Chronic toxicity and oncogenicity studies of ingested 1, 3-dichloropropene in rats and mice.
Fischer 344 rats and B6C3F1 mice were administered 1, 3-dichloropropene (1,3-D) via their diets for up to 2 years, at dose levels of 0, 2.5, 12.5, or 25 mg 1,3-D/kg body wt/day for rats and 0, 2.5, 25, or 50 mg 1,3-D/kg body wt/day for mice. The test material was stabilized in the feed by microencapsulation in a starch/sucrose matrix (80/20%). Rats given 12.5 or 25 mg/kg/day, and mice given 25 or 50 mg/kg/day, had decreased body weights and body weight gains. There were no effects on survival or clinical pathology parameters for rats or mice. Histopathologic effects attributed to treatment in rats consisted of basal cell hyperplasia of the nonglandular mucosa of the stomach in males and females given 12.5 or 25 mg/kg/day for 12 and 24 months and an increased number of hepatocellular adenomas in males given 12.5 or 25 mg/kg/day and females given 25 mg/kg/day for 24 months. The increase in hepatocellular adenomas was statistically identified by pairwise comparison only in males given 25 mg/kg/day. An increased incidence of eosinophilic foci of altered cells in the liver was also noted in all treated groups of rats at 24 months. The latter observation, however, was considered of equivocal toxicological significance because of the common spontaneous occurrence of liver foci in aged Fischer 344 rats. The only histologic change attributed to treatment in mice was decreased size of hepatocytes in males given 50 mg/kg/day for 12 months. The decreased size of hepatocytes was consistent with decreased cytoplasmic glycogen content and corresponded to decreased liver weights. This effect was not present at 24 months. There was no oncogenic response observed in mice. The low-dose level of 2.5 mg/kg/day was interpreted as the no-observed-adverse-effect level (NOAEL) for systemic chronic toxicity of 1,3-D in the Fischer 344 rat. The no-observed-effect level (NOEL) for chronic systemic toxicity was 2.5 mg/kg/day in the B6C3F1 mouse.
Stebbins
K E
KE
Toxicology & Environmental Research and Consulting, The Dow Chemical Company, 1803 Building, Midland, Michigan, 48674, USA. kstebbins@dow.com
Johnson
K A
KA
Jeffries
T K
TK
Redmond
J M
JM
Haut
K T
KT
Shabrang
S N
SN
Stott
W T
WT
D000236:Adenoma / Q000139:chemically induced / Q000473:pathology; D000284:Administration, Oral; D000498:Allyl Compounds / Q000008:administration & dosage / Q000633:toxicity*; D000818:Animals; D001835:Body Weight / Q000187:drug effects; D015197:Carcinogenicity Tests; D002908:Chronic Disease; D004032:Diet; D004339:Drug Compounding; D005260:Female; D022781:Hepatocytes / Q000187:drug effects / Q000473:pathology; D006843:Hydrocarbons, Chlorinated; D006965:Hyperplasia; D007306:Insecticides / Q000008:administration & dosage / Q000633:toxicity*; D007674:Kidney Diseases / Q000139:chemically induced / Q000473:pathology; D007928:Lethal Dose 50; D008113:Liver Neoplasms / Q000139:chemically induced / Q000473:pathology; D008297:Male; D051379:Mice; D008815:Mice, Inbred Strains; D009374:Neoplasms, Experimental / Q000139:chemically induced / Q000473:pathology; D019055:No-Observed-Adverse-Effect Level; D051381:Rats; D011916:Rats, Inbred F344; D013270:Stomach / Q000187:drug effects / Q000473:pathology
D000498:Allyl Compounds; D006843:Hydrocarbons, Chlorinated; D007306:Insecticides; C023891:1,3-dichloro-1-propene