API PUBL 4743:2005 pdf download.Hazard Narrative for Tertiary-Butyl Alcohol (TBA)
Tertiary Butyl Alcohol (TBA) has multiple industrial and chemical uses. 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 (1995) has conducted a 2-year drinking water bioassay with TBA in rats and mice. Results of this study showed increases in the incidence of renal tubule hyperplasia and renal 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, the incidence of thyroid follicular cell hyperplasia was increased, and in female mice, the incidence of thyroid follicular cell adenoma was also increased. Based on these findings, the NTP (1995) concluded that there was: 1) some evidence of carcinogenic activity in male rats and female mice; 2) equivocal evidence of carcinogenicity in male mice; and 3) no evidence of carcinogenicity in female rats. The results of genotoxicity tests (Salmonella reverse mutation assay, mouse lymphoma cell mutation test, sister chromatid exchange assay, chromosomal aberration assay in Chinese hamster ovary (CHO) cells and micronucleus assay) conducted by NTP (1995) with TBA were negative.
The California Office of Environmental Health Hazard Assessment (OEHHA) (CALEPA 1999) developed an interim drinking water level of 12 µg/L based on the incidence of kidney tumors reported in male rats in the NTP (1995) study. In this calculation, OEHHA estimated a cancer slope factor using linear extrapolation and body weight 3/4 scaling to extrapolate to the human equivalent concentration at a 1 x 10 -6 extra lifetime cancer risk level. Default assumptions were used for body weight (70 kg) and water consumption (2 L/day). In the period since OEHHA developed their interim water level, additional data has been published that suggests the kidney tumors observed in male rats form as a result of TBA binding to α2u- globulin (Borghoff et al. 2001; Williams and Borghoff 2001), the protein that also plays a key role in the development of protein droplet (α2u) nephropathy in male rats. Protein droplet nephropathy occurs when α2u-globulin, a protein synthesized in the liver of male rats, accumulates in tubular cells in the kidney (CIIT 1996).