SUBCHRONIC TOXICITY STUDIES OF 3-METHYL-1-BUTANOL AND 2-METHYL-1-PROPANOL IN RATS

1 90-day subchronic toxicity studies with 3-methyl-1-butanol (MEB) and 2-methyl-1-propanol (MEP) were performed on rats to evaluate the toxi cological profile of the compounds under conditions of drinking water studies, to identify the potential target organs, and to determine no- observable-adverse-effect-levels (NOAELs) respective of the substances . The test substances were administered to groups of 10 male and 10 fe male Wistar rats in drinking water at concentrations of 0, 1000 p.p.m. (about 80 mg/kg/d), 4000 p.p.m. (about 340 mg/kg/d) and 16 000 p.p.m. (about 1250 and 1450 mg/kg/d of MEB and MEP respectively). 2 16 000 p .p.m. was found to be the maximal concentration for both alcohols appl icable to rats in drinking water. Higher concentrations had an influen ce on palatability and could thus not be tested in drinking water stud ies. 3 At 16 000 p.p.m. MEB a marginal increase in the red blood cell count as well as a slight decrease in the mean corpuscular volume and the mean corpuscular hemoglobin content was observed in males only. Th ese changes are considered to be treatment-related, although the toxic ological significance of these findings is unclear. No other substance -related effects were found on body weight (b.w.), mortality, various parameters of clinical chemistry, organ weights, gross pathology and h istopathology. 4000 p.p.m. MEB did not cause any substance-induced cha nges. Therefore, the NOAEL of MEB was defined as 4000 p.p.m. for male and 16 000 p.p.m. for female rats under conditions of oral application via drinking water. 4 MEP concentrations up to and including 16 000 p .p.m. did not induce any signs of toxicity and were therefore defined as the NOAEL respective of this substance for rats under conditions of drinking water application.