Sensitization potential of low-monomer diisocyanate prepolymers responsible classification

Transcription

1 Sensitization potential of low-monomer diisocyanate prepolymers responsible classification Polyurethane Manufacturers Association 40th Anniversary Annual Meeting Mike Woolhiser, Ph.D. Toxicology & Environmental Research and Consulting The Dow Chemical Company Rui Xie, Ph.D. Technical Leader, Epoxy Specialty Products The Dow Chemical Company Paul Fitzgerald, C Chem MRSC. DipM Global Business Leader, Engineering Elastomers Dow Chemical UK Limited 1

2 Background - objectives p From the perspective of environmental, health and safety, diisocyanate prepolymers have had limited concern for toxicity due to their chemical and physical characteristics. p Diisocyanates are under increasing scrutiny by regulators around the world as chemicals that may pose a concern to the public. p A consistent industry approach will contribute to advocacy in response to this public concern. 2

3 Background - hazard classification p Diisocyanates are considered to be strong sensitizers. p Most prepolymer products contain concentrations of residual diisocyanate monomer (e.g., TDI, MDI) which drive classification, labeling, and safe handling procedures. Products with >0.1% TDI are labeled as hazardous. p For these products, the ability to test and directly interpret toxicity of potential for the prepolymers is challenging, although they have largely been considered to be nonhazardous. p With the development of low, monomer-free prepolymer products, product toxicity potential is questioned. p With NCO functionality, these isocyanate products must carry sensitization warnings unless one has evidence to refute. 3

4 Objective - understand sensitization potential p Determine sensitization potential of low-monomer prepolymer product p Sensitization testing n Guinea pigs traditional assay n Mouse LLNA new gold standard dose response quantitative potency Skin layers Chemical exposure Lymph flow Local, draining lymph node 4

5 Local Lymph Node Assay (LLNA) p USEPA OPPTS , OECD 429 guideline Sensitization / Lymph Node Proliferation 3 H-thymidine Incorporated into DNA of dividing cells Treat Days 1, 2, 3 Rest Days 4, 5 Inject 3 H-thymidine Day 6 5 hours Remove Lymph Nodes Day 6 Auricular Nodes Prepare Single, Cell Suspension Measure 3 H-thymidine Incorporation 5

6 Criteria - Stimulation index LLNA Stimulation Index Vehicle TDI pos control (0.1%) 6

7 Potency Effective Concentration (3-fold) stimulation index A B Substance A is stronger senstizer than substance B takes less chemical to elicit response EC3 0.06% EC3 0.87% 7

8 Study design p TDI Prepolymer up to 3 test concentrations (dose-response) p Negative (vehicle) control p Polyol p Positive control TDI p Residual control % % wt. TDI - near EC3 response using animal tests 8

9 Preliminary testing Proof of concept studies were conducted on an experimental prepolymer to test hypothesis that prepolymers can be non-hazardous Test Material: TDI-PTMEG Stripped Prepolymer Molecular weight: 2,950 g/mole Diiso functionality: ~ 2 Residual free-tdi: 0.02% wt. (~0.3 ppm) Initiator: Poly tetra methylene ether glycol 9

10 Preliminary testing Stimulation Index LLNA Comparison to TDI controls suggest TDI-PTMEG (2,950 g/mole) does not likely possess sensitization potential which is separate and distinct from residual TDI 10

11 Results prepolymer products Diiso PTMEG (950 g/mole) Diiso Adipate (1800 g/mole) Stimulation Index Low monomer prepolymer substances can demonstrate sensitization potential which is separate and distinct from residual TDI. cle % % % ol %) %) Stimulation Index cle % % % ol %) 11 %)

12 Results comparison Prepolymer MW (g/mole) % wt NCO Residual TDI (% wt) EC3 (potency) TDI monomer 174 ~48% -- ~0.02% TDI-PTMEG 950 ~9% % 0.11% TDI-Adipate 1800 ~5% 0.025% 7% TDI-PTMEG 2950 ~3% 0.016% Negative (50%) Sensitization potential decreases as.. - molecular weight increases, and - % NCO decreases. 12

13 Urethanes Technology International Vol. 25 No. 2. April/May 2008 p "From the viewpoint of occupation health & safety, low-free TDI prepolymers appear to be non-problematic, as a result of their low monomer content. However, recent tests carried out in an accredited test laboratory on an LF-TDI prepolymer with less than 0.1 percent free TDI and a low isocyanate content of around 1.6 percent show that these can have a sensitizing effect on the skin. As a result, all LF-TDI prepolymers with a free TDI content of less than 0.1 percent are labeled with the risk phrase 43 ("May cause sensitization by skin contact") and the risk symbol Xi ("irritant") at Bayer MaterialScience. 13

14 Conclusions p Low monomer prepolymer substances can demonstrate sensitization potential. Potency is order of magnitude less than diisocyanate monomer alone. p Default labeling should include warnings of sensitization for low monomer TDI prepolymer products unless proven to not possess sensitization potential. p Consistency in classification and labeling is essential to mitigate the risk of health effects amongst users of these prepolymers and to meet the principles of Responsible Care. p Diisocyanates are under increasing scrutiny by agencies around the world as chemicals that may pose heighten risk to workers, and the public. - USEPA s proposed Chemical Action Plan - Canada s Challenge Program (CSDSL) - A consistent industry approach will contribute to advocacy in response to this public concern. 14

15 Acknowledgements p Amber Stephenson, Ashley Breed p Darrell Boverhof, Lindsay Sosinski p Bob West, Steve Erskine 15