tails). The 925-mg/kg-d dose level was chosen as the LOAEL based on increased liver weight (absolute and relative in both sexes) accompanied by an increased incidence of distinctly abnormal fatty accumulation in the liver and, in males, a small reduction in body weight gain. The 450-mg/kg-d dose level (the mean value for males and females) was selected as the NOAEL because the more subtle changes in liver weight and histology at this dose level are not considered to be adverse effects. An uncertainty factor of 3,000 was applied (10 for extrapolation from rats to humans, 10 for intraspecies variation, 10 for extrapolation from subchronic to chronic duration, and 3 to account for database deficiencies including lack of a two-generation reproductive study and a developmental toxicity study in a second species). Therefore, based on a NOAEL of 450 mg/kg-d and an uncertainty factor of 3,000, an RfD of 0.2 mg/kg-d was calculated for HBCD (see Table 4–4).

Confidence in the critical study (Zeller and Kirsch 1970 is medium. The study included an adequate number of rats of both sexes and investigated a variety of endpoints, but reporting of experimental methods and results was only marginally adequate. Confidence in the database is low because of the lack of availability of other subchronic/chronic studies. Therefore, confidence in the oral RfD is low.

In an 18-mo feeding study of HBCD in mice, Kurokawa et al. (Marcia Hardy, Albermarle Corporation, pers. commun., August 3, 1999) found no