||Two Generation Reproduction Study in Rats with Cover Letter and Summary.
||International Research and Development Corp., Mattawan, MI.; Monsanto Co., Dayton, OH.; Environmental Protection Agency, Washington, DC. Office of Toxic Substances.
Health effects ;
Hexamethylene Diamine ;
Reproduction/fertility Effects ;
Combined Teratogenicity/reproductive Effects ;
Toxic substances ;
Laboratory animals ;
CAS No 124-09-4
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Hexamethylene Diamine (78.02%, CAS No. 124-09-4) was evaluated in Charles River COBS CD rats (26/sex/dosage group) administered measured dietary doses 0, 50, 150 and 500 mg/kg bodyweight at 78.2% in two successive generations (F0 and F1). A control group received the basal laboratory diet with an ethanol (solvent) concentration equivalent to that in the high-dose diet. F0 and F1 were mated once to produce F1 and F2 progeny respectively. Treatment was associated with reduced bodyweight gains in high- and mid-dose F0 and F1 males and in high-dose F1 females. Food consumption was reduced in F0 and F1 females. High- dose F0 and F1 females demonstrated significantly lower weight gains during gestational periods. Fertility indices of dams and sires and the testes weights of males without litters did not reveal an adverse effect of treatment; Copulation, gestation and weaning intervals and dynamics of dams were comparable to controls at all treatment levels in both generations. A 500 mg/kg high dose was associated with significant (p<0.05) reductions in both F1 and F2 progeny numbers as well as pup weights on lactation days 14 and 21. Smaller viable litter sizes did not correlate with increased numbers of dead pups. Survival through weaning was comparable in the progeny of control and all treated rats of both generations. Antemortem pathology on terminal necropsy of all high-dose and control parents revealed no gross lesions and no microscopic changes related to treatment. A dietary 'no effect' level was 150 mg/kg day and researchers concluded that fetal developmental toxicity was produced only at levels associated with significant maternal toxicity.