selection of green solvents - industrial green … 2015/sym… · selection of green solvents ......

| 1Green Solvents

Selection of Green Solvents

Denis PRAT, Process Safety & Environment Chemistry & Biochemistry

Sanofi Chimie, Gentilly (France)

4th Industrial Green Chemistry World Conference, Mumbai,

05 December 2015

Green Solvents | 2

AGENDA

● Sanofi Social Responsibility

● What is a green solvent

● Published solvent selection guides

● Including Sanofi’s !!

● The CHEM21 European project

● Comparison of solvent guides

● Elaboration of CHEM21 solvent guide

● How to rank bio-derived solvents?

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SANOFI CORPORATE SOCIAL RESPONSIBILITY: 4 PILLARS

• Ethics in R&D

• Business Ethics

• Human Rights

ETHICS

PLANET

PATIENT

• Access to Healthcare

• Patient Safety

• Innovation for the Patient

PEOPLE

• Health & Safety

• Diversity

• Workforce Development

• CO2 reduction

• Water

• Green chemistry

Green Solvents

Green Solvents | 4

SANOFI’S INDUSTRIAL PRODUCTION OF SEMISYNTHETIC ARTEMISININ IN YEAST

ispAtHMGR AmorphadieneArtemisinic

AcidADS

Mevalonate pathway

(TOP)

H

H

Mevalonate pathway

(BOTTOM)

p450

OPP

SynthaseHydroxyase

Unit

FPPMevalonate CPR

OH

OHCH3

HO2CH3C SCoA

O

Acetyl-

CoA

Green Chemistry

Synthetic Biology

Purification

H

H

O

HO

idiMPDPMKMKHMGSatoB

Artemisinin

O

O

O

O

O

H

HHHO

O

H

H

HOO

Artemisinic Acid

Réduction

Dérivatisation

Photo oxidation

CyclisationH

H

O

HORO

O

H

H

H

J. D. Keasling et al., Nature, 2006, 440, 940-943

J. Turconi et al., OPRD, 2014, 18, 417

S. cerevisiae

Green Solvents | 5

IMPACT OF SOLVENTS IN THE PROCESS GREENNESS

● 1 kg of API necessitates more than 100 kg of material

● PMI

● Solvents and water represent >80% of these

● Reduce the impact by reduction of solvent & water amount

● Use the “greenest” solvents

C. Jimenez-Gonzalez et al, OPRD, 2011, 15, 912.

56%

32%

7% 5%

Green Solvents | 6

SOLVENTS IMPACT IN THE PROCESS GREENNESS

● Whatever the metrics considered, the yield (process efficiency) has a direct impact on the synthesis greenness

● But solvents are most often the main contributors

Cumulated

Energy Demand

Global Warming

Potential

CO2 Impact

Life Cycle

Assessment

PMI

Green Solvents | 7

WHAT IS A GREEN SOLVENT?

● Criteria for a green solvent

● From renewable feedstock

● Low energy demand

● Biodegradable

● Not soluble in water

● No VOCs (BP not too low)

● Easy to recycle: BP not too high

● Criteria for a safe solvent

● Stability

● Low flammability (high FP)

● Moderate toxicity

P. G. Jessop, Green Chem,

2011, 13, 1391.

Green Solvents | 8

SOLVENT SELECTION GUIDES

● The definition of a green solvent is not straightforward

● Some criteria are contradictory

● There is no universal metrics set to compare the greenness criteria

Green Solvents | 9

SOLVENT SELECTION GUIDES

● The definition of a green solvent is not straightforward

● Some criteria are contradictory

● There is no universal metrics set to compare the greenness criteria

● Some companies/ institutions have edited solvent selection guides in

order to help chemists in their choice

● Occupational health

● Safety (Flash point, resistivity, peroxides,…)

● Environment

● Industrial & regulation issues

● These guides reflect their policy and culture

● Local constraints

● Accidents

● Habits

Green Solvents | 10

PFIZER’S SOLVENT GUIDE

Green Chem, 2008, 10, 31

Green Solvents | 11

GSK SOLVENT GUIDE

Green Chem, 2011, 13, 854

Green Solvents | 12

GCI-PR GUIDE

Green Solvents | 13

GENESIS OF SANOFI’S SOLVENT GUIDE

● We did not have a common vision of the preferred solvents

● Sanofi-Synthelabo-Hoechst-Marion-Roussel-Rhone-Poulenc-Rorer

● Research vs Production

● Working group created in 2009

● Reshaping of former HSE guide

● Integration of industrial constraints

● Integration of GHS/ CLP

● Constraints:

● Increasing difficulties to change the solvents during development

● Purposes:

● To educate chemists to SH&E, regulatory & industrial issues.

● To promote renewable solvents

● To give clear recommendations, but with supporting data

● To make proposals for substitution of undesirable solvents (e. g. CMR)

● To offer useful data and advice

Green Solvents | 14

STRUCTURE OF SANOFI’S SOLVENTS GUIDE

● One chapter per solvent family

● Alcohols, ketones, esters, ethers, hydrocarbons, halogenated, aprotic polar,

bifunctional, miscellaneous.

● In these chapters, one paragraph per solvent

Green Solvents | 15

SANOFI’S SOLVENTS GUIDE

● First level of lecture

● Overview per family of solvents, with clear recommendations

• Which is the most advisable aprotic polar solvent?

OPRD, 2013, 17, 1517

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● Second level of lecture

● One ID card for each solvent

● Third level

● One paragraph per solvent

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● Four levels of ranking

OPRD, 2013, 17, 1517

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THE IMI-CHEM21 PROJECT

● IMI-CHEM21 project:

● Created in 2012

● 4-year project

● Six pharmaceutical companies from the European Foundation of

Pharmaceutical Industries and Associations (EFPIA)

● Ten Universities

● Five small to medium companies

● Funded by EFPIA and the European Union

● Develops sustainable biological and chemical methodologies

● Supports research projects

• Catalytic chemistry

• Enzymatic chemistry

• Synthetic biology

● Provides training packages

• Education of the future chemists

Green Solvents | 19

THE IMI-CHEM21 PROJECT

● Benchmark and gap analysis (WP1)

● Portfolio review: the most used reactions in Pharmaceutical Industry

● Catalysts to be replaced (critical elements)

● Chemicals of concern & regulatory issues

● Survey of solvent selection guides

● Education and Training Package (WP5)

● Green metrics

● Renewable resources

• York University

● New transformations

● CHEM21 solvent selection guide

• Including bio-derived solvents

Green Solvents | 20

SOLVENT GUIDES COMPARISON

● Pfizer: 3 levels of ranking

● Preferred, Usable, Undesirable

● Sanofi: 4 levels of ranking

● Recommended, Subst. advisable, Subst. requested, Banned

Green Solvents | 21


● Pfizer: 3 levels of ranking

● Preferred, Usable, Undesirable

● Sanofi: 4 levels of ranking

● Recommended, Subst. advisable, Subst. requested, Banned

● Astra Zeneca: no clear ranking

● 2 Safety criteria, 1 health, 7 environment

● Criteria scored from 1 (best) to 10 (worse)

● GCI-PR: similar, but simpler

● 1 safety criterion, 1 health, 3 environment

● Criteria scored from 1 (best) to 10 (worse)

● GSK: similar

● Plus legislation flags and EHS flags

● But scored from 10 (best) to 1 (worse)!

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● What is the level of convergence of

these guides?

● Survey based on 51 solvents

● Some manipulation was needed to

establish a solvent ranking from AZ,

GSK and GCI-PR guides

● Limit the number of criteria

• One of each: Health, Safety,

Environment

• Select the most stringent one in

each category

● Ex: GCI-PR guide

Green Solvents | 23


● transformation of AZ, GSK and GCI-PR

guides

● Sum of H, S, E scores

● Arithmetical mean of this sum

● 3 groups of similar sizes centred on

this mean

● 3-color code

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SOLVENT GUIDES SURVEY

● Based on qualitative rankings (51 solvents)

● If large majority, easy conclusion

● Other cases: to be confirmed (TBC)

Green Solvents | 25

COMPARISON OF THE DIFFERENT GUIDES

● Aligned with regulations

● 67% convergence

● The divergences reflect the different weighing of criteria

D. Prat, J. Hayler, A. Wells, Green Chem., 2014, 16, 4546

Ranking Solvents

Recommended Water, EtOH, iPrOH, nBuOH, AcOEt, AcOiPr, AcOnBu, PhOMe, sulfolane

Recommended or Problematic ?

MeOH, tBuOH, BnOH, ethylene glycol, acetone, MEK, MIBK, cyclohexanone, AcOMe, AcOH, Ac2O

Problematic Me-THF, heptane, Me-cyclohexane, toluene, xylene, chlorobenzene, acetonitrile, DMPU, DMSO

Problematic or Hazardous ?

THF, MTBE, cyclohexane, DCM, formic acid, pyridine

Hazardous iPr2O, dioxane, DME, pentane, hexane, DMF, DMA, NMP, TEA, methoxyethanol

Highly hazardous Et2O, Benzene, CCl4, chloroform, DCE, nitromethane

Green Solvents | 26

CHEM21 SOLVENT GUIDE

● CHEM21 solvent guide based on this survey

● A simple ranking methodology was needed

● Based on HSE criteria

● To rank the intermediate solvents

● To rank newer/ bio-derived solvents

Ranking Solvents

Recommended Water, EtOH, iPrOH, nBuOH, AcOEt, AcOiPr, AcOnBu, PhOMe, sulfolane

Recommended or Problematic ?


Problematic Me-THF, heptane, Me-cyclohexane, toluene, xylene, chlorobenzene, acetonitrile, DMPU, DMSO



Hazardous iPr2O, dioxane, DME, pentane, hexane, DMF, DMA, NMP, TEA, methoxyethanol

Highly hazardous Et2O, benzene, CCl4, chloroform, DCE, nitromethane

● Ranking methodology

1) Collect physical data and GHS statements from the Safety Data Sheets

Family Solvent BP

(°C)

FP

(°C)

AIT

(°C)

Worst

H3xx

H4xx

Water Water 100 na na none none

Alcohols EtOH 78 13 423 H319 none

i-PrOH 82 12 456 H319 none

n-BuOH 118 29 367 H318 none

Esters Ethyl acetate 77 -4 484 H319 none

i-PrOAc 89 2 460 H319 none

n-BuOAc 126 22 421 H336 none

Ethers Diethyl ether 34 -45 160 H302 none

Diisopropyl ether 69 -28 405 H336 none

Me-THF 80 -11 270 H318 none

1,4-Dioxane 101 12 180 H351 none

Anisole 154 52 475 none none

DME 85 -6 200 H360 none

Hydrocarbons Pentane 36 -40 285 H304 H411

Hexane 69 -22 225 H361 H411

Heptane 98 -4 215 H304 H410

Me-Cyclohexane 101 -4 258 H304 H411

Benzene 80 -11 562 H350 none

Toluene 111 4 480 H351 none

Xylenes 140 27 480 H312 none

Green Solvents | 27



2) The safety score is calculated from the FP, the AIT, the resistivity, etc

Family Solvent FP

(°C)

AIT

(°C)

Safety

score

Water Water na na 1

Alcohols EtOH 13 423 4

i-PrOH 12 456 4

n-BuOH 29 367 3

Esters Ethyl acetate -4 484 5

i-PrOAc 2 460 4

n-BuOAc 22 421 4

Ethers Diethyl ether -45 160 10

Diisopropyl ether -28 405 9

Me-THF -11 270 6

1,4-Dioxane 12 180 7

Anisole 52 475 4

DME -6 200 7

Hydrocarbons Pentane -40 285 8

Hexane -22 225 8

Heptane -4 215 6

Me-Cyclohexane -4 258 6

Benzene -11 562 6

Toluene 4 480 5

Xylenes 27 480 4

Green Solvents | 28

Basic

Safety

score

1 3 4 5 7

Flash Point

(°C)

> 60 23 to 60 22 to 0 -1 to -20 < -20

GHS - H226 H225 or H224

1 is added to the safety score for each of the following properties:

- AIT < 200°C

- Resistivity > 108 W.m

- Ability to form peroxides (EUH019)



3) The health score derives from the most stringent H3xx statement

+ 1 if BP < 85°C

Family Solvent BP

(°C)

Worst

H3xx

Health

score

Water Water 100 none 1

Alcohols EtOH 78 H319 3

i-PrOH 82 H319 3

n-BuOH 118 H318 4

Esters Ethyl acetate 77 H319 3

i-PrOAc 89 H319 2

n-BuOAc 126 H336 2

Ethers Diethyl ether 34 H302 3

Diisopropyl ether 69 H336 3

Me-THF 80 H318 5

1,4-Dioxane 101 H351 6

Anisole 154 none 1

DME 85 H360 9

Hydrocarbons Pentane 36 H304 3

Hexane 69 H361 7

Heptane 98 H304 2

Me-Cyclohexane 101 H304 2

Benzene 80 H350 10

Toluene 111 H351 6

Xylenes 140 H312 2

Green Solvents | 29

Health score 2 4 6 7 9

CMR H341 H351

H361

(cat. 2)

H340 H350

H360

(cat. 1)

STOT H371 H373 H334 H370 H372

Acute toxicity

H302 H312

H332 H336

H301 H311

H331

H300 H310

H330

Irritation

H315 H317

H319 H335

H318

(eyes)

H314 (skin)



4) The Environment score depends on the BP and on the H4xx statement

Family Solvent BP

(°C)

H4xx Env.

score

Water Water 100 none 1

Alcohols EtOH 78 none 3

i-PrOH 82 none 3

n-BuOH 118 none 3

Esters Ethyl acetate 77 none 3

i-PrOAc 89 none 3

n-BuOAc 126 none 3

Ethers Diethyl ether 34 none 7

Diisopropyl ether 69 none 5

Me-THF 80 none 3

1,4-Dioxane 101 none 3

Anisole 154 none 5

DME 85 none 3

Hydrocarbons Pentane 36 H411 7

Hexane 69 H411 7

Heptane 98 H410 7

Me-Cyclohexane 101 H411 7

Benzene 80 none 3

Toluene 111 none 3

Xylenes 140 none 5

Green Solvents | 30

Environment

score

3 5 7

BP (°C) 70-139 50-69

140-200

<50

>200

GHS No H4xx after full

REACh registration

H412 H413 H400 H410 H411

Other No, or partial REACh

registration

Water: score= 1

H420 (ozone layer hazard): score = 10



5) The ranking by default is given by the combination of HS&E scores

Family Solvent Safety

score

Health

score

Env.

score

Ranking by

default

Water Water 1 1 1 Recommended

Alcohols EtOH 4 3 3 Recommended

i-PrOH 4 3 3 Recommended

n-BuOH 3 4 3 Recommended

Esters Ethyl acetate 5 3 3 Recommended

i-PrOAc 4 2 3 Recommended

n-BuOAc 4 2 3 Recommended

Ethers Diethyl ether 10 3 7 Hazardous

Diisopropyl ether 9 3 5 Hazardous

Me-THF 6 5 3 Problematic

1,4-Dioxane 7 6 3 Problematic

Anisole 4 1 5 Problematic

DME 7 9 3 Hazardous

Hydrocarbons Pentane 8 3 7 Hazardous

Hexane 8 7 7 Hazardous

Heptane 6 2 7 Problematic

Me-Cyclohexane 6 2 7 Problematic

Benzene 6 10 3 Hazardous

Toluene 5 6 3 Problematic

Xylenes 4 2 5 Problematic

Combination of

SH&E scores

Solvent ranking by

default

One score > 8

(red)

Hazardous

Two scores > 7

(red)

Hazardous

One score = 7

(red)

Problematic

4 < Two scores < 6

(yellow)

Problematic

Other Recommended

Green Solvents | 31


● The ranking thus obtained is consistent with the ranking based on the

survey of classical solvents (81% agreement)

Family Solvent BP

(°C)

FP

(°C)

Worst

H3xx

H4xx Safety

score

Health

score

Env.

score

Ranking by

default

Ranking from

the survey

Water Water 100 na none none 1 1 1 Recommended Recommended

Alcohols EtOH 78 13 H319 none 4 3 3 Recommended Recommended

i-PrOH 82 12 H319 none 4 3 3 Recommended Recommended

n-BuOH 118 29 H318 none 3 4 3 Recommended Recommended

Esters Ethyl acetate 77 -4 H319 none 5 3 3 Recommended Recommended

i-PrOAc 89 2 H319 none 4 2 3 Recommended Recommended

n-BuOAc 126 22 H336 none 4 2 3 Recommended Recommended

Ethers Diethyl ether 34 -45 H302 none 10 3 7 Hazardous HH

Diisopropyl ether 69 -28 H336 none 9 3 5 Hazardous Hazardous

Me-THF 80 -11 H318 none 6 5 3 Problematic Problematic

1,4-Dioxane 101 12 H351 none 7 6 3 Problematic Hazardous

Anisole 154 52 none none 4 1 5 Problematic Recommended

DME 85 -6 H360 none 7 9 3 Hazardous Hazardous

Hydrocarbons Pentane 36 -40 H304 H411 8 3 7 Hazardous Hazardous

Hexane 69 -22 H361 H411 8 7 7 Hazardous Hazardous

Heptane 98 -4 H304 H410 6 2 7 Problematic Problematic

Me-Cyclohexane 101 -4 H304 H411 6 2 7 Problematic Problematic

Benzene 80 -11 H350 none 6 10 3 Hazardous HH

Toluene 111 4 H351 none 5 6 3 Problematic Problematic

Xylenes 140 27 H312 none 4 2 5 Problematic Problematic

Green Solvents | 32


● As the model is valid, it can be used to assign a preliminary greenness

assessment of any solvent

● Intermediate solvents

● Bio-derived solvents

● Newer solventsRanking Solvents

Recommended or Problematic

?




Green Solvents | 33


● Ranking of intermediate solvents

● A debate is needed (chemists + occupational hygienists)


score

Health

score

Env. score Ranking by default

Alcohols MeOH 4 7 5 Problematic

t-BuOH 4 3 3 Recommended

Benzyl alcohol 1 2 7 Problematic

Ethylene glycol 1 2 5 Recommended

Ketones Acetone 5 3 5 Problematic

MEK 5 3 3 Recommended

MIBK 4 2 3 Recommended

Cyclohexanone 3 2 5 Recommended

Esters Methyl acetate 5 3 5 Problematic

Ethers MTBE 8 3 5 Hazardous

THF 6 7 5 Problematic

Hydrocarbons Cyclohexane 6 3 7 Problematic

Halogenated DCM 1 7 7 Hazardous

Amines Pyridine 4 2 3 Recommended

Acids Formic acid 3 7 3 Problematic

Acetic acid 3 7 3 Problematic

Ac2O 3 7 3 Problematic

Green Solvents | 34


● Ranking of intermediate solvents

● A debate is needed (chemists + occupational hygienists)


score

Health

score

Env. score Ranking by default Ranking after

discussion

Alcohols MeOH 4 7 5 Problematic Recommended

t-BuOH 4 3 3 Recommended Recommended

Benzyl alcohol 1 2 7 Problematic Problematic

Ethylene glycol 1 2 5 Recommended Recommended

Ketones Acetone 5 3 5 Problematic Recommended

MEK 5 3 3 Recommended Recommended

MIBK 4 2 3 Recommended Recommended

Cyclohexanone 3 2 5 Recommended Problematic

Esters Methyl acetate 5 3 5 Problematic Problematic

Ethers MTBE 8 3 5 Hazardous Hazardous

THF 6 7 5 Problematic Problematic

Hydrocarbons Cyclohexane 6 3 7 Problematic Problematic

Halogenated DCM 1 7 7 Hazardous Hazardous

Amines Pyridine 4 2 3 Recommended Hazardous

Acids Formic acid 3 7 3 Problematic Problematic

Acetic acid 3 7 3 Problematic Problematic

Ac2O 3 7 3 Problematic Problematic

Green Solvents | 35


● Ranking of bio-derived solvents

Family Solvent BP (°C) FP (°C) Worst

H3xx

H4xx Safety

score#

Health

score

Env.

score

Ranking by

default

Alcohols i-Butanol 107 28 H318 none 3 4 3 Recommended

i-Amyl alcohol 131 43 H315 none 3 2 3 Recommended

1, 3-Propane diol 214 >100 none none 1 1 7 Problematic

Glycerol 290 177 none none 1 1 7 Problematic

Esters i-Butyl acetate 115 22 H336 none 4 2 3 Recommended

i-Amyl acetate 142 25 none none 3 1 5 Recommended

Glycol diacetate 186 82 none none 1 1 5 Recommended

g-Valerolactone 207 100 n.a. n.a. 1 5 7 Problematic

Diethyl succinate 218 91 n.a. n.a. 1 5 7 Problematic

Hydrocarbons D-Limonene 175 49 H304 H400 4 2 7 Problematic

Turpentine 166 38 H302 H411 4 2 7 Problematic

p-Cymene 177 27 n.a. n.a. 4 5 5 Problematic

Aprotic polar Dimethyl carbonate 90 16 none none 4 1 3 Recommended

Ethylene carbonate 248 143 H302 none 1 2 7 Problematic

Propylene carbonate 242 132 H319 none 1 2 7 Problematic

Cyrene 203 61 H319 n.a. 1 2 7 Problematic

Miscellaneous Ethyl lactate 155 47 H318 none 3 4 5 Problematic

Lactic acid 230 113 H318 none 1 4 7 Problematic

TH-Furfuryl alcohol 178 75 H360 none 1 9 5 Hazardous

Green Solvents | 36


● Ranking of ethers

Solvent BP (°C) FP (°C) Worst

H3xx

H4xx Safety

score#

Health

score

Env.

score

Ranking by

default

MTBE 55 -28 H315 none 8 3 5 Hazardous

ETBE 72 -19 H336 none 7 3 3 Problematic

CPME 106 -1 H302 H412 7 2 5 Problematic

TAME 86 -7 H302 none 6 2 3 Recommended

THF 66 -14 H351 none 6 7 5 Problematic

Me-THF 80 -11 H318 none 6 5 3 Problematic

Green Solvents | 37


● Gives a preliminary desirability of any solvents for fine chemistry scale-

up purposes

● Classical solvents

● Bio-derived solvents

● Newer solvents

● Is the fruit of a successful collaboration between (inter alia) Sanofi, GSK,

Pfizer, Orion, J&J, and the University of York.

● The methodology is not perfect

● The health criterion should be based on OEL

● It only gives a preliminary assessment, a discussion is needed in each

institution to challenge the ranking

● The environment criterion should include the CO2 synthesis impact

D. Prat, A. Wells, J. Hayler, H. Sneddon, C. R. McElroy, S. Abou-

Shehada, P. J. Dunn, Green Chem., advance article

Green Solvents | 38


CONCLUSIONS

● There is no universal solvent guide but:

● Guides tend to homogenize, inspired by each others

● Regulations are the same for everyone, and restrain the solvent choice

● CHEM21 solvent guide is very useful for a preliminary ranking

● Especially when little data are available

● But a discussion between experts will always be necessary to give a final

ranking

● Companies guide, like Sanofi’s, will continue to exist and evolve

● Solvents guide have been elaborated for pharma of fine chemical industries

● This does not favor bio-sourced solvents (high BP)

● The field of green chemistry is wider

● Solvents guide are needed for other applications

● The methodology of CHEM21 guide can be adapted to these applications

• Different weighing of criteria

Green Solvents | 39

Green Solvents | 40

Main contributors:

Sanofi: O. Pardigon, H. Flemming, S. Letestu, V. Ducandas, P. Isnard, E. Guntrum, T. Senac, S. Ruisseau, P. Cruciani and P. Hosek.

CHEM21: A. Wells (Charnwood Consulting), J. Hayler & H. Sneddon (GSK) , C.R. McElroy & S. Abou-Shehada (York), P. J. Dunn (Pfizer).

The research for this work has received funding from the Innovative Medicines Initiative joint undertaking project CHEM21 grant agreement n°115360, resources of which are composed of financial contribution from the European Union’s Seventh Framework Programme (FP7/2007-2013) and EFPIA companies in kind contribution.

The conclusions reached in this presentation are the collective opinion of the authors who contribute to the CHEM21 consortium and do not reflect, at this time, official policy of any individual company or institution.

Green Solvents | 41

HEMI-SYNTHESIS OF ARTEMISININE

Green Solvents | 42

HEMI-SYNTHESIS OF ARTEMISININE

CHEM21- Who We Are

● EFPIA● GSK (coordinator), Sanofi (co-coordinator), Orion, J & J, Bayer, Pfizer

● Universities● University of Manchester (Managing Entity)

● Austrian Center of Industrial Biotechnology

● University of Stuttgart (Institute for Technical Biochemistry)

● University of Leeds

● University of Antwerp

● University of Durham

● Leibniz Institute for Catalysis (LIKAT)

● University of York

● Small and medium companies● Charnwood Technical Consulting

● Evolva Biotec

● Reaxa Ltd.

● CatSci Ltc.

● VU Amsterdam

Green Solvents | 43

selection of green solvents - industrial green … 2015/sym… · selection of green solvents ......

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