Neurodevelopmental effects of decabromodiphenyl ether (BDE-209) and implications for the reference dose.

On June 30, 2008, the US EPA's IRIS updated their toxicological review on the 2,2',4,4',5,5',6,6'-decabromodiphenyl ether congener and published a revised oral RfD of 0.007mg/kg day based on a NOAEL for neurobehavioral effects of 2.22mg/kg day, as reported by Viberg, H. et al., 2003b. Neurobehavioral derangements in adult mice receiving decabrominated diphenyl ether (PBDE 209) during a defined period of neonatal brain development. Toxicol. Sci. 76, 112-120 (Comment in: Toxicol. Sci. (2004) 2079, 2205-2206, author reply 2207-2208, Comment in: Toxicol. Sci. (2004) 2081, 2528-2529)], and a total uncertainty factor of 300. To evaluate IRIS' updated RfD, we conducted a weight-of-evidence analysis of developmental neurobehavioral effects. The evidence consists of four studies from two laboratories [Viberg et al., 2003b; Viberg, H. et al., 2007. Changes in spontaneous behaviour and altered response to nicotine in the adult rat, after neonatal exposure to the brominated flame retardant, decabrominated diphenyl ether (PBDE 209), Neurotoxicology 28, 136-142; Johansson, N. et al., 2008. Neonatal exposure to decabrominated diphenyl ether (PBDE 209) causes dose-response changes in spontaneous behaviour and cholinergic susceptibility in adult mice. Neurotoxicology; Rice, D.C. et al., 2007. Developmental delays and locomotor activity in the C57BL6/J mouse following neonatal exposure to the fully brominated PBDE, decabromodiphenyl ether, Neurotoxicol. Teratol. 29, 511-520]. The reported effects from these laboratories were in opposite directions - Rice et al. (2007) found mice treated with 20mg/kg day BDE-209 initially had higher activity and an increased habituation, while the Viberg group reported mice and rats treated with >or=20mg/kg BDE-209 (Viberg et al., 2003b, 2007) or mice treated with 2mg/kg BDE-209 (Johansson et al., 2008) had lower initial activity and decreased habituation (although inappropriate statistical methods may have affected results). There was also an overall lack of effects noted in the Functional Observational Battery conducted by Rice et al. (2007). Thus, the Viberg et al. (2003b) study, even in conjunction with other studies, is not suitable for establishing an RfD for BDE-209 or the commercial decabromodiphenyl ether product.