Risk assessment for consumer exposure to toluene diisocyanate (TDI) derived from polyurethane flexible foam

Regulatory Toxicology and Pharmacology

Volumn 64, Issue 3, 1970, Pages 504-515

  Arnold, Scott M ^a   Collins, Michael A ^b   Graham, Cynthia ^c   Jolly, Athena T ^d   Parod, Ralph J ^e   Poole, Alan ^f   Schupp, Thomas ^g   Shiotsuka, Ronald N ^h   Woolhiser, Michael R ^a  

^a DOW CHEMICAL COMPANY   (United States)

^b International Isocyanate Institute Inc   (United Kingdom)

^c Huntsman International LLC   (United States)

^d Occupational and Environmental Medicine ^*  (United States)

^e BASF CORPORATION   (United States)

^f DOW EUROPE GMBH   (Switzerland)

^g BASF SE   (Germany)

^h Formerly Baver Material Science AG   (United States)

Author keywords

Consumer exposure; Polyurethane flexible foam; Risk assessment; Toluene diisocyanate

Indexed keywords

POLYURETHAN FOAM; TOLUENE DIISOCYANATE; POLYURETHAN;

ADOLESCENT; ADULT; ANIMAL EXPERIMENT; ANIMAL MODEL; ANIMAL TISSUE; ARTICLE; BENCHMARKING; CANCER RISK; CARCINOGEN TESTING; CHILD; CONSUMER; CONTROLLED STUDY; ENVIRONMENTAL EXPOSURE; EVALUATION STUDY; HEALTH HAZARD; HUMAN; HUMAN CELL; INDUSTRIAL WASTE; MALE; NONHUMAN; PRIORITY JOURNAL; RESPIRATORY TRACT ALLERGY; RISK ASSESSMENT; SKIN IRRITATION; SKIN SENSITIZATION; SLEEP; TOXICITY TESTING; ANIMAL; BED; CHEMISTRY; COMPUTER PROGRAM; QUALITY CONTROL;

ANIMALS; BEDS; BENCHMARKING; ENVIRONMENTAL EXPOSURE; HUMANS; POLYURETHANES; RISK ASSESSMENT; SOFTWARE; TOLUENE 2,4-DIISOCYANATE;

EID: 84869120705     PISSN: 02732300     EISSN: 10960295     Source Type: Journal    
DOI: 10.1016/j.yrtph.2012.07.006     Document Type: Article

References (116)

1. ACGIH, 2010. 2010 TLVs and BEIs: based on the documentation of the threshold limit values for chemical substances and physical agents and biological exposure indices’ American Conference of Governmental Industrial Hygienists, Cincinnati.
2. Adams, W.G.F., Long-term effects on the health of men engaged in the manufacture of tolylene di-isocyanate. Br. J. Ind. Med. 32 (1975), 72–78.
3. AGS, 2006. Begründung zu 4-Methyl-m-phenylendiisocyanat in TRGS 900. Ausschuss für Gefahrstoffe, Bundesanstalt für Arbeitsschutz und Arbeitsmedizin (BAuA), Dortmund, Germany. < http://www.baua.de/nn_5846/de/Themen-von-A-Z/Gefahrstoffe/TRGS/pdf/900/900-4-methyl-m-phenylendiisocyanat.pdf> (accessed August 2011).
4. Auletta, C.S., 1984. A closed-patch repeated insult dermal sensitization study in guinea pigs with TDI, MDI, p-TMXDI, IPDI, m-TMXDI, HMDI and m-TMI (modified Buehler method) with cover letter 100592. EPA Doc. 86-930000053. Bio/dynamics Inc. Submission to TSCA on behalf of American Cyanamid Company.
5. Bakerly, N.D., Moore, V.C., Vellore, A.D., Jaakkola, M.S., Robertson, A.S., Burge, P.S., Fifteen-year trends in occupational asthma: data from the Shield surveillance scheme. Occup. Med. (Lond.) 58:3 (2008), 169–174.
6. Baur, X., 1985. Isocyanate hypersensitivity. III Report No. 10349. International Isocyanate Institute, Manchester, UK.
7. Bolognesi, C., Baur, X., Marczynski, B., Norppa, H., Sepai, O., Sabbioni, G., Carcinogenic risk of toluene diisocyanate and 4,4′-methylenediphenyl diisocyanate: epidemiological and experimental evidence. Crit. Rev. Toxicol. 31 (2001), 737–772.
8. Botham, P.A., Hext, P.M., Rattray, N.J., Walsh, S.T., Woodcock, D.R., Sensitisation of guinea pigs by inhalation exposure to low molecular weight chemicals. Toxicol. Lett. 41 (1988), 159–173.
9. Brown, W.E., Burkert, A.L., Biomarkers of toluene diisocyanate exposure. Appl. Occup. Environ. Hyg. 17:12 (2002), 40–45.
10. Bruynzeel, D., Andersen, K., Camarasa, J., Lachapelle, J., Menné T., White, I., The European standard series. European Environmental and Contact Dermatitis Research Group (EECDRG). Contact Derm. 33:3 (1995), 145–148.
11. Bugler, J., Clark, R.L., Hill, I.D., McDermott, M., 1991. The acute and long-term respiratory effects of aromatic di-isocyanates: a five year longitudinal study of polyurethane foam workers. III Report No. 10848. International Isocyanate Institute, Manchester, UK.
12. Buyantseva, L.V., Liss, G.M., Ribeiro, M., Manno, M., Luce, C.E., Tarlo, S.M., Reduction in diisocyanate and non-diisocyanate sensitizer-induced occupational asthma in Ontario. J. Occup. Environ. Med. 53:4 (2011), 420–426.
13. Canadian Government, 2008. Screening assessment for the challenge toluene diisocyanate. Benzene, 2,4,-diisocyanato-1-methyl-(2,4-TDI), CAS RN 584-84-9; benzene, 1,3,-diisocyanato-2-methyl-(2,6-TDI), CAS RN 91-08-7; benzene, 1,3,-diisocyanatomethyl-(TDI mixed isomers), CAS RN 26471-62-5. Environment Canada; Health Canada. < http://www.ec.gc.ca/substances/ese/eng/challenge/batch1/batch1_TDI.cfm> (accessed August 2011).
14. Chester, E.H., Martinez-Catinchi, F.L., Schwartz. H.J., Horowitz, J., Fleming, G.M., Gerblich, A., McDonald, E.W., Brethauer, R., 1979. Patterns of airway reactivity to asthma produced by exposure to toluene di-isocyanate. Chest 75, 229–231.
15. Clark, R.L., Bugler, J., Paddle, G.M., Chamberlain, J.D., Allport, D.C., A 17-year epidemiological study on changes in lung function in toluene diisocyanate foam workers. Int. Arch. Occup. Environ. Health 76 (2003), 295–301.
16. Cleet, C., 2005. Isocyanates in flexible polyurethane foams. Letter to the editor. Bull. Environ. Contam. Toxicol. 74(1), 1–3 (authors’ reply, 4–7).
17. Cole, K.C., Van Gheluwe, P., Hebrard, M.J., Leroux, J., Flexible polyurethane foam. I. FTIR analysis of residual isocyanate. J. Appl. Polym. Sci. 34 (1987), 395–407.
18. Collins, M.A., Toxicology of toluene diisocyanate. Appl. Occup. Environ. Hyg. 17:12 (2002), 846–855.
19. Daftarian, H.S., Lushniak, B.D., Reh, C.M., Lewis, D.M., Evaluation of self-reported skin problems among workers exposed to toluene diisocyanate (TDI) at a foam manufacturing facility. J. Occup. Environ. Med. 44:12 (2002), 1197–1202.
20. Day, B.W., Jin, R., Basalyga, D.M., Kramarik, J.A., Karol, M.H., Formation, solvolysis, and transcarbamoylation reactions of bis(s-glutathionyl) adducts of 2,4- and 2,6-diisocyanatotoluene. Chem. Res. Toxicol. 10:4 (1997), 424–431.
21. De Marzo, N., Jovine, L., Rizzotti, P., Cassetti, P., Boschetto, P., Miotto, D., Saetta, M., Maestrelli, P., Mapp, C.E., Modification of serum proteins in guinea pigs immunized and challenged with toluene diisocyanates. Scand. J. Work Environ. Health 26:2 (2000), 153–160.
22. DFG, Toluene diisocyanate. Greim, H., (eds.) Occupational Toxicants: Critical Data Evaluation for MAK Values and Classification of Carcinogens, vol. 20, 2003, Wiley-VCH, Weinheim, 291–338.
23. Diem, J., Jones, R., Hendrick, D., Glindmeyer, H., Butcher, B., Salvaggio, J., Dharmarajan, V., Weill, H., Five-year longitudinal study of workers employed in a new TDI manufacturing plant. Am. Rev. Respir. Dis. 126 (1982), 420–428.
24. Dieter, M.P., Boorman, G.A., Jameson, C.W., Matthews, H.B., Huff, J.E., The carcinogenic activity of commercial grade toluene diisocyanate in rats and mice in relation to the metabolism of the 2,4- and 2,6-TDI isomers. Toxicol. Ind. Health 6:6 (1990), 599–621.
25. Dieterich, D., Grigat, E., Hahn, W., Hespe, H., Schmelzer, H.G., 1993. Principles of polyurethane chemistry and special applications. In: Oertel, G. (Ed.), Polyurethane handbook. Chemistry – raw materials – processing – application – properties, 2nd ed. Carl Hanser Verlag, Munich, pp. 11–53 (Chapter 2).
26. Diller, W.F., 1998. Critical review of the human toxicology of TDI. III Report No. 11198. International Isocyanate Institute, Manchester, UK.
27. Duprat, P., Gradiski, D., Marignac, B., Irritating and allergizing power of two isocyanates; toluene diisocyanate (TDI), diphenylmethane diisocyanate (MDI). Eur. J. Toxicol. 9:1 (1976), 41–53.
28. European Chemicals Bureau, 2003. Technical guidance document on risk assessment in support of: Commission Directive 93/67/EEC on risk assessment for new notified substances; Commission regulation (EC) 1488/94 on risk assessment for existing substances; Directive 98/8/EC of the European Parliament and of the Council concerning the placing of biocidal products on the market, second ed. Parts I & II. European Commission, Joint Research Centre, Italy.
29. ECETOC, 2008. Potency values from the local lymph node assay: application to classification, labelling and risk assessment. ECETOC Document No. 46. European Centre for Ecotoxicology and Toxicology of Chemicals, Brussels, Belgium.
30. ECHA, 2010. Guidance on information requirements and chemical safety assessment. Chapter R.8: characterisation of dose [concentration]–response for human health, version 2, December 2010. European Chemicals Agency, Helsinki. < http://guidance.echa.europa.eu/docs/guidance_document/information_requirements_r8_en.pdf?vers=16_12_10> (accessed August 2011).
31. ECHA, 2011. m-Tolylidene diisocyanate (EC No: 247-722-4, CAS No: 26471-62-5) [REACH online dossier]. European Chemicals Agency, Helsinki. < http://apps.echa.europa.eu/registered/data/dossiers/DISS-9eaa0e2f-2626-4d70-e044-00144f67d031/DISS-9eaa0e2f-2626-4d70-e044-00144f67d031_DISS-9eaa0e2f-2626-4d70-e044-00144f67d031.html> (accessed December 2011).
32. European Commission, 1998. Commission Directive 98/98/EC of 15 December 1998 adapting to technical progress for the 25 time Council Directive 67/548/EEC on the approximation of laws, regulations and administrative provisions relating to the classification, packaging and labelling of dangerous substances. Off. J. Eur. Commun. 41, L355, 30 December, 386–389.
33. European Commission Joint Research Centre, 2000. IUCLID CD-ROM year 2000 edition: public data on high volume chemicals. Report EUR 19559 EN. European Chemical Bureau, Ispra (VA), Italy.
34. European Commission, 2010. Risk characterisation of local effects. European Commission, Joint Research Centre, Institute for Health and Consumer Protection. Ispra, Italy. < http://ihcp.jrc.ec.europa.eu/our_activities/health-env/risk_assessment_of_Biocides/guidance-documents> (accessed February 2012).
35. Fabbri, L.M., Boschetto, P., Zocca, E., Milani, G., Pivirotto, F., Plebani, M., Burlina, A., Licata, B., Mapp, C.E., Bronchoalveolar neutrophilia during late asthmatic reactions induced by toluene diisocyanate. Am. Rev. Respir. Dis. 136 (1987), 36–42.
36. Felter, S.P., Ryan, C.A., Basketter, D.A., Gilmour, N.J., Gerberick, G.F., Application of the risk assessment paradigm to the induction of allergic contact dermatitis. Regul. Toxicol. Pharmacol. 37:1 (2003), 1–10.
37. Gagné S., Lesage, J., Ostiguy, C., Van Tra, H., Determination of unreacted 2,4-toluene diisocyanate (2,4TDI) and 2,6-toluene diisocyanate (2,6TDI) in foams at ultratrace level by using HPLC–CIS–MS–MS. Analyst 128:12 (2003), 1447–1451.
38. Gandevia, B., Studies of ventilatory capacity and histamine response during exposure to isocyanate vapour in polyurethane foam manufacture. Br. J. Ind. Med. 20 (1963), 204–209.
39. Graham, C., Ott, M.G., Hoffmann, H-D., Shiotsuka, R.N., Davies, P., Landry, T.D., Collins, M.A., 2002. Respiratory sensitization: the role of dermal contact with MDI and TDI. GIL Report 2002/D. Gilbert International Ltd., Manchester, UK.
40. Griem, P., Goebel, C., Scheffler, H., Proposal for a risk assessment methodology for skin sensitization based on sensitization potency data. Regul. Toxicol. Pharmacol. 38:3 (2003), 269–290.
41. Hagmar, L., Welinder, H., Mikoczy, Z., Cancer incidence and mortality in the Swedish polyurethane foam manufacturing industry. Br. J. Ind. Med. 50 (1993), 537–543.
42. Hagmar, L., Stroemberg, U., Welinder, H., Mikoczy, Z., Incidence of cancer and exposure to toluene diisocyanate and methylene diphenyldiisocyanate: a cohort based case-referent study in the polyurethane foam manufacturing industry. Br. J. Ind. Med. 50 (1993), 1003–1007.
43. Henschler, D., Assmann, W., Meyer, K.O., Zur Toxikologie der Toluylendiisocyanate. Arch. Toxikol. 19 (1962), 364–387.
44. Hilton, J., Dearman, R.J., Basketter, D.A., Kimber, I., Identification of chemical respiratory allergens: dose–response relationships in the mouse IgE test. Toxicol. Methods 5:1 (1995), 51–60.
45. 14C-methylene diphenyl diisocyanate (MDI) in male rats. Clinical signs and histopathology following dermal exposure of male rats to TDI. Toxicol. Lett. 199 (2010), 364–371.
46. Holness, D., Broder, I., Corey, P., Booth, N., Mozzon, D., Nazar, M., Guirguis, S., Respiratory variables and exposure–effect relationships in isocyanate-exposed workers. J. Occ. Med. 26:6 (1984), 449–455.
47. Huang, J., Wang, X., Chen, B., Ueda, A., Aoyama, K., Matsushita, T., Immunological effects of toluene diisocyanate exposure on painters. Arch. Environ. Contam. Toxicol. 21 (1991), 607–611.
48. Hugo, J.M., Spence, M.W., Lickly, T.D., The determination of the ability of polyurethane foam to release toluene diisocyanate into air. Appl. Occup. Environ. Hyg. 15:6 (2000), 512–519.
49. IARC, 1999. IARC Monographs on the Evaluation of Carcinogenic Risks to Humans, vol. 71, Part 3. Re-evaluation of some organic chemicals, hydrazine and hydrogen peroxide. International Agency for Research on Cancer, Lyon.
50. Jeffcoat, A.R., 1988. Absorption and disposition of orally administered 2,4-toluene diisocyanate in the Fischer 344 rat. Project Report No. 2. Report RTI/3662/02P. Research Triangle Institute, NC.
51. Jennings, P., Hammerstrom, K., Colemen Adkins, L., Chambers, T., Dixon, D., 1987. Methods for assessing exposure to chemical substances. Methods for assessing consumer exposure to chemical substances. Report No. EPA 560/5-85-007, 7, 71. US Environmental Protection Agency, Office of Toxic Substances, Washington, DC.
52. Jordt, S.E., Bautista, D.M., Chuang, H.H., McKemy, D.D., Zygmunt, P.M., Högestätt, E.D., Meng, I.D., Julius, D., Mustard oils and cannabinoids excite sensory nerve fibres through the TRP channel ANKTM1. Nature 427:6971 (2004), 260–265.
53. Kanerva, L., Jolanki, R., Alanko, K., Estlander, T., Patch-test reactions to plastic and glue allergens. Acta Derm. Venereol. 79:4 (1999), 296–300.
54. Karol, M.H., Hauth, B.A., Riley, E.J., Magreni, C.M., Dermal contact with toluene diisocyanate (TDI) produces respiratory tract hypersensitivity in guinea pigs. Toxicol. Appl. Pharmacol. 58 (1981), 221–230.
55. Karol, M.H., Concentration-dependent immunologic response to toluene diisocyanate (TDI) following inhalation exposure. Toxicol. Appl. Pharmacol. 68 (1983), 229–241.
56. Kennedy, A.L., Brown, W.E., 1998. Investigation of the chemistry of TDI in biological materials. III Report No. 11320. International Isocyanate Institute, Manchester, UK.
57. Kimber, I., Basketter, D.A., Berthold, K., Butler, M., Garrigue, J.-L., Lea, L., Newsome, C., Roggeband, R., Steiling, W., Stropp, G., Waterman, S., Wiemann, C., Skin sensitization testing in potency and risk assessment. Toxicol. Sci. 59 (2001), 198–208.
58. Kimber, I., Dearman, R.J., Basketter, D.A., Ryan, C.A., Gerberick, G.F., McNamee, P.M., Lalko, J., Api, A.M., Dose metrics in the acquisition of skin sensitization: thresholds and importance of dose per unit area. Regul. Toxicol. Pharmacol. 52:1 (2008), 39–45.
59. Knapp, R., Baker, R.G., 1974. Primary skin irritation test with toluene diisocyanate in albino rabbits: report to BASF Wyandotte Corporation. IBT No. 601-05008. Industrial Bio-Test Laboratories, Inc., Northbrook, Illinois 60062, USA.
60. Krone, C.A., Ely, J.T.A., Klingner, T., Rando, R.J., Isocyanates in flexible polyurethane foams. Bull. Environ. Contam. Toxicol. 70 (2003), 328–335.
61. Lange, R.W., Day, B.W., Lemus, R., Tyurin, V.A., Gagan, V.E., Karol, M.H., Intracellular S-glutathionyl adducts in murine lung and human bronchoepithelial cells after exposure to diisocyanatotoluene. Chem. Res. Toxicol. 12 (1999), 931–936.
62. Liippo, J., Lammintausta, K., Contact sensitization to 4,4′-diaminodiphenylmethane and to isocyanates among general dermatology patients. Contact Dermatitis 59:2 (2008), 109–114.
63. Löser, E., Long-term toxicity and carcinogenicity studies with 2,4/2,6-toluene-diisocyanate (80/20) in rats and mice. Toxicol. Lett. 15 (1983), 71–81.
64. Loveless, S.E., Api, A.M., Crevel, R.W., Debruyne, E., Gamer, A., Jowsey, I.R., Kern, P., Kimber, I., Lea, L., Lloyd, P., Mehmood, Z., Steiling, W., Veenstra, G., Woolhiser, M., Hennes, C., Potency values from the local lymph node assay: application to classification, labelling and risk assessment. Regul. Toxicol. Pharmacol. 56:1 (2010), 54–66.
65. Matheson, J.M., Johnson, V.J., Vallyathan, V., Luster, M.I., Exposure and immunological determinants in a murine model for toluene diisocyanate (TDI) asthma. Toxicol. Sci. 84 (2005), 88–98.
66. Mikoczy, Z., Welinder, H., Tinnerberg, H., Hagmar, L., Cancer incidence and mortality of isocyanate exposed workers from the Swedish polyurethane foam industry: updated findings 1959–98. Occup. Environ. Med. 61:5 (2004), 432–437.
67. Moller, D.R., McKay, R.T., Bernstein, I.L., Brooks, S.M., Persistent airways disease caused by toluene diisocyanate. Am. Rev. Respir. Dis. 134 (1986), 175–176.
68. Mormann, W., Vaquero, R.L., Seel, K., Interactions of aromatic isocyanates with N-acetyl-L-cyteine(sic) under physiological conditions: formation of conjugates, ureas and amines. EXCLI J. 5 (2006), 191–208.
69. Mráz, J., Simek, P., Nohová H., Bouskova, S., Gálová E., Linhart, I., Smejkal, J., 1998. Identification of 2,4-toluenediisocyanate (2,4-TDI) adducts with globin and albumin. In: Abstr. Paper, 4th Int. Symp. on Biological Monitoring in Occup. Environ. Health, Seoul, Korea, 23–25 September, 1998.
70. Mráz, J., Simek, P., Nohová H., Duskova, S., Gálová E., Hornychová M., Linhart, I., 2000. Studies on diisocyanate adducts with blood proteins as potential biomarkers of exposure. In: Paper presented at Isocyanate 2000: First International Symposium on Isocyanates in Occupational Environments, Stockholm, 19–21 June, 2000, pp. 68–70.
71. Musk, A.W., Peters, J.M., Bernstein, L., Absence of respiratory effects in subjects exposed to low concentrations of TDI and MDI: a reevaluation. J. Occup. Med. 27:12 (1985), 917–920.
72. National Research Council, 1983. Risk assessment in the Federal Government: managing the process. National Academies Press, Washington, DC.
73. National Research Council, 2004. Toluene 2,4- and 2,6-diisocyanate: acute exposure guideline levels. In: Acute Exposure Guideline Levels for Selected Airborne Chemicals, vol. 4. Appendix 4. National Academies Press, Washington, DC.
74. NCI, 1979. Bioassay of 2,4-diaminotoluene for possible carcinogenicity. National Cancer Institute Carcinogenesis Technical Report Series No. 162; DHEW Publication No. (NIH) 79-1718; PB 293593. US Department of Health, Education & Welfare, Public Health Service, National Institutes of Health.
75. Nethercott, J.R., Practical problems in the use of patch testing in the evaluation of patients with contact dermatitis. Curr. Probl. Dermatol. 2:4 (1990), 97–123.
76. NTP, 1986. Toxicology and carcinogenesis studies of commercial grade 2,4(80%)- and 2,6(20%)-toluene diisocyanate in F344/N rats and B6C3F1 mice (gavage studies).US Department of Health and Human Services. National Toxicology Program. NTP TR 251; NIH Publication No. 86-2507. Research Triangle Park, NC.
77. NTP, 2011. Report on Carcinogens, 12th ed., US Department of Health and Human Services, Public Health Service, National Toxicology Program.
78. O'Brien, I.M., Newman-Taylor, A.J., Burge, P.S., Harries, M.G., Fawcett, I.W., Pepys, J., TDI-induced asthma II. Inhalation challenge tests and bronchial reactivity studies. Clin. Allergy 9 (1979), 7–15.
79. Ogawa, M., Oyama, T., Isse, T., Yamaguchi, T., Murakami, T., Endo, Y., Kawamoto, T., Hemoglobin adducts as a marker of exposure to chemical substances, especially PRTR class I designated chemical substances. J. Occup. Health 48:5 (2006), 314–328.
80. Ott, M.G., Klees, J.E., Poche, S.L., Respiratory health surveillance in a toluene di-isocyanate production unit, 1967–97: clinical observations and lung function analyses. Occup. Environ. Med. 57:1 (2000), 43–52.
81. Ott, M.G., Occupational asthma, lung function decrement, and toluene diisocyanate (TDI) exposure: a critical review of exposure–response relationships. Appl. Occup. Environ. Hyg. 17:12 (2002), 891–901.
82. Ott, M.G., Diller, W.F., Jolly, A.T., Respiratory effects of toluene diisocyanate in the workplace: a discussion of exposure–response relationships. Crit. Rev. Toxicol. 33:1 (2003), 1–59.
83. Owen, P.E., 1984. The toxicity and carcinogenicity to rats of toluene diisocyanate vapour administered by inhalation for a period of 113 weeks. Addendum Report Volume 1. III Report No. 10233. International Isocyanate Institute, Manchester, UK.
84. Paris, C., Ngatchou-Wandji, J., Luc, A., et al. Work-related asthma in France: recent trends for the period 2001–2009. Occup. Environ. Med., 2012, 10.1136/oemed-2011-100487.
85. Pauluhn, J., Mohr, U., Assessment of respiratory hypersensitivity in guinea pigs sensitized to toluene diisocyanate: a comparison of sensitization protocols. Inhal. Toxicol. 10 (1998), 131–154.
86. Peters, J.M., Wegman, D.H., Epidemiology of TDI-induced respiratory disease. Environ. Health Perspect 11 (1975), 97–100.
87. Rosenberg, C., Savolainen, H., Detection of urinary amine metabolites in toluene diisocyanate exposed rats. J. Chromatogr. 323 (1985), 429–433.
88. Safford, R.J., The dermal sensitisation threshold – a TTC approach for allergic contact dermatitis. Regul. Toxicol. Pharmacol. 51:2 (2008), 195–200.
89. Schnorr, T.M., Steenland, K., Egeland, G.M., Boeniger, M., Egilman, D., Mortality of workers exposed to toluene diisocyanate in the polyurethane foam industry. Occup. Environ. Med. 53:10 (1996), 703–707.
90. Seel, K., Walber, U., Herbold, B., Kopp, R., Chemical behaviour of seven aromatic diisocyanates (toluenediisocyanates and diphenylmethanediisocyanates) under in vitro conditions in relationship to their results in the Salmonella/microsome test. Mutat. Res. 438 (1999), 109–123.
91. Selgrade, M., Boykin, E., Haykal-Coates, N., Woolhiser, M., Wiescinski, C., Andrews, D., Farraj, A., Doerfler, D., Gavett, S., Inconsistencies between cytokine profiles, antibody responses, and respiratory hyperresponsiveness following dermal exposure to isocyanates. Toxicol. Sci. 94 (2006), 108–117.
92. Sielken, R.L., Bretzlaff, R.S., Valdez-Flores, C., Parod, R., in press. Statistical comparison of carcinogenic effects and dose-response relationships in rats and mice for 2,4-toluene diamine to those ascribed to toluene diisocyanate. Hum. Ecol. Risk. Assess.
93. Skarping, G., Dalene, M., Lind, P., Determination of toluenediamine isomers by capillary gas chromatography and chemical ionization mass spectrometry with special reference to the biological monitoring of 2,4- and 2,6-toluene diisocyanate. J. Chromatogr. A 663 (1994), 199–210.
94. Sorahan, T., Nichols, L., Mortality and cancer morbidity of production workers in the UK flexible polyurethane foam industry: updated findings, 1958–98. Occup. Environ. Med. 59:11 (2002), 751–758.
95. Sorahan, T., Pope, D., Mortality and cancer morbidity of production workers in the United Kingdom flexible polyurethane foam industry. Br. J. Ind. Med. 50 (1993), 528–536.
96. Suberg, H., Löser, E., Kaliner, G., 1984. Toluylendiisocyanat (TDI): Untersuchungen zur primär reizenden/ätzenden Wirkung an der Kaninchenhaut. Bericht Nr: 12533. Bayer AG, Wuppertal, Germany.
97. Tarlo, S.M., Liss, G.M., Dias, C., Banks, D.E., Assessment of the relationship between isocyanate exposure levels and occupational asthma. Am. J. Ind. Med. 32 (1997), 517–521.
98. Taylor-Clark, T.E., Kiros, F., Carr, M.J., McAlexander, M.A., Transient receptor potential ankyrin 1 mediates toluene diisocyanate-evoked respiratory irritation. Am. J. Respir. Cell Mol. Biol. 40:6 (2009), 756–762.
99. Thorne, P.S., Hillebrand, J.A., Lewis, G.R., Karol, M.H., Contact sensitivity by diisocyanates: potencies and cross-reactivities. Toxicol. Appl. Pharmacol. 87 (1987), 155–165.
100. 14C]toluene 2,4-diamine in Fischer 344 rats. Toxicol. Appl. Pharmacol. 124 (1994), 181–190.
101. USEPA, 1989. Risk assessment guidance for Superfund. Volume I: human health evaluation manual (Part A). Interim final. Report No. EPA/540/1-89/002. Section 5.3.3. US Environmental Protection Agency, Office of Emergency and Remedial Response, Washington, DC.
102. USEPA, 1995. 2,4-/2,6-Toluene diisocyanate mixture (TDI) (CASRN 26471-62- 5). Integrated Risk Information System (IRIS) Database. US Environmental Protection Agency. < http://www.epa.gov/iris/subst/0503.htm> (accessed August 2011).
103. USEPA, 2005. Supplemental guidance for assessing susceptibility from early-life exposure to carcinogens. Report No. EPA/630/R-03/003F. Risk Assessment Forum. US Environmental Protection Agency, Washington, DC.
104. USEPA, 2011a. Toluene diisocyanate (TDI) and related compounds: action plan [RIN 2070-ZA14]. US Environmental Protection Agency. < http://www.epa.gov/oppt/existingchemicals/pubs/actionplans/tdi.pdf> (accessed February 2012).
105. USEPA, 2011b. Exposure factors handbook: 2011 edition. National Center for Environmental Assessment, Washington, DC; EPA/600/R-09/052F. Available from the National Technical Information Service, Springfield, VA, and online at < http://www.epa.gov/ncea/efh>.
106. Valstar, D.L., Schijf, M.A., Nijkamp, F.P., Bloksma, N., Henricks, P.A.J., Glutathione-conjugated toluene diisocyanate causes airway inflammation in sensitised mice. Arch. Toxicol. 78:9 (2004), 533–539.
107. Vandenplas, O., Lantin, A.C., D'Alpaos, V., Larbanois, A., Hoet, P., Vandeweerdt, M., Thimpont, J., Speybroeck, N., Time trends in occupational asthma in Belgium. Respir. Med. 105:9 (2011), 1364–1372.
108. Vangronsveld, E., Berckmans, S., Spence, M., 2012. Measurement of Toluene Diisocyanate (TDI) emission to air and migration to a surface from flexible polyurethane foam. Accepted for Publication in Annals Occup. Hygiene.
109. van Och, F.M.M., Slob, W., de Jong, W.H., Vandebriel, R.J., van Loveren, H., A quantitative method for assessing the sensitizing potency of low molecular weight chemicals using a local lymph node assay: employment of a regression method that includes determination of the uncertainty margins. Toxicology 146:1 (2000), 49–59.
110. Wazeter, F.X., Buller, R.H., Geil, R.G., 1964. Toluene diisocyanate (TDI) and polymethylene polyphenylisocyanate (PAPI): acute dermal toxicity studies (LD50) in the albino rabbit. Unpublished report by the International Research and Development Corporation.
111. Wegman, D., Pagnotto, L., Fine, L., Peters, J., A dose–response relationship in TDI workers. J. Occup. Med. 16:4 (1974), 258–260.
112. Weill, H., Butcher, B., Dharmarajan, V., Glindmeyer, H., Jones, R., Carr, J., O'Neil, C., Salvaggio, J., 1981. Respiratory and immunologic evaluation of isocyanate exposure in a new manufacturing plant. DHHS (NIOSH) Publication No. 81-125. US Department of Health and Human Services, Morgantown, West Virginia, USA.
113. Wisnewski, A.V., Redlich, C.A., Ye, Y-M., Park, H-S., 2006. Biophysical/chemical and immunological changes in human albumin exposed to TDI. Poster presented at ATS 2006: Int. Conf. American Thoracic Society, San Diego, 19–24 May, 2006.
114. Woolhiser, M.R., Hayes, B.B., Meade, B.J., A combined murine local lymph node and irritancy assay to predict sensitization and irritancy potential of chemicals. Toxicol. Methods 8:4 (1998), 245–256.
115. Ye, Y.-M., Kim, C.-W., Kim, H.-R., Kim, H.-M., Suh, C.-H., Nahm, D.-H., Park, H.-S., Redlich, C.A., Wisnewski, A.V., Biophysical determinants of toluene diisocyanate antigenicity associated with exposure and asthma. J. Allergy Clin. Immunol. 118:4 (2006), 885–891.
116. Zissu, D., Binet, S., Limasset, J.-C., Cutaneous sensitization to some polyisocyanate prepolymers in guinea pigs. Contact Derm. 39 (1998), 248–251.