Evaluation of the subchronic and reproductive effects of a series of chlorinated propanes in the rat. I. Toxicity of 1,2,3-trichloropropane.
Repeated inhalation exposure and 1-generation reproduction studies have been conducted in the rat to address the adequacy of the 10 ppm occupational exposure limit established for 1,2,3-trichloropropane (TriCP). Groups of 5 rats per sex were exposed for 6 h/d, 5 d/wk up to 4 wk to target TriCP concentrations of 0-900 ppm. Nine of 10 rats died after a single exposure at 900 ppm. Additional deaths were seen in the 300 (1 death) and 600 (3 deaths) ppm test groups. Mean body weights for all TriCP-treated groups were lower than control values. Liver weights were increased in animals of both sexes at 600 ppm and lower. For females ovary weights for the 300 and 600 ppm groups and spleen weights for the 300 ppm group were lower than those of controls. Males exhibited decreased testes weights only at the 600 ppm TriCP level (not evaluated at 900 ppm). Results of a 13-wk exposure, 6 h/d, 5 d/wk of 15 rats/sex.group to TriCP target vapor concentrations of 5, 15, or 50 ppm also resulted in liver weight increases at all test levels. Histopathologic examination showed hepatocellular hypertrophy in male rats at all TriCP levels. Other microscopic findings related to treatment in rats exposed to 15 ppm and to 5 ppm TriCP included lung hyperplasia (both sexes) and splenic extramedullary hematopoiesis (females only) and parallel observed organ weight increases. No treatment-related deaths were observed in this study, nor were there apparent effects on the hematology or clinical chemistries. Group mean body weights at 50 ppm (both sexes) and 15 ppm (females only) TriCP were reduced when compared to controls. In a 13-wk follow-up study in rats at 0, 0.5, and 1.5 ppm TriCP, no gross or microscopic findings related to treatment were found. Groups of 10 male and 20 female rats were exposed 6 h/d, 5 d/wk to 0, 5, or 15 ppm TriCP vapor during premating and mating. Females also were exposed during gestation. Low mating performance was observed in all groups of female rats including the controls, although fewer females in the 15-ppm group mated than in other study groups. Mating and fertility indices of male rats in both treated and control groups were generally low. All measured progeny indices appeared unaffected by treatment. A follow-up study of the same design was conducted at levels of 0, 0.5, and 1.5 ppm TriCP.(ABSTRACT TRUNCATED AT 250 WORDS)
Johannsen
F R
FR
Department of Medicine and Health Sciences, Monsanto Company, St. Louis, Missouri 63167.
Levinskas
G J
GJ
Rusch
G M
GM
Terrill
J B
JB
Schroeder
R E
RE
D000818:Animals; D001835:Body Weight / Q000187:drug effects; D004305:Dose-Response Relationship, Drug; D005260:Female; D005500:Follow-Up Studies; D005835:Genitalia / Q000033:anatomy & histology / Q000187:drug effects; D007668:Kidney / Q000033:anatomy & histology / Q000187:drug effects; D008098:Litter Size / Q000187:drug effects; D008099:Liver / Q000033:anatomy & histology / Q000187:drug effects; D008297:Male; D010865:Pilot Projects; D011407:Propane / Q000008:administration & dosage / Q000031:analogs & derivatives* / Q000633:toxicity; D051381:Rats; D012098:Reproduction / Q000187:drug effects*; D012137:Respiratory System / Q000187:drug effects* / Q000473:pathology; D013997:Time Factors
C009536:1,2,3-trichloropropane; D011407:Propane