Development of toxicity values and exposure estimates for tetrabromobisphenol A: application in a margin of exposure assessment.

Tetrabromobisphenol A (TBBPA) is used in a diverse array of products to improve fire safety. The National Toxicology Program (NTP) recently completed a 2-year bioassay for TBBPA. The objective of the present study was to develop a cancer-based and a non-cancer based toxicity value and to compare such to appropriate estimates of human exposure. Data from the NTP 2-year and 13-week studies were selected to develop candidate toxicity values. Benchmark dose modeling and subsequent evaluation of candidate values resulted in selection of an oral reference dose (RfD) of 0.6 mg kg(-1) day(-1) based on uterine hyperplasia in rats and an oral cancer slope factor (OSF) of 0.00315 per mg kg(-1) day(-1) based on an increased incidence of uterine tumors in rats. Lifetime average daily dose (LADD) estimates ranged from 2.2 E(-7) to 3.9 E(-6) mg kg(-1) day(-1) based on age-adjusted exposures to TBBPA via breast milk consumption, dietary intake, soil/dust ingestion and drinking water ingestion in infants, young children, older children and adults. Average daily dose (ADD) estimates ranged from 3.2 E (-7) to 8.4 E(-5) mg kg(-1) day(-1). Resulting margin of exposure (MOE) values were > 800 000 for non-cancer endpoints and > 32,000,000 for cancer-based endpoints. These data collectively indicate a low level of health concern associated with exposures to TBBPA based on current data. It is anticipated that the exposure estimates, along with the toxicity values described within, should be informative for understanding human health hazards associated with TBBPA.