epa.gov/heasd/research/sheds/user_information.html/). In our aggregate VX-809 mouse permethrin evaluation (Zartarian et al., 2012), permethrin contribution to DCCA and 3-PBA metabolites was ~ 50%, which is consistent with the 60% contribution of total exposure from permethrin for the general population in this cumulative pyrethroids analysis (Fig. 5a). This is also consistent with findings by Morgan et al.: the mean and 95th percentile for measured urinary 3-PBA concentrations were 0.9 and 1.9 μg/L, respectively, and the authors estimated that the

aggregate absorbed doses of permethrin accounted for about 60% of the excreted amounts of 3-PBA found in the children’s urine (Morgan et al., 2007). We used REJV data to simulate pyrethroid residential users and non-users; ~ 16% of pyrethroid residential use was simulated per REJV data, which is comparable with 13% of the participants in CTEPP-Ohio and 14% of the participants in CTEPP-North Carolina (Morgan et al., 2005). In comparison with EPA/OPP’s pyrethroids, the relevant values that can be used for comparison are the 95th and 99th percentiles of dietary exposure (with the RPF method) for 3–5 year olds 1.68E-4 and 7.1E-4 mg/kg/day (Table 5.3a from EPA OPP, 2011) versus the 95th and 99th percentiles from SHEDS-Multimedia 4.04E-5 and 6.38E-5. The difference

is comparable, but results from the OPP assessment are higher, since OPP values are for short-term exposures R428 and the SHEDS-Multimedia values are annual averages. The SHEDS-Multimedia modeling of permethrin (Zartarian et al., 2012), applied a fractional absorption of permethrin based on the dermal dose-excretion study of Tomalik-Scharte et al. (2005). Here we modified our method according to Kissel (2011), who observed that in flux-limited systems (i.e., dermal studies conducted with high surface loadings) an inverse proportionality between surface loading and fractional absorption may be observed. We confirmed this observation and used this relationship to correct the fractional absorption applied by SHEDS in accordance with the estimated surface loading. The Acetophenone three dermal studies informing the correction

were conducted with cypermethrin and permethrin. Here, we assumed that the physicochemical properties of these chemicals are the driver for dermal flux and reasonably representative of the other pyrethroids. The percentage of dermal contribution increased, but the new approach did not change the order by exposure pathway. Although the new method increased the fractional absorption for lower surface loadings, the impact was offset to a large degree by the actual lower surface loadings. Important shortcomings of our approach include: (1) extrapolation of our fractional absorption model to very low dermal surface loadings; (2) implicit assumption that dermal flux is comparable in children and adults; and, (3) we do not account for the effect that the pyrethroid vehicle/matrix may exert in modulating dermal absorption.