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Short description of key information on bioaccumulation potential result: 
Several in vivo absorption, distribution, metabolism, elimination (ADME) studies, as well as one comparative in vitro metabolism study have been conducted with different isomers of divinylbenzene. In addition, read-across data with ethylbenzene and styrene are available.

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Additional information

Several in vivo absorption, distribution, metabolism, elimination (ADME) studies, as well as one comparative in vitro metabolism study have been conducted with different isomers of divinylbenzene. In addition, several read-across studies with ethylbenzene and styrene are available. Divinylbenzene (diethenylbenzene, DVB) consists primarily of two isomers: 1,4- and 1,3- also defined as pDVB and mDVB, respectively. The 1,2- (oDVB) isomer is a minor component in commercial DVB. These DVB isomers are structurally related to styrene (vinylbenzene) and ethylbenzene. 

Discussion on bioaccumulation potential result:

Several in vivo absorption, distribution, metabolism, elimination (ADME) studies, as well as one comparative in vitro metabolism study have been conducted with DVB. Linhart et al. identified numerous metabolites arising from oxidation and subsequent conjugation of one of the vinyl moieties of 1,4-DVB (Linhart, Hanus et al. 1989; Linhart and Novak 1990). These metabolites, except for one unique aldehyde metabolite, were all vinyl analogs of known styrene metabolites. Additional studies with the 1,3- and 1,2-DVB isomers also afforded similar results (Jeffcoat A.R. 1990; Linhart, Mitera et al. 1992; Linhart, Vosmanska et al. 1992; Linhart, Weidenhoffer et al. 1996). An in vitro study comparing the relative rates and routes of metabolism of 1,3-DVB was conducted (Jeffcoat A.R. 1999). Radiolabeled 1,3-DVB was incubated with liver tissue slices from rat, mouse and human donors. Metabolites were characterized by HPLC analysis at 1, 2.25 and 5 hr. Three common metabolites were identified in incubates from all three species. The least polar metabolite was identified as the 1,2-diol of 1,3-DVB, also identifed as an in vivo metabolite in rat urine, and consistent with the analogous 1,2-glycol metabolite of styrene. The remaining two metabolites were unidentified, but the most polar one was characterized as a possible sulfate conjugate. The rate, or amount of metabolism was fairly comparable between species, with 12.4, 23.2 and 25.3% of the substrate metabolized within 5 hr in mouse, rat and human tissue, respectively. These studies with DVB represent primarily hepatic metabolism. No reports of non-hepatic ADME experiments have been found. However, related studies with styrene and ethylbenzene have been conducted to evaluate the metabolic fate and enzyme systems responsible for major and reactive metabolite formation of these two compounds in lung tissue. Data on the metabolic fate of 4-hydroxystyrene (4-vinylphenol; 4-VP) in liver tissue of mouse as well as lung tissue of mouse, rat and human donors was has been presented in the EU risk assessment report for styrene and was published by Cruzan et al 2009. Isomers of the reactive, side-chain epoxide metabolite of 4-VP (4-VPO), trapped as glutathione (GSH) conjugates, were identifed and quantitated. Microsomes of mouse lung were approximately two-fold more active in formation of 4-VPO than rat. 4-VPO formation in rat lung microsomes was also 2-5 fold higher than human. Co-incubation with specific enzyme inhibitors showed that 4-VPO arose primarily via CYP-2F2 oxidation, with lesser amounts arising from the CYP-2E1 isoform. Data on ethylbenzene (EB) metabolism has also been presented in the EU risk assessment report for ethylbenzene and was published by Cruzan et al 2009

. The major metabolites arising from incubation with liver or lung microsomes of mouse, rat and human donors were determined. EB was preferentially metabolized to 1-phenylethanol by liver microsomes, with conversion in the order of mouse >> rat ~ human. Both mouse and rat lung microsomes were more active in metabolizing EB than liver microsomes. Similar to liver, the major metabolite of EB was 1-phenylethanol in both mouse and rat lung microsomes, with mouse tissue having higher activity. A subsequent study was then conducted, in which dihydroxylated metabolites of EB were quantitated, as GSH adducts, in microsomal incubations of liver or lung tissue from mouse, rat and human donors. As with styrene, the formation rate of GSH-trapped reactive metabolites in lung microsomes was found to be mouse > rat >> human. Although CYP isoforms responsible for this reactive metabolite formation were not determined, the authors postulate that CYP-2F2 was primarily responsible for ring-hydroxylation of EB and CYP-2E1 for side-chain oxidation. In conclusion, studies have been conducted to show that the major routes of DVB hepatic metabolism are comparable to styrene, both in vivo and in vitro. Based on these similarities in hepatic metabolism, it is expected that the routes of non-hepatic metabolism of DVB would be also consistent with those observed for styrene as well as ethylbenzene. It would also be expected that rates of non-hepatic metabolism of DVB isomers to minor, reactive metabolites, capable of covalent binding to tissue macromolecules, would follow the order of: mouse > rat > human.