home edit2 whole TSD November 2002 PDF format - OEHHA

(technical grade; 98% pure) by gavage daily 5 days/week for 78 weeks (NCI, 1977). Exposure groups
for mice were initially 172 or 199 mg/kg body weight for males and 129 or 258 mg/kg for females.
Exposure groups for rats were initially 70 or 140 mg/kg body weight for males and 55 or 110 mg/kg for
females. Due to toxicity, the initial doses were reduced as the study progressed. Final time-weighted
average doses for the 78 week dosing period were 172 and 199 mg/kg/day for male mice; 129 and
258 mg/kg/day for female mice; 57 and 77 mg/kg/day for male rats and 55 and 73 mg/kg/day for
female rats. Mice and rats were observed for an additional 13 and 30-33 weeks after the end of the
dosing period, respectively. Excessive mortality (50% after 14-38 weeks) was noted in the high-dose
rats (both sexes) and male mice. The number of surviving animals in all low-dose groups and high-dose
female mice were adequate to evaluate late-developing tumor risk.
No significant increases in tumor incidence were noted in rats. Proliferative nonneoplastic lesions of the
stomach were noted in mice of both sexes. In male mice, squamous cell carcinomas of the stomach
were found in 0/29 controls (17 vehicle and 12 untreated), 2/36 low-dose animals, and 0/10 high-dose
animals (only 10 survived past 52 weeks). In female mice, squamous cell papillomas and carcinomas of
the forestomach were found in 0/39 controls (19 vehicle and 20 untreated), 3/47 low-dose animals (2
carcinomas) and 3/45 high-dose animals (no carcinomas). Tumor incidence was not significantly
increased compared to controls for either dose group of either sex. However, the combined tumor
incidence in females and the carcinoma incidence in low-dose males was significantly increased at both
doses compared to historical vehicle controls (1/180 female mice with squamous cell papilloma or
carcinoma of the forestomach; 1/180 male mice with squamous cell carcinoma of the forestomach).
The authors considered the findings to be strongly suggestive of carcinogenicity in mice because of the
rarity of the tumor type involved and because the proliferative lesions demonstrated could be
preneoplastic.
Female Ha:ICR Swiss mice (30/group) were exposed to allyl chloride by topical application (31 or 94
mg allyl chloride in 0.2 ml acetone) 3 times/week for 63-85 weeks (Van Duuren et al., 1979). Skin
tumors were not induced. Lung and stomach papillomas were induced in both the low dose group (3
stomach, 14 lung papillomas) and the high dose group (3 stomach, 12 lung papillomas, 1 glandular
stomach adenocarcinoma). Tumor incidences were not significantly increased compared to vehicle or
untreated controls (control incidence not reported).
Female Ha:ICR Swiss mice (30/group) received a single dermal application of 94 mg technical grade
allyl chloride in 0.2 ml acetone followed 2 weeks later by dermal applications of 5 µg 12-Otetradecanoylphorbol
13-acetate (TPA) 3 times/week for life (median survival 61-82 weeks) (Van
Duuren et al., 1979). Skin papilloma incidence was significantly increased (7/30 treated animals
compared to 6/90 TPA control animals, p < 0.025) and time to tumor was decreased (first tumor in
treated animals at day 197 compared to day 449 in TPA controls) in allyl chloride -treated animals.
Male and female A/St mice (10/group) received intraperitoneal injections of allyl chloride in tricaprylin 3
times/week for 8 weeks; total doses were 1.2, 2.9 and 5.9 g/kg body weight (Theiss et al., 1979).
Animals were killed 24 weeks after exposure initiation. The only pathological endpoint examined was
the induction of lung tumors as determined by gross examination. The average number of
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