Evaluation of normal human epidermal keratinocyte cultures as a test system for the assessment of the dermal irritancy of pesticides

Abstract

Dermal irritation studies are an essential part of the regulatory assessment of potential occupational and environmental health hazards of pesticides. The in vivo methods now widely used have not been improved substantially since the late 1940s, despite several shortcomings. These include: the subjectivity of the assessment of irritation; interlaboratory variability; and differences between animal and human skin permeability, thickness and sensitivity to irritants. Relatively little research has thus far been undertaken in Canada to determine the suitability of cell culture assays as alternatives for the assessment of dermal irritancy. Recently, cultured normal human epidermal keratinocytes (NHEK) have been proposed as a good model system for the assessment of dermal irritancy and toxicity. Epidermal keratinocytes are useful for this because they participate in dermal inflammation, and therefore constitute valid components of the reactions of human skin to toxins. The usefulness of this approach for dermal irritancy/toxicity evaluation of pesticide ingredients and formulations will be assessed by measuring the release of [ 3H]arachidonic acid from prelabelled NHEK cultures in response to pesticides added to the tissue culture medium. Dose-response relationships for pesticides of well characterized in vivo dermal irritancy will be determined and a rank-order correlation of the in vitro/in vivo data will also be performed.