Chronic toxicology and carcinogenesis studies of Telone II by gavage in Fischer-344 rats and B6C3F1 mice.
Telone II (technical grade, 1,3-dichloropropene), a soil fumigant, was evaluated in chronic toxicology/carcinogenicity studies using Fischer-344 (F344) rats and B6C3F1 mice of both sexes. Doses administered were 0, 25, or 50 mg/kg to rats and 0, 50, or 100 mg/kg to mice. Telone II was given in corn oil by gavage 3 times per week for 104 wk. Ancillary studies were conducted to determine time-related effects, in which dose groups containing 5 male and 5 females rats were killed after receiving Telone II for 9, 16, 21, 24, or 27 mo. The primary organs affected were the forestomach (rats and mice), urinary bladder (mice), lung (mice), and liver (rats). Compound-related non-neoplastic lesions included basal-cell or epithelial hyperplasia of the forestomach (rats and mice), epithelial hyperplasia of the urinary bladder (mice), and hydronephrosis (mice). Neoplastic lesions associated with administration of Telone II included squamous-cell papillomas of the forestomach (male and female rats, female mice), squamous-cell carcinomas of the forestomach (Male rats, female mice), transitional-cell carcinomas of the urinary bladder (female mice), alveolar/bronchiolar adenomas (female mice), and neoplastic nodules of the liver (male rats). Although cis- and trans-1,3-dichloropropene are the principal components of Telone II, the presence of 1% epichlorohydrin, a direct-acting mutagen and carcinogen added as stabilizer, may have influenced the development of forestomach lesions. The results of the ancillary studies supported the findings of the carcinogenesis studies and demonstrated the time-dependent development of lesions in the forestomach (basal-cell hyperplasia and squamous-cell papilloma). Under the conditions of these gavage studies, Telone II was shown to be carcinogenic in male and female F344 rats and female B6C3F1 mice. Although the study in male B6C3F1 mice was considered inadequate because of the low survival resulting from suppurative inflammation of the heart (myocarditis) in the control group, there was some indication of Telone II-related increases of transitional-cell carcinomas of the urinary bladder, squamous-cell papillomas of the forestomach, and alveolar/bronchiolar adenomas and carcinomas of the lung.
Yang
R S
RS
Huff
J E
JE
Boorman
G A
GA
Haseman
J K
JK
Kornreich
M
M
Stookey
J L
JL
D000498:Allyl Compounds; D000818:Animals; D001835:Body Weight / Q000187:drug effects; D002273:Carcinogens; D004811:Epichlorohydrin; D005260:Female; D006843:Hydrocarbons, Chlorinated; D007680:Kidney Neoplasms / Q000139:chemically induced; D008113:Liver Neoplasms / Q000139:chemically induced; D008175:Lung Neoplasms / Q000139:chemically induced; D008297:Male; D051379:Mice; D051381:Rats; D011916:Rats, Inbred F344; D013274:Stomach Neoplasms / Q000139:chemically induced; D013329:Structure-Activity Relationship; D013997:Time Factors; D001749:Urinary Bladder Neoplasms / Q000139:chemically induced
D000498:Allyl Compounds; D002273:Carcinogens; D006843:Hydrocarbons, Chlorinated; D004811:Epichlorohydrin; C023891:1,3-dichloro-1-propene