Chronic (24-month) inhalation exposure to 5 or 10 ppm allyl glycidyl ether (AGE) induced nasal lesions in Osborne-Mendel rats and B6C3F1 mice. Inflammation, degeneration, regeneration, metaplasia, hyperplasia, and neoplasia were observed in the nasal mucosa. Squamous metaplasia and hyperplasia of the respiratory epithelium and degeneration and regeneration with subsequent squamous and/or respiratory metaplasia of the olfactory epithelium were observed in many AGE-exposed animals. Three primary nasal neoplasms (1 papillary adenoma, 1 squamous cell carcinoma, and 1 olfactory epithelial carcinoma) were observed in rats exposed to 10 ppm AGE, and 1 nasal papillary adenoma was observed in a rat exposed to 5 ppm. Four papillary adenomas and 2 hemangiomas were observed in the noses of mice exposed to 10 ppm AGE. Although the incidence of primary nasal tumors in AGE-exposed rats or mice was not statistically significant compared to the incidence in concurrent controls, the relative rarity of primary nasal tumors in historical controls and the concurrent presence of metaplastic and hyperplastic nasal lesions similar to those reported to be associated with induced tumors of nasal epithelia by other chemicals suggest that the nasal tumors observed may be related to AGE exposure. It was concluded that, in addition to lesions indicating a toxic effect on the nasal mucosa, inhalation exposure to AGE for 24 months resulted in some evidence of carcinogenicity of AGE for male mice, equivocal evidence of carcinogenicity for female mice and male rats, and no evidence of carcinogenicity for female rats.
Boorman GABrown R., Gupta BNUraih LC, and Bucher JR (1987). Pathologic changes following acute methyl isocyanate inhalation and recovery in B6C3F1 mice. Toxicol. Appl. Pharmacol . 87: 446-456.
2.
Brown HR (1990). Neoplastic and potentially pre-neoplastic changes in the upper respiratory tract of rats and mice. Environ. Health Perspect. 85: 291-304.
3.
Brown MG and Moss OR (1981). An inhalation exposure chamber designed for animal handling. Lab. Anim. Sci. 31: 717-720.
4.
Clayton GD and Clayton FE (eds) (1981). Patty's Industrial Hygiene and Toxicology, Vol. 2A, 3rd ed. John Wiley & Sons, New York, pp. 2197-2200.
5.
Dawes JDK (1952). The course of the nasal air-streams. J. Laryngol. Otol. 66: 583-593.
6.
Feron VJ, Woutersen RA, and Spit BJ (1986). Pathology of chronic nasal responses including cancer. In: Toxicology of the Nasal Passages, CS Barrow (ed). Hemisphere Publishing , Washington, DC, pp. 67-89.
7.
Fregert S. and Rorsman H. (1964). Allergens in epoxy resins. Acta Allergol. 19: 296-299.
8.
Gagnaire F., Zissn D., Bonnet P., and DeCeaurriz J. (1987). Nasal and pulmonary toxicity of allyl glycidyl ether in mice. Toxicol. Lett. 39: 139-145.
9.
Gaskell BA (1990). Nonneoplastic changes in the olfactory epithelium-Experimental studies. Environ. Health Perspect. 85: 275-289.
10.
Harkema JR (1990). Comparative pathology of the nasal mucosa in laboratory animals exposed to inhaled irritants. Environ. Health Perspect . 85: 231-238.
11.
Haseman JK , Arnold J., and Eustis SL (1990). Tumor incidences in Fischer 344 rats: NTP historical data. In: Pathology of the Fischer Rat, GA Boorman, SL Eustis , MR Elwell, CA Montgomery , and WF MacKenzie (eds). Academic Press, San Diego, pp. 555-564.
12.
Haseman JK, Huff J., Rao GN, Arnold J., Boorman GA, and McConnell EE (1985). Neoplasms observed in untreated and corn oil gavage control groups of F344/N rats and (C57BL/6N×C3H/HeN) F, (B6C3F1) mice. J. Natl. Cancer Inst. 75: 975-984.
13.
Hine CH, Kodama JK, Wellington JS, Dunlap MK, and Anderson HH (1956). The toxicology of glycidyl and some glycidyl ethers . AMA Arch. Ind. Health14: 250-264.
14.
Hsu SM, Raine L., and Fanger H. (1981). Use of avidin-biotin-peroxidase complex (ABC) in immunoperoxidase techniques: A comparison between ABC and unlabeled antibody (PAP) procedures. J. Histochem. Cytochem. 29: 577-580.
15.
Institute of Laboratory Animal Resources (1978). Guide for the Care and Use of Laboratory Animals . NIH Publication No. 78-23, National Institutes of Health, Research Triangle Park, North Carolina.
16.
Jiang XZ, Buckley LA, and Morgan KT (1983). Pathology of toxic responses to the RD50 concentration of chlorine gas in the nasal passages of rats and mice. Toxicol. Appl. Pharmacol. 71: 225-236.
17.
Jiang XZ, Morgan KT, and Beauchamp RO (1986). Histopathology of acute and subacute nasal toxicity . In: Toxicology of the Nasal Passages, CS Barrow (ed). Hemisphere Publishing , Washington, DC, pp. 51-66.
18.
Kerns WD (1985). Polypoid adenoma, nasal mucosa, rat. In: Monographs of Pathology of Laboratory Animals. Respiratory System , TC Jones, U Mohr , and RD Hunt (eds). Springer-Verlag, New York, pp. 41-47.
19.
Kerns WD (1985). Squamous cell carcinoma, nasal mucosa, rat. In: Monographs of Pathology of Laboratory Animals. Respiratory System , TC Jones, U Mohr, and RD Hunt (eds). Springer-Verlag, New York, pp. 54-61.
20.
Kerns WD, Pavkov KL, Donofrio DJ, Gralla EJ, and Swenberg JA (1983). Carcinogenicity of formaldehyde in rats and mice after long-term inhalation exposure. Cancer Res. 43: 4382-4392.
21.
Lee KP, Schneider PW, and Trochimowicz HJ (1983). Morphologic expression of glandular differentiation in the epidermoid nasal carcinomas induced by phenylglycidyl ether inhalation . Am. J. Pathol. 111: 140-148.
22.
Monticello TM, Morgan KT, and Uraih LC (1990). Nonneoplastic nasal lesions in rats and mice. Environ. Health Perspect. 85: 249-274.
23.
Morgan KT, Kimbell JS, Monticello TM, Patra AL, and Fleishman A. (1991). Studies of inspiratory airflow patterns in the nasal passages of the F344 rat and Rhesus monkey using nasal molds: Relevance to formaldehyde toxicity. Toxicol. Appl. Pharmacol. 110: 223-240.
24.
Moss OR (1980). A chamber providing uniform concentration of particulates for exposure of animals on tiers separated by catch pans. In: Workshop on Inhalation Chamber Technology, RT Drew (ed). BNL-51318, Brookhaven National Laboratory, Associated Universities, Upton, New York.
25.
Moss OR, Decker JR, and Cannon WC (1982). Aerosol mixing in an animal exposure chamber having three levels of caging with excreta pans. Am. Ind. Hyg. Assoc. J. 43: 244-249.
26.
National Institute for Occupational Safety and Health (1978). Criteria for a Recommended Standard. Occupational Exposure to Glycidyl Ethers. Hew Publication #78-166, US Department of Health, Education and Welfare, PHS, CDC , Washington, DC.
27.
National Toxicology Program ( 1990). Toxicology and Carcinogenesis Studies of Allyl Glycidyl Ether (CAS No. 106-92-3) in Osborne-Mendel rats and B6C3F1 Mice (Inhalation Studies). Technical Report No. 376, Public Health Service, National Institutes of Health, NIH Publication No. 90-2831, Research Triangle Park, North Carolina.
28.
Pour P., Krueger FW, Althoff J., and Mohr U. (1975). Effect of beta-oxidized nitrosamines on Syrian hamsters. III. 2,2'-Dihydroxy di-n-propylnitrosamine. J. Natl. Cancer Inst.54: 141.
29.
Pour P., Stanton MF, Kuschner M., Laskin S., and Shabad LM (1976). Tumors of the respiratory tract. In: Pathology of Tumors in Laboratory Animals, Vol. 1, Tumors of the Rat, Part 2, VS Turosov (ed). IARC, Lyon, pp. 1-40.
30.
Proctor DF and Chang JCF (1983). Comparative anatomy and physiology of the nasal cavity. In: Nasal Tumors in Animals and Man, Vol. 1, Anatomy, Physiology, and Epidemiology, G Reznik and SF Stinson (eds). CRC Press , Boca Raton, Florida .
31.
Renne RA, Giddens WE, Boorman GA, Kovatch R., Haseman JE, and Clarke WJ (1986). Nasal cavity neoplasia in F344/N rats and (C57BL/6 x C3H)F1 mice inhaling propylene oxide for up to two years. J. Natl Cancer Inst. 77: 573-582.
32.
Reznik G., Reznik-Schüller HM, Hayden DW, Russfield A., and Murthy ASK (1981). Morphology of nasal cavity neoplasms in F344 rats after chronic feeding of p-cresidine, an intermediate of dyes and pigments . Anticancer Res. 1: 279-286.
33.
Reznik-Schüller HM (1983). Nitrosamine-induced nasal cavity carcinogenesis. In: Nasal Tumors in Animals and Man, Vol. 3, Experimental Nasal Carcinogenesis, G Reznik and S Stinson (eds). CRC Press, Boca Raton, Florida, pp. 48-77.
34.
Reznik-Schüller HM (1983). Pathogenesis of tumors induced with N-nitrosomethylpiperazine in the olfactory region of the rat nasal cavity. J. Natl. Cancer Inst. 71: 165-172.
35.
Squire RA, Goodman DG, Valerio MG, Fredrickson TN, Strandberg JD, Levitt MH, Lingeman CH, Harshbarger JC, and Dawe CJ (1978). Tumors. In: Pathology of Laboratory Animals, Vol. 2, K Bernirschke, FM Garner, and TC Jones (eds). Springer-Verlag, New York, pp. 1052-1283.
36.
Stein HP, Leidel NA, and Lane JM (1979). Glycidyl ethers. Am. Ind. Hyg. Assoc. J. 40: A36-A48.
37.
Stinson SF and Reznik-Schüller HM (1985). Neoplasms, mucosa, ethmoid turbinates, rat. In: Monographs of Pathology of Laboratory Animals. Respiratory System, TC Jones , U Mohr, and RD Hunt (eds). Springer-Verlag, New York, pp. 47-54.
38.
Swenberg JA , Kerns WD, Mitchell RI, Gralla EJ, and Pavkov KL (1980). Induction of squamous cell carcinomas of the rat nasal cavity by inhalation exposure to formaldehyde vapor. Cancer Res. 40: 3398-3402.
39.
Uraih LC and Maronpot RR (1990). Normal histology of the nasal cavity and application of special techniques. Environ. Health Perspect. 85: 187-208.
40.
US Environmental Protection Agency (1982). Toxic Substance Control Act 8(a); Preliminary Assessment Information, Final rule. Fed. Reg. 47: 26992, 1983.
41.
Wade MJ, Moyer JW, and Hine GH (1979). Mutagenic action of a series of epoxides. Mutat. Res.66: 367-371.
42.
Weisburger JH and Williams GM (1975). Metabolism of chemical carcinogens. In: Cancer-A Comprehensive Treatise, Vol. 1, FF Becker (ed). Plenum Press, New York, pp. 241-334.
