Plasticisers: An Update

David Cadogan

Plasttekniske Dager

Oslo, 8-9 November 2006

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Outline

ECPI

Plasticiser requirements

Are phthalates a threat to human health

Legislative actions

– Classification and labelling

– Risk assessments

– Toys, food contact materials, medical devices

– Reach

Market trends

Summary

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ECPI

European Council for Plasticisers and Intermediates

A Sector Group of CEFIC – the European Chemical Industry Council

European producers of plasticisers, alcohols and acids

Sponsorship of scientific studies by independent experts

Provide users, legislators and other interested bodies with information on safety, health and the environment

Close liaison with trade organisations in USA and Japan

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Plasticiser requirements

Compatible with PVC

Efficient

Ease of processing

Low volatility

Low migration/extraction

Flexibility at low temperatures

High temperature performance

Electrical resistance

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93% of Plasticisers are Phthalates

Phthalates have :Optimum balance of polar / non-polar groupsBest all round performance / price ratio

C4 - C7 alcohol : Lower viscosity, faster processingC8 – C10 alcohols : General purpose C11-C13 alcohols : High temperature performance>80% linear : Better low / high temperature performance

DEHP

Performance can be fine tuned by using appropriate alcohol

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93% of Plasticisers are Phthalates

More polar groups – Increased compatibility with PVC and easier processing BBP – Fast processing and stain resistance

BBP

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Are phthalates a threat to human health?

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Potential Health Impact - Carcinogenicity

1982 – Liver tumours in rodents caused IARC to classify DEHP as “possibly carcinogenic to humans”

18 years of research showed :

Phthalates, hypolipidaemic drugs and other chemicals cause tumours in rodents by peroxisome proliferation (PP)

No PP or liver damage in monkeys fed DEHP and DINP

No PP or liver damage in humans taking hypolipidaemic drugs

No DEHP induced liver tumours in mice lacking PP receptor

2000 - IARC Reclassified DEHP - Phthalate induced liver cancer in rats and mice is not relevant to humans

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Potential Health Impact - Reproductive Effects

High levels of some phthalates produce testicular atrophy in rodents

Little, if any, effects seen with DMP, DEP, DINP and DIDP

Levels can be defined at which no effects occur (NOAEL)

In general NOAELs are orders of magnitude higher than levels of exposure. Therefore no risk

Studies ongoing to identify the mechanism underlying the reproductive effects in rodents – are they relevant to humans?

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The facts are:No evidence of any phthalate having an adverse effect on human health

20 year follow-up study on 242 low birth weight individuals (high DEHP exposure in intensive care) showed no effects on male fertility

Adolescents exposed to DEHP via ECMO as neonates show no adverse effects on growth or sexual maturity

Adverse effects are only seen in rodent studies

Adverse effects not seen in non-human primates

However - There are now two studies claiming to see effects in humans

Adverse Effects on Human Health

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Swan et al. (August 2005) measured Anogenital Index (AGI) in 85 boys aged between 2 and 36 months. (AGI = AGD / Weight).

Smaller AGI in boys said to correlate with higher levels of metabolites of DEP, DBP, DIBP and BBP in mothers urine during pregnancy

AGI is smaller in females than in males hence these phthalates are said to have a feminising effect

Highly publicised – press conference more important than peer review.

Baby Boys Feminised by Prenatal Phthalate Exposure - Claims

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Inadequate measurement of maternal phthalate exposure

Only one urine sample taken during pregnancy

Studies by Hauser et al (2004) and Hoppin et al (2002) indicate that repeated urine measurements are necessary to determine exposure

Concerns re measurement of AGD in boys

Poor planning. AGD changes rapidly with age but they measured at ages ranging from 2 – 36 months. Hence needed extensive regression analysis

The only other study (Salazar-Martinez et al, 2004) was systematic - 45 boys measured at 6 hours old. No regression needed – apparently less variation in AGD / weight

Prenatal Phthalates Feminise Baby Boys – The Facts

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Authors attempt to make case stronger than it is

Independent statisticians find the conclusions are unsound

US National Toxicology Programme panel of 11 toxicologists have concluded that the findings are not reliable

No correlation between AGI and primary metabolite of DEHP in mother’s urine but weak correlation with the level of secondary metabolites - not logical

Strong correlation with MEP in urine – contrary to many other studies on DEP

Prenatal Phthalates Feminise Baby Boys – The Facts

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Main et al. (February 2006) measured levels of phthalate monoesters in breast milk of 130 mothers of baby boys at 1-3 months postnatally.

Subjects selected so that approximately half of the boys had undescended testes.

No correlation found between undescended testes and monoesters in breast milk – main aim of the study but gets little mention in the report

Measured levels of reproductive hormones in boys at three months and investigated link with levels of phthalate monoesters in breast milk.

A link is proposed between levels of some phthalate metabolites in breast milk and some hormone levels in male offspring

Phthalates in Breast Milk Effect Baby Boys - Claims

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Statistical treatment of data and interpretation of results questioned

Independent statisticians agree that there is no real correlation.

The authors discount results which do not fit their hypothesis as being “random findings”

The lack of a link between MEHP and hormone levels is said to be due to the “limited number of samples in the study”

Study rejected by EU Member States Experts in DEHP Risk Assessment

US Expert Panel on Human Reproduction believes that some hormone measurements are not relevant and breast milk samples are most likely contaminated

Phthalates in Breast Milk Effect Baby Boys – The Facts

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Legislative Actions

Classification and labelling of dangerous substances

Existing substances legislation – Risk assessment and management

Toys and childcare articles

Food contact materials

Medical devices

REACH

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Hazard - Classification and Labelling

Category 1 Substances known to cause effects in humans. Based on epidemiological data. Category 2 Substances to be regarded as if they cause effects in humans. Based on clear evidence in animal studies. Category 3 Substances causing concern for humans. Based on less convincing evidence in animal studies.

Classification and labelling does not apply to articles

Aim – To ensure safe handling and use in the workplace

Backbone Fertility

Developmental

DMP 1 None None

DEP 2 None None

DPrP 3 None None

DIBP SCL = 25% 3 Cat 3 Cat 2

DBP 4 Cat 3 Cat 2

DPP 4 - 5 Cat 2 Cat 2BBP 4 - 7 Cat 3 Cat 2DIHP 5 - 6 None Cat 2

DEHP 6 Cat 2 Cat 2

711P (Branched) 5 - 9 Cat 3 Cat 2

DINP 7 - 8 None None

DIDP 8 - 9 None None

79P (Linear) 7 - 9 None None

911P (Linear) 9 - 11 None None

Classification and Labelling

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Existing Substances Legislation

To properly assess the risks imparted by all chemicals

To both humans and the environment

Margin of Safety (MOS) = NOAEL / Exposure

MOS > 100 = No Risk

To identify risk management requirements if necessary and implement a Risk Reduction Strategy

Council Regulation EEC / 793 / 93 on the evaluation and control of the risks of existing substances

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Risk Assessments and Risk Reduction Strategies published in Official Journal on 13 April 2006

Human health risks:DBP – No consumer risks including cosmetics. Risk to workers assuming worst case exposure – OEL to be implemented DIDP – Theoretical risks for children via toys – Toy legislation

DINP – No risks in any current use – Toy legislation due to difference of opinion between RAR and CSTEE

Environmental risks:DBP – Possible risk to vegetation near some processing plants - Extra monitoring data on exhaust air

DINP and DIDP – No risks

DBP, DINP, DIDP Risk Assessments / Reduction

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Two versatile high volume phthalates

Finally perceived as being “Risk Free” following revision of legislation for use in toys

For both health and environmental effects

Can be used in all applications except toys and childcare articles “which can be put in the mouth”

Not hazardous - not classified CMR or Dangerous to the Environment

Large shift in consumption to DINP and DIDP

DINP & DIDP Risk Assessments / Risk Reduction

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Risk assessments to be completed via “written procedure” during Q4 2006. Publication in 2006 / 2007

Human health risks:BBP – few, if any, risks anticipated – Consumption falling rapidlyDEHP

Workers – OEL to be defined and implementedChildren via toys – New legislation Haemodialysis and long term transfusion in children / neonates - Requested opinion of expert medical committee Possibly children living near some processing plants – Agree Marketing and Use Directive to control DEHP emissions

BBP & DEHP Risk Assessments / Risk Reduction

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Environmental risks:

BBP – Possible risk to water and sediment near processing plants - Fish study and processing plant emission data

DEHP –Risks only seen for default emission levels from hypothetical plants. No risks when using real emission data which are 1000 times lower.

General population via the environment - Kemi wanted to ban DEHP in all outdoor applications. Commission not convinced – no risk identified.

Biomonitoring more than 3.000 people - shows no risks to man at regional level (MOS range from 280 to 1700)

Risk Assessments / Risk Reduction

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Legislative Actions - Toys and childcare articles

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Permanent measures published in the Official Journal on 27 December 2005

• DBP, BBP and DEHP banned in all toys and childcare articles

• DINP, DIDP and DNOP banned in toys and childcare articles which can be put in the mouth

• National legislation to be enacted from 16 January 2007

• Entirely political decision ignoring science based risk assessments

A range of alternative plasticisers available – citrates, etc.

Toys and Childcare Articles

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Legislative Actions – Food contact materials

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New legislation is expected to come into force in the EU during Q4 2006

EFSA Scientific Panel has re-examined the phthalate toxicity data and published TDI values.

Concluded that phthalates may be used in a variety of repeat and single use food contact applications

DEHA and polymeric plasticisers will continue to be used in a wide range of food contact applications, especially clingfilm

Food Contact Materials

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Flexible PVC in medical applications

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DEHP Risk Assessment identifies risks to patients (MOS < 100) via :• Long term haemodialysis (adults)• Transfusions (neonates)• Long term blood transfusion (children) (Lowest MOS via IV = 800)

It is possible that these three applications will move from DEHP to alternatives such as ATBC, DINCH, trimellitates, acetylated glycerol esters or polymeric plasticisers.

However this sector is conservative and reluctant to change away from plasticisers which have given no adverse effects in patients

Threats from activists (HCWH) and from other polymers continue but it is difficult to match the cost / performance characteristics of PVC

Medical Applications

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SCMPMD Opinion of September 2002 concluded that no specific recommendation could be made to limit the use of DEHP

We must await the Opinion of the new Scientific Committee on Emerging and Newly Identified Health Risks (SCENIHR) – February 2006

However the attacks continue:

EU Parliament Environment Committee (w/c 2nd October) agreed an amendment to the Medical Devices Directive prohibiting the use of CMR substances in medical devices. This still has to be voted on in plenary

Many drugs are CMR but are used on a risk/benefit basis

This amendment is based on hazard – there may be little exposure and hence no risk

Medical Applications

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Phthalate Alternatives Confer Special Properties

Adipates – Low temperature flexibility - food and medical

Polyesters – Low migration into oil, etc - food and medical

Trimellitates – High temperature cable sheathing

Citrates – PVdC film, some medical – Some adverse human reactions

Benzoates – Easy processing like BBP

Phosphates – Fire resistance

Alkyl sulphonates – Easy processing, weather resistance

DINCH – Possible use in medical and food contact – EFSA approval

Acetylated glycerol esters – Food contact

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REACH – Registration, Evaluation and Authorisation of Chemicals

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The commonly used plasticisers are data-rich and have been subjected to various risk assessments so no problems regarding registration.

CMR substances will be subject to authorisation to allow them to be used in each application.

We have the risk assessment data but will it be accepted or will substitution be demanded ?

Some Member States may propose that even those phthalates which are not classified as CMR should be subject to authorisation because they give rise to an “equivalent level of concern”

Environment Committee (10th October) voted to increase pressure for substitution and reduce level of scientific evidence needed to prove that a substance is of “equivalent concern”

Impact of REACH on Plasticisers

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Western Europe Plasticiser Consumption

0

200

400

600

800

1000

1200

19

79

19

80

19

81

19

82

19

83

19

84

19

85

19

86

19

87

19

88

19

89

19

90

19

91

19

92

19

93

19

94

19

95

19

96

19

97

19

98

19

99

20

00

20

01

20

02

20

03

20

04

20

05

(‘000s of tons)

Source: ECPI, 2006

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European Plasticiser Consumption - Trends

DEHP21%

Other Phthalates

12%

Other Plasticisers

7%

DINP/DIDP60%

DEHP42%Other

Phthalates15%

Other Plasticisers

8%

DINP/DIDP35%

1999

2005

Source: ECPI, 2006

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The family of phthalates satisfy the performance, health and safety requirements of the vast majority of applications.

Classification, labelling and risk assessment has resulted in a move to DINP and DIDP and a decrease in DEHP, DBP and BBP consumption

Alternatives to phthalates already exist or are being developed for certain applications

Food contact materials, medical devices, toys and childcare articles

• Low migrating plasticisers – polymerics and trimellitates

• Lower animal toxicity – adipates, citrates, terephthalates, DINCH, acetylated glycerol esters

Plasticisers – The Way Forward

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Phthalates and speciality esters meet the needs of all PVC applicationsIncrease in DINP and DIDP use due to positive risk assessmentsDecrease in DEHP, DBP and BBP due to Hazard ClassificationHealth effects not seen in primates - only in rodent studiesNo human cancer concern. Investigating relevance to humans of rodent reproductive effectsHigh profile human toxicological studies are not based on sound scienceBiomonitoring data very helpful in risk assessment and risk reduction There will be moves to new plasticisers due to new legislation and concerns regarding toys, food contact and medical devicesThere is still a very strong future for flexible PVC

Summary