Evaluation of 3D-human skin equivalents for assessment of human dermal absorption of some brominated flame retardants

Abstract

Ethical and technical difficulties inherent to studies in human tissues are impeding assessment of the dermal bioavailability of brominated flame retardants (BFRs). This is further complicated by increasing restrictions on the use of animals in toxicity testing, and the uncertainties associated with extrapolating data from animal studies to humans due to inter-species variations. To overcome these difficulties, we evaluate 3D-human skin equivalents (3D-HSE) as a novel in vitro alternative to human and animal testing for assessment of dermal absorption of BFRs. The percutaneous penetration of hexabromocyclododecanes (HBCD) and tetrabromobisphenol-A (TBBP-A) through two commercially available 3D-HSE models was studied and compared to data obtained for human ex vivo skin according to a standard protocol. No statistically significant differences were observed between the results obtained using 3D-HSE and human ex vivo skin at two exposure levels. The absorbed dose was low (less than 7%) and was significantly correlated with log Kow of the tested BFR. Permeability coefficient values showed increasing dermal resistance to the penetration of γ-HBCD>β-HBCD>α-HBCD>TBBPA. The estimated long lag times (>30 min) suggests that frequent hand washing may reduce human exposure to HBCDs and TBBPA via dermal contact.

The biological fate of decabromodiphenyl ethane following oral, dermal or intravenous administration

“…Contrary to previous reports where DBDPE was used as a negative control (Abdallah et al, 2015b), we found that a small amount of DBDPE was able to permeate human and rat skin after 24 h of continuous exposure. Dermal uptake and penetrance were greater than expected when compared to previous dermal disposition studies performed in this laboratory (Knudsen et al, 2015, Knudsen et al, submitted 2016).…”

From air to clothing: characterizing the accumulation of semi-volatile organic compounds to fabrics in indoor environments

“…Finally, these results have implications for human exposure. A growing literature indicates that dermal uptake of SVOCs prevalent indoors could play a role in overall exposure . As noted above, Morrison et al .…”

“…A growing literature indicates that dermal uptake of SVOCs prevalent indoors could play a role in overall exposure. 68,[70][71][72][73] As noted above, Morrison et al 10 found that wearing cotton clothing exposed to phthalates increased dermal uptake relative to wearing unexposed clean clothing.…”

Dermal Uptake from Airborne Organics as an Important Route of Human Exposure to E-Waste Combustion Fumes

“…BDE-209 showed low penetration (0.3%) to the receptor fluid, with up to 20% of the dose remaining in skin after 24 h. TDCPP penetrated more (39−57%) to the receptor fluid than BDE-209, with 28−35% of the dose remaining in the skin. In another human ex vivo skin study, 46 the absorbed doses of α-, β-, and γ-hexabromocyclododecanes (HBCD) and tetrabromobisphenol A were less than 7%, whereas 23−31% of the administered doses remained in the skin tissues.…”

“…Park et al 28 also reported lower serum PBDE concentrations in firefighters who cleaned their turnout gear after fire events than those in Figure 2. Distributions of flame retardants (expressed as % of exposure dose) absorbed (present in the receptor compartment), unabsorbed (remaining in the donor compartment and on skin surface) and accumulated in the skin tissue of different samples for the in vivo and in vitro dermal absorption studies following 24 h exposure (compiled from Garner and Matthews, 43 Hughes et al, 45 and Abdallah et al 44,46 ). firefighters who did not.…”