Estimation of human percutaneous bioavailability for two novel brominated flame retardants 2-ethylhexyl 2345-tetrabromobenzoate (EH-TBB) and bis(2-ethylhexyl) tetrabromophthalate (BEH-TEBP)

摘要

2-ethylhexyl-2,3,4,5-tetrabromobenzoate (EH-TBB) and bis(2-ethylhexyl)tetrabromophthalate (BEH-TEBP) are novel brominated flame retardants used in consumer products. A parallelogram approach was used to predict human dermal absorption and flux for EH-TBB and BEH-TEBP. [¹⁴C]-EH-TBB or [¹⁴C]-BEH-TEBP was applied to human or rat skin at 100 nmol/cm² using a flow-through system. Intact rats received analogous dermal doses. Treated skin was washed and tape-stripped to remove “unabsorbed” [¹⁴C]-radioactivity after continuous exposure (24h). “Absorbed” was quantified using dermally retained [¹⁴C]-radioactivity; “penetrated” was calculated based on [¹⁴C]-radioactivity in media (in vitro) or excreta+tissues (in vivo). Human skin absorbed EH-TBB (24±1%) while 0.2±0.1% penetrated skin. Rat skin absorbed more (51±10%) and was more permeable (2±0.5%) to EH-TBB in vitro; maximal EH-TBB flux was 11±7 and 102±24 pmol-eq/cm²/h for human and rat skin, respectively. In vivo, 27±5% was absorbed and 13% reached systemic circulation after 24 h (maximum flux was 464±65 pmol-eq/cm²/h). BEH-TEBP in vitro penetrance was minimal (<0.01%) for rat or human skin. BEH-TEBP absorption was 12±11% for human skin and 41±3% for rat skin. In vivo, total absorption was 27±9%; 1.2% reached systemic circulation. In vitro maximal BEH-TEBP flux was 0.3±0.2 and 1±0.3 pmol-eq/cm²/h for human and rat skin; in vivo maximum flux for rat skin was 16±7 pmol-eq/cm²/h. EH-TBB was metabolized in rat and human skin to tetrabromobenzoic acid. BEH-TEBP-derived [¹⁴C]-radioactivity in the perfusion media could not be characterized. Less than 1% of the dose of EH-TBB and BEH-TEHP is estimated to reach the systemic circulation following human dermal exposure under the conditions tested.