Dermal uptake and percutaneous penetration of ten flame retardants in a human skin ex vivo model

Abstract

The dermal uptake and percutaneous penetration of ten organic flame retardants was measured using an ex vivo human skin model. The studied compounds were DBDPE, BTBPE, TBP-DBPE, EH-TBB, BEH-TEBP, α, β and γ-HBCDD as well as syn- and anti-DDC-CO. Little or none of the applied flame retardants was recovered in either type of the receptor fluids used (physiological and worst-case). However, significant fractions were recovered in the skin depot, particularly in the upper skin layers. The primary effect of the worst-case receptor fluid was deeper penetration into the skin. The recovered mass was used to calculate lower- and upper-bound permeability coefficients kp. Despite large structural variation between the studied compounds, a clear, significant decreasing trend of kp was observed with increasing log Kow. The results indicate that the dermis may provide a significant barrier for these highly lipophilic compounds. However, based on our results, dermal uptake should be considered in exposure assessments, though it may proceed in a time-lagged manner compared to less hydrophobic compounds.

Dermal uptake and percutaneous penetration of organophosphate esters in a human skin ex vivo model

“…We have previously reported decreasing k p with increasing log K ow for highly lipophilic halogenated flame retardants (log K ow 6.34-13.6, EpiSuite v. 4.11). The OPEs penetrated the skin both faster and to a greater extent than we had previously observed for highly lipophilic brominated and chlorinated flame retardants (Frederiksen et al, 2016), in accordance with our expectations based on their physical-chemical properties i.e. primarily there lipophilicity.…”

“…Thus, compounds with both hydrophilic as well as lipophilic characteristics (-2 < log K ow < 2) have an easier passage (Nielsen et al, 2009), whereas the permeation coefficient is expected to decrease at higher as well as lower log K ow values. Therefore, we hypothesize that the OPEs of this study have higher permeability coefficients than previously tested extremely lipophilic novel halogenated flame retardants (Frederiksen et al, 2016). The aim of this study is to provide data for estimating dermal uptake of eight OPEs and for ranking OPEs in risk assessments.…”

“…Dermal uptake and percutaneous penetration were studied in a Franz diffusion cell system as previously described for brominated and chlorinated flame retardants (Frederiksen et al, 2016). In brief, skin patches from plastic surgery were used (three female donors: age 42-50 y; abdominal region; average skin thickness of 0.99 mm).…”

“…The diffusion cells were taken down at three time points: 24 h (n=3), 48 h (n=5) and 72 h (n=4). From each cell the following compartments were sampled: donor cell wash, epidermis, dermis and receptor fluid as previously described in detail in Frederiksen et al (2016). In brief, the residue in the donor chamber was collected using cotton swabs, then the skin and donor chamber was gently washed twice with ethyl acetate soaked cotton swabs, and finally the skin was dried with cotton swabs, all swabs were collectively analyzed as remains in the donor chamber.…”

Estimation of human percutaneous bioavailability for two novel brominated flame retardants, 2-ethylhexyl 2,3,4,5-tetrabromobenzoate (EH-TBB) and bis(2-ethylhexyl) tetrabromophthalate (BEH-TEBP)

“…Previous studies in this laboratory (53) estimated approximately 6% of a 100 nmol/cm 2 dose of tetrabromobisphenol A would be dermally bioavailable to humans based on in vitro human data (4%) normalized to rat in vitro and in vivo data (13% and 22%, respectively). A recent study describing dermal disposition of ten different BFRs (including EH-TBB and BEH-TEBP) in full thickness human skin showed similar results when the chemicals were applied in ethanol and allowed to perfuse for 72 h (79). …”