Initial Submission: Toxicity Studies in Rats with 2-Butanol including Growth, Reproduction, and Teratologic observations with Cover Letter dated 09/24/1992

摘要

A single generation reproduction study in rats has been completed to evaluate the toxicologic potential of 2-butanol administered via the drinking water. A teratologic phase was also incorporated in which the parent dams were rebred (2nd litters) and subjected to Caesarean Section on Day 20 of gestation. The 71 generation animals were reared to maturity, mated to produce one set of litters, then sacrificed for gross and microscopic pathologic evaluation. Hematologic, biochemical, and urinary examinations were conducted terminally on the Fl rats. Secondary butanol was administered at three levels, viz., 0.3, 1.0, and 2.0% of the drinking water during the second generation study (Fy) and the effects compared to those of 2.0%-isopropano1 similarly administered as well as with water controls. The 2.0% level was selected as the highest dose after initial results with the PO rats showed toxicity at a level of 3.0%. All findings with 2-butanol at both 0.3 and 1.0% in the drinking water were negative with respect to signs of toxicity in terms of both growth and reproduction efficiency. However, at 2.0%, both isopropano1 and 2-butano1 caused a significant depression in growth of weanling rats and both caused a depression in the weight of fetuses in utero, with evidence of retarded skeletal maturation. hile the numbers of observations were small, there was some suggestion that isopropanol may be a teratogen for the rat when administered at 2.0% in the drinking water of the pregnant females. Similar data for 2-butanol did not show this finding.