BIOLOGICAL MONITORING FOR PESTICIDE EXPOSURE - THE ROLE OF HUMAN VOLUNTEER STUDIES

Predictions of human pesticide metabolism which are needed for the int erpretation of biological monitoring data are frequently made from ani mal studies. Consequently, assumptions have to be made about the relat ionship between absorbed dose and metabolite excretion. The results fr om two human volunteer studies highlight the problems associated with extrapolating from animal studies in this way. The pyrethroid insectic ide cypermethrin shows markedly different metabolite patterns when adm inistered orally or dermally in man. Following dermal dosing the ratio of trans/cis cyclopropane acids is approximately 1:1, compared to 2:1 after oral administration. The ratio of total cyclopropane acids to p henoxybenzoic acids also differs depending on the route (dermal 1:4, o ral 1:0.8). A knowledge of human metabolism by these two routes enable s a much more meaningful interpretation of biological monitoring measu rements. The herbicide molinate forms a mercapturate conjugate as a ma jor urinary metabolite in the rat (35%). In volunteers at low dose lev els this metabolite is present at insignificant levels (< 1%) and 4-hy droxymolinatc is a much more abundant metabolite (39%). This shows tha t extrapolation between species can be very misleading. It is conclude d that the benefits of using human volunteers for metabolism studies a t low doses far outweigh the minimal risks involved. As a basis for bi ological monitoring such studies can lead to a greatly improved risk a ssessment for pesticides in use.