Rodent carcinogenicity bioassay

Purdy R. A mechanism-mediated model for carcinogenicity model content and prediction of the outcome of rodent carcinogenicity bioassays currently being conducted on 25 organic chemicals. Environ Health Perspect 1996 104 1085-94. 

DAVIES T s and monro a (1994) The rodent carcinogenicity bioassay produces a similar frequency of tumor increases and decreases implications for risk assessment . Regulatory Toxicol Pharmacol. 20 281-301. 

Tennant, R.W. and Spalding, J., Predictions for the outcome of rodent carcinogenicity bioassays identification of trans-species carcinogens and noncarcinogens, Environ. Health Perspect., 104 (Suppl. 5), 1095-1100,... 

Boorman GA, Maronpot RR, Eustis SL. Rodent carcinogenicity bioassay past, present and future. Toxicol Pathol 1994 22(2) 105-11. 

Storer RD, French JE, Haseman J, Hajian G, LeGrand EK, Long GG, Mixon LA, Ochoa L, Sagartz J, Soper KA (2001) p53+/- hemizygous knockout mouse overview of available data. Toxicologic Pathology 29 30-50 Tennant RW(1993) Stratification of rodent carcinogenicity bioassay results to reflect relative human hazard. Mutation Research 286 111-118... 

King, R.D. and Srinivasan, A. (1996). Prediction of Rodent Carcinogenicity Bioassays from Molecular Structure Using Inductive Logic Programming. Environ.Health Persp., 104,1031-1040. 

King RD, Srinivasan A. Prediction of rodent carcinogenicity bioassays from molecular structure using inductive logic programming. Environ Health Perspect 1996 104 1031-40. 

Shlyakhter, A. I., Goodman, G., and Wilson, R. (1992). Monte Carlo simulation of rodent carcinogenicity bioassays. Risk Anal 12, 73-82. 

JP-8 has not been tested in lifetime rodent carcinogenicity bioassays by the inhalation route. It has been tested in rats and mice of both sexes in studies with 90-day exposures and then observation until the age of 24 mo (Mattie et al. 1991, discussed in NRC 1996). F344 rats and C57BL/6 mice were exposed continuously to JP-8 vapor at 0, 500, or 1,000 mg/m3 for 90 days and then allowed to recover until the age of 24 mo. No treatment-related tumors were seen in rats or mice of either sex. Male rats exhibited treatment-related accumulation of hyaline droplets in the proximal convoluted tubular epithelium of the kidney, which was consistent with male alpha 2u-globulin nephropathy. The short duration of exposure to JP-8 in the studies severely limits their usefulness for purposes of carcinogenicity assessment. 

Other jet fuels have not been tested in lifetime rodent carcinogenicity bioassays by the inhalation route, but 12-mo exposure studies of JP-4 and 90-day continuous-exposure studies of JP-5 discussed in the 1996 National Research Council report are briefly described here. Bruner etal. (1993) exposed groups of 100 F344 rats of each gender and 100 C57B1/6 mice of each gender to JP-4 at 1,000 or 5,000 mg/m3 for 6 hr/day, 5 days/wk for 12 mo animals were allowed to live unexposed for an additional 12 mo. In rats, an increase in renal-cell tumors (three renal-cell adenomas, one carcinoma, and one sar-... 

JP-8 has not been tested in lifetime rodent carcinogenicity bioassays by the oral route. A 90-day gavage study in male Sprague-Dawley rats, although inadequate for purposes of carcinogenicity assessment, reported that JP-8 treatment was associated with the development of alpha 2u-globulin nephropathy (Mattie et al. 1995). 

Rossman TG, Molina M, Meyer L, Boon P, Klein CB, Wang Z, Li F, Lin WC, Kinney PL (1991) Performance of 133 compounds in the lambda induction endpoint of the Microscreen assay and a comparison with Salmonella mutagenicity and rodent carcinogenicity bioassays. Mutat Res 260 349-367 Roy NK, Rossman TG (1992) Mutagenesis and comutagenesis by lead compounds. Mutat Res 298 97-103... 

Like isometamidium, it has not been tested in rodent carcinogenicity bioassays. It has been tested in teratogenicity studies in rats and although it produced maternotoxicity and embryotoxicity, there was no evidence of teratogenic effects." " ... 

---