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Tetrachlorvinphos (TCVP) is the pesticidal active ingredient in some collars for dogs and cats. The objective of this study was to provide a refined estimate of dermal penetration of TCVP in humans using  in silico  predictions as well as  in vitro  and  in vivo  data. The  in vivo  dermal absorption of TCVP was previously studied in the rat and shown to be saturable, ranging from 21.7% (10 µg/cm 2 ) down to 3% (1000 µg/cm 2 ) Subsequent  in silico  predictions were conducted for rats and humans to provide initial evaluations of species and dose-dependent differences in dermal absorption. A definitive comparison of TCVP systemic exposure in rat and human following dermal application was then conducted via a standard  in vitro  assay. TCVP dose levels of 10, 100, or 1000 μg/cm 2  were applied to excised rat and human skin mounted in flow-through diffusion cells. The vehicle was 1% hydroxypropylmethylcellulose (HPMC) in water. An additional 5 μg/cm 2  dose was applied to excised human skin only. The  in vitro  dermal absorption of TCVP was also assessed from artificial sebum at dose levels of 5, 10, or 100 μg/cm 2  applied to human skin only. Utilizing the so-called triple pack approach with  in vitro  and  in vivo  rat data and  in vitro  human data, dermal absorption for TCVP was calculated for humans.  In silico  modeling indicated absorption of TCVP through human skin might be 3- to 4- fold lower than rat skin at all application levels, with a maximum dermal absorption of 9.6% at the lowest exposure of 10 µg/cm 2 , down to 0.1% at 1000 µg/cm 2 . Similar species differences were also found in the definitive  in vitro  absorption assays. Modeling overestimated TCVP human dermal absorption (9.6%) as compared to excised human skin results (1.7%) for the HPMC vehicle at the lowest exposure (10 µg/cm 2 ), with better agreement at the higher exposures. Conversely, modeling accurately predicted rat dermal absorption (27.9%) as compared to  in vivo  rat results (21.7%) at the lowest exposure in HPMC, with diminished agreement at the higher exposures. As a first approximation,  in silico  estimates of dermal absorption are useful; however, these tend to be more variable than  in vitro  or  in vivo  measurements. TCVP dermal penetration measured  in vitro  was lower in 1% HPMC vehicle as compared to artificial sebum. For the 1% HPMC vehicle,  in vitro  rat dermal absorption was similar to data obtained for  in vivo  rats, giving confidence in the triple pack approach. In consideration of the triple pack approach, estimated human dermal absorption from 1% HPMC was ≤2%. Based upon excised human skin determinations directly, estimated human dermal absorption of TCVP from artificial sebum was ≤7%.

Estimated Dermal Penetration of Tetrachlorvinphos (TCVP) in Humans Based on In Silico Modeling and In Vitro and In Vivo Data