CAS Number 75-65-0
API Publication 4743 October 2005
Tertiary Butyl Alcohol (TBA) has many industrial and chemical uses (NTP 1995). TBA is used in the manufacture of perfumes and cosmetics, as an additive in gasoline to improve the oxygen content, and is a metabolite of the fuel oxygenate, methyl-tert-butylether (MTBE) (NTP 1995).
The National Toxicology Program (NTP 1995) has conducted a two-year drinking water bioassay with TBA in male and female rats and mice. Results of these studies showed increases in the incidence of renal tubule hyperplasia and renal tubule adenomas in male rats; however, the incidence of renal tubule hyperplasia or adenoma was not significantly increased in female rats. In male and female mice, incidence of thyroid follicular cell hyperplasia was increased, and the incidence of thyroid follicular cell adenoma was increased in female mice. Based on these findings, the NTP (1995) concluded there was some evidence of carcinogenic activity in male rats and female mice, there was equivocal evidence of carcinogenicity in male mice and no evidence of carcinogenicity in female rats.
The purpose of this investigation was to conduct a quantitative risk assessment according to USEPA guidelines (USEPA 2005) in which data on the mode of action by which TBA induced renal tumors in rats and thyroid tumors in mice was considered. When data from animal studies, such as the TBA bioassays, are extrapolated to humans to provide estimates of lifetime cancer risks, then potential differences in pharmacokinetics (metabolism) and pharmacodynamics (sensitivity and mode of action) between the animal species and humans is considered in the estimation of human equivalent doses and in extrapolation from high doses typically used in the animal bioassays to low doses to which humans may be potentially exposed. Pharmacokinetic, toxicity, and mode of action data for TBA were reviewed and data selected for quantitative dose-response modeling.
Key Results: The RfD estimated using the non-linear approaches to low dose extrapolation was 220 μg/kg/day. Assuming an average body weight of 70 kg and an average daily water consumption of 2 liters, the average drinking water concentration for TBA associated with the RfD would be approximately 8 mg/L.