Chronic inhalation exposures of Fischer 344 rats to 1,6-hexamethylene diisocyanate did not reveal a carcinogenic potential

Inhalation Toxicology

Volumn 22, Issue 10, 2010, Pages 875-887

  Shiotsuka, Ronald N ^a   Stuart, Barry P ^b   Charles, Jeffrey M ^c   Simon, Glenn S ^d   Malichky, Paul ^e   Mostowy, Janet M ^a  

^a Formerly Baver Material Science AG   (United States)

^b Stonehedge Pathology Services   (United States)

^c Toxicology Consultant   (United States)

^d Rhodia Inc   (United States)

^e PPG INDUSTRIES   (United States)

Author keywords

1,6 hexamethylene diisocyanate; Carcinogenicity; HDI; Oncogenicity

Indexed keywords

HEXAMETHYLENE DIISOCYANATE;

ANIMAL CELL; ANIMAL EXPERIMENT; ANIMAL TISSUE; ARTICLE; CARCINOGEN TESTING; CARCINOGENICITY; CELL HYPERPLASIA; CHRONIC INFLAMMATION; CONTROLLED STUDY; ENVIRONMENTAL EXPOSURE; EYE IRRITATION; FEMALE; FISCHER 344 RAT; HISTOPATHOLOGY; HYPERKERATOSIS; LONG TERM EXPOSURE; MALE; MAXIMUM TOLERATED DOSE; MUCOUS CELL; NONHUMAN; NOSE CAVITY; NOSE MUCOSA; NOSE ULCER; OLFACTORY EPITHELIUM; PRIORITY JOURNAL; RAT; RESPIRATORY EPITHELIUM; RESPIRATORY SYSTEM; SQUAMOUS CELL METAPLASIA; STATISTICAL SIGNIFICANCE; TISSUE REACTION; TOXICITY TESTING; WEIGHT REDUCTION;

AIR POLLUTANTS; ANIMALS; BODY WEIGHT; CARCINOGENICITY TESTS; CARCINOGENS; CYANATES; EYE INJURIES; FEMALE; INHALATION EXPOSURE; IRRITANTS; LONGEVITY; MALE; MAXIMUM TOLERATED DOSE; NASAL CAVITY; RATS; RATS, INBRED F344; RESPIRATORY SYSTEM; TOXICITY TESTS, CHRONIC;

RATTUS;

EID: 77955482417     PISSN: 08958378     EISSN: 10917691     Source Type: Journal    
DOI: 10.3109/08958370903572862     Document Type: Article

References (37)

1. Abdo KM, Haseman JK, Nyska A. 1998. Isobutyraldehyde administered by inhalation (whole body exposure) for up to thirteen weeks or two years was a respiratory tract toxicant but was not carcinogenic in F344/N rats and B6C3F1 mice. Toxicol Sci 42:136-151.
2. ACGIH. 2009. Americal Conference of Governmental Industrial Hygienists.
3. Astroff AB, Sheets LP, Sturdivant DW, Stuart BP, Shiotsuka RN, Simon GS, Andrews LS. 2000a. A combined reproduction, neonatal development, and neurotoxicity study with 1,6-hexamehtylene diisocyanate (HDI) in the rat. Reprod Toxicol 14:135-146.
4. Astroff AB, Sturdivant DW, Lake SG, Shiotsuka RN, Simon GS, Andrews LS. 2000b. Developmental toxicity of 1,6-hexamethylene diisocyanate (HDI) in the Sprague-Dawley rat. Teratology 62:205-213.
5. Banks D, Butcher B, Salvagio J. 1986. Review article: Isocyanate-induced respiratory disease. Annu Allergy 57:389-396.
6. Bernstein L. 1982. Isocyanate-induced pulmonary disease: A current perspective. J Allergy Clin Immunol 70:24-31.
7. Day BW, Jin R, Basalyga DM, Kramarik JA, Karol MH. 1997. Formatioin, solvoly-sis and transcarbamoylation reactions of bis(S-glutathionyl) adducts of 2,4-and 2,6-diisocyanatotoluene. Chem Res Toxicol 10:424-431.
8. Feron VJ, Arts JHE, Kuper CF, Slootweg PJ, Woutersen RA. 2001. Health risks associated with inhaled nasal toxicants. Crit Rev Toxicol 31:313-347.
9. Foureman GL, Greenberg MM, Sangha GK, Stuart BP, Shiotsuka RN, Thyssen JH. 1994. Evaluation of nasal tract lesions in derivation of the inhalation reference concentration for hexamethylene diisocyanate. Inhal Toxicol 6(Suppl):341-355.
10. Gaskell BA. 1990. Nonneoplastic changes in the olfactory epithelium-Experimental studies. Environ Health Perspect 85:275-289.
11. Gledhill A, Wake A, Hext P, Leibold E, Shiotsuka R. 2005. Absorption, distribution, metabolism and excretion of an inhaled dose of [14C]4,4'-methylenediphenyl diisocyanate in the male rat. Xenobiotica 35:273-292.
12. Harkema JR, Morgan KT. 1996. Proliferative and metaplastic lesions in non-olfactory nasal epithelia induced by inhaled chemical. In: Jones TC, Dungrowth DL, Mohr U, eds. Respiratory System. 2nd ed. Berlin: Springer-Verlag, 18-28.
13. Haseman JK, Hailey JR, Morris RW. 1998. Spontaneous neoplasm incidences in Fischer 344 rats and B6C3F1 mice in two year carcinogenicity studies: A National Toxicology Program Update. Toxicol Pathol 26:428-441.
14. Hoymann HG, Buschmann J, Heinrich U. 1995. Untersuchengen zur chro-nischen Toxizitat/Kanzerogenitat von 4,4'-Methylendiphenyl-Diisocyanat (MDI). FHG-ITA Hannover Forschungsbericht 116 06 114 im Auftrag des Umveltbundesamtes.
15. Janko M, McCarthy K, Fajer M, Van Raalte J. 1992. Occupational exposure to 1,6-hexamethylene diisocyanate-based polyisocyanates in the State of Oregon, 1980-1990. Am Ind Hyg Assoc J 53:331-338.
16. Jiang X-Z, Morgan KT, Beauchamp RO, Jr. 1986. Histopathology of acute and subacute nasal toxicity. In: Barrow CS, ed. Toxicology of the Nasal Passages. Washington, DC: Hemisphere, 51-66.
17. Karol MH. 1985. Respiratory effects of inhaled isocyanates. CRC Crit Rev Toxicol 16:349-379.
18. Kennedy AL, Brown WE. 1992. Isocyanates and lung disease: Experimental approaches to molecular mechanisms. Occup Med State Art Rev 7:301-329.
19. Kilgour JD, Rattray NJ, Foster J, Soames A, Hext PM. 2002. Pulmonary responses and recovery following single and repeated inhalation exposure of rats to polymeric methylene diphenyl diisocyanate aerosols. J Appl Toxicol 22:371-385.
20. Lange RW., Day B, Lemus R, Tyurin VA, Kagan VE, Karol MH. 1999. Intracellular S-glutathionyl adducts in murine lung and human bronchoepithelial cells after exposure to diisocyanatotoluene. Chem Res Toxicol 12:931-936.
21. Loeser E. 1983. Long-term toxicity and carcinogenicity studies with 2,4-/2,6-TDI (80/20) in rats and mice. Toxicol Lett 15:71-81.
22. Miles, Inc. 1988. 90-Day inhalation toxicity study with 1,6-hexamethylene diisocyanate in rats (with attached appendices and cover letter dated 01/18/89). TSCATS/401508. EPA/OTS Document 86-890000080.
23. Miles, Inc. 1989. Chronic inhalation toxicity and oncogenicity study with 1,6-hexamethylene diisocyanate (HDI) in rats (final report), with attached appendices and cover letter dated 12/20/89. TSCATS/405187. EPA/OTS Document 86-900000055.
24. Musk A, Peters J, Wegman D. 1988. Isocyanates and respiratory disease: Current status. Am J Indus Med 13:331-349.
25. NTP. 1983. National Toxicology Bulletin No. 10, Rodent Control Database, 1983, 9-10.
26. NTP. 1986. National Toxicology Program. Toxicology and carcinogenicity studies of commercial grade 2,4(80%)-and 2,6(20%)-toluene diisocyanate (CAS 26471-62-5) in F344/N rats and B6C3F1 mice (gavage studies). NTP TR 251. NIH Publication No. 86-2507. US Dept. of Health and Human Services, August 1986.
27. OECD SIDS. 1996. United Nations Environment Programme Chemicals Branch, Screening Information Data Sets (SIDS) for High Volume Chemicals, Hexamethylenediamine (CAS No. 124-09-4), July 1996.
28. Peel M, Marczynski B, Baur X. 1997. Comparison of the binding potential of various diisocyanates on DNA in vitro. J Toxicol Environ Health 52:517-526.
29. Reuzel PGJ, Arts HE, Lomax LG, Kuypers MHM, Kuper CF, Gembardt C, Feron VJ, loeser E. 1994. Chronic inhalation toxicity and carcinogenicity study of respirable polymeric methylene diphenyl diisocyanate (polymeric MDI) aerosol in rats. Fundam Appl Toxicol 22:195-210.
30. SAS Institute Inc. Cary, NC, USA.
31. Shiotsuka RN, Stuart BP, Sangha GK, Sturdivant DW, Hoss H. 2006. Subacute inhalation exposure of rats to 1,6-hexamethylene diisocyanate with recovery period. Inhal Toxicol 18:659-665.
32. Timchalk C, Smith FA, Bartels MH 1994. Route-dependent comparative metabolism of [14C]toluene 2,4-diisocyanate and [14C]toluene 2,4-diamine in Fischer 344 rats. Toxicol Appl Pharmacol 124:181-190.
33. US EPA. 1994. United States Environmental Protection Agency. Integrated Risk Information System. Report on 1,6-Hexamethylene Diisocyanate. CASRN: 822-06-10, 09/01/1994. Available at: iris/subst/0638.htm#refinhal.
34. Vandenplas O, Malo J-L, Saetta M, Mapp C, Fabbri L. 1993. Occupational asthma and extrinsic alveolitis due to isocyanates: Current status and perspectives. Br J Indust Med 50:13-228.
35. Von Berg R. 1993. Toxicology update: Hexamethylene diisocyanate. J Appl Toxicol 13:435-439.
36. Wagner VO, San RH, Gudi R, Hilaski RJ, Jacobson-Kram D. 2000. Lack of mutagenic activity of 1,6-hexamethylene diisocyanate. Toxicol Sci 55:376-382.
37. Zeiger E, M Woolhiser. 2007. The genetic toxicity of diisocyanates in humans and laboratory animals. Toxicologist 96:347.