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Key value for chemical safety assessment

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The uptake, distribution, and elimination of the commercial BDE-209 product(s) after oral, intravenous (IV), or intraperitoneal administration in rats have been evaluated in several studies (El Dareer et al., 1987; Mörck et al., 2003; Norris et al., 1973, 1974, 1975; NTP, 1986; Riu et al., 2008; Sandholm et al., 2003; Biesemeier et al. 2010). Certain of these studies followed total 14C-radioactivity or total bromine content via neutron activation analysis. Others used methods based on detection of individual BDE congeners. Absorption and metabolism has also been followed in the dairy cow and the seal (Kierkegaard et al., 2007; Thomas et al., 2005). An in vitro study has also been conducted using hepatic microsomes from a marine mammal (Gebbink et al., 2006). Further, an in vitro dermal absorption study has been conducted (Hughes et al., 2001).

The various studies on the commercial product or noncommercial BDE-209 congener indicate poor oral absorption, and essentially no elimination in the urine with typically greater than 90% of an oral dose eliminated in the feces within 72 h as the parent molecule or bound residues. As expected, gavage administration may result in slightly more uptake than administration via the diet. Removal of bromine atoms from the parent molecule to produce lower BDE congeners, if it occurs, represents only a minor fraction of the dose (<3%). At most, it appears that only 1 or 2 bromine atoms may be removed metabolically either in the liver or by gut bacteria. Blood and tissue levels following oral exposure are routinely very low, and represent only a small fraction of the oral dose. After oral dosing, highest concentrations of the parent molecule are typically found in the liver, and are likely related to the venous blood flow from the digestive tract. Direct elimination into the bile, without prior systemic circulation, of a substantial fraction of the absorbed dose likely accounts for the low blood levels. A low uptake from the gut coupled with direct elimination from the liver to the bile results in only a small fraction of an oral dose reaching the systemic circulation and, ultimately, tissues. Skin absorption is negligible. Accumulation after repeated doses is minimal. Blood levels of nonaBDEs, commonly ascribed as metabolites of BDE-209, are typically <0.5% of that of the parent and are indicative of low absorption and/or minimal formation. The designation of nona- and octaBDEs as BDE-209 metabolites is complicated by their presence in test articles. The above findings are relevant for reference value development because they indicate that comparable ADME properties for BDE-209 exist in different species, which supports the use of allometric scaling for addressing interspecies differences in toxicokinetics. See Hardy et al (2009) Critical Reviews in Toxicology 39(S3):1 -44 for a detailed discussion of the BDE-209 ADME studies.