Consideration of individual susceptibility in adverse pesticide effects

The modern environmental awareness leads to the realisation that the human metabolism is stressed by a huge number of chemical substances. Generally, these background exposures, consisting predominantly from natural and partl y from industrial as well as life style sources, are tolerated without any adverse effects. Pesticides are chemicals intentionally introduced to the e nvironment and have become necessities in modern agriculture as well as in indoor pest control. Their residues, therefore, is attracting more and more concern. For the majority of pesticides neither occupational nor environme ntal medical risk evaluations are so far available. Therefore, at the momen t the occupational as well as the environmental supported preventive concep t may only be achieved, if binding instructions upon experience and guide v alues are developed for the assessment of the individual risk of handling p esticides. In the occupational and environmental pesticide prophylaxis the ubiquitous background exposure levels in consideration with individual susc eptibility factors should be recommended as provisional biological toleranc e guide values. The suitability of this guide values concept for pesticides is demonstrated by determining the background exposure and the biomarkers of susceptibility of 250 unexposed persons as well as of more than 1200 occ upationally exposed persons. As a result, a significant dependence of their health fidelity from the background exposure profile impressed on the indi vidual polymorphism of the key enzymes was observed. Especially, the cumula tive adducts of electrophilic substances and their metabolites with macromo lecules like HSA and Hb turned our to be sensitive markers for the capacity of the individual metabolic rate. For alkylating and arylating pesticides the observed interindividual susceptibility to their adverse effects depend s on the variability of the individual 'toxifying' and 'detoxifying' metabo lic rates. Until scientific evaluation of official biological tolerance val ues for pesticides is carried out, it is advisable for risk prophylaxis to orientate the assessment of any individual tolerable stress and strain from pesticides to the synergism between background exposure, life style factor s and biomarkers of specific susceptibility. They may be examined by a moni toring of conjugates and polymorphism marked by the individual metabolic ra te. The monitoring and surveillance of pesticide exposures is mainly introd uced by the recommendation of tolerable biological values from the referenc e value concept. This concept is an essential contribution to an objective risk discussion with regard to individual stress and strain profiles in env ironmental exposure scenarios. (C) 1999 Elsevier Science Ireland Ltd. All r ights reserved.