Synthetic membranes as an alternative model to animal skin to investigate dermal permeation of chlorpyrifos

Dermal exposure to air pollutants is gaining increasing interest at toxicological level. Chlorpyrifos is a broad-spectrum pesticide used for treatments revised by authorities as representing a risk for human health. Few studies investigated the permeation of chlorpyrifos through skin either by using ex vivo animal skin or human skin, but this practice urges for a more ethical mode of action in scientific research.

The purpose of this study was to assess two synthetic membranes as non-animal alternatives to study the dermal permeation of chlorpyrifos for human health risk assessment.

Permeation assays were performed using silicone and Strat-M® membranes mounted on Franz cells with different receptor compositions. Sampling was conducted for HPLC quantification. The permeation kinetic fluxes obtained for the pesticide were calculated and compared to those reported in the literature for in vitro and in vivo human skin.

For both membranes, faster permeation of chlorpyrifos was observed for the highest concentration of ethanol used in the receptor fluid. Therefore, after 8h – work shift time - there was also a higher concentration of the pesticide that permeated both membranes. Regarding the time lag (Tlag), values inferior to 1h were obtained for both membranes and for receptor conditions containing ethanol between 10 and 50%.

Adopting these conditions, the flux values obtained for silicone and Strat-M® membranes were 1.5 ± 0.1 and 1.9 ± 1.2 µg cm^-2h^-1. Importantly, the flux and the Tlag values obtained are close to those reported in human skin studies, supporting the use of these membranes as non-animal systems mimicking the permeation of chlorpyrifos through human skin.

Up to our knowledge, this is the first study where alternative synthetic membranes are used achieving values close to those found for in vivo human exposure to a pesticide, validating experimental conditions to be considered in this research field.