undecylenoyl Hydrolyzed Soy Protein Sodium/TEA-Undecylenoyl Hydrolyzed Wheat Protein TEA-Abietoyl Hydrolyzed Collagen TEA-Cocoyl Hydrolyzed Soy Protein TEA-Dextrin Octenylsuccinate TEA-Lauroyl Collagen Amino Acids TEA-Lauroyl Hydrolyzed Collagen TEA-Lauroyl Keratin Amino Acids TEA-Myristoyl Hydrolyzed Collagen TEA-Oleoyl Hydrolyzed Collagen TEA-Undecylenoyl Hydrolyzed Collagen

Polymer Salts TEA-Acrylates/Acrylonitrogens Copolymer TEA-Acrylates/Ethylhexyl Acrylate Copolymer TEA-Carbomer TEA-Diethanolaminoethyl Polyisobutenylsuccinate

The ingredients marked with an asterisk have been previously reviewed by the CIR, and the conclusions of the

safety assessments of these ingredients are provided in Table 1.

CHEMISTRY

TEA is an amino alcohol. TEA is produced commercially by aminating ethylene oxide with ammonia. The replacement of three hydrogens of ammonia with ethanol groups produces TEA. (Figure 1). TEA contains small amounts of diethanolamine (DEA) and ethanolamine (MEA).

HON

OH

OH

Figure 1. TEA TEA is reactive and bifunctional, combining the properties of alcohols and amines. The reaction of ethanolamines and sulfuric acid produces sulfates. TEA can act as an antioxidant against the autoxidation of fats of both animal and vegetable origin. TEA can react with nitrite or oxides of nitrogen to form N-nitrosodiethanolamine (NDELA). The optimum pH for nitrosamine formation is between 1 and 6; however the rate of NDELA formation in the pH range of 4-9 is four to six times greater in the presence of formaldehyde. From the Final Report on the Safety Assessment of Triethanolamine, Diethanolamine, and Monoethanolamine1


Panel Book Page 21

3

TEA-cocoyl hydrolyzed collagen is prepared by the hydrolysis of collagen to short-chain polypeptides, followed by the addition of coconut fatty acid, and then neutralization of the terminal carboxyl group of the fatty acid with TEA. Impurities reported in TEA-cocoyl hydrolyzed collagen include coconut fatty acids, hydrolyzed animal protein (collagen), TEA sulfate, sodium chloride, and sodium sulfate. From the Final Report on the Safety Assessment of Triethanolamine-Coco-Hydrolyzed Animal Protein2

Of concern in cosmetics is the conversion (nitrosation) of secondary amines (R1-NH-R2), such as DEA (wherein R1

and R2 are each ethanol), into N-nitrosamines that may be carcinogenic. Tertiary alkyl amines (NR1R2R3), such as TEA

(wherein R1, R2, and R3 are each ethanol), however, do not tend to react with nitrosating agents to form nitrosamines directly.

However, tertiary amines can act as precursors in nitrosamine formation by undergoing nitrosative cleavage (e.g., one ethanol

functional group can be cleaved off of TEA to generate DEA). The resultant secondary amine (i.e. DEA) can then be

nitrosated (i.e. to NDELA).

Acid Salts

The acid salts (inorganic salts, organic acid salts, and hydroxy acid salts), mentioned above, are ion pairs which

freely dissociate in water (e.g., Figure 2). Therefore, these salts are closely related to the corresponding free acids and TEA.

In other words, TEA stearate is closely related to stearic acid and TEA.

Figure 2. TEA Stearate

Amine and Amide Acid Salts The amine and amide acid salts consist of organic acid salts which have the additional functional group of either an

amine or an amide (e.g., Figure 3). Therefore, these salts are closely related to the corresponding amine or amide containing

free acids and TEA. In other words, TEA-myristaminopropionate is closely related to myristaminopropionic acid and TEA.

Figure 3. TEA-Myristaminopropionate Organo-Substituted Inorganic Acid Salts

The organo-substituted inorganic acid salts can be segregated into sulfur or phosphorus acids. The sulfates and

sulfonates consist of organic acid salts which have the additional functional group of sulfate or sulfonate. For example, TEA

lauryl sulfate is a twelve carbon alkyl chain (i.e. lauryl) attached to a sulfate anion, balanced with a triethanolammonium

cation (Figure 4).


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4

Figure 4. TEA-Myristaminopropionate

Protein Salts, Polysaccharide Salts, and Polymer Salts

The protein, polysaccharide, and polymer salts consist of natural and synthetic polymers which have at least one

carboxylate anion paired with a triethanolammonium cation. For example, TEA-acrylates/acrylonitrogens copolymer is the

polymer formed from the partial hydrolysis of polyacrylonitrile, neutralized by TEA (Figure 5). Therein, the acrylonitrile

residues are segregated into blocks of 1) untouched, acrylonitrile residues, 2) partial hydrosylate, acrylamide residues, and 3)

hydrosylate, acrylate residues (which are later converted to the TEA salt).

Figure 5. TEA-Acrylates/Acrylonitrogens Copolymer

Some of the acids or salts that comprise these ingredients have been reviewed by the CIR. Conclusions of these

reports are provided in Table 1.

Definition and Structure

The definitions and structures of TEA and the possible add-on ingredients are provided in Table 2. Chemical and

physical properties are described in Table 3.


TEA

TEA is produced by reacting 3 moles of ethylene oxide with 1 mole of ammonia; additional ethylene oxide will con-

tinue to react to produce higher ethylene oxide adducts of TEA.3 Typically, ethylene oxide is reacted with ammonia in a

batch process to produce a crude mixture of approximately one-third each MEA, DEA, and TEA. The crude mixture is later

separated by distillation.

TEA-Stearate

TEA stearate was produced by mixing partially neutralized stearic acid and TEA at temperatures above 80°C, and

then cooling.4 It was determined that the acid-soap complex at a 2:1 fixed stoichiometric ratio was formed between TEA

stearate and stearic acid.

TEA-Lauryl Sulfate

TEA-lauryl sulfate is manufactured by neutralizing lauryl sulfuric acid with aq. TEA. From the Final Report on the Safety Assessment of TEA-Lauryl Sulfate.5


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Commercial alkyl sulfates are produced by the sulfation of primary alcohols using sulfur trioxide or chlorosulfonic

acid followed by neutralization with a base to produce the corresponding salt.6

Stability

TEA-Stearate

TEA stearate was produced as described previously. On cooling, a lamellar gel phase formed.7 Solid crystals were

observed after 5 h. Upon storage, the sample gradually separated into two phases; after a few weeks, a separate liquid phase

and a solid-pearly crystalline phase were observed.

Impurities

TEA

Based on unpublished survey data collected by the Food and Drug Administration (FDA), a DEA impurity level of

0.3% was found in TEA samples.8

TEA Lauryl Sulfate

Impurities in TEA-lauryl sulfate may include TEA, TEA-sulfate, unsulfated alcohol, TEA chloride, and formaldehyde (some grades). From the Final Report on the Safety Assessment of TEA-Lauryl Sulfate.5

Sodium sulfate and residual alcohols may be present as impurities in commercial alkyl sulfate products.6 Typically,

industrial alkyl sulfates contain 1-4% sodium sulfate and 0.5-18% residual alcohol.

N-Nitrosodiethanolamine Formation

Nitrosamines are compounds containing the R1R2N-NO functional group. Nitrosation is the process of converting

organic compounds (e.g., alkyl amines) into nitroso derivatives (e.g., nitrosamines) by reaction with nitrosating agents.

These agents include nitrous acid (HNO2), oxides of nitrogen (e.g., nitrites), and other compounds capable of generating a

nitrosonium ion, NO+.

The formation of a specific nitrosamine, NDELA, from reaction of TEA with nitrite was examined in vitro and in

vivo.9 The TEA used in these studies had an impurity content of 0.4% DEA. In an aqueous (aq.) matrix, approximately 3%

TEA converted to NDELA at a pH of 4.0 in the presence of acetic acid. At the same pH, in the presence of sulfuric or hydro-

chloric acid, only about 1% of the TEA was nitrosated. At pH 7, the greatest nitrosation to NDELA, 0.5%, occurred in the

presence of sulfuric acid. No conversion of TEA to NDELA was detected at pH 2 or 10. In nutrient broth cultures (neutral

pH), 0.08% and 0.68% of the TEA was nitrosated to NDELA in a diluted (high cecal inoculum) and full-strength (low cecal

inoculum) media. (The percent nitrosation was determined using values that were corrected for DEA impurity-related

NDELA formation).

In vivo, female B6C3F1 mice were dosed dermally or orally with 1000 mg/kg TEA, in conjunction with oral expo-

sure to sodium nitrite.9 Following 7 days of dermal dosing, no NDELA was detected in the blood, ingesta, or urine of test,

vehicle control, or sodium nitrite control mice. (The limits of detection for the blood, ingesta, and urine were 0.001, 0.006,

and 0.47 µg/ml, respectively). With a single oral dose, the concentrations of NDELA found in the blood and ingesta of mice

2 h post-dosing were 0.001 ± 0.0005 µg/g and 0.044 ± 0.059 µg/g, respectively.

USE

Cosmetic

TEA functions in cosmetics as a surfactant or pH adjuster, and it can be used in fragrances.10 Most of the other TEA

ingredients function in cosmetics as surfactants, viscosity increasing agents, skin conditioning agents, or hair conditioning

agents. A few ingredients may function as a chelating agent, binder, film former, or emulsion stabilizer. Notable exceptions


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are TEA-sorbate, which functions as a preservative, and TEA-salicylate, which functions as a light stabilizer or sunscreen

agent.

Voluntary Cosmetic Registration Program (VCRP) data obtained from the FDA in 2011 indicate that TEA is used in

3745 formulations; 3023 of those products are leave-on formulations, and 3100 formulations involve dermal exposure.11

According to data submitted by industry in response to a survey conducted by the Personal Care Products Council (Council),

TEA is used at concentrations of 0.0002-19%.12 In leave-on products, the reported use concentrations range from 0.0002-

6%. The number of leave-on and dermal contact uses have increased substantially since the original 1983 review, and the

maximum concentration of use has decreased. The number of non-coloring hair formulations and formulations involving

mucous membrane exposure increased greatly since 1981.

Three other TEA ingredients had greater than 100 uses: TEA-lauryl sulfate (3202 uses), TEA-stearate (130 uses),

and TEA-dodecylbenzenesulfonate (116 uses).11 TEA-lauryl sulfate had the highest concentrations of use, with ≤40% being

reported for rinse-off and ≤8% for leave-on formulations.13 The available use data on all in-use ingredients are provided in

Table 4a. Ingredients not reported to be in use, according to VCRP data and a Council survey, are listed in Table 4b

The dermal exposure of consumers to TEA was estimated assuming 2.5% TEA in cosmetic products (based on the

limit set by the European Commission [EC]) and that all TEA is unreacted.14 Using an EC algorithm method, the dermal

exposure of consumers to an eye make-up powder is 0.0125 mg/kg bw/day and to a body lotion is 6.25 mg/kg bw/day. Using

a DERMAL program method, the dermal potential dose rate for a bar soap containing 2.5% TEA is 5.182 mg/day.

Products containing TEA may be applied to baby skin, used near the eye area or mucous membranes, or could

possibly be ingested or inhaled. Since TEA is reported to be in products that could be inhaled, and effects on the lungs that

may be induced by aerosolized products containing these ingredients are of concern. The particle size of aerosol hair sprays

and in pump hair sprays is around 38 μm and >80 μm, respectively, and is large compared to respirable particle sizes (≤10

μm). Therefore, because of their size, most aerosol particles are deposited in the nasopharyngeal region and are not

respirable. The melting point of TEA is very close to room temperature. Accordingly, depending on storage and application

conditions, aerosolized TEA may be a liquid/vapor, instead of a particle.

All of the ingredients named in this report are listed by the EC in Annex III Part 1, i.e. the list of substances which

cosmetic products must not contain, except subject to the restrictions and conditions laid down.15 The ingredients reviewed

in this safety assessment, trialkylamine, trialkanolamines, and their salts, are allowed at up to 2.5% in non rinse-off products.

In leave-on and rinse-off, the following limitations apply: do not use with nitrosating systems; minimum allowable purity is

99%; maximum allowable secondary amine content is 0.5% in raw material; maximum allowable nitrosamine content is 50

µg/kg; must be kept in nitrite-free containers. The following ingredients are listed by the EC for use as preservatives, with

the maximum concentration of use based on the free acid: TEA-undecylenate (0.2%). TEA-sorbate (0.6%), and TEA-

salicylate (0.5%).16

According to data obtained from Health Canada, some leave-on type products reportedly use TEA as high 10 and

30%, with some reporting 100% TEA (Health Canada, personal communication).

Non-Cosmetic

TEA

TEA is used in the manufacture of emulsifiers and dispersing agents for textile specialties, agricultural chemicals, waxes, min-eral and vegetable oils, paraffin, polishes, cutting oils, petroleum demulsifiers, and cement additives. It is an intermediate for resins, plasticizers, and rubber chemicals. It is used as a lubricant in the textile industry, as a humectant and softening agent for hides, as an alkalizing agent and surfactant in pharmaceuticals, as an absorbent for acid gases, and in organic syntheses. From the Final Report on the Safety Assessment of Triethanolamine, Diethanolamine, and Monoethanolamine.1


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TEA, TEA-myristate, TEA-palmitate, TEA-oleate, TEA-cocoate, and TEA-tallate have uses as an indirect food

additive.17 TEA is used as a rust inhibitor in water-based metalworking fluids.18 TEA-salicylate is approved as an

ultraviolet filter in sunscreens at concentrations up to 12%.19

TOXICOKINETICS

Dermal absorption studies of TEA were performed using mice and rats. In mice, [14C]TEA in acetone was rapidly absorbed, and absorption increased with increasing dose. The majority of the radioactivity was excreted in the urine, 48-56% in 72 h, primarily as unchanged TEA. TEA was absorbed more slowly and less extensively in rats than mice. Over a 72-h period, 19-28% of the dose was absorbed, and 13-24% of the dose was recovered in the urine, mostly as unchanged TEA. In an oral dosing study with rats, TEA was rapidly absorbed in the gastro-intestinal tract and excreted mostly in the form of unchanged TEA. The dermal penetration of salicylate from a formulation containing 10% TEA-salicylate was investigated in vitro and in vivo. In vitro, 1 g of the formulation was applied to full-thickness skin samples from rats and humans. The penetration of salicylate measured as flux was 39.9 µg/cm2/h with rat skin and 8.7 µg/cm2/h with human skin. With in vivo testing, the formulations were applied to rat skin for intervals of up to 6 h. No salicylate was found in the deep muscle or fat under the application site, and very little salicylate was found in the plasma. In humans there was no evidence of direct tissue penetration of salicylate following dermal application.

Dermal

In Vitro TEA-Salicylate

The dermal penetration of TEA-salicylate was determined using full-thickness skin from male Wistar rats.20 One g

of a formulation containing 10% TEA-salicylate was applied to a 1.3 cm2 area for 28 h. Three skin samples were tested. The

test site was then wiped and tape stripped one time. The permeability of salicylate measured as flux was 39.9 µg/cm2/h, and

the permeability coefficient was 0.798 x 10-3 cm/h. The amount of salicylate absorbed in 24 h was 1029.4 µg/cm2, and the

amount of salicylate remaining in the tissue after the 28-h application was 653.3 µg/g.

Full-thickness human breast skin and epidermal membranes were used in an in vitro study examining the dermal

penetration of salicylic acid from TEA-salicylate.21 Five samples were used. One g of a formulation containing 10% TEA-

salicylate was applied to a 1.3 cm2 area for 24 h. Using full-thickness skin samples, the permeability of salicylic acid as flux

was 8.7 µg/cm2/h. After removing the top layer of the stratum corneum with a single tape strip, the amount of salicylic acid

in 100 mg of the full-thickness human skin sample after exposure to TEA-salicylate was 73.8 µg. In the epidermal mem-

branes exposed to TEA-salicylate, penetration of salicylic acid measured as flux was 26.7 µg/cm2/h and the amount of sali-

cylic acid in 100 mg of the sample after exposure was 1579.7 µg.

Non-Human TEA

The blood kinetics and absorption, distribution, metabolism, and excretion (ADME) of [14C]TEA were determined

following dermal application of 2000 mg/kg neat [14C]TEA without occlusion to 24 male C3H/HeJ mice and with occlusion

to 3 male mice.22 (Non-radiolabeled TEA was 99.6% pure; radiochemical purity was 98.6%). TEA was extensively and

rapidly absorbed following a single open application of 2000 ml/kg neat [14C]TEA. The majority of the radioactivity, 49-

62% of the total dose (~58-72% of the absorbed dose), was excreted in the urine, primarily as unmetabolized TEA. DEA and

MEA were not detected in the urine. Approximately 18-28% of the total dose (~20-32% of the absorbed dose) was excreted

in the feces. The amount of radioactivity remaining in the body after 48 h ranged from 3.3-6.1%, and the amount recovered

at the application site ranged from 1.2-2.1% for the open applications and 6-11% for the

The National Toxicology Program (NTP) examined the ADME of TEA following dermal administration to B6C3F1

mice and F344 rats.23 With mice, groups of 4 females were given a single dose of 79 or 1120 mg/kg [14C]TEA in acetone;


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the dose contained 12-15 µCi, with the appropriate amount of non-labeled TEA in a volume of 190 µl/dose. (Radiochemical

purity of [14C]TEA was 97%; the purity of non-labeled TEA was confirmed, but the purity was not stated). The dose was ap-

plied to a 1.44 cm2 area of clipped skin, and a non-occlusive cover was used. Approximately 60-80% of the dose was ab-

sorbed, and absorption increased with increasing dose. In the urine 22.5-27.5% and 48-56% of the dose was recovered after

24 and 72 h, respectively, and TEA was excreted mostly unchanged. Approximately 5-9 and 8-13% of the dose was recov-

ered in the feces at the same time periods.

With rats, groups of 4 females were given a single dermal dose of 68 or 276 mg/kg [14C]TEA in acetone; the dose

contained 65 µCi, with the appropriate amount of non-labeled TEA in a volume of 190 µl/dose. The dose was applied to a 12

cm2 area of clipped skin, and a non-occlusive cover was used. Only 19-28% of the dose was absorbed over 72 h; absorption

increased with increasing dose, but not significantly. In the urine, 13-24% of the dose was recovered in 72 h as mostly un-

changed TEA. The amount recovered in the feces after 72 h was <0.25%. Very little radioactivity, <1%, was present in the

tissues; a number of tissues had elevated concentrations of radiolabel relative to blood.

TEA-Salicylate

In a dermal absorption study in rabbits, 14.59% of a 36.2 mmol/100g dose of TEA-salicylate (applied for 6 h) was excreted in the urine in 48 h. In Beagle dogs 1 h after dermal application of up to 10 g TEA-salicylate, most of the dose was recovered at the application site. More than 82% of a dermal application of 1.5 g of a 10% TEA-salicylate formulation was absorbed in Yorkshire swine. From the Final Report on the Safety Assessment of Salicylic Acid [and Salicylates]24

The absorption of salicylate from dermally applied TEA-salicylate was determined using groups of 3 male Wistar

rats per time point examined.20 One g of a formulation containing 10% TEA-salicylate was applied to a 9.6 cm2 area of the

abdomen of anesthetized rats. There is no indication that the test site was occluded. Blood samples were taken at 0.5, 1, 2, 4,

and 6 h, and the animals were then killed. Tissue samples that included deep muscle and fat were excised at the test site; the

epidermis was removed. At 6 h after dosing, 1400, 650, and 200 µg/g total salicylate was found in the dermis, subcutaneous

tissue, superficial muscle, respectively. In these three tissues, the salicylate levels rose for the first hour, were decreased at 2

h, and then increased until the end of the study. No salicylate was found in the deep muscle or fat. Very little (approximately

10 µg/ml) salicylate was found in the plasma at any of the time points.

TEA-Lauryl Sulfate

Skin irritation tests in guinea pigs suggested that TEA-lauryl sulfate may be absorbed in toxic amounts. From the Final Report on the Safety Assessment of TEA-Lauryl Sulfate.5

Human TEA-Salicylate

In dermal absorption studies in arthritic males, only small amounts of salicylate were found in the synovial fluid, blood, and urine. From the Final Report on the Safety Assessment of Salicylic Acid [and Salicylates]24

Cutaneous microdialysis was performed to determine the penetration of salicylic acid from dermally applied TEA-

salicylate.21 A “dermal” probe and a “subcutaneous” probe were inserted superficially into the forearms of 4 subjects. The

dermal probe, but not the subcutaneous probe, was inserted in a way that would cause an axon reflex flare. A formulation

containing 10% TEA-salicylate was applied to a 16 cm2 area of skin over the probe tips, 10 mm away from the insertion

points, and dialysate samples were collected at 30-60 min intervals for up to 360 min. The researchers stated that the formu-

lations were reapplied every 2 h during sampling, but the actual dose applied was not given. Two of the subjects applied

“liberal amounts” of the test formulation every 2-3 h, 24 h prior to probe insertion. The levels of salicylate in the dermal and

subcutaneous probes were low, near the limits of detection, in both the pre-exposed and non-pre-exposed subjects. The tissue


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concentration of salicylate ranged from 0.001-0.08 µg/ml in the dermal probe and from 0.001-0.03 µg/ml in the subcutaneous

probes. The tissue:plasma ratio following dermal application of 10% TEA-salicylate ranged from 0.1-4.4 with the dermal

probes and from 0.1-1.5 with the subcutaneous probes. The researchers stated that the 10% TEA-salicylate formulation

showed no evidence of direct tissue penetration following topical application.

Oral

Non-Human TEA

TEA (purity not specified) was administered orally to male and female rats as a single dose or as a repeated dose for

5-6 days.25 (Dosing details were not described). At 24 h after administration of the single dose, the excretion ratio of un-

changed TEA in the urine and feces was 53 and 20% of the dose, respectively. With repeated administration, the excretion

ratio per day remained constant. Gender did not affect the ratios. TEA glucuronide was detected, but in a very small amount.

(Actual concentration not specified). TEA was rapidly absorbed in the gastrointestinal tract, and excreted mostly in the urine

in unchanged form.

Other

Non-Human TEA

A group of 27 male C3H/HeJ mice was given an intravenous (i.v.) injection of 1 mg/kg [14C]TEA as an aq. solution

(0.5 mg/ml), and the dose volume was 2 ml/kg.22 (Non-radiolabeled TEA was 99.6% pure; radiochemical purity was 98.6%).

Radioactivity in the blood declined in a biphasic, exponential manner for 24 h, with a relatively rapid initial phase of [14C]

elimination, followed by a slower terminal phase. The majority of the radioactivity, approximately 69%, was excreted in the

urine, primarily as unmetabolized TEA. DEA and MEA were not detected in the urine. Some of the radioactivity, ~17%,

was excreted in the feces. The average amount of radioactivity recovered in the tissues was 3.1%.

The NTP examined the ADME of TEA following i.v. administration to B6C3F1 mice and F344 rats.23 Groups of 4

female mice and 4 female rats were given a single i.v. dose of 3 mg/kg [14C]TEA in isotonic saline. For mice, the dose con-

tained 6 µCi, with the appropriate amount of non-labeled TEA, for a dosing volume of 2 ml/kg. (Radiochemical purity of

[14C]TEA was 97%; the purity of non-labeled TEA was confirmed, but the purity was not stated). At 24 h, 26 and 14% of the

dose was excreted in the urine and feces, respectively, while at 72 h, these values were 62 and 28%, respectively. TEA was

excreted mostly unchanged. Little, <0.5%, was detected in expired carbon dioxide. A number of tissues contained higher

concentrations of TEA equivalents relative to blood. For rats, the dose contained 47 µCi, with the appropriate amount of

non-labeled TEA, for a dosing volume of 1 ml/kg. Much more of the radioactivity was excreted in the urine for rats com-

pared to mice, and excretion was more rapid. Approximately 90% of the dose was recovered in the urine in 24 h, and 98% in

72 h, mostly as unchanged TEA. Like mice, <0.5%, was detected in expired carbon dioxide. Only 0.9% of the radioactivity

was detected in the tissues after 72 h.

TOXICOLOGICAL STUDIES

In 2 and 13-wk repeated dose dermal toxicity studies in mice with 250-2000 mg/kg bw TEA in acetone or 4000 mg/kg bw neat, dermal irritation was observed in the highest dose group, and kidney and liver weights were increased with the higher doses. In rats, 125-1000 mg/kg bw TEA in acetone or 24000 mg/kg bw neat was applied to rats for 13 wks, irritation was observed at the dosing site. Kidney weights were increased in males and females of rats dosed with ≥500 mg/kg TEA, and dosed females had higher incidences of nephropathy. In a 14-day drinking water study, animals given 8%TEA in drinking water were all killed due to severe hydration before study terminations. Treatment-related changes were not observed for animals given 2 or 4^% TEA in their water.


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Acute (Single) Dose Toxicity

Dermal

TEA

The acute dermal toxicity of TEA was examined using groups of 6 rabbits. Undiluted TEA, 91.8 and 88.1% active, was applied to the intact and abraded skin of 3 rabbits under a 24 h occlusive patch. The exposure to actual TEA was 2 g/kg. None of the animals died. Mild erythema and edema were reported at 24 h. From the Final Report on the Safety Assessment of Triethanolamine, Diethanolamine, and Monoethanolamine.1

Oral

TEA

The acute oral toxicity of TEA was determined using guinea pigs and rats. In guinea pigs, undiluted TEA has an LD50 of 8 g/kg, and the LD50 of TEA in a gum arabic solution was between 1.4 and 7.0 g/kg. Using rats, the oral LD50 of undiluted TEA ranged from 4.19 g/kg- 11.26 g/kg. The purity ranged from 78.6% TEA (with 8.6% DEA and 1.7% MEA) to unspecified high purity. From the Final Report on the Safety Assessment of Triethanolamine, Diethanolamine, and Monoethanolamine1 TEA-cocoyl Hydrolyzed Collage was practically non-toxic in rats. From the Final Report on the Safety Assessment of Triethanolamine-Coco-Hydrolyzed Animal Protein2

TEA-Lauryl Sulfate

TEA-lauryl sulfate was moderately to slightly toxic in acute oral studies with rats, LD50 values ranged from 0.27 > 1.95 g/kg. From the Final Report on the Safety Assessment of TEA-Lauryl Sulfate.5

The LD50 of TEA-lauryl sulfate in male and female Wistar rats was >2 g/kg.26

TEA-Dodecylbenzenesulfonate

The acute oral toxicity of 10% aq. TEA-dodecylbenzenesulfonate was determined using female albino rats, 5 per

group.27 Doses of 0.252-7.95 g/kg bw were administered by gavage. The oral LD50 of TEA-dodecylbenzenesulfonate in

rabbits was 1.5 g/kg.

Other

TEA

The intraperitoneal LD50 of TEA was 1.45 g/kg for mice. From the Final Report on the Safety Assessment of Triethanolamine, Diethanolamine, and Monoethanolamine.1

Repeated Dose Toxicity

Dermal

TEA

A closed-patch continuous exposure test was performed using 10 guinea pigs in which commercial and high purity TEA, 8 g/kg, was applied daily 5 days/wk. All guinea pigs died by the 17th application; adrenal, pulmonary, hepatic, and renal damage were observed. In a 13-wk study, 1 mg/kg of a hair dye formulation containing 0.1-0.15% or 1.5% TEA was applied to the backs of 12 rabbits for 1 h, twice weekly. The test site skin was abraded for half of the animals. No systemic toxicity was observed, and there was no histomorphologic evidence of toxicity. In a 6-mos study in which TEA was applied caudally to rats for 1 h/day, 5 days/wk, no toxic effects were observed with a 6.5% solution. However, using a 13% solution, changes (not specified) were seen in liver and central nervous system function. The addition of 1.4 mg/l TEA to the drinking water of the rats dosed dermally with 13% TEA did not increase the toxic effects. In inhalation studies with TEA in rats and mice, no observations were reported that were indicative of a toxic pulmonary effect. From the Final Report on the Safety Assessment of Triethanolamine, Diethanolamine, and Monoethanolamine.1

In a 2-wk study, undiluted TEA (purity not specified) was applied dermally to B6C3F1 mice at doses of 0.21-3.37

g/kg and to F344 rats at doses of 0.14-2.25 g/kg, 5 days/wk.28 Chronic active necrotizing inflammation of the skin at the

application site occurred at a greater frequency and severity in rats than in mice. No renal or hepatic lesions were detected

with either species.


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In a 2 wk and a 13-wk dermal study with up to 100% TEA (99.3% pure) in acetone using male and female C3H/HeJ

mice, no toxicity or irritation was observed. 29 The only treatment-related effect was a mild thickening of the epidermis. In a

13-wk NTP dermal study using male and female B6C3F1 mice, application of 250-2000 mg/kg bw TEA in acetone or 4000

mg/kg neat resulted in decreased mean body weights and body weight gains for some male mice.30 (Purity of TEA was 99%.

Functional group titration indicated <0.4% MEA or DEA). Irritation was observed for the highest dose group. Microscopi-

cally, inflammation was observed for this dose group and acanthosis was noted for all dose groups, with severity increasing

with dose. Absolute kidney and liver weights of males and females of the 4000 mg/kg group and relative kidney to body

weights of males dosed with ≥1000 mg/kg were increased compared to controls. Absolute and relative spleen weights were

also significantly increased in high dose female mice compared to controls.

In a 13-wk dermal study using male and female F344/N rats, application of 125-1000 mg/kg bw TEA (99% pure) in

acetone or 2000 mg/kg neat, resulted in significant decreases of mean body weights and body weight gains in the high dose

animals.30 (Functional group titration indicated <0.4% MEA or DEA present). Irritation was observed at the application site.

Microscopic lesions included acanthosis and inflammation. Kidney weights of males and females dosed with ≥500 mg/kg

were increased compared to controls, and dosed females, but not males, had greater incidences of nephropathy, as compared

to controls.

TEA-Lauryl Sulfate

In a 28-day dermal study, application of a diluted shampoo containing 1% TEA-lauryl sulfate to rabbit skin caused erythema, edema, wrinkling, eschar formation, and severe desquamation. In a 13-wk dermal study in rabbits with a diluted shampoo containing 2.4% TEA-lauryl sulfate, mild erythema and dryness were observed. From the Final Report on the Safety Assessment of TEA-Lauryl Sulfate.5

Oral

TEA

Oral studies were conducted in which groups of 8-20 rats were dosed with 0.2-2.61 g/kg/day TEA for 60 days to 6 mos, and groups of 8 guinea pigs were dosed with 0.2-1.6 g/kg/day TEA for 60 or 120 doses. Repeated oral ingestion of TEA produced evidence of hepatic and renal damage. Some deaths occurred in groups of rats fed ≥0.17 g/kg/day TEA. From the Final Report on the Safety Assessment of Triethanolamine, Diethanolamine, and Monoethanolamine.1

Male and female B6C3F1 mice and F344 rats were given drinking water containing 2 -8% TEA (purity not speci-

fied) for 14 days.31,32 Male and female high dose mice, and male and female rats given ≥4% TEA, had decreased body

weights. All but one of the high dose rats were euthanized early due to severe dehydration. No treatment-related changes

were observed in mice given 4% TEA or rats given 2% TEA in the drinking water.

Inhalation

TEA

In a 5-day dose-range finding inhalation study, 5 male and 5 female Wistar rats were exposed, nose only, to target

concentrations of 100-400 mg/m3 TEA (98.9% pure) for 6 h.33 Concentration-dependent laryngeal inflammation and edema

were observed at microscopic examination, and the no observed adverse effect concentration (NOAEC) was 100 mg/m3. The

full, 28 day/20 exposure study used target concentrations of 0, 20, 100, and 500 mg/m3, and the mass median aerodynamic

diameter (MMAD) was 0.7-1.1 µm. A functional observational battery was conducted using 7 rats/sex/group. Minimal to

moderate focal inflammation in the submucosa of the larynx was observed; effects were concentration-dependent. No sys-

temic toxicity was observed, and there were no effects on organ weights. There were no indications of neurotoxicological

effects. Based on the results of this study, the 90-day NOAEC for local irritation was calculated to be 4.7 mg/m3. (The

extrapolation of the 28-day laryngeal irritation used the calculation of benchmark concentrations for a 5% incidence of

mucosal inflammation, without consideration of severity, using a multistage model).


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In a 14-day inhalation study, B6C3F1 mice and F344 rats were exposed to 125-2000 mg/m3 TEA (purity not

specified) 6h/day, 5 days/wk, for 2 wks.34,35 Female mice and male and female rats of the high dose group had decreased

body weights, and male mice of the high dose group had increased kidney weights. Increased kidney weights in rats dosed

with ≥500 mg/m3, and decreased thymus and heart weights in mice at all doses, were not clearly associated with TEA. The

only histopathologic observation was a minimal acute inflammation of the laryngeal submucosa in both mice and rats;

however, this occurred sporadically and there was no dose-response associated with this lesion.

REPRODUCTIVE AND DEVELOPMENTAL STUDIES

No adverse reproductive effects were seen in dermal studies in which rats and mice were dosed with TEA in acetone from before mating through lactation or in an oral teratogenicity screening test in mice.

Dermal

TEA

Hair dyes containing 0.1-0.15% or 1.5% TEA were applied topically to the shaved skin of groups of 20 gravid rats on days, 1, 4, 7, 10, 13, 16, and 19 of gestation, and the rats were killed on day 20 of gestation. No developmental or reproductive effects were observed. From the Final Report on the Safety Assessment of Triethanolamine, Diethanolamine, and Monoethanolamine.1

TEA, 0.5 g/kg in acetone (purity not stated), was applied dermally to clipped skin on the back of male and female

F344 rats.36 A volume of 1.8 ml/kg was applied daily for 10 wks prior to mating, during mating, and through gestation and

lactation. No effect on mating or fertility or offspring growth or survival was observed. A similar study was performed in

which Swiss CD-1 mice were given daily applications of 2 g/kg TEA at a volume of 3.6 ml/kg.37 No adverse reproductive

effects were observed.

Oral

TEA

A Chernoff-Kavlock teratogenicity screening test was performed using mated female CD-1 mice, in which the ani-

mals were dosed by gavage with 1125 mg/kg/day TEA on days 6-15 of gestation.38 (It was stated that the TEA was the

“purest grade commercially available”). No adverse reproductive effects were observed.

GENOTOXICITY

TEA was negative for genotoxic effects in an Ames test with or without metabolic activation, gene conversion assay, rec assay, sister chromatid exchange assay with or without metabolic activation, chromosomal aberration assay, and cell transformation assay.

In Vitro

TEA

Undiluted TEA, at concentrations of ≤100 mg/plate, was not mutagenic in Salmonella typhimurium with or without metabolic activation. TEA with sodium nitrite, but not TEA alone, was mutagenic in Bacillus subtilis without metabolic activation. NDELA, which is not mutagenic in B. subtilis without metabolic activation, was found in the mixture. In an unscheduled DNA synthesis test in which primary rat hepatocyte cultures were exposed to 10-8 to 10-1 M TEA and [3H]thymidine, simultaneously, TEA did not appear to cause DNA-damage-inducible repair. From the Final Report on the Safety Assessment of Triethanolamine, Diethanolamine, and Monoethanolamine.1

TEA, in distilled water or dimethylsulfoxide, was not mutagenic to Escherichia coli39 or S. typhimurium, with or

without metabolic activation, at doses of 0-20,000 µg/plate.39-41 TEA (88.2% purity) did not cause gene conversion in

Saccharomyces cerevisiae.40 TEA was negative in a rec assay at doses of 0-4000 µg/disk. No induction of sister chromatid

exchanges occurred in Chinese hamster ovary (CHO) cells at 0-1010 µg/ml without metabolic activation or 0-10,100 µg/ml

with metabolic activation,42 and chromosomal aberrations were not induced in cultured rat liver cells40 or at doses of 5-100


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µg/ml in cultured Chinese hamster cells.39,42 TEA, 25-500 µg/ml, was negative in a cell transformation assay using hamster

embryo cells.39

In Vivo

TEA

A mouse peripheral blood micronucleus test was performed using samples collected from mice that were dosed

dermally for 90-days with 0-4 g/kg TEA in an NTP study.43 Results were negative in both male and female mice.

CARCINOGENICITY

In a 2-yr dermal carcinogenicity study of TEA in mice and a 2-yr study in rats, it was concluded that TEA produced equivocal evidence of carcinogenic activity in male mice based on the occurrence of liver hemangiosarcoma, some evidence of carcinogenic activity in female mice based on increased incidences of hepatocellular adenoma, equivocal evidence of carcinogenic activity in male rats based on a marginal increase in the incidence of renal tubule cell adenoma, and no evidence of carcinogenic activity in female rats. In oral car-cinogenicity studies in rats and mice, TEA was not carcinogenic to rats or mice, but it was toxic to the kidneys of rats, especially females. It has been speculated that TEA may cause liver tumors in mice via a choline-depletion mode of action.

Dermal

TEA

In a series of 3 experiments using a total of 560 CBA x C57Bl6 male mice, the carcinogenic effects of 99%+ pure TEA and 80%+ industrial grade TEA and the cocarcinogenic effect of TEA and syntanol DC-10 (alcohols C10-18 ethoxylated) were examined over a 14-18 mo timeframe. TEA was not carcinogenic or cocarcinogenic. From the Final Report on the Safety Assessment of Triethanolamine, Diethanolamine, and Monoethanolamine.1

An initial carcinogenicity study of TEA using B6C3F1 mice performed by the NTP was deemed inadequate due to a

Helicobacter hepaticus infection.30 Therefore, a second 2-yr study was performed in which TEA in acetone was applied der-

mally at doses of 200-2000 mg/kg/day to male B6C3F1 mice and at doses of 100-1000 mg/kg/day to female B6C3F1 mice.44

(Purity of TEA was 99+%. Using high-performance liquid chromatography/mass spectrometry, 0.491% DEA was detected

as an impurity. A slight increase in DEA was seen in acetone and ethanol solutions after 11 days of storage; the dose

formulations were prepared approximately every 2 wks). The body weights of high dose males were decreased compared to

controls during wks 17-37 and at the end of the study. Dermal irritation increased with increasing dose, and was more severe

in males than in females. At necropsy, treatment-related epidermal hyperplasia, suppurative inflammation, and ulceration

and dermal chronic inflammation occurred at the application site in most test groups, and the incidence and severity increased

with increasing dose. Lesions were found, and it was concluded that there was equivocal evidence of carcinogenic activity of

TEA in male mice, based on the occurrence of liver hemangiosarcoma, and some evidence of carcinogenic activity in female

mice, based on increased incidences of hepatocellular adenoma.

In a 2-yr NTP dermal carcinogenicity study using F344/N rats, TEA in acetone was applied at doses of 32- 125

mg/kg/day in acetone to males and at doses of 63-250 mg/kg/day to females.30 (Purity of TEA was 99%. Functional group

titration indicated <0.4% MEA or DEA). Irritation was observed at the application site, and frequency increased with

increasing dose. At the interim necropsy, the absolute and relative kidney weights of high dose females were significantly

greater than the controls. Microscopically, at the site of application, dermal lesions, including acanthosis, inflammation,

and/or ulceration, were observed. It was concluded that there was equivocal evidence of carcinogenic activity in male rats,

based on a marginal increase in the incidences of renal tubule cell adenoma, and there was no evidence of carcinogenic

activity in female rats.


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The carcinogenic potential of TEA was evaluated using a Tg·AC transgenic mouse model.45 Groups of 10-15 female

homozygous mice were dosed dermally with 3-30 mg TEA/mouse in acetone, 5x/wk for 20 wks. TEA was inactive in

Tg·AC mice.

Oral

TEA

Groups of 40 male and 40 female ICR-JCL mice were fed a diet containing 0.01, 0.03, or 0.3% TEA throughout their lifetime. The malignant tumor incidence was 2.8, 27, and 36% for females, respectively, and 2.9, 9.1, and 3.6% for males, respectively. Treated females had a much higher incidence of thymic and non-thymic tumors in lymphoid tissues than treated males. Survival was similar for treated and control animals. From the Final Report on the Safety Assessment of Triethanolamine, Diethanolamine, and Monoethanolamine.1

The oral carcinogenic potential of TEA was examined by administering 1 or 2% TEA in drinking water to groups of

male and female B6C3F1 mice for 82 wks.46 (DEA was present as an impurity at 1.9 %). Body weights of male mice of the

2% group were decreased during wks 1-20 when compared to controls. No significant changes in organ weights were

observed. No dose-related increase of the incidence of any tumors was observed in the treated groups, and there was no

evidence of carcinogenic potential of TEA upon oral administration.

Drinking water containing 1 or 2% TEA was given to groups of male and female F344 rats for 2 yrs.47 (DEA was

present as an impurity at 1.9%). From wk 69 on, the dose concentrations for females were reduced by half because of

associated nephrotoxicity. A dose-related decrease in body weight gain was reported for male and female test group rats, and

a dose-dependent increase in mortality, starting at wk 60, was observed. Absolute and relative kidney-to-body weights were

significantly increased in males and females, and the increase was dose-related. Severe chronic nephropathy was statistically

significantly increased in males of the high dose group and females of both dose groups. No treatment-related effects were

found in the liver. There was no increase in the incidence of any tumors in the treated groups compared to controls when

using the Chi-square test. Since increased nephrotoxicity appeared to affect the lifespan of the treated animals, especially the

females, an age-adjusted statistical analysis was performed on the incidences of main tumors or tumor groups for males and

females, and a positive trend was noted in the occurrence of hepatic tumors (neoplastic nodule/hepatocellular carcinoma) in

males and of uterine endometrial sarcomas and renal-cell adenomas in females. The researchers stated that, because these

tumors have been observed spontaneously in F344 rats, and since their incidences in the control group was lower than that of

historical controls, the occurrence of the tumors may not be attributable to TEA. Instead, increased incidence of renal tumors

in the high-dose group may have been associated with renal damage. The researchers concluded that TEA was toxic to the

kidneys, especially in females, but it was not carcinogenic to F344 rats.

Possible Mode of Action for Carcinogenic Effects of TEA

It has been reported that choline deficiency induces liver cancer in rodents;48,49 therefore, the potential of TEA to

cause choline deficiency in the liver of female B6C3F1 mice was investigated as a mode of tumorigenesis.50 Female mice

were dosed dermally with unoccluded applications of 10-1000 mg/kg/day TEA in acetone, 5 days/wk for 3 wks, and female

CDF rats were dosed in a similar manner with 250 mg/kg/day TEA. (Purity of TEA was 99+%; DEA impurity levels were

0.04 and 0.45%). No clinical signs of toxicity were noted for mice or rats. Phosphocholine and betaine levels were

statistically significantly decreased in the high dose mice, and choline levels were decreased in these mice. The decrease in

phosphocholine levels was variable, but dose-related. (More pronounced effects were observed when the TEA having 0.45%

DEA impurity was used). In rats, no changes in choline or its metabolites were noted. The potential of TEA to inhibit the

uptake of [3H]choline by CHO cells was also investigated, and a dose-related decrease was observed. The researchers

concluded that TEA may cause liver tumors in mice via a choline-depletion mode of action, and this effect is likely caused by


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the inhibition of choline uptake by the cells. The researchers stated that, while DEA impurity may contribute to choline

depletion, a choline-deficiency mode of tumorigenesis appears to be a property of TEA, exclusive of any DEA impurity.

Carcinogenic Potential in Humans

TEA

According to an evaluation of TEA by the International Agency for Research on Cancer (IARC) Working Group,

there is inadequate evidence in humans, as well as in animals, for the carcinogenicity of TEA.51 The overall evaluation of the

IARC is that TEA is not classifiable as to its carcinogenicity to humans (Group 3).

IRRITATION AND SENSITIZATION

TEA can be a dermal irritant in both animals and human, but it has not been shown to be a sensitizer. Many of the ingredients in this report are surfactants, which can be irritating to skin and eyes.

Irritation

Skin

In Vitro TEA

The dermal irritation potential of TEA was determined in two in vitro assays, and these results were compared to

results obtained in the in vivo Draize test and human patch test.52 The tissues used in the in vitro tests were fully-differen-

tiated three-dimensional reconstituted human epidermal cultures. Each in vitro test was performed in triplicate. In the first

test, the in vitro patch test, TEA was applied to the skin samples for 4 h using a 0.95 cm2 polypropylene chamber. In the

second in vitro test, the direct topical application test, 100 µl TEA was applied directly to a 0.63 cm2 area of the epidermal

surface for 4 h. Histology, cell viability determined via 3-[4,5-dimethyl-thiazol-2-yl]-2,5-diphenyl tetrazolium bromide

(MTT) reduction, and interleukin (IL)-1α release endpoints were measured in both tests, and a combination of the outcomes

of these endpoints was used to determine the potential for irritation. TEA, which was described as “non-classified” in the

Draize and human patch tests, was classified as a non-irritant in the in vitro patch test and an irritant in the direct topical

application test. The irritant classification was based on tissue necrosis and a higher amount of released IL-1α compared to

the negative control (water). The concentration of TEA tested for each of the studies was not specified.

TEA-Laurate; TEA-Oleate

The binding of surfactants to stratum corneum proteins appears to play a role in the harshness of the surfactants to

skin.53 Human stratum corneum samples were used to evaluate the binding of sodium/TEA-laurate and sodium/TEA-oleate.

At low surfactant levels (<20 mM), higher levels of sodium/TEA-oleate than sodium/TEA-laurate were bound to the stratum

corneum 1 min after exposure. TEA-oleate binding stabilized at concentrations of 20-50 mM, with binding of approximately

0.016-0.017 mg surfactant/mg stratum corneum. With sodium/TEA-laurate, binding increased with increasing surfactant

concentration; at a concentration of 50 mM sodium,/TEA-laurate, binding was approximately 0.025 mg/mg stratum corneum.

Non-Human TEA

The primary skin irritation potential of undiluted TEA was determined using rabbits. After 10 open applications of 0.1 ml to rabbit ears and 10 unoccluded applications to the intact skin of the abdomen, and 3 semi-occluded 24-h applications to abraded skin, it was concluded that TEA was slightly to moderately irritating, and prolonged or repeated exposure may be irritating. Twenty-four h occluded patch tests using groups of 8 male rabbits were performed in 22 laboratories; the primary irritation score ranged from 0-5.5/24, and the total score for all 22 laboratories was 27.3/400. In a preliminary study, occlusive dermal applications of 50-100% aq. TEA to pairs of guinea pigs resulted in one erythematic reaction to undiluted TEA, and in another preliminary study, no irritation was observed when 5, 10, or 25% TEA was applied to the backs of guinea pigs. From the Final Report on the Safety Assessment of Triethanolamine, Diethanolamine, and Monoethanolamine.1


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The irritancy potential of TEA (purity not specified) was evaluated in an ear swelling test using female BALB/c

mice.54 A significant increase in irritancy was observed with 25 and 50% TEA compared to the vehicle (4:1 acetone/olive

oil).

TEA-Lauryl Sulfate

The dermal irritation of TEA-lauryl sulfate ranged from not-irritating to moderately irritating to rabbit skin at concentrations up to 46%. From the Final Report on the Safety Assessment of TEA-Lauryl Sulfate.5


Albino rabbits (number per group not specified) were used to evaluate the dermal irritation potential of aq. TEA-

dodecylbenzenesulfonate.27 Ten applications of 1, 5, or 25% TEA-dodecylbenzenesulfonate were made to intact skin over a

14-day period, and three application were made to abraded skin during the same 14-day period. A 1 cm2 cotton pad was used

to apply 5 ml of the test material, and the test sites were wrapped following dosing. TEA-dodecylbenzenesulfonate was not

irritating to very slight irritating at 1%, very slightly to slightly irritating at 5%, and slightly to moderately irritating to rabbit

skin at a concentration of 25%.

TEA-dodecylbenzenesulfonate was applied to the intact ears of albino rabbits (number per group not specified)

using the same application protocol. In rabbit ears, irritation was slight irritation at 1% aq., very slight to slight irritation at

5% aq., and slight to moderate at 25% aq. TEA-dodecylbenzenesulfonate.

TEA-Cocoyl Hydrolyzed Collagen

TEA-cocoyl hydrolyzed collagen was non-irritating to mildly irritating to rabbit skin at concentrations of 10-50%. From the Final Report on the Safety Assessment of Triethanolamine-Coco-Hydrolyzed Animal Protein2

Human TEA

Clinical studies were performed with formulations containing TEA. In a few studies on formulations containing 0.45-2.4% TEA, the researchers concluded that no irritation was observed, while short-lived acute irritation was reported for formulations containing 1.9-2.6% TEA. However, according to the Expert Panel’s interpretation of the results of a number of other studies, formulations containing 0.83-20.04% TEA were irritating. In clinical provocative testing using 5-10 “hyper reactors,” 100% TEA produced an irritant reaction on non-scarified skin, 10% TEA in ethanol was a marked irritant on scarified skin, while 5% in ethanol was a slight irritant on scarified skin. From the Final Report on the Safety Assessment of Triethanolamine, Diethanolamine, and Monoethanolamine.1

A patch test with TEA (purity not specified) was performed on 20 subjects, and erythema and transepidermal water

loss (TEWL) were measured, and the contents of suction blister fluids (SBF) were evaluated for primary proinflammatory

mediators.55 Aq. TEA, 50-100%, was applied occlusively for 24 h; 100-200 µl, concentrated to 20 µl with drying, were ap-

plied. The percent of non-responders to 100% TEA was 80%; those that did respond had weak and non-uniform erythema.

The incidence was below or about that found with the solvent controls. For the challenge phase, 765 µmol/cm2 TEA was

applied occlusively to 12 subjects for 6-24 h. No increase in TEWL or change in eicosanoid profile of the SBF was ob-

served. TEA was a non-irritant.

TEA-Lauryl Sulfate

In clinical studies, shampoos containing 10.5% TEA-lauryl sulfate caused no irritation with semi-occlusive patches or “use” testing, while diluted shampoos containing 0.15-7.5% produced no to moderate irritation. In an occlusive patch test, a diluted shampoo containing 4.4% TEA-lauryl sulfate was highly irritating in a 21-day cumulative irritation test. From the Final Report on the Safety Assessment of TEA-Lauryl Sulfate.5

The dermal irritation potential of a 10% solution of TEA-lauryl sulfate (vehicle not identified) at neutral pH was

determined using 10 subjects.56 Duhring chambers were applied to the forearm of each subject for 5 days. A 10% solution of


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TEA-lauryl sulfate caused intense erythema in nearly all subjects by day 4. Testing was terminated. (Additional details were

not provided).


TEA-cocoyl hydrolyzed collagen, 10%, was non-irritating in clinical single insult patch tests. From the Final Report on the Safety Assessment of Triethanolamine-Coco-Hydrolyzed Animal Protein2

Mucosal

In Vitro TEA

The ocular irritation potential of TEA was evaluated in two in vitro studies. In the luminescent bacterial toxicity test

(i.e. the Microtox® test), TEA had an EC50 of 110 mg/l, corresponding to non/moderate irritant potential.57 In the EYTEX

assay, TEA had an EYTEX/Draize equivalent of 42.1, corresponding to a prediction of severe ocular irritant.58

Non-Human TEA

The ocular irritation potential of 0.005-0.1 ml undiluted TEA was evaluated in a number of studies using rabbits. With high concentrations and long contact time, TEA may be irritating to rabbit eyes. Using rabbits, 10% aq. TEA produced essentially no irritation with or without rinsing. A formulation containing 12.6% TEA, 0.1 ml, was evaluated in a study using 6 rhesus monkeys. Slit lamp examination revealed some corneal effects in 2 monkeys at 24 h and slight positive fluorescein staining in one monkey at 72 h. The vaginal irritation potential of a spermicidal formulation containing 1.92% TEA was evaluated by placing 0.5 ml of the ointment inside the vaginas of 6 rats for 3 days. The formulation was a non-irritant. From the Final Report on the Safety Assessment of Triethanolamine, Diethanolamine, and Monoethanolamine.1

TEA-Lauryl Sulfate

The ocular irritation potential of TEA-lauryl sulfate was evaluated in rabbit eyes; irritation ranged from not-irritating to severely irritating at concentrations up to 40%. From the Final Report on the Safety Assessment of TEA-Lauryl Sulfate.5


The ocular irritation potential of aq. TEA-dodecylbenzenesulfonate was evaluated using albino rabbits (number per

group not specified).27 Two drops of 1, 5, or 25% TEA-dodecylbenzenesulfonate were instilled into the eyes of rabbits. One

eye of each rabbit was rinsed after 30 sec, the other eye was not rinsed. Without rinsing, a 1% solution was very slightly

irritating, a 5% solution was very slightly to slightly irritating, and a 25% solution was moderately to severely irritating.

With rinsing, very slight to slight irritation was observed in the eyes of rabbits dosed with 5 and 25% aq. TEA-

dodecylbenzenesulfonate.


TEA-cocoyl hydrolyzed collagen was practically non-irritating to mildly irritating at concentrations of 10-100% in rabbit eyes. From the Final Report on the Safety Assessment of Triethanolamine-Coco-Hydrolyzed Animal Protein2

Sensitization

TEA was not a sensitizer to guinea pigs when 20 guinea pigs were given dermal applications of undiluted TEA 1x/wk for 3 wks, followed by challenge applications 14 and 21 days after dosing. No sensitization was seen when four lots of TEA were evaluated using groups of 20 guinea pigs; induction applications were applied for up to 6 h, 1x/wk, for 3 wks, and the challenge was performed after 14 days. One of the studies used undiluted TEA during induction, while the other 3 studies used 50% TEA at induction. All four studies used challenge patches with 90% TEA. No sensitization was observed in a similar study in which induction patches contained a 25% active TEA solution, and a challenge patch with the 25% solution was applied after 1 wk of non-treatment. From the Final Report on the Safety Assessment of Triethanolamine, Diethanolamine, and Monoethanolamine.1


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Non-Human TEA

The sensitization potential of TEA was evaluated in a local lymph node assay (LLNA) performed with groups of 5

BALB/c mice.54 This study was performed in conjunction with the ear-swelling test described previously. Lymphocyte pro-

liferation increased with dose, but the increases were not statistically significant. TEA was not identified as a sensitizer in the

LLNA.

The hypersensitivity of mice to TEA (99+% pure) was determined.59 TEA, in an acetone:olive oil mixture (4:1) at

concentrations of 3%, 10%, or 30%, was applied daily for 5 consecutive days to groups of 8 female B6C3F1 mice, and the

animals were challenged 7 days later with a 30% solution. For some animals, dermabrasion, as well as intradermal injections

of Freund’s complete adjuvant (FCA), was used. There were no treatment-related effects on survival or body weights. There

were no statistically significant or dose-related hypersensitivity responses to TEA observed with a radioisotopic method or in

an ear swelling test, with or without FCA.

Results were negative in three maximization studies examining the sensitization potential of TEA.18 In the first test,

performed using Pirbright-White guinea pigs, induction consisted of intradermal injections of 2% TEA (98.9% pure) in iso-

tonic saline and epicutaneous application of undiluted TEA, and challenge used 10% TEA in isotonic saline. In the second

test using 20 Dunkin-Hartley guinea pigs, intradermal and epicutaneous inductions used 1.5% technical grade TEA and 25%

technical grade TEA with 10% sodium lauryl sulfate pre-treatment, respectively, and challenge doses consisted of 1, 5, and

10% technical and analytical grade TEA. In the third study, with 15 animals and the same induction protocol just described

(grade of TEA not specified); 2/15 reacted to 10% TEA after 1, but not 3, days.


TEA-cocoyl hydrolyzed collagen was not a sensitizer in guinea-pigs studies. From the Final Report on the Safety Assessment of Triethanolamine-Coco-Hydrolyzed Animal Protein2

Human TEA

In cumulative reports on patch tests conducted over a number of years, TEA, tested at 2% aq, 5% (vehicle not specified), or 5% in petrolatum, had positive reactions for contact dermatitis in 23/500, 9/479, and 2/100 subjects. The Expert Panel interpreted these findings as sensitizing. In a patch test with 64 subjects in which 0.5 ml of 1% TEA (containing 88.6% TEA and 6% DEA) was used, the test solution was not sensitizing. The majority of formulations containing 0.83-4.2% TEA were not sensitizing, and a formulation containing 20.04% TEA, tested on 26 subjects, was not considered sensitizing when it produced 2 slight reactions upon challenge. However, according to the interpretation of the Expert Panel, there were a few cosmetic formulations containing 2.1 and 2.4% TEA that the Panel determined to be sensitizing. In other studies with cosmetic formulations containing 2.1% TEA, the researchers concluded that reactions observed at challenge were probably due to skin fatigue. From the Final Report on the Safety Assessment of Triethanolamine, Diethanolamine, and Monoethanolamine.1

TEA-Lauryl Sulfate

Undiluted shampoo formulations containing 10.5% TEA-lauryl sulfate and dilutions of formulations containing 0.15-7.5% TEA-lauryl sulfate were not sensitizers in clinical studies. Aq. shampoo formulations containing 0.3-0.42% TEA-lauryl sulfate were not photosensitizers. From the Final Report on the Safety Assessment of TEA-Lauryl Sulfate.5

Provocative Testing

A group of 737 patients was patch tested with 6 different emulsifiers, including 2.5% TEA (purity not specified) in

petrolatum.60 The patch tests were performed according to International Contact Dermatitis Research Group (ICDRG)

recommendations. A total of 39 patients had positive reactions to the emulsifiers, and 20 of those patients, 5 males and 15

females, had positive reactions to TEA. There were 106 irritant reactions reported. The results were clinically relevant in 7

patients. Many of the patients allergic to TEA were also allergic to other ingredients.


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Over a 15-yr period, provocative patch testing using TEA was performed on 85,098 dermatological patients.18

There were 323 positive reactions to TEA, and most of the reactions (289) were weak positives. The researchers stated that

occupational exposure was not a risk factor for TEA contact allergy.

Phototoxicity/Photoallergenicity

Non-Human TEA

A formulation containing 1% TEA was applied to the stripped skin of 6 guinea pigs, and each animal was then exposed to ultraviolet A (UVA) light for 2 h. No erythema or edema was observed. From the Final Report on the Safety Assessment of Triethanolamine, Diethanolamine, and Monoethanolamine.1

Human TEA

There were no phototoxicity or photosensitization reactions in clinical studies with a number of formulations containing 0.45-4.2% TEA, nor were there any reactions with a formulation containing 20.04% TEA. However, in one study with a formula-tion containing 4.2% TEA, the Expert Panel felt that the formulation was either mildly phototoxic or there was UV enhancement of an irritant response. From the Final Report on the Safety Assessment of Triethanolamine, Diethanolamine, and Monoethanolamine.1

CLINICAL ASSESSMENT

Case Reports

TEA

Eczema of the face of 2 female patients was exacerbated by a cream that contained TEA.61 Patch testing was per-

formed using the ICDRG standard series, a cosmetic battery, the TEA-containing cream, and TEA at 1%, 2%, and 5% in

petrolatum (pet.). Both patients reacted to the TEA-containing cream (+ reaction) and to 5% TEA pet. (++ reaction). One

patient reacted to 2% TEA (+ reaction), and neither reacted to 1% TEA pet. Patch tests were negative for all other com-

pounds. In a control group of 50 subjects, patch testing with 5% TEA pet. was negative.

Over a 4-yr period, the incidences of positive patch test reactions to the same TEA-containing cream were 69/171

patients in one clinic and 49/191 in another.62 It was hypothesized that the difference between the clinics was due to differ-

ences in sampling methods; the first clinic tested only those patients that had recently used the TEA-containing cream or who

had suspected reactions. In follow-up patch testing with a total of 54 subjects from the 2 clinics, 15 of which were controls,

19 subjects had a positive allergic response to the TEA-containing cream, 40 had a positive irritant response, and 13 had neg-

ative responses. With 1.45-5% TEA, 6 subjects had a positive response. However, with 5-20% TEA stearate, 8/8 patients

and 15/15 controls had a positive irritant response. (TEA stearate was tested because it was demonstrated that TEA stearate

was formed from the combination of TEA and stearic acid in formulation). The researchers postulated the reactions were

irritant reactions to TEA stearate. (The amount of TEA stearate present in formulation was estimated to be 4.8%, and 6/23

subjects patch tested with 5% TEA stearate had irritant reactions).

Two cases of occupational asthma in metal workers exposed to cutting fluid containing TEA were reported.63

Exposure to TEA at temperatures higher than that of ambient air was a common feature.

TEA-PEG-3 Cocamide Sulfate

Two patients with a reaction to a shampoo were patch tested with the ICDRG standard series and a 1% aq. solution

of the shampoo.64 Both patients had positive patch results to the shampoo only. Subsequent patch test with 1% aq. TEA-

PEG-3 Cocamide DEA (as well as 1% cocamidopropyl betaine) yielded produced positive results in both patients. Twenty

eczema patients patch used as controls had negative patch test results to 10% aq. TEA-PEG-3 Cocamide DEA.


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SUMMARY

This report is a re-review of the safety of TEA as used in cosmetics. TEA can function as a surfactant or pH

adjuster, and is reported to be used in 3745 cosmetic ingredients at concentrations up to 6% in leave-on formulations, 19%

in rinse-off formulations, and 0.7% in products that are diluted for use. TEA may contain DEA as an impurity.

The ingredients reviewed in this report, as trialkylamines, trialkanolamines, and their salts, are allowed at up to 2.5%

in leave-on-products. There are additional restrictions regarding conditions for use in leave-on and rinse-off products.

Dermal absorption studies of TEA were performed using mice and rats. In mice, [14C]TEA in acetone was rapidly

absorbed, and absorption increased with increasing dose. The majority of the radioactivity was excreted in the urine, 48-56%

in 72 h, primarily as unchanged TEA. TEA was absorbed more slowly and less extensively in rats than mice. Over a 72-h

period, 19-28% of the dose was absorbed, and 13-24% of the dose was recovered in the urine, mostly as unchanged TEA. In

an oral dosing study with rats, TEA was rapidly absorbed in the gastrointestinal tract and excreted mostly in the form of

unchanged TEA.

The dermal penetration of salicylate from a formulation containing 10% TEA-salicylate was investigated in vitro

and in vivo. In vitro, 1 g of the formulation was applied to full-thickness skin samples from rats and humans. The

penetration of salicylate measured as flux was 39.9 µg/cm2/h with rat skin and 8.7 µg/cm2/h with human skin. With in vivo

testing, the formulations were applied to rat skin for intervals of up to 6 h. No salicylate was found in the deep muscle or fat

under the application site, and very little salicylate was found in the plasma. In humans there was no evidence of direct tissue

penetration of salicylate following dermal application.

In 2 and 13-wk repeated dose dermal toxicity studies in mice with 250-2000 mg/kg bw TEA in acetone or 4000

mg/kg bw neat, , dermal irritation was observed in the highest dose group, and kidney and liver weights were increased with

the higher doses. In rats, 125-1000 mg/kg bw TEA in acetone or 24000 mg/kg bw neat was applied to rats for 13 wks,

irritation was observed at the dosing site. Kidney weights were increased in males and females of rats dosed with ≥500

mg/kg TEA, and dosed females had higher incidences of nephropathy. . In a 14-day drinking water study, animals given

8%TEA in drinking water were all killed due to severe hydration before study terminations. Treatment-related changes were

not observed for animals given 2 or 4^% TEA in their water. In inhalation studies with TEA in rats and mice, no observa-

tions were reported that were indicative of a toxic pulmonary effect.

No adverse reproductive effects were seen in dermal studies in which rats and mice were dosed with TEA in acetone

from before mating through lactation or in an oral teratogenicity screening test in mice.

TEA was negative for genotoxic effects in an Ames test with or without metabolic activation, gene conversion

assay, rec assay, sister chromatid exchange assay with or without metabolic activation, chromosomal aberration assay, and

cell transformation assay.

In a 2-yr dermal carcinogenicity study of TEA in mice and a 2-yr study in rats, it was concluded that TEA produced

equivocal evidence of carcinogenic activity in male mice based on the occurrence of liver hemangiosarcoma, some evidence

of carcinogenic activity in female mice based on increased incidences of hepatocellular adenoma, equivocal evidence of

carcinogenic activity in male rats based on a marginal increase in the incidence of renal tubule cell adenoma, and no evidence

of carcinogenic activity in female rats. In oral carcinogenicity studies in rats and mice, TEA was not carcinogenic to rats or

mice, but it was toxic to the kidneys of rats, especially females. It has been speculated that TEA may cause liver tumors in

mice via a choline-depletion mode of action.

TEA can be a dermal irritant in both animals and human, but it has not been shown to be a sensitizer. Many of the

ingredients in this report are surfactants, which can be irritating to skin and eyes.


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TABLES

Table 1. Conclusions of previously reviewed ingredients and components

Ingredient Conclusion Reference

PREVIOUSLY REVIEWED INGREDIENTS

TEA safe for use in cosmetic formulations designed for discontinuous, brief use followed by thorough rinsing from the surface of the skin; in products intended for prolonged contact with the skin, the concentration of DEA should not exceed 5%; should not be used with products containing N-nitrosating agents.

1

TEA-Cocoyl Hydrolyzed Collagen safe as used 2

TEA Dodecylbenzenesulfonate TEA Tridecylbenzenesulfonate

safe as used when formulated to be non-irritating 65

TEA-EDTA safe as used 66

TEA-Lactate safe for use in cosmetic products at concentrations ≤10%, at final formulation pH≥3.5, when formulated to avoid increasing sun sensitivity or when directions for use include the daily use of sun protection. These ingredients are safe for use in salon products at concentrations ≤30%, at final formulation pH≥3.0, in products designed for brief, discontinuous use followed by thorough rinsing from the skin, when applied by trained professionals, and when application is accompanied by directions for the daily use of sun protection

67

TEA-Lauryl Sulfate can be used without significant irritation at a final concentration thereof not exceeding 10.5%; greater concentrations may cause irritation, especially if allowed to remain in contact with the skin for significant periods of time

5

TEA-Salicylate safe as used when formulated to avoid skin irritation and when formulated to avoid increasing the skin’s sun sensitivity, or when increased sun sensitivity would be expected, directions for use include the daily use of sun protection

24

TEA Stearate safe as used in cosmetic formulations designed for discontinuous, brief use followed by thorough rinsing; in products intended for prolonged contact with the skin, the concentration should not exceed 15% in formulation; should not be in products under conditions resulting in N-nitrosation reactions

68

PREVIOUSLY REVIEWED COMPONENTS

Alkyl PEG Ethers safe as used when formulated to be non –irritating 69

Ammonium Lauryl Sulfate Sodium Lauryl Sulfate

safe in formulations designed for discontinuous, brief use followed by thorough rinsing from the surface of the skin; in products intended for prolonged contact with skin, concentrations should not exceed 1%

70

Coconut Ingredients safe as used 71

Cocoyl Sarcosine Lauroyl Sarcosine Oleoyl Sarcosine

safe as used in rinse-off products, safe for use in leave-on products at concentrations of ≤5%, and the data were insufficient to determine the safety for use in products where cocoyl sarcosine is likely to be inhaled; should not be used in cosmetic products in which N-nitroso compounds may be formed

72

Dimethicone Copolyol safe as used 73

Isostearic Acid safe as used 74

Lauric Acid Myristic Acid Oleic Acid Palmitic Acid Stearic Acid

safe as used 75 76

PCA safe as used; should not be used in products containing nitrosating agents 77

Plant-Derived Fatty Acid Oils safe as used 78

Ricinoleic Acid safe as used 79

Sodium Cetearyl Sulfate and Related Alkyl Sulfates

safe as used 80

Sodium Lauraminopropionate insufficient data (extensive list of data needs) 81

Sodium Laureth Sulfate and Sulfated Ethoxylated Alcohols

safe as used when formulated to be non-irritating 82,83

Sorbic Acid safe as used 84

Tall Oil Acid safe as used 85


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Table 2. Definitions and structures

Ingredient CAS No. Definition Formula/structure

Triethanolamine (TEA) and inorganic salts Triethanolamine 102-71-6

Triethanolamine is a tertiary amine with three ethanol functional groups.

HON

OH

OH

TEA-Hydrochloride 637-39-8

TEA-Hydrochloride is the triethanolamine salt of hydrochloric acid.

TEA-Sulfate 7376-31-0

TEA-Sulfate is the triethanolamine salt of sulfuric acid.

HON

OH

OHHO S OH

O

Om n

Organic acid salts TEA-Laurate 2224-49-9

TEA-Laurate is the triethanolamine salt of a twelve carbon fatty acid, lauric acid.

TEA-Laurate/ Myristate

TEA-Laurate/Myristate is the triethanolamine salt of a mixture of a twelve carbon fatty acid, lauric acid, and a fourteen carbon fatty acid, myristic acid.

HONH

OH

OH

O

OH3C

HONH

OH

OH

O

OH3C

TEA-Myristate 41669-40-3

TEA-Myristate is the triethanolamine salt of a fourteen carbon fatty acid, myristic acid.

TEA-Palmitate 49719-60-0

TEA-Palmitate is the triethanolamine salt of a sixteen carbon fatty acid, palmitic acid.

TEA-Stearate 4568-28-9

TEA-Stearate is the triethanolamine salt of an eighteen carbon fatty acid, stearic acid.


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TEA-Isostearate 88120-12-1

TEA-Isostearate is the triethanolamine salt of a branched, eighteen carbon fatty acid, isostearic acid.

one example of an “iso” TEA-Undecylenate

TEA-Undecylenate is the triethanol-amine salt of a terminally unsaturated, eleven carbon fatty acid, undecylenic acid.

TEA-Sorbate

TEA-Sorbate is the triethanolamine salt of an α, β, γ, δ-unsaturated six carbon acid, sorbic acid.

TEA-Oleate 2717-15-9

TEA-Oleate is the triethanolamine salt of an eighteen carbon, Ω-9 fatty acid, oleic acid.

TEA-Canolate

TEA-Canolate is the triethanolamine salt of the fatty acids derived from canola oil.

wherein RC(O)O- = the fatty acid anions derived from Canola Oil TEA-Cocoate 61790-64-5

TEA-Cocoate is the triethanolamine salt derived from coconut fatty acids.

wherein RC(O)O- = the fatty acid anions derived from coconut TEA-Hydrogenated Cocoate

TEA-Hydrogenated Cocoate is the triethanolamine salt of hydrogenated coconut fatty acids

wherein RC(O)O- = the fatty acid anions derived from hydrogenated coconut


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TEA-Rosinate

TEA-Rosinate is the triethanolamine salt of the acids derived from rosin.

wherein RC(O)O- = the fatty acid anions derived from Rosin TEA-Tallate 8043-27-4 67784-78-5

TEA-Tallate is the triethanolamine salt of tall oil acid.

wherein RC(O)O- = the fatty acid anions derived from Tall Oil Acid TEA-Glyceryl Dimaleate [63358-71-4] per CAS

TEA-Glyceryl Dimaleate is the trietha-nolamine salt of the diester of glycerin and maleic acid.

Not enough information for a structure

Triethanolamine diester TEA-Diricinoleate 351216-93-8

TEA-Diricinoleate is diester of the Ω-8 hydroxy, Ω-9 unsaturated, eighteen carbon fatty acid, ricinoleic acid.

Hydroxy Acid Salts TEA-Lactate 20475-12-1

TEA-Lactate is the triethanolamine salt of the three carbon, α-hydroxy acid, lactic acid

TEA-Salicylate 2174-16-5

TEA-Salicylate is the triethanolamine salt of the ß-hydroxy acid, salicylic acid

Amine & Amide Acid Salts TEA-EDTA 60544-70-9

TEA-EDTA is the triethanolamine salt of ethylenediamine-tetraacetic acid (EDTA).


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TEA-Myristaminopropionate 61791-98-8

TEA-Myristaminopropionate is the triethanolamine salt of myristamino-propionic acid.

TEA-Lauraminopropionate 14171-00-7 32494-87-4

TEA-Lauraminopropionate is the triethanolamine salt of N-dodecyl substituted alanine.

Di-TEA-Palmitoyl Aspartate

Di-TEA-Palmitoyl Aspartate is the triethanolamine salt of the palmitic amide of aspartic acid

HONH

O

OH

O

O

NH

O

H3C

HONH

O

OH

O O

TEA-Cocoyl Glycinate

TEA-Cocoyl Glycinate is the triethanol-amine salt of the coconut acid amide of acetate.

wherein RCO- represents the fatty acids derived from coconut acid

TEA-Cocamide Diacetate

TEA-Cocamide Diacetate is the tri-ethanolamine salt of the coconut acid amide of diacetate.

wherein RCO- represents the fatty acids derived from coconut oil

TEA-Cocoyl Alaninate

TEA-Cocoyl Alaninate is the triethanol-amine salt of the coconut acid amide of alanine.


TEA-Cocoyl Sarcosinate 68411-96-1

TEA-Cocoyl Sarcosinate is the tri-ethanolamine salt of cocoyl sarcosine.

wherein RCO- represents the fatty acids derived from coconut oil


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TEA-Hydrogenated Tallowoyl Glutamate

TEA-Hydrogenated Tallowoyl Glutamate is the triethanolamine salt of the hydrogenated tallow acid amide of glutamic acid.

wherein RCO- represents the fatty acids derived from hydrogenated tallow

TEA-Lauroyl Glutamate 31955-67-6 53576-49-1

TEA-Lauroyl Glutamate is the trietha-nolamine salt of the lauric acid amide of glutamic acid.

TEA-Lauroyl Methylamino-propionate

TEA-Lauroyl Methylaminopropionate is the triethanolamine salt of the lauric acid amide of N-methylalanine.

TEA-Lauroyl/Myristoyl Aspartate

TEA-Lauroyl/Myristoyl Aspartate is the triethanolamine salt of a mixture of the lauric acid amide of glutamic acid and the myristic acid amide or glutamic acid.

TEA-Lauroyl Sarcosinate 16693-53-1

TEA-Lauroyl Sarcosinate is the trietha-nolamine salt of lauroyl sarcosine

TEA-Oleoyl Sarcosinate 17736-08-2

TEA-Oleoyl Sarcosinate is the tri-ethanolamine salt of oleoyl sarcosine


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TEA-PCA 55901-20-7

TEA-PCA is the triethanolamine salt of pyrrolidone-carboxylic acid (PCA).

Di-TEA Cocamide Diacetate

Di-TEA Cocamide Diacetate is the triethanolamine salt, w/RCO- representing fatty acids from coconut oil.


TEA-Cocoyl Glutamate 68187-29-1

TEA-Cocoyl Glutamate is the 1:1 triethanolamine salt of the coconut acid amide of glutamic acid

wherein RCO- represents the fatty acids derived from coconut acid and R’

represents hydrogen or a negative chargeTEA-Cocoyl Glutaminate

TEA-Cocoyl Glutaminate is the triethanolamine salt of the coconut acid amide of glutamine.


TEA-Palm Kernel Sarcosinate

TEA-Palm Kernel Sarcosinate is the triethanolamine salt of the palm kernel acid amide of sarcosine; RCO- represents the fatty acids derived from palm kernel oil

wherein RCO- represents the fatty acids derived from palm kernel acid

Ester Acid Salts TEA-PEG-50 Hydrogenated Castor Oil Succinate

TEA-PEG-50 Hydrogenated Castor Oil Succinate is the triethanolamine salt of the hydrogenated castor oil ether of poly-ethoxylated succinic acid.

wherein R represents the fatty acid residue from hydrogenated castor oil


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TEA-Lauroyl Lactylate

TEA-Lauroyl Lactylate is the triethanolamine salt of the lauric acid ester of lactyl lactylate.

wherein R represents the fatty acid residue from hydrogenated castor oil

Inorganic Acid Salts -Sulfates and Sulfonates Magnesium/TEA-Coco-Sulfate

Magnesium/TEA-Coco-Sulfate is the mixed magnesium and triethanolamine salt of coco-sulfate.

where R represents the alkyl groups derived from coconut oil

Sodium/TEA C12-13 Pareth-3 Sulfate

Sodium/TEA C12-13 Pareth-3 Sulfate is the mixed sodium and triethanolamine salt of the sulfate ester of C12-13 pareth-3.

Di-TEA-Oleamido PEG-2 Sulfosuccinate

Di-TEA-Oleamido PEG-2 Sulfosucci-nate is the bis (triethanolamine salt) of the monooleyl amide of the diglycol half ester of sulfosuccinic acid.

TEA-Lauryl Sulfate 139-96-8

TEA-Lauryl Sulfate is the triethanol-amine salt of lauryl sulfuric acid.


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TEA-Laneth-5 Sulfate

TEA-Laneth-5 Sulfate is the triethanol-amine salt of the sulfate ester of laneth-5

TEA-Laureth Sulfate 27028-82-6

TEA-Laureth Sulfate is the triethanol-amine salt of polyethoxylated lauryl sulfate.

where n = 1-4

TEA-Oleyl Sulfate

TEA-Oleyl Sulfate is the triethanol-amine salt of Ω-9 unsaturated eighteen carbon alkyl sulfate, oleyl sulfate.

TEA-C10-15 Alkyl Sulfate

TEA-C10-15 Alkyl Sulfate is the mixture of 10 to 15 carbon alkyl sulfate trietha-nolamine salts.


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TEA C14-17 Alkyl Sec Sulfonate

TEA C14-17 Alkyl Sec Sulfonate is the mixture of 14 to 17 carbon, alkyl 2-sulfate triethanolamine salts.

TEA-Coco-Sulfate

TEA-Coco-Sulfate is the triethanol-amine salt of sulfated Coconut Alcohol.

where R represents the alkyl groups derived from coconut oil

TEA-C11-15 Pareth Sulfate

TEA-C11-15 Pareth Sulfate is the tri-ethanolamine salt of the sulfate ester of a mixture of monoethoxylated, 11 to 15 carbon fatty alcohols.

TEA-C12-13 Pareth-3 Sulfate

TEA-C12-13 Pareth-3 Sulfate is the tri-ethanolamine salt of the sulfate ester of a mixture of triethoxylated, 12 to 13 carbon fatty alcohols.


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TEA-PEG-3 Cocamide Sulfate

TEA-PEG-3 Cocamide Sulfate is the tri-ethanolamine salt of the sulfate ester of triethoxylated cocamide.

where RCO- represents the fatty acids derived from coconut oil

TEA-Dodecylbenzene-sulfonate 27323-41-7

TEA-Dodecylbenzenesulfonate is the triethanolamine salt of p-dodecyl (i.e. para-12 carbon alkyl chain) substituted benzenesulfonate.

TEA-Tridecylbenzene-sulfonate 59599-58-5 6186-59-7

TEA-Tridecylbenzenesulfonate is the triethanolamine salt of p-tridecyl (i.e. para-13 carbon alkyl chain) substituted benzenesulfonate.

-Phosphates TEA-Lauryl Phosphate [59146-94-0] per CAS

TEA-Lauryl Phosphate is the triethanolamine salt of a complex mixture of esters of phosphoric acid and a twelve carbon alcohol, lauryl alcohol.

where R represents either hydrogen or a lauryl chain

TEA-Laureth-4 Phosphate

TEA-Laureth-4 Phosphate is the triethanolamine salt of a complex mixture of phosphate esters of Laureth-4.

HONH

OH

OH

O P

O

OR

OO

OO

OH3C

where R represents either hydrogen or a laureth-4 chain

TEA-C12-13 Alkyl Phosphate

TEA-C12-13 Alkyl Phosphate is the triethanolamine salt of a complex mixture of esters of phosphoric acid and twelve to thirteen carbon alcohols.

where R represents hydrogen, a 12 carbon alkyl chain or a 13 carbon alkyl

chain


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TEA-C12-14 Alkyl Phosphate

TEA-C12-14 Alkyl Phosphate is the triethanolamine salt of a complex mixture of esters of phosphoric acid and twelve to fourteen carbon alcohols.

HONH

OH

OHO P

O

OR

OH3C

HONH

OH

OHO P

O

OR

OH3C

HONH

OH

OHO P

O

OR

OH3C

where R represents hydrogen, a twelve carbon alkyl chain, a 13 carbon alkyl chain or a 14 carbon chain TEA-Dimethicone PEG-7 Phosphate

TEA-Dimethicone PEG-7 Phosphate is the triethanolamine salt of a dimethicone terminated polyethylene glycol phosphate.

TEA-Polyphosphate 68131-71-5 68308-31-6

TEA-Polyphosphate is triethanolamine salt of polyphosphoric acid.

Polysaccharide & Protein Salts TEA-Cocoyl Hydrolyzed Collagen 68952-16-9

TEA-Cocoyl Hydrolyzed Collagen is the triethanolamine salt of the condensation product of coconut acid chloride and hydrolyzed collagen.

HONH

OH

OH

R O

O

R'

where RCO- represents the fatty acids derived from coconut oil and R’

represents hydrolyzed collagen TEA-Alginate

TEA-Alginate is the triethanolamine salt of alginic acid. (Alginic acid is a linear, anionic polysaccharide consisting of β-D-mannuronopyranosyl (M) and α-L-gulur-onopyranosyl (G) residues, arranged in blocks of repeating M residues (MM blocks), blocks of repeating G residues (GG blocks), and blocks of mixed M and G residues (MG blocks), extracted from various species of brown seaweed, Phaeophyceae.)


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TEA-Isostearoyl Hydrolyzed Collagen

TEA-Isostearoyl Hydrolyzed Collagen is the triethanolamine salt of the condensation product of isostearic acid chloride and Hydrolyzed Collagen

HONH

OH

OH

O

O

RH3C

CH3 where R represents hydrolyzed collagen

Sodium/TEA-Lauroyl Collagen Amino Acids

Sodium/TEA-Lauroyl Collagen Amino Acids is a mixture of sodium and trietha-nolamine salts of the condensation product of lauric acid chloride and collagen amino acids

where R represents collagen amino acids

Sodium/TEA-Lauroyl Hydrolyzed Collagen

Sodium/TEA-Lauroyl Hydrolyzed Collagen is a mixture of sodium and triethanolamine salt of the condensation product of lauric acid chloride and Hydrolyzed Collagen

HONH

OH

OH

O

O

RH3C

Na

2

where R represents hydrolyzed collagen

Sodium/TEA-Lauroyl Hydrolyzed Keratin

Sodium/TEA-Lauroyl Hydrolyzed Keratin is a mixture of sodium and triethanolamine salts of the condensation product of lauric chloride and Hydrolyzed Keratin

where R represents hydrolyzed keratin

Sodium/TEA-Lauroyl Keratin Amino Acids

Sodium/TEA-Lauroyl Keratin Amino Acids is a mixture of sodium and triethanolamine salts of the condensation product of Lauric Acid and Keratin Amino Acids

where R represents keratin amino acids

Sodium/TEA-Undecylenoyl Alginate

Sodium/TEA-Undecylenoyl Alginate is a mixture of sodium and triethanolamine salts of the condensation product of undecylenic acid chloride and Alginic Acid


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Sodium/TEA-Undecylenoyl Carrageenan

Sodium/TEA-Undecylenoyl Carrageenan is a mixture of sodium and triethanol-amine salts of the condensation product of undecylenic acid chloride and Carrageenan. Carrageenans are a family of sulfated polysaccharides with a linear chain of D-galactose, linked alternately alpha(l→3) and β(l→4). The sulfate groups are present at the 2, 4, or 6 positions. Some of the galactose residues are converted to 3,6-anhydrogalactose by the formation of a bridging bond across the ring between the C-3 and C-6.

where R represents hydrogen, sulfate or undecylenoyl and some of the galactose units have been converted to 3,6-anhydrogalactose

Sodium/TEA-Undecylenoyl Collagen Amino Acids

Sodium/TEA-Undecylenoyl Collagen Amino Acids is a mixture of sodium and triethanolamine salts of the condensation product of undecylenic acid chloride and Collagen Amino Acids

HONH

OH

OH

O

O

RH3C

Na

2

where R represents collagen amino acids Sodium/TEA-Undecylenoyl Hydrolyzed Collagen

Sodium/TEA-Undecylenoyl Hydrolyzed Collagen is a mixture of sodium and tri-ethanolamine salts of the condensation product of undecylenic acid chloride and Hydrolyzed Collagen

where R represents hydrolyzed collagen Sodium/TEA-Undecylenoyl Hydrolyzed Corn Protein

Sodium/TEA-Undecylenoyl Hydrolyzed Corn Protein is a mixture of sodium and triethanolamine salts of the condensation product of undecylenic acid chloride and Hydrolyzed Corn Protein

where R represents hydrolyzed corn protein

Sodium/TEA-Undecylenoyl Hydrolyzed Soy Protein

Sodium/TEA-Undecylenoyl Hydrolyzed Soy Protein is a mixture of sodium and triethanolamine salts of the condensation product of undecylenic acid chloride and Hydrolyzed Soy Protein

where R represents hydrolyzed soy protein


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Sodium/TEA-Undecylenoyl Hydrolyzed Wheat Protein

Sodium/TEA-Undecylenoyl Hydrolyzed Wheat Protein is a mixture of sodium and triethanolamine salts of the condensation product of undecylenic acid chloride and Hydrolyzed Wheat Protein

where R represents hydrolyzed wheat protein

TEA-Abietoyl Hydrolyzed Collagen 68918-77-4

TEA-Abietoyl Hydrolyzed Collagen is the triethanolamine salt of the condensation product of abietic acid chloride and Hydrolyzed Collagen


TEA-Cocoyl Hydrolyzed Soy Protein

TEA-Cocoyl Hydrolyzed Soy Protein is the triethanolamine salt of the condensation product of coconut acid chloride with Hydrolyzed Soy Protein

where RCO- represents the fatty acids derived from coconut oil and R’

represents hydrolyzed soy protein TEA-Dextrin Octenylsuccinate

TEA-Dextrin Octenylsuccinate is the triethanolamine salt of the rxn product of octenylsuccinic anhydride with Dextrin. Dextrin is the glucose polysaccharide obtained from partial hydrolysis of starch.

where R represents dextrin or a negative charge

TEA-Lauroyl Collagen Amino Acids

TEA-Lauroyl Collagen Amino Acids is the triethanolamine salt of the condensation product of lauric acid chloride and Collagen Amino Acids

where R represents collagen amino acids

TEA-Lauroyl Hydrolyzed Collagen

TEA-Lauroyl Hydrolyzed Collagen is the triethanolamine salt of the condensation product of Hydrolyzed Collagen and lauric acid chloride


TEA-Lauroyl Keratin Amino Acids

TEA-Lauroyl Keratin Amino Acids is the triethanolamine salt of the condensation product of lauric acid chloride and Keratin Amino Acids

where R represents keratin amino acids

TEA-Myristoyl Hydrolyzed Collagen

TEA-Myristoyl Hydrolyzed Collagen is the triethanolamine salt of the condensation product of myristic acid chloride and Hydrolyzed Collagen



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TEA-Oleoyl Hydrolyzed Collagen

TEA-Oleoyl Hydrolyzed Collagen is the triethanolamine salt of the condensation product of oleic acid chloride and hydrolyzed collagen.

where R represents hydrolyzed collagen TEA-Undecylenoyl Hydrolyzed Collagen 68951-91-7

TEA-Undecylenoyl Hydrolyzed Collagen is the triethanolamine salt of the condensation product of undecylenic acid chloride and Hydrolyzed Collagen


Polymer Salts TEA-Acrylates/ Acrylonitrogens Copolymer

TEA-Acrylates/ Acrylonitrogens Copolymer is the polymer formed from the controlled hydrolysis of polyacrylo-nitrile neutralized by triethanolamine.

TEA-Acrylates/ Ethylhexyl Acrylate Copolymer

TEA-Acrylates/ Ethylhexyl Acrylate Copolymer is a copolymer of ethylhexyl acrylate and the triethanolamine salt of one or more monomers consisting of acrylic acid, methacrylic acid, or one of their simple esters. Wherein “simple esters” means esters wherein the alcohol residue is one to 4 carbons long.

where R represents hydrogen or a methyl group, and R’ represents hydrogen

or an alkyl group, one to four carbons in length. TEA-Carbomer

TEA-Carbomer is the triethanolamine salt of Carbomer. Wherein carbomer is a homopolymer of acrylic acid crosslinked with an allyl ether of pentaerythritol, an allyl ether of sucrose, or an allyl ether of propylene.

where R is hydrogen during the polymerization, but is then converted to the

triethanolammonium


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TEA-Diethanolaminoethyl Polyisobutenyl-succinate 67762-80-5

TEA-Diethanolaminoethyl Polyiso-butenyl-succinate is triethanolamine salt where R represents the polyisobutenyl succinic anhydride moiety.

Table 3. Physical and Chemical Properties

Property Value Reference

Triethanolamine Physical Form clear viscous liquid 1 Color colorless to pale yellow 23 Odor ammonical 1 Molecular Weight 149.19 1 Melting Point 21.6°C 23 Boiling Point 335.4°C @ 760 mm Hg 23 Water Solubility miscible in water 23 Other Solubility insoluble in benzene, ether, and petroleum distillates 1 miscible with methanol or acetone; sparingly soluble in hydrocarbon solvents; readily

forms salts with organic and inorganic acids 86

log Kow -1.59 @ 20°C 14 pKa 7.76 @ 25°C 33 Viscosity 590.5 cP @25°C 86

TEA-Hydrochloride Melting Point 177°C 87

TEA-Diricinoleate Molecular Weight 710.08 88 Boiling Point 755.6°C 88 Density 0.990 g/cm3 (20°C; 7600 Torr) 88 log P 12.182 (25°C0 88 pKa (25°C) 14.53 (most acidic)

5.91 (most basic)

88

TEA-Lactate Melting Point -54.9°C 89 Density 1.222 g/cm3 89

TEA Lauryl Sulfate Density approx. 1 g/cm3 (20°C) 6


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Table 4a. Frequency and concentration of use according to duration and type of exposure

# of Uses11,90 Conc of Use (%)12 # of Uses11,90 Conc of Use (%)12 # of Uses11,90 Conc of Use (%)12

Triethanolamine Di-TEA Palmitoyl Aspartate TEA-Abietoyl Hydrolyzed Collagen

Totals* 3745 0.0002-19 1 0.4 NR 0.002-0.4

Duration of Use

Leave-On 3023 0.0002-6 NR NR NR 0.002-0.4

Rinse-Off 697 0.0003-19 1 0.4 NR 0.2

Diluted for Use 25 0.4-0.7 NR NR NR NR

Exposure Type

Eye Area 413 0.2-4 NR NR NR 0.3

Possible Ingestion 18 0.2-1 NR NR NR NR

Inhalation 79 0.001-2 NR NR NR NR

Dermal Contact 3100 0.0002-19 1 0.4 NR 0.002

Deodorant (underarm) 11 0.1-0.4 NR NR NR NR

Hair - Non-Coloring 373 0.0003-6 NR NR NR 0.2-0.4

Hair-Coloring 5 1-13 NR NR NR NR

Nail 14 0.2-3 NR NR NR NR

Mucous Membrane 174 0.2-19 NR 0.4 NR NR

Bath Products 25 0.4-0.7 NR NR NR NR

Baby Products 16 0.2-2 NR NR NR NR

TEA-Carbomer TEA-Cocoate TEA Cocoyl Alaninate Totals* 24 NR 2 NR 2 NR Duration of Use Leave-On 21 NR 1 NR 1 NR

Rinse Off 3 NR 1 NR 1 NR

Diluted for Use NR NR NR NR NR NR

Exposure Type

Eye Area 1 NR NR NR NR NR

Possible Ingestion 1 NR NR NR NR NR

Inhalation NR NR NR NR NR NR

Dermal Contact 24 NR 2 NR 2 NR

Deodorant (underarm) NR NR NR NR NR NR

Hair - Non-Coloring 2 NR NR NR NR NR

Hair-Coloring NR NR NR NR NR NR

Nail NR NR NR NR NR NR

Mucous Membrane NR NR 1 NR 1 NR

Bath Products NR NR NR NR NR NR

Baby Products NR NR NR NR NR NR

TEA Cocoyl Glutamate TEA-Cocoyl Hydrolyzed Collagen TEA Cocoyl Hydrolyzed Soy Protein

Totals* 69 0.3-8 8 0.3 25 0.001-0.005 Duration of Use Leave-On 8 NR NR NR 2 NR Rinse-Off 61 0.3-8 7 0.3 23 0.001-0.005 Diluted for Use NR 3 1 NR NR NR

Exposure Type

Eye Area NR NR NR NR NR NR Possible Ingestion NR NR NR NR NR NR Inhalation 1 NR NR NR NR NR Dermal Contact 68 0.3-5 6 NR NR NR Deodorant (underarm) NR NR NR NR NR NR Hair - Non-Coloring 1 8 2 0.3 25 0.001-0.005 Hair-Coloring NR NR NR NR NR 0.005 Nail NR NR NR NR NR NR Mucous Membrane 42 0.3-5 2 NR NR NR Bath Products NR 5 1 NR NR NR Baby Products 1 NR NR NR NR NR


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# of Uses11,90 Conc of Use (%)12 # of Uses11,90 Conc of Use (%)12 # of Uses11,90 Conc of Use (%)12 TEA-Cocoyl Sarcosinate TEA-Dodecylbenzenesulfonate TEA-Hydrochloride

Totals NR 1-5 116 0.2-6 NR 0.5

Duration of Use

Leave-On NR NR 21 0.8 NR NR Rinse Off NR 1-5 95 0.2-6 NR 0.5R Diluted for Use NR NR NR NR NR NR

Exposure Type

Eye Area NR NR NR NR NR NR Possible Ingestion NR NR NR NR NR NR Inhalation NR NR NR NR NR NR Dermal Contact NR 1-5 4 0.2-0.9 NR NR Deodorant (underarm) NR NR NR NR NR NR Hair - Non-Coloring NR 2 112 0.2-0.8 NR 0.5 Hair-Coloring NR NR NR 6 NR NR Nail NR NR NR NR NR NR Mucous Membrane NR 5 2 0.2-0.6 NR NR Bath Products NR NR NR NR NR NR Baby Products NR NR NR NR NR NR

TEA-Isostearate TEA Lactate TEA Laurate

Totals* 1 NR 13 0.06 NR 8

Duration of Use

Leave-On 1 NR 13 NR NR NR

Rinse-Off NR NR NR NR NR 8


Exposure Type Eye Area NR NR NR NR NR NR Possible Ingestion NR NR NR NR NR NR Inhalation NR NR NR NR NR NR Dermal Contact 1 NR 13 0.06 NR 8 Deodorant (underarm) NR NR NR NR NR NR Hair - Non-Coloring NR NR NR NR NR NR Hair-Coloring NR NR NR NR NR NR Nail NR NR NR NR NR NR Mucous Membrane NR NR NR NR NR NR Bath Products NR NR NR NR NR NR Baby Products NR NR NR NR NR NR

TEA-Laureth Sulfate TEA-Lauroyl Collagen Amino Acid TEA-Lauryl Sulfate

Totals* 17 3-14 3 0.4 302 0.0009-40

Duration of Use

Leave-On 2 NR 3 0.4 29 0.0009-8

Rinse-Off 15 3-14 NR NR 241 0.0009-40

Diluted for Use NR 3 NR NR 32 12-15

Exposure Type

Eye Area NR NR NR NR NR NR

Possible Ingestion NR NR NR NR NR NR

Inhalation NR NR NR NR NR 8

Dermal Contact 3 3-9 NR NR 236 0.2-40

Deodorant (underarm) NR NR NR NR NR NR

Hair - Non-Coloring 14 14 3 0.4 65 0.0009-40

Hair-Coloring NR 6 NR NR NR 2

Nail NR NR NR NR NR NR

Mucous Membrane 1 9 NR NR 147 5-30

Bath Products NR 3 NR NR 32 12-15

Baby Products NR NR NR NR 2 NR


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# of Uses11,90 Conc of Use (%)12 # of Uses11,90 Conc of Use (%)12 # of Uses11,90 Conc of Use (%)12 TEA-Myristate TEA-Palmitate TEA-PCA Totals* 2 NR 5 14 NR 0.3-1

Duration of Use

Leave-On NR NR 3 NR NR 0.3-1

Rinse-Off 2 NR 2 NR NR NR


Exposure Type

Eye Area NR NR 1 NR NR NR Possible Ingestion NR NR NR NR NR NR Inhalation NR NR NR NR NR NR Dermal Contact 2 NR 4 14 NR 0.3-1 Deodorant (underarm) NR NR NR NR NR NR Hair - Non-Coloring NR NR NR NR NR NR Hair-Coloring NR NR NR NR NR NR Nail NR NR NR NR NR NR Mucous Membrane NR NR NR NR NR NR Bath Products NR NR NR NR NR NR Baby Products NR NR NR NR NR NR TEA-Rosinate TEA-Salicylate TEA-Stearate

Totals* 1 NR 3 NR 130 9

Duration of Use

Leave-On NR NR NR NR 108 NR

Rinse-Off 1 NR 3 NR 22 NR


Exposure Type

Eye Area NR NR NR NR 9 NR Possible Ingestion NR NR NR NR 1 NR Inhalation NR NR NR NR 1 NR Dermal Contact 1 NR NR NR 110 9 Deodorant (underarm) NR NR NR NR NR NR Hair - Non-Coloring NR NR 3 NR 16 NR Hair-Coloring NR NR NR NR 1 NR Nail NR NR NR NR NR NR Mucous Membrane NR NR NR NR 13 NR Bath Products NR NR NR NR NR NR Baby Products NR NR NR NR NR NR

TEA-Sulfate TEA-Undecylenoyl Hydrolyzed

Animal Protein

Totals* 6 0.2 6 NR

Duration of Use

Leave-On NR NR NR

Rinse-Off 6 0.2 6

Diluted for Use NR NR NR0

Exposure Type

Eye Area NR NR NR Possible Ingestion NR NR NR Inhalation NR NR NR Dermal Contact NR NR 6 Deodorant (underarm) NR NR NR Hair - Non-Coloring 6 0.2 NR Hair-Coloring NR NR NR Nail NR NR NR Mucous Membrane NR NR NR Bath Products NR NR NR Baby Products NR NR NR

* Because each ingredient may be used in cosmetics with multiple exposure types, the sum of all exposure types my not equal the sum of total uses. NR – no reported uses


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Table 4b. Ingredients not reported to be used Di-TEA Cocamide Diacetate Di-TEA-Oleamido PEG-2 Sulfosuccinate Magnesium/TEA-Coco-Sulfate Sodium/TEA-Lauroyl Hydrolyzed Collagen Sodium/TEA C12-13 Pareth-3 Sulfate Sodium/TEA-Lauroyl Collagen Amino Acids Sodium/TEA-Lauroyl Hydrolyzed Keratin Sodium/TEA-Lauroyl Keratin Amino Acids Sodium/TEA-Undecylenoyl Alginate Sodium/TEA-Undecylenoyl Carrageenan Sodium/TEA-Undecylenoyl Collagen Amino Acids Sodium/TEA-Undecylenoyl Hydrolyzed Collagen Sodium/TEA-Undecylenoyl Hydrolyzed Corn Protein Sodium/TEA-Undecylenoyl Hydrolyzed Soy Protein Sodium/TEA-Undecylenoyl Hydrolyzed Wheat Protein TEA C14-17 Alkyl Sec Sulfonate TEA-Acrylates/ Acrylonitrogens Copolymer TEA-Acrylates/ Ethylhexyl Acrylate Copolymer TEA-Alginate TEA-C10-15 Alkyl Sulfate TEA-C11-15 Alkyl Sulfate TEA-C12-13 Alkyl Sulfate TEA-C12-13 Alkyl Sulfate TEA-C12-14 Alkyl Sulfate TEA-C12-15 Alkyl Sulfate TEA-C12-13 Alkyl Phosphate TEA-C12-14 Alkyl Phosphate TEA-C11-15 Pareth Sulfate TEA-C12-13 Pareth-3 Sulfate TEA-Canolate TEA-Cocamide Diacetate TEA-Coco-Sulfate TEA-Cocoyl Glutaminate TEA-Cocoyl Glycinate TEA-Dextrin Octenylsuccinate

TEA-Diethanolaminoethyl Polyisobutenylsuccinate TEA-Dimethicone PEG-7 Phosphate TEA-Diricinoleate TEA-EDTA TEA-Glyceryl Dimaleate TEA-Hydrogenated Cocoate TEA-Hydrogenated Tallowoyl Glutamate TEA-Isostearoyl Hydrolyzed Collagen TEA-Laneth-5 Sulfate TEA-Lauraminopropionate TEA-Laurate/ Myristate TEA-Laureth-4 Phosphate TEA-Lauroyl Glutamate TEA-Lauroyl Hydrolyzed Collagen TEA-Lauroyl Keratin Amino Acids TEA-Lauroyl Lactylate TEA-Lauroyl Methylaminopropionate TEA-Lauroyl Sarcosinate TEA-Lauroyl/Myristoyl Aspartate TEA-Lauryl Phosphate TEA-Myristaminopropionate TEA-Myristoyl Hydrolyzed Collagen TEA-Oleate TEA-Oleoyl Hydrolyzed Collagen TEA-Oleoyl Sarcosinate TEA-Oleyl Sulfate TEA-Palm Kernel Sarcosinate TEA-PEG-3 Cocamide Sulfate TEA-PEG-50 Hydrogenated Castor Oil Succinate TEA-Polyphosphate TEA-Sorbate TEA-Tallate TEA-Tridecylbenzenesulfonate TEA-Undecylenate


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REFERENCES

1. Elder RE (ed). Final Report on the Safety Assessment of Triethanolamine, Diethanolamine, and Monoethanolamine. J Am Coll Toxicol. 1983;2:(7):183-235.

2. Elder RE (ed). Final report on the safety assessment of potassium-coco-hydrolyzed animal protein and triethanolamine-coco-hydrolyzed animal protein. J Am Coll Toxicol. 1983;2:(7):75-86.

3. Dow Chemical Company. The alkanolamines handbook. 1988. Midland, MI: The Dow Chemical Company.Secondary reference in Knaak et al. 1997.

4. Zhu, S., Heppenstall-Butler, M., Butler, M. F., Pudney, P. D. A., Ferdinando, D., and Mutch, K. J. Acid Soap and Phase Behavior of Stearic Acid and Triethanolamine Stearate. Journal of Physical Chemistry B. 2005;109:(23):11753-11761.

5. Elder RE (ed). Final report on the safety assessment of TEA-Lauryl Sulfate. J Am Coll Toxicol. 1982;1:(4):143-167.

6. Organisation for Economic Co-operation and Development. SIDS Dossier on Chem ID: 139-96-6 (TEA-lauryl sulfate). http://webnet.oecd.org/hpv/ui/Publications.aspx. 4-14-2008. Date Accessed 5-14-2011.

7. Zhu, S., Pudney, P. D. A., Heppenstall-Butler, M., Butler, M. F., Ferdinando, D., and Kirkland, M. Interaction of the Acid Soap of Triethanolamine Stearate and Stearic Acid with Water. Journal of Physical Chemistry B. 2007;111:(5):1016-1024.

8. Kraeling MEK, Yourick JJ, and Bronaugh RL. In vitro human skin penetration of diethanolamine. Food Chem Toxicol. 2004;42:1553-1561.

9. Saghir SA, Brzak A, Markham DA, Bartels MJ, and Stott WT. Investigation of the formation of N-nitrosodiethanolamine in B6C3F1 mice following topical administration of triethanolamine. REg Toxicol Pharmacol. 2005;43:10-18.

10. Gottschalck T.E. and Bailey, J. E. eds. International Cosmetic Ingredient Dictionary and Handbook. Washington, DC: Personal Care Products Council, 2010.

11. Food and Drug Administration (FDA). Frequency of use of cosmetic ingredients. FDA Database. 2011. Washington, DC: FDA.Updated Feb 25.

12. Personal Care Products Council. Updated concentration of use by FDA product category: TEA-containing ingredients. 5-16-2011. Unpublished data submitted by the Council on May 17, 2011. ( 3 pp).

13. Personal Care Products Council. Concentration of use by FDA product category: TEA Containing Ingredients. 3-15-2011. Unpublished data submitted by the Council on March 15, 2011. (3 pp).

14. Organisation for Economic Co-operation and Development. SIDS Initial Assessment Report for SIAM 3 (Triethanolamine). http://webnet.oecd.org/Hpv/UI/SIDS_Details.aspx?id=CEF02D50-2294-462B-8027-FB4EC67D5D81. 2-16-1995. Date Accessed 10-8-2010

15. European Commission. European Commission Enterprise and Industry. Cosmetics - Cosing. Annex III/1,62 - Trialkylamines, trialkanolamines and their salts. http://ec.europa.eu/consumers/cosmetics/cosing/index.cfm?fuseaction=search.results. 2-7-2011. Date Accessed 6-7-2010.

16. European Commission. Cosing Database. Annex V. List of preservatives allowed in cosmetic products; EC Regulation (v.2). http://ec.europa.eu/consumers/cosmetics/cosing/index.cfm?fuseaction=search.results&annex_v2=V&search#. 2009. Date Accessed 5-14-2011.

17. Food and Drug Administration. Everything Added to Food in the United States (EAFUS). http://www.fda.gov/Food/FoodIngredientsPackaging/ucm115326.htm. 5-27-0010. Date Accessed 6-8-2010.

18. Lessmann H, Uter W, Schnuch A, and Geier J. Skin sensitizing properties of ethanolamines mono-, di-, and triethanolamine. Data analysis of a multicentre surveillance network (IVDK) and review of literature. Contact Derm. 2009;60:243-255.

19. Food and Drug Administration. Sunscreen drug products for over-the-counter human use; final rule. Fed Regist. 5-21-1999;64:27666-27693.

20. Cross, Sheree E., Megwa, Stella A., Benson, Heather A. E., and Roberts, Michael S. Self promotion of deep tissue penetration and distribution of methylsalicylate after topical application. Pharmaceutical Research. 1999;16:(3):427-433.


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21. Cross, Sheree E., Anderson, Chris, and Roberts, Michael S. Topical penetration of commercial salicylate esters and salts using human isolated skin and clinical microdialysis studies. British Journal of Clinical Pharmacology. 1998;46:(1):29-35.

22. Stott WT, Waechter JM, Rick DL, and Mendrala AL. Absorption, distribution, metabolism and excretion of intravenously and dermally administered triethanolamine in mice. Food Chem Toxicol. 2000;38:1043-1051.

23. National Toxicology Program. NTP Technical report on the toxicology and carcinogenesis studies of triethanolamine (CAS No. 102-71-6) in B6C3F1 mice. (Dermal study). NTP TR 518. 2004.

24. Andersen FA (ed). Safety assessment of salicylic acid, butyloctyl salicylate, calcium salicylate, C12-15 alkyl salicylate, capryloyl salicylic acid, hexyldodecyl salicylate, isocetyl salicylate, isodecyl salicylate, magnesium salicylate, MEA-salicyalte, ethylhexyl salicylate, potassium salicylate, methyl salicylate, myristyl salicylate, sodium salicylate, TEA-salicylate, and tridecyl salicylate. Int J Toxicol. 2003;22:(Suppl 3):1-108.

25. Kohri N, Matsuda T, Umeniwa K, Miyazaki K, and Arita T. Development of assay method in biological fluids and biological fate of triethanolamine. Yakuzaigaku. 1982;42:(4):342348.

26. Kao Company. Acute oral toxicity test in rats. Fixed dose method (Unpublished Report No. CD-95/4286T). 1995. Unpublished data cited in the SIDS Dossier on Chem ID: 139-96-6 (TEA-lauryl sulfate), 2008.

27. Olson, K. J., Dupree, R. W., Plomer, E. T., and Rowe, V. K. Toxicological properties of several commercially available surfactants. Journal of the Society of Cosmetic Chemists. 1962;13:469-479.

28. Melnick R and Hejtmancki M Mezza L Ryan M persing R Peters A. Comparative effects of triethanolamine (TEA) and diethanolamine (DEA) in short-term dermal studies. (Secondary reference in Melnick and Tomaszewski 1990). The Toxiologist. 1988;8:127.

29. DePass LR, Fowler EH, and Leung H-W. Subchronic dermal toxicity study of triethanolamine in C3H/HeJ mice. Fd Chem Toxicol. 1995;33:(8):675-680.

30. National Toxicology Program. Toxicology and carcinogenesis studies of triethanolamine (CAS No. 102-71-6) in F344/N rats and B6C3F1 mice. (Dermal studies.) TR No. 449. 1999.

31. Hejtmancik M, Mezza L, Peters AC, and Athey PM. The repeated dose dosed water study of triethanolamine (CAS No. 102-71-6) in Fischer-344 rats. 1985. Columbus OH: Columbus Division Laboratories.Unpublished data summarized in Knaak et al. 1997.

32. Hejtmancik M, Mezza L, Peters A, and Athey PM. The repeated dose dosed water study of triethanolamine (CAS No. 102-71-6) in B6C3F1 mice. 1985. Columbus Division Laboratories.Unpublished data summarized in Knaak et al. 1997.

33. Gamer AO, Rossbacher R, Kaufmann W, and van Ravenzwaay B. The inhalation toxicity of di- and triethanolamine upon repeated exposure. Food Chem Toxicol. 2008;46:2173-2183.

34. Mosberg A, McNEill D, Hejtmancik M, Persing RL, and Peters A. The repeated dsoe inhalation study of triethanolamine (CAS No. 102-71-6) in Fischer-344 rats. 1985. Columbus OH: Battelle Columbus Division Laboratories.Unpublished data summarized in Knaak et al. 1997.

35. Mosberg A, McNEill D, Hejtmancik M, Persing RL, and Peters A. The repeated dose inhalation study of triethanolamine (CAS No. 102-71-6) in B6C3F1 mice. 1985. Columbus OH: Battelle Columbus Division Laboratories.Unpublished data summarized in Knaak et al. 1997.

36. Battelle Columbus Laboratories. Mating trial dermal study of triethanolamine (CAS No. 102-71-6) in Fischer 344 rats. Final report (NIH Cotnract No. N01-ES-45068). Secondary reference in NTP 2004. 1988.

37. Battelle Columbus Laboratories. Mating trial dermal study of triethanolamine (CAS No. 102-71-6) in Swiss CD-1 mice. Final report (NIH Cotnract No. N01-ES-45068). Secondary reference in NTP 2004. 1988. Secondary reference in NTP 2004.- TR 518.

38. Environmental Protection Agency. High Production Volume (HPV) Challenge Program Revised Test Plan and Robust Summaries for Polyphosphoric Acid Esters of Triethanolamine, Sodium Salts. http://www.epa.gov/oppt/chemrtk/pubs/summaries/plyacdts/c14950rr.pdf. 11-30-2004.


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39. Inoue K, Sunakawa T, Okamoto K, and Tanaka Y. Mutagenicity tests and in vitro transformation assays on triethanolamine. Mutat Res. 1982;101:305-313.

40. Dean BJ, Brooks TM, Hodson-Walker G, and Hutson DH. Genetic toxicology testing of 41 industrial chemicals. Mutat Res. 1985;153:57-77.

41. Mortelmans K, Haworth S, Lawlor T, Speck W, Tainer B, and Zeiger E. Salmonella mutagenicity tests: II. Results from the testing of 270 chemicals. Environ Mutagen. 1986;8:(Suppl 7):1-119.

42. Galloway SM, Armstrong MJ, Reuben, Colman, Brown B, Cannon C, Bloom AD, Nakamura F, Ahmed M, Duk S, Rimpo J, Margolin BH, Resnick MA, Anderson B, and Zeiger E. Chromosome aberrations and sister chromatid exchanges in Chinese hamster ovary cells: Evaluation of 108 chemicals. Environ Mol Mutagen. 1987;10:(Suppl 10):1-175.

43. Witt KL, Knapton A, Wehr CM, Hook GJ, Mirsalis J, Shelby MD, and MacGregor JT. Micronucleated erythrocyte frequency in peripheral blood of B6C3F1mice from short-term. prechronic, and chronic studies of the NTP carcinogenesis bioassay program. Environ Mol Mutagen. 2000;36:163-194.

44. National Toxicology Program. Toxicology and carcinogenesis studies of triethanolamine (CAS NO. 102-71-6) in B6C3F1 mice. (Dermal study.) NTP TR 518. 2004. Report No. NIH Publication NO 04-4452.

45. Tennant RW, French JE, and Spalding JW. Identifying chemical carcinogens and assessing potential risk in short-term bioassays using transgenic mouse models. Environ Health Perspect. 1995;103:942-950.

46. Konishi, Y., Denda, A., Uchida, K., Emi, Y., Ura, H., Yokose, Y., Shiraiwa, K., and Tsutsumi, M. Chronic toxicity carcinogenicity studies of triethanolamine in B6C3F1, mice. Fundam.Appl Toxicol. 1992;18:(1):25-29.

47. Maekawa, A., Onodera, H., Tanigawa, H., Furuta, K., Kanno, J., Matsuoka, C., Ogiu, T., and Hayashi, Y. Lack of carcinogenicity of triethanolamine in F344 rats. J Toxicol Environ Health. 1986;19:(3):345-357.

48. Ghoshal AK and Farber E. The induction of liver cancer by dietary deficieny of choline and methionine without added carcinogens. Carcinogenesis. 1984;5:(10):1367-1370.

49. Rogers AE. Methyl donors in the diet and responses to chemical carcinogens. Am J Clin Nutr. 1995;61:(Suppl):659S-665S.

50. Stott WT, Radtke BJ, LinscombeVA, Mar MH, and Zeisel SH. Evaluation of the potential of triethanolamine to alter hepatic choline levels in female B6C3F1 mice. Toxicol Sci. 2004;79:(2):242-247.

51. International Agency for Research on Cancer (IARC). Triethanolamine. IARC Monogr Eval.Carcinog Risks Hum. 2000;77:381-401.

52. Tornier, Carine, Rosdy, Martin, and Maibach, Howard I. In vitro skin irritation testing on reconstituted human epidermis: Reproducibility for 50 chemicals tested with two protocols. Toxicology in Vitro. 2006;20:(4):401-416.

53. Ananthapadmanabhan, K. P., Yu, K. K., Meyers, C. L., and Aronson, M. P. Binding of surfactants to stratum corneum. Journal of the Society of Cosmetic Chemists. 1996;47:(4):185-200.

54. Anderson SE, Brown KK, Butterworth LF, Fedorowicz A, Jackson LG, Frasch HF, Beezhold D, Munson AE, and Meade BJ. Evaluation of irritancy and sensitization potential of metalworking fluid mixtures and components. J Immunotoxicol. 2009;6:(1):19-29.

55. Müller-Decker K, Heinzelmann T, Fürstenberger G, Kecskes A, Lehmann W-D, and Marks F. Arachidonic acid metabolism in primary irritant dermatitis produced by patch testing of human skin with surfactants. Toxicol Appl Pharmacol. 1998;153:59-67.

56. Tavss, Edward A., Eigen, Edward, and Kligman, Albert M. Anionic detergent-induced skin irritation and anionic detergent-induced pH rise of bovine serum albumin. Journal of the Society of Cosmetic Chemists. 1988;39:(4):267-272.

57. Bulich AA, Tung K-K, and Scheibner G. The luminescent bacteria toxicity test: Its potential as an in vitro alternative. J Biolumin Chemilumin. 1990;5:71-77.

58. Gordon VC. Utilization of biomacromolecular in vitro assay systems in the prediction of in vivo toxic responses. Lens and Eye Toxicity Research. 1992;9:(3&4):211-227.


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59. National Toxicology Program. Abstract for IMM90005. The immunotoxicity of triethanolamine (CAS No. 102-71-6). http://ntp.niehs.nih.gov/?objectid=03E847AC-AC78-4065-BE8E52A8BB9CFBA7. 2-21-2005. Date Accessed 10-14-2010.

60. Tosti A, Morelli R, and Bardazzi F. Prevalence and sources of sensitization to emulsifiers: a clinical study. Contact Derm. 1990;23:68-72.

61. Jones SK and Kennedy TC. Contact dermatitis from triethanolamine in E45 cream. Contact Derm. 1988;19:(3):230.

62. Batten TL, Wakeel RA, Douglas WS, Evans C, White MI, Moody R, and Ormerod AD. Contact dermatitis from the old formula E45 cream. Contact Derm. 1994;30:159-161.

63. Savonius B, Keskinen H, Tupperainen M, and Kanerva L. Occupational asthma caused by ethanolamines. Allergy. 1994;49:877-881.

64. Andersen, K. E., Roed-Petersen, J., and Kamp, P. Contact allergy related to TEA-PEG-3 cocamide sulfate and cocamidopropyl betaine in a shampoo. Contact Dermatitis. 1984;11:(3):192-193.

65. Becker LC, Bergfeld W, Belsito DV, Hill RA, Klaassen CD, Liebler DC, Marks JG, Shank RS, Slaga TJ, Snyder PW, and Andersen FA. Amended safety assessment of dodecylbenezenesulfonate, decylbenzenesulfonate, and tridecylbenzenesulfonate salts as used in cosmetics. Int J Toxicol. 2010;29:(Suppl 4):288S-305S.

66. Andersen FA (ed). Final report on the safety assessment of EDTA, calcium disodium EDTA, diammonium EDTA, dipotassium EDTA, disodium EDTA, TEA-EDTA, tetrasodium EDTA, tripotassium EDTA, trisodium EDTA, HEDTA, and trisodium EDTA. Int J Toxicol. 2002;21:(Suppl 2):95-142.

67. Andersen FA (ed). Final report on the safety assessment of glycolic acid, ammonium, calcium, potassium, and sodium glycolates, methyl, ethyl, propyl, and butyl glycolates, and lactic acid, ammonium, calcium, potassium, sodium, and TEA-lactates, methyl, ethyl, isoprpyl, and butyl lactates, and lauryl, myristyl, and cetyl lactates. Int J Toxicol. 1998;17:(Suppl 1):1-241.

68. Andersen FA (ed). Final report on the safety assessment of TEA Stearate. J Am Coll Toxicol. 1995;14:(3):240-248.

69. Fiume MM, Heldreth BA, Bergfeld WF, Belsito DV, Klaassen CD, Liebler DC, Hill RA, Marks JG, Shank RC, Slaga TJ, Snyder PW, and Andersen FA. CIR Expert Panel final amended report on alkyl PEG ethers as used in cosmetics. 2010. Available from the CIR, 1101 17th Street, NW, Ste 412, Washington DC 20036. http://cir-safety.org.

70. Elder RL (ed). Final report on the safety assessment of sodium lauryl sulfate and ammonium lauryl sulfate. J Am Coll Toxicol. 1983;2:(7):127-181.

71. Diamante C, Bergfeld WF, Belsito DV, Klaassen CD, Hill RA, Liebler DC, Marks JG, Shank RC, Slaga TJ, Snyder PW, and Andersen FA. Amended Safety Assessment of Cocos Nucifera (Coconut) Oil, Coconut Acid, Hydrogenated Coconut Acid, Hydrogenated Coconut Oil, Ammonium Cocomonoglyceride Sulfate, Butylene Glycol Cocoate, Caprylic/Capric/Coco Glycerides, Cocoglycerides, Coconut Alcohol, Coconut Oil Decyl Esters, Decyl Cocoate, Ethylhexyl Cocoate, Hydrogenated Coco-Glycerides, Isodecyl Cocoate, Lauryl Cocoate, Magnesium Cocoate, Methyl Cocoate, Octyldodecyl Cocoate, Pentaerythrityl Cocoate, Potassium Cocoate, Potassium Hydrogenated Cocoate, Sodium Cocoate, Sodium Cocomonoglyceride Sulfate, Sodium Hydrogenated Cocoate, and Tridecyl Cocoate. 2008. Available from the CIR, 1101 17th Street, NW, Ste 412, Washington DC 20036. http://cir-safety.org.

72. Andersen FA (ed). Final report on the safety assessment of cocoyl sarcosine, lauroyl sarcosine, myristoyl sarcosine, oleoyl sarcosin, stearoyl sarcosine, sodium cocoyl sarcosinate, sodium lauroyl sarcosinate, sodium myristoyl sarcosinate, ammonium cocoyl sarcosinate, and ammonium lauroyl sarcosinate. Int J Toxicol. 2001;20:(Suppl 1):1-14.

73. Elder RE (ed). Final report on the safety assessment of dimethicone copolyol. J Am Coll Toxicol. 1982;1:(4):33-54.

74. Elder RL (ed). Final report on the safety assessment of isostearic acid. J Am Coll Toxicol. 1983;2:(7):61-74.

75. Elder RL (ed). Final report on the safety assessment of oleic acid, lauric acid, palmitic acid, myristic acid, and stearic acid. J Am Coll Toxicol. 1987;6:(3):321-401.

76. Becker LC, Bergfeld WF, Belsito DV, Hill RA, Klaassen CD, Marks JG, Shank RC, Slaga TJ, Snyder PW, and Andersen FA. Final report of the amended safety assessment of myristic acid and its salts and esters as used in cosmetics. Int J Toxicol. 2010;29:(3):162S-186S.


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77. Andersen FA (ed). Final safety assessment for PCA and Sodium PCA. Int J Toxicol. 1999;18:(Suppl 2):25-34.

78. Burnett CL, Fiume MM, Bergfeld WF, Belsito DV, Klaassen CD, Liebler DC, Hill RA, Marks JG, Shank RC, Slaga TJ, Snyder PW, and Andersen FA. Final report of the CIR Expert Panel on the safety of plant-derived fatty acid oils and used in cosmetics. 2011. Available from the CIR, 1101 17th Street, NW, Ste 412, Washington DC 20036. http://cir-safety.org.

79. Andersen FA (ed). Final report on the safety assessment of Ricinus Communis (Castor) Seed Oil, Hydrogenated Castor Oil, Glyceryl Ricinoleate, Glyceryl Ricinoleate SE, Ricinoleic Acid, Potassium Ricinoleate, Sodium Ricinoleate, Zinc Ricinoleate, Cetyl Ricinoleate, Ethyl Ricinoleate, Glycol Ricinoleate, Isopropyl Ricinoleate, Methyl Ricinoleate, and Octyldodecyl Ricinoleate. Int J Toxicol. 2007;26:(Suppl 3):31-77.

80. Fiume MM, Bergfeld WF, Belsito DV, Klaassen CD, Marks JG, Shank RC, Slaga TJ, Snyder PW, and Andersen FA. Final report on the safety assessment of sodium cetearyl sulfate and related alkyl sulfates as used in cosmetics. Int J Toxicol. 2010;29:(Suppl 2):115S-132S.

81. Andersen FA (ed). Final report on the safety assessment of sodium lauraminopropionate and sodium lauriminodipropionate. Int J Toxicol. 1997;16:(Suppl 1):1-9.

82. Robinson VC, Bergfeld WF, Belsito DV, Hill RA, Klaassen CD, Marks JG, Shank RC, Slaga TJ, Snyder PW, and Andersen FA. Final report of the amended safety assessment of sodium laureth sulfate and related salts of sulfated ethoxylated alcohols. Int J Toxicol. 2010;29:(Suppl 3):151S-161S.

83. Elder RL (ed). Final report on the safety assessment of sodium laureth sulfate and ammonium laureth sulfate. J Am Coll Toxicol. 1983;2:(5):1-34.

84. Elder RE (ed). Final report on the safety assessment of sorbic acid and potassium sorbate. J Am Coll Toxicol. 1988;7:(6):837-880.

85. Robinson VC, Bergfeld WF, Belsito DV, Klaassen CD, Marks JG, Shank RC, Slaga TJ, Snyder PW, and Andersen FA. Amended safety assessment of tall oil acid, sodium tallate, potasstium tallate, and ammonium tallate. Int J Toxicol. 2009;28:(Suppl 3):252S-258S.

86. Melnick RL and Tomaszewski KE. Triethanolamine. Chapter: 7.6. Buhler DR and Reed DJ.In: Ethel Browning's Toxicity and Metabolism of Industrial Solvents. Vol. II: Nitrogen and Phosphorus Solvents. 2nd ed. Amsterdam/New York/Oxford: Elsevier; 1990:41-50.

87. Rohmann C and Wischniewski T. Sulfur-containing esters of morpholinoethanol and thiomorpholinoethanol. Archives der Pharmazie und Berichet der Deutschen Pharmazeutischen Gesellschaft. 1959;292:797-792.

88. ACD/Labs. Advanced Chemistry Development (ACD/Labs) Software. 1994. (8.19):As cited in Chemical Abstracts Services Registry. Date Accessed 2011

89. Yuan XL, Jiang S, and Mei X. Hydroxyl ammonium ionic liquids: Synthesis, properties, and solubility of SO2. Jorunal of Chemical & Engineering Data. 2007;52:(2):596-599.

90. Personal Care Products Council. Updated concentration of use of triethanolamine. 11-8-2010. Unpublished data submitted by the Council (3 pp).


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Personal Care Products CouncilCommitted to Safety,Qualify & Innovation

Memorandum

TO: F. Alan Andersen, Ph.D.Director - COSMETIC INGREDIENT REVIEW (CIR)

FROM: John Bailey, Ph.D.Industry Liaison to the CIR Expert Panel

DATE: December 10, 2010

SUBJECT: Comments on the Draft Reports on Triethanolamine, Diethanolamine and EthanolaminePrepared for the December 13-14, 2010 CIR Expert Panel Meeting

Memo - Rather than Acute (Single Dose) Toxicity and Repeated Dose Toxicity, the sections should betitled Acute (Single) Dose Exposure and Repeated Dose Exposure. Acute and Repeated Dosedescribe the exposure rather than toxicity.

Triethanolaminep.1 - What is missing from the following sentence? “The crude is later separated by distillation.”p.1 - It would be helpful to indicate where in the report the in vivo studies of NDELA formation are

presented.p.2 - The meaning of the following sentence is not clear, “Accordingly, depending on storage and

application conditions, aerosolized TEA may be a liquidlvapor instead of a particle.” Aerosolproducts will produce aerosols. For compounds that are part of the formulation that haverelatively high vapor pressures, the more important exposure will likely be inhalation of a vaporrather than inhalation of the aerosol.

p.2 - Where did the information on use from Health Canada come from? The website listed inreference 13 (the Canadian Hotlist) was checked and use information for individual ingredientsis not included on this website.

p.3 - The first two paragraphs of the Absorption, Distribution, Metabolism and Excretion study aredescribing the same study. Reference 16 is the unpublished version of the dermal studydescribed in reference 17.

p.4- - Where was the TEA-glucuronide found (reference 20)?p.6 - How was the 90-day NOAEC for local irritation calculated, e.g., using safety factors or modeling?p.7 - Searching the internet indicates that syntanol DC-b is CAS 85422-93-1 alcohols Cb0-18

ethoxylated.p.9 - LLNA’s are not in vitro studies. They are considered alternatives because they reduce distress.

As LLNAs are useful for quantitative risk assessment., please include the doses used in thisstudy.

1101 17th Street, N.W., Suite 3OO Washington, D.C. 20036-4702 202.331.1770 202.331.1969 (fax) www.personalcarecouncil.org


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p.10 - Were the human studies described in the summary of the original report single patch tests orrepeated patch tests? Were the subjects patients or volunteers with no dermal conditions?

p.10 - Were the subjects tested in reference 15 patients with dermatological conditions?p.11 - It would be helpful if the information on in vivo N-nitrosodiethanolamine formation were

presented as a subsection under Absorption, Distribution, Metabolism and Excretion.p.11 - Please present the carcinogenicity mechanism information as a subsection under

Carcinogenicity.p.12 - The exposure information should be presented in the Cosmetic Use section and the cancer

evaluation should be the last item presented in the Carcinogenicity section.p.13, Table 1 - Please provide the references for this Table.p.14, 15 reference 19 and reference 38 - These two references are the same.

Diethanolaminep.2 - As there are inhalation data on Diethanolamine, is the aerosol boilerplate information necessary?p.2-3, 6-7 - It is not clear why the in vitro dermal penetration data is presented in two different

subsections.p.4 - Please defined PC and PE the first time they appear.p.S - In the description of reference 20 should “5 mi/kg bw” be “5 mg/kg bw” as the units for the rest of

the doses are mg/kg?p.S - The i.v. study described in reference 22 appears to be the same study as that described in reference

20. Please provide the dose used in reference 20. =

p.6 - Please change “The percutaneous absorption of cosmetic formulations...” to “The percutaneousabsorption of DEA in cosmetic formulations...”

p.8 - In the description of reference 30, should “125-500 ppm” be “125-500 mg/kg”? The units in therest of the paragraph are mg/kg.

p.9 - In the summary of the inhalation data from the original report, please give the duration of theshort-term inhalation exposure.

p.10 - It would be helpful if the 45-day inhalation study were presented before the 90-day inhalationstudies.

p.10 - In reference 35, were any dermal effects observed in the male mice treated with Diethanolamine?Were there any effects on the number of offspring?

p.11 - “Vehicle not specified” is not necessary for reference 40, 41, an inhalation study.p.13 - LLNA’s are not in vitro studies. They are considered alternatives because the reduce distress.

As LLNAs are useful for quantitative risk assessment, please include the doses used in thisstudy.

p.13 - The internet indicates that FORAFAC 1203 is an additive used in portable fire extinguishers. Asit is not possible to tell which component resulted in the sensitization, this study is not veryhelpful and can be deleted.

p.14 - It would be helpful if the information on in vivo N-nitrosodiethanolamine formation werepresented as a subsection under Absorption, Distribution, Metabolism and Excretion.

p.16 - Please present the carcinogenicity mechanism information as a subsection underCarcinogenicity.

2


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p.17 - If the OSHA and ACGIH values are presented, they should be cited to OSHA and ACGIHreferences, respectively. The NIOSH Safety Card (link from the On-Line) indicates that OSHAdoes not have a Permissible Exposure limit for Diethanolamine. NIOSH has a recommendationof 3 ppm.

p.17 - The IARC cancer review should be moved to the end of the Carcinogenicity section.p.18, Table 1 - Please provide references for this table.

Ethanolaminep.1 - Where did the information on use from Health Canada come from? The website listed in

reference 5 (the Canadian Hotlist) was checked and use information for individual ingredientsis not included on this website.

p.6 - LLNA’s are not in vitro studies. They are considered alternatives because the reduce distress.p.6 - Please provide OSHA and ACGIII references for the exposure limits.p.7, Table 1 - Please provide references for this table.

3


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TO:

iProducts Council

F. Alan Andersen, Ph.D.Director - COSMETIC NGREDIENT REVIEW (CW)

Committed to Safety,Quality & Innovation

FROM:

DATE:

John Bailey, Ph.D.Industry Liaison to the CIR Expert Panel

May 17, 2011

SUBJECT: Updated Concentration of Use by FDA Product Category: TEA Containing Ingredients

1101 17th Street, N.W., Suite 3O0 Washington, D.C. 20036-4702 202.331.1770 202.331.1969 (fax) www.personalcarecouncil.org

Personal Care

Memorandum


Panel Book Page 70

Concentration of Use by FDA Product CategoryTEA-Hydrochloride, TEA-Sulfate, TEA-Undecylenate, TEA-Laurate, TEA-Laurate/Myristate,

TEA-Myristate, TEA-Palmitate, TEA-Stearate, TEA-Isostearate, TEA-Sorbate, TEA-Oleate, TEA-Canolate,TEA-Cocoate, TEA-Hydrogenated Cocoate, TEA-Rosinate, TEA-Tallate, TEA-Lactate, TEA-Diricinoleate,

TEA-Glyceryl Dimaleate, TEA-Salicylate, TEA-EDTA, TEA-Myristaminopropionate,TEA-Lauraminopropionate, Di-TEA Cocamide Diacetate, Di-TEA-Palmitoyl Aspartate, TEA-Cocamide

Diacetate, TEA-Cocoyl Alaninate, TEA-Cocoyl Glutamate, TEA-Cocoyl Glutaminate, TEA-Cocoyl Glycinate,TEA-Cocoyl Sarcosinate, TEA-Hydrogenated Tallowoyl Glutamate, TEA-Lauroyl Glutamate, TEA-Lauroyl

Methylaminopropionate, TEA-Lauroyl/Myristoyl Aspartate, TEA-Lauroyl Sarcosinate, TEA-OleoylSarcosinate, TEA-Palm Kernel Sarcosinate, TEA-PCA, TEA-Lauroyl Lactylate, TEA-PEG-50 Hydrogenated

Castor Oil Succinate, Magnesium/TEA-Coco-Sulfate, Sodium/TEA C12-13 Pareth-3 Sulfate,Di-TEA-Oleamido PEG-2 Sulfosuccinate, TEA-Lauryl Sulfate, TEA-Laneth-5 Sulfate, TEA-Laureth Sulfate,

TEA-Oleyl Sulfate, TEA-C1O-15 Alkyl Sulfate, TEA-C11-15 Alkyl Sulfate, TEA-C12-13 Alkyl Sulfate,TEA-C12-14 Alkyl Sulfate, TEA-C12-15 Alkyl Sulfate, TEA C14-17 Alkyl Sec Sulfonate, TEA-Coco-Sulfate,

TEA-C11-15 Pareth Sulfate, TEA-C12-13 Pareth-3 Sulfate, TEA-PEG-3 Cocamide Sulfate, TEA-LaurylPhosphate, TEA-C12-13 Alkyl Phosphate, TEA-C12-14 Alkyl Phosphate, TEA-Dimethicone PEG-7

Phosphate, TEA-Laureth-4 Phosphate, TEA-Tridecylbenzenesulfonate, TEA-Dodecylbenzenesulfonate,TEA-Cocoyl Hydrolyzed Collagen, TEA-Alginate, TEA-Isostearoyl Hydrolyzed Collagen,Sodium/TEA-Lauroyl Collagen Amino Acids, Sodium/TEA-Lauroyl Hydrolyzed Collagen,SodiumITEA-Lauroyl Hydrolyzed Keratin, Sodiurn/TEA-Lauroyl Keratin Amino Acids,

Sodium/TEA-Undecylenoyl Alginate, Sodium/TEA-Undecylenoyl Carrageenan, Sodiuni/TEA-UndecylenoylCollagen Amino Acids, Sodium/TEA-Undecylenoyl Hydrolyzed Collagen, SodiumJTEA-Undecylenoyl

Hydrolyzed Corn Protein, Sodium/TEA-Undecylenoyl Hydrolyzed Soy Protein, Sodium/TEA-UndecylenoylHydrolyzed Wheat Protein, TEA-Abietoyl Hydrolyzed Collagen, TEA-Cocoyl Hydrolyzed Soy Protein,

TEA-Dextrin Octenylsuccinate, TEA-Lauroyl Collagen Amino Acids, TEA-Lauroyl Hydrolyzed Collagen,’TEA-Lauroyl Keratin Amino Acids, TEA-Myristoyl Hydrolyzed Collagen

TEA-Oleoyl Hydrolyzed Collagen, TEA-Undecylenoyl Hydrolyzed Collagen, TEA-Acrylates/AcrylonitrogensCopolymer, TEA-Acrylates/Ethylhexyl Acrylate Copolymer, TEA-Carbomer, TEA-Diethanolaminoethyl

Polyisobutenylsuccinate, TEA-Diricinoleate/IPDI Copolymer and Triethanolamine PolyoxyethyleneAlkylphenylether Phosphate

Ingredient Product Category Concentration ofUse

TEA-Hydrochloride Shampoos (noncoloring) 0.5%

TEA-Sulfate Shampoos (noncoloring) 0.2%

TEA-Laurate Skin cleansing (cold creams, cleansing lotions, 8%liquids and pads)

TEA-Palmitate f Shaving cream (aerosol, brushless and lather) 14%

TEA-Stearate Shaving cream (aerosol, brushless and later) 9%

TEA-Lactate Face and neck creams, lotions and powders 0.06%

Di-TEA-Palmitoyl Aspartate f Other personal cleanliness products 0.4%

TEA-Cocoyl Glutamate Bubble baths 3%

TEA-Cocoyl Glutamate Other bath preparations 3%

TEA-Cocoyl Glutamate Shampoos (noncoloring) 8%

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TEA-Cocoyl Glutamate Bath soaps and detergents 5%

TEA-Cocoyl Glutamate Other personal cleanliness products1 0.3-3%

TEA-Cocoyl Glutamate Shaving cream (aerosol, brushless and lather) 4%

TEA-Cocoyl Glutamate Skin cleansing (cold creams, cleansing lotions, 2-4%liquids and pads)

TEA-Cocoyl Sarconsinate Shampoos (noncoloring) 2%

TEA-Cocoyl Sarconsinate Other personal cleanliness products2 5%

TEA-Cocoyl Sarconsinate Shaving cream (aerosol, brushless and lather) 1%

TEA-Cocoyl Sarconsinate Skin cleansing (cold creams, cleansing lotions, 4%liquids and pads)

TEA-PCA Face and neck creams, lotions and powders 1%

TEA-PCA Moisturizing creams, lotions and powders 0.3%

TEA-Lauryl Sulfate Bubble baths 12-15%

TEA-Lauryl Sulfate Other fragrance preparations 4% . ‘.

TEA-Lauryl Sulfate Hair conditioners 0.0009%

TEA Lauryl Sulfate Shampoos (noncoloring) 0 0009 40%

TEA-Lauryl Sulfate Bath soaps and detergents 5-30%

TEA-Lauryl Sulfate Other personal cleanliness products3 6-11%

TEA-Lauryl Sulfate Shaving cream (aerosol, brushless and lather) 2%

TEA-Lauryl Sulfate Skin cleansing (cold creams, cleansing lotions, 2-40%liquids and pads)

TEA-Lauryl Sulfate Body and hand creams, lotions and powders 0.3%

TEA-Lauryl Sulfate Foot powders and sprays 8%

TEA-Lauryl Sulfate Moisturizing creams, lotions and powders 0.2%

TEA-Lauryl Sulfate Other skin care preparations4 6%

TEA-Laureth Sulfate Bath oils, tablets and salts 3%

TEA-Laureth Sulfate Shampoos (noncoloring) 14%

TEA-Laureth Sulfate Hair tints 6%

-

‘•...U;’’

TEA-Lauryl Sulfate Tonics, dressings and other hair grooming aids

TEA-Lauryl Sulfate Hair dyes and colors (all types requiring cautionstatement and patch test)

0.0009-2%

2%

Page 2 of 3


Panel Book Page 72

TEA-Laureth Sulfate Other personal cleanliness products5 9%

TEA-Laureth Sulfate Skin cleansing (cold creams, cleansing lotions, 3%liquids and pads)

TEA-Dodecylbenzenesulfonate Hair conditioners 0.2-0.6%

TEA-Dodecylbenzenesulfonate Shampoos (noncoloring) 0.3-0.6%

TEA-Dodecylbenzenesulfonate Tonics, dressings and other hair grooming aids 0.8%

TEA-Dodecylbenzenesulfonate Hair tints 6%

TEA-Dodecylbenzenesulfonate Bath soaps and detergents 0.2-0.6%

TEA-Dodecylbenzenesulfonate Skin cleansing (cold creams, cleansing lotions, 0.9%liquids and pads)

TEA-Cocoyl Hydrolyzed Collagen Hair conditioners 0.3%

TEA-Abietoyl Hydrolyzed Collagen Masacara 0.3%

TEA-Abietoyl Hydrolyzed Collagen Hair conditioners 0.2%

TEA-Abietoyl Hydrolyzed Collagen Shampoos (noncoloring) 0.2%

TEA-Abietoyl Hydrolyzed Collagen Tonics, dressings and other hair grooming aids 0.4%

TEA-Abietoyl Hydrolyzed Collagen Foundations 1 . 0.002%

TEA-Cocoyl Hydrolyzed Soy Protein Tonics, dressings and other hair grooming aids 0.005%

TEA-Cocoyl Hydrolyzed Soy Protein Hair dyes and colors (all types requiring caution 0.00 1%statement and patch test)

TEA-Lauroyl Collagen Amino Acids Tonics, dressings and other hair grooming aids 0.4%*Ingredients included in the title of the table but not found in the table were included in the concentration of usesurvey, but no uses were reported.13% in a body wash and shower gel25% in a make-up removing mousse35% in a shower gel; 11% in a body wash6% in a rinse-off product59% in a body wash

Information collected in 2011Table prepared March 14, 2011

Table updated May 16, 2011 TEA-Lauryl Sulfate: added hair dyes and colors; TEA-Cocoyl Hydrolyzed Collagen:added ingredient

TEA-Cocoyl Hydrolyzed Soy Protein Hair conditioners

TEA-Cocoyl Hydrolyzed Soy Protein Shampoos (noncoloring)

0.001%

0.00 1%

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Panel Book Page 73

TRIETHANOLAMINE 1 01A - Baby ShampoosTRIETHANOLAMINE 11 01B - Baby Lotions, Oils, Powders, and CreamsTRIETHANOLAMINE 4 01C - Other Baby ProductsTRIETHANOLAMINE 2 02A - Bath Oils, Tablets, and SaltsTRIETHANOLAMINE 5 02B - Bubble BathsTRIETHANOLAMINE 18 02D - Other Bath PreparationsTRIETHANOLAMINE 3 03A - Eyebrow PencilTRIETHANOLAMINE 27 03B - EyelinerTRIETHANOLAMINE 20 03C - Eye ShadowTRIETHANOLAMINE 40 03D - Eye LotionTRIETHANOLAMINE 11 03E - Eye Makeup RemoverTRIETHANOLAMINE 239 03F - MascaraTRIETHANOLAMINE 73 03G - Other Eye Makeup PreparationsTRIETHANOLAMINE 8 04A - Cologne and Toilet watersTRIETHANOLAMINE 12 04B - PerfumesTRIETHANOLAMINE 2 04D - SachetsTRIETHANOLAMINE 36 04E - Other Fragrance PreparationTRIETHANOLAMINE 46 05A - Hair ConditionerTRIETHANOLAMINE 14 05B - Hair Spray (aerosol fixatives)TRIETHANOLAMINE 1 05D - Permanent WavesTRIETHANOLAMINE 2 05E - Rinses (non-coloring)TRIETHANOLAMINE 41 05F - Shampoos (non-coloring)TRIETHANOLAMINE 162 05G - Tonics, Dressings, and Other Hair Grooming AidsTRIETHANOLAMINE 8 05H - Wave SetsTRIETHANOLAMINE 98 05I - Other Hair PreparationsTRIETHANOLAMINE 1 06B - Hair TintsTRIETHANOLAMINE 4 06H - Other Hair Coloring PreparationTRIETHANOLAMINE 11 07A - Blushers (all types)TRIETHANOLAMINE 3 07B - Face PowdersTRIETHANOLAMINE 57 07C - FoundationsTRIETHANOLAMINE 3 07D - Leg and Body PaintsTRIETHANOLAMINE 4 07E - LipstickTRIETHANOLAMINE 25 07F - Makeup BasesTRIETHANOLAMINE 20 07I - Other Makeup PreparationsTRIETHANOLAMINE 1 08A - Basecoats and UndercoatsTRIETHANOLAMINE 5 08B - Cuticle SoftenersTRIETHANOLAMINE 2 08C - Nail Creams and LotionsTRIETHANOLAMINE 1 08E - Nail Polish and EnamelTRIETHANOLAMINE 5 08G - Other Manicuring PreparationsTRIETHANOLAMINE 14 09C - Other Oral Hygiene ProductsTRIETHANOLAMINE 91 10A - Bath Soaps and DetergentsTRIETHANOLAMINE 11 10B - Deodorants (underarm)TRIETHANOLAMINE 1 10C - DouchesTRIETHANOLAMINE 68 10E - Other Personal Cleanliness ProductsTRIETHANOLAMINE 66 11A - Aftershave LotionTRIETHANOLAMINE 62 11E - Shaving CreamTRIETHANOLAMINE 64 11G - Other Shaving Preparation ProductsTRIETHANOLAMINE 222 12A - CleansingTRIETHANOLAMINE 342 12C - Face and Neck (exc shave)TRIETHANOLAMINE 646 12D - Body and Hand (exc shave)TRIETHANOLAMINE 7 12E - Foot Powders and SpraysTRIETHANOLAMINE 680 12F - MoisturizingTRIETHANOLAMINE 80 12G - NightTRIETHANOLAMINE 60 12H - Paste Masks (mud packs)TRIETHANOLAMINE 18 12I - Skin FreshenersTRIETHANOLAMINE 255 12J - Other Skin Care PrepsTRIETHANOLAMINE 27 13A - Suntan Gels, Creams, and LiquidsTRIETHANOLAMINE 5 13B - Indoor Tanning PreparationsTRIETHANOLAMINE 11 13C - Other Suntan Preparations

DI-TEA-PALMITOYL ASPARTATE 1 12A - Cleansing

TEA-CARBOMER 1 03B - EyelinerTEA-CARBOMER 2 05G - Tonics, Dressings, and Other Hair Grooming Aids


Panel Book Page 74

TEA-CARBOMER 1 07E - LipstickTEA-CARBOMER 2 11A - Aftershave LotionTEA-CARBOMER 3 12A - CleansingTEA-CARBOMER 4 12D - Body and Hand (exc shave)TEA-CARBOMER 9 12F - MoisturizingTEA-CARBOMER 1 12G - NightTEA-CARBOMER 1 12I - Skin Fresheners

TEA-COCO-HYDROLYZED ANIM 1 02A - Bath Oils, Tablets, and SaltsTEA-COCO-HYDROLYZED ANIM 2 05F - Shampoos (non-coloring)TEA-COCO-HYDROLYZED ANIM 1 10A - Bath Soaps and DetergentsTEA-COCO-HYDROLYZED ANIM 1 10E - Other Personal Cleanliness ProductsTEA-COCO-HYDROLYZED ANIM 1 11E - Shaving CreamTEA-COCO-HYDROLYZED ANIM 1 12A - Cleansing

TEA-COCOATE 1 10A - Bath Soaps and DetergentsTEA-COCOATE 1 12C - Face and Neck (exc shave)

TEA-COCOYL ALANINATE 2 12A - Cleansing

TEA-COCOYL GLUTAMATE 1 01C - Other Baby ProductsTEA-COCOYL GLUTAMATE 1 04E - Other Fragrance PreparationTEA-COCOYL GLUTAMATE 1 05F - Shampoos (non-coloring)TEA-COCOYL GLUTAMATE 2 07I - Other Makeup PreparationsTEA-COCOYL GLUTAMATE 12 10A - Bath Soaps and DetergentsTEA-COCOYL GLUTAMATE 30 10E - Other Personal Cleanliness ProductsTEA-COCOYL GLUTAMATE 1 11E - Shaving CreamTEA-COCOYL GLUTAMATE 17 12A - CleansingTEA-COCOYL GLUTAMATE 4 12C - Face and Neck (exc shave)

TEA-COCOYL HYDROLYZED CO 1 05A - Hair Conditioner

TEA-COCOYL HYDROLYZED SO 10 05A - Hair ConditionerTEA-COCOYL HYDROLYZED SO 13 05F - Shampoos (non-coloring)TEA-COCOYL HYDROLYZED SO 2 05I - Other Hair Preparations

TEA-DODECYLBENZENESULFO 28 05A - Hair ConditionerTEA-DODECYLBENZENESULFO 1 05E - Rinses (non-coloring)TEA-DODECYLBENZENESULFO 62 05F - Shampoos (non-coloring)TEA-DODECYLBENZENESULFO 18 05G - Tonics, Dressings, and Other Hair Grooming AidsTEA-DODECYLBENZENESULFO 3 05I - Other Hair PreparationsTEA-DODECYLBENZENESULFO 2 10E - Other Personal Cleanliness ProductsTEA-DODECYLBENZENESULFO 2 12A - Cleansing

TEA-ISOSTEARATE 1 07C - Foundations

TEA-LACTATE 1 11A - Aftershave LotionTEA-LACTATE 3 12C - Face and Neck (exc shave)TEA-LACTATE 1 12D - Body and Hand (exc shave)TEA-LACTATE 4 12F - MoisturizingTEA-LACTATE 1 12I - Skin FreshenersTEA-LACTATE 3 12J - Other Skin Care Preps

TEA-LAURETH SULFATE 1 05D - Permanent WavesTEA-LAURETH SULFATE 13 05F - Shampoos (non-coloring)TEA-LAURETH SULFATE 1 10A - Bath Soaps and Detergents


Panel Book Page 75

TEA-LAURETH SULFATE 2 12A - Cleansing

TEA-LAURYL SULFATE 1 01A - Baby ShampoosTEA-LAURYL SULFATE 1 01C - Other Baby ProductsTEA-LAURYL SULFATE 2 02A - Bath Oils, Tablets, and SaltsTEA-LAURYL SULFATE 18 02B - Bubble BathsTEA-LAURYL SULFATE 12 02D - Other Bath PreparationsTEA-LAURYL SULFATE 61 05F - Shampoos (non-coloring)TEA-LAURYL SULFATE 4 05I - Other Hair PreparationsTEA-LAURYL SULFATE 1 07F - Makeup BasesTEA-LAURYL SULFATE 97 10A - Bath Soaps and DetergentsTEA-LAURYL SULFATE 50 10E - Other Personal Cleanliness ProductsTEA-LAURYL SULFATE 1 11F - Shaving SoapTEA-LAURYL SULFATE 1 11G - Other Shaving Preparation ProductsTEA-LAURYL SULFATE 27 12A - CleansingTEA-LAURYL SULFATE 5 12C - Face and Neck (exc shave)TEA-LAURYL SULFATE 12 12D - Body and Hand (exc shave)TEA-LAURYL SULFATE 2 12F - MoisturizingTEA-LAURYL SULFATE 3 12H - Paste Masks (mud packs)TEA-LAURYL SULFATE 3 12J - Other Skin Care PrepsTEA-LAURYL SULFATE 1 13C - Other Suntan Preparations

TEA-MYRISTATE 2 11E - Shaving Cream

TEA-PALMITATE 1 03F - MascaraTEA-PALMITATE 1 07C - FoundationsTEA-PALMITATE 2 11E - Shaving CreamTEA-PALMITATE 1 12D - Body and Hand (exc shave)

TEA-ROSINATE 1 12B - Depilatories

TEA-SALICYLATE 2 05A - Hair ConditionerTEA-SALICYLATE 1 05F - Shampoos (non-coloring)

TEA-STEARATE 5 03B - EyelinerTEA-STEARATE 1 03C - Eye ShadowTEA-STEARATE 3 03F - MascaraTEA-STEARATE 3 05A - Hair ConditionerTEA-STEARATE 1 05B - Hair Spray (aerosol fixatives)TEA-STEARATE 2 05E - Rinses (non-coloring)TEA-STEARATE 3 05F - Shampoos (non-coloring)TEA-STEARATE 7 05G - Tonics, Dressings, and Other Hair Grooming AidsTEA-STEARATE 1 06H - Other Hair Coloring PreparationTEA-STEARATE 1 07A - Blushers (all types)TEA-STEARATE 2 07B - Face PowdersTEA-STEARATE 11 07C - FoundationsTEA-STEARATE 1 07E - LipstickTEA-STEARATE 3 10A - Bath Soaps and DetergentsTEA-STEARATE 10 11E - Shaving CreamTEA-STEARATE 10 12C - Face and Neck (exc shave)TEA-STEARATE 29 12D - Body and Hand (exc shave)TEA-STEARATE 29 12F - MoisturizingTEA-STEARATE 2 12G - NightTEA-STEARATE 5 12J - Other Skin Care PrepsTEA-STEARATE 1 13A - Suntan Gels, Creams, and Liquids


Panel Book Page 76

TEA-SULFATE 6 05F - Shampoos (non-coloring)

TEA-UNDECYLENOYL HYDROLY 1 12H - Paste Masks (mud packs)


Panel Book Page 77

green tea - cosmetic ingredient reviewfor example, tea-isostearate is the tea salt of isostearic...

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