In vitro modelling of dermal absorption of chemicals following environmental or accidental exposure

Abstract

These studies were aimed at identifying potential surrogate compounds for dermal absorption of bioactive agents in vitro using flow through and static cell diffusion systems, and also to generate novel data on the effects of application vehicle on chemical absorption following low level exposure. For protection and risk assessment purposes, the influence of ‘everyday’ clothing, and skin surface decontamination on dermal chemical absorption was also assessed. The model compounds (caffeine and benzoic acid), and the surrogate compounds (chlorpyrifos, dichlorvos and phorate) were generally found to be poor marker chemicals for comparison with HD absorption through human and pig skin in vitro. However, benzoic acid absorption from a finite dose in IPA more closely matched the absorption profile of HD applied as a finite dose in IPA. Dichlorvos absorption was greatest from all vehicles compared with chlorpyrifos and HD absorption in vitro. Dermal absorption of chlorpyrifos was enhanced when applied in PG compared with absorption from IPA or IPM. No differences were observed between absorption of neat HD and HD in IPA in terms of percentage of applied dose absorbed at 24 hours. Absorption of HD through full thickness pig skin more closely matched absorption through full thickness human skin, split thickness pig skin overestimated absorption of HD in vitro in comparison. ‘Everyday’ clothing (cotton shirt) significantly reduced absorption of dichlorvos, chlorpyrifos and HD through human skin. Chemicals were applied to clothed skin in IPA to mimic finite exposure, and left in contact for 30 minutes (dichlorvos), 4 hours (chlorpyrifos), and 1 hour (HD). For all chemicals, removal of clothing followed by immediate skin surface decontamination with 0.5% (v/v) soap solution further reduced absorption compared with removal of clothing alone. Despite these differences not being significant, in terms or civilian exposure, it would be recommended to remove clothing and decontaminate as early as possible postexposure to minimise the potential for dermal absorption and localised toxicity within the skin. In conclusion, the organophosphate compounds used in these studies (chlorpyrifos and dichlorvos) could potentially be useful surrogates for organophosphate agents such as VX or sarin, however, further work is needed to make these comparisons. The vehicle in which a chemical is applied to the skin can have a profound effect on dermal absorption, and this knowledge is important for risk assessment for exposure to a range of chemicals. Cotton shirt material significantly reduced dermal absorption of all chemicals used compared with 24 hour exposure. Despite this clothing not being designed for protective purposes, this may have a significant impact for reducing dermal absorption and toxicity in vivo as a result of chemical exposure. Further investigation is needed to assess absorption of a wider range of chemicals and application vehicles for risk assessment purposes, and to identify chemicals that more closely mimic dermal absorption of bioactive agents in vitro for extrapolation to in vivo exposure scenarios