In vitro dermal absorption of metiram using human skin preparations

Abstract

Metiram is a polymeric plant protection fungicidal product. Since farm workers can potentially be exposed to the used solo-formulation, polyram, its dermal penetration is important for the assessment of its safety. Previous dermal penetration studies indicated a low penetration of metiram (≤ 1% of the applied dose), when applied in polyram or in the almost identical technical concentrate, metiram TK. Here, we present an in vitro human skin absorption study conducted according to OECD guideline 428. In this study, synthesized polymeric ¹⁴C-radiolabelled metiram in polymeric "unlabeled" solo-formulation, polyram, was used. Single doses of radioactive metiram were applied to human skin preparations in vitro (4 donors per dose group, 2 replicates each) for 8 h, under semi-occluded conditions in Franz-like diffusion cells, using a flow-through diffusion system. Under these test conditions, dermal absorption of the low dose, which represents spray dilution concentrations, was 0.34 ± 0.48% of applied dose; and dermal absorption of the high dose (formulation concentrate) was negligible (<0.0015 % of the applied dose). These results confirm the low dermal absorption of polymeric metiram and indicate that slight differences in applied formulations have minimal impact on its penetration properties.

Keywords: Dermal penetration; Formulation; Human skin; In vitro; Metiram; Plant protection product.