1,1'-(isopropylidene)bis[3,5-dibromo-4-(2,3-dibromopropoxy)benzene]

Endpoint summary

Description of key information

Short description of key information on bioaccumulation potential result: 
One publication is available: "Absorption, distribution, metabolism, and excretion of intravenously and orally administered tetrabromobisphenol A[2,3-dibromopropyl ether] in male Fischer-344 rats", by Knudsen, G.A., Jacobs, L.M., Kuester, R.K., Sipes, I.G. (Toxicology 237 (2007) 158-167).

Key value for chemical safety assessment

Bioaccumulation potential:

low bioaccumulation potential

Additional information

Studies regarding the absorption, distribution, metabolism, and excretion of TBBA-DBPE were conducted. Male Fischer-344 rats were dosed with TBBA-DBPE (20mg/kg) by oral gavage or IV administration. Following a single oral administration of TBBA-DBPE, elimination of [¹⁴C] equivalents in feces was extensive and rapid (95% by 96 hours). Following repeated daily oral doses for 5 or 10 days, route and rate of elimination was similar to single administration of TBBA-DBPE. After IV administration, fecal excretion of [¹⁴C] equivalents was much slower (27% of dose eliminated by 36h, 71% by 96h). Urinary elimination was minimal (<0.1%) following oral and IV administration. A single peak that co-eluted with the standard of TBBA-DBPE was detected in extracts of whole blood following oral or IV administration. TBBA-DBPE elimination from the blood was slow. Kinetic constants following IV dosing were: t_1/2b: 24.8h; CL_b: 0.1mL/min. Kinetic constants following oral dosing were: t_1/2a: 2.5h:13.9h; CL_{b :4.6mL/min.}

Systemic bioavailability was 2.2%. Liver was the major site of disposition following oral or IV administration. After oral administration, 1% of the dose was eliminated in bile in 24h as metabolites. Inin vitro experiments utilizing hepatocytes or liver microsomal protein, no detectable metabolism of TBBA-DBPE occurred. These data indicate that TBBA-DBPE is poorly absorbed from the gastrointestinal tract. Compound which is absorbed is sequestered in the liver, slowly metabolized, and eliminated in the feces.

The results of these studies show that the likelihood of systemic exposure following ingestion of [14C] TBBA-DBPE is low. Additionally, disposition in liver tissue was minimal, and metabolite formation was slow. Consequently, it was determined that the probability of formation of the carcinogenic moiety DBP was low.

In summary, these data show that TBBA-DBPE was poorly absorbed across the gut lumen following oral administration. However, that which was absorbed was rapidly sequestered in the liver, was slowly metabolized and finally eliminated in the bile for fecal excretion.