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 partly from industrial as well as life style sources, are tolerated without any adverse effects. Pesticides are chemicals intentionally introduced to the environment 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 environmental medical risk evaluations are so far available. Therefore, at the moment the occupational as well as the environmental supported preventive concept may only be achieved, if binding instructions upon experience and guide values are developed for the assessment of the individual risk of handling pesticides. In the occupational and environmental pesticide prophylaxis the ubiquitous background exposure levels in consideration with individual susceptibility factors should be recommended as provisional biological tolerance 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 occupationally exposed persons. As a result, a significant dependence of their health fidelity from the background exposure profile impressed on the individual polymorphism of the key enzymes was observed. Especially, the cumulative adducts of electrophilic substances and their metabolites with macromolecules like HSA and Hb turned out 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 depends on the variability of the individual 'toxifying' and 'detoxifying' metabolic rates. Until scientific evaluation of official biological tolerance values 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 factors and biomarkers of specific susceptibility. They may be examined by a monitoring of conjugates and polymorphism marked by the individual metabolic rate. The monitoring and surveillance of pesticide exposures is mainly introduced by the recommendation of tolerable biological values from the reference value concept. This concept is an essential contribution to an objective risk discussion with regard to individual stress and strain profiles in environmental exposure scenarios.
BAYER AG, Medical Services LEV, Leverkusen, Germany.
J
J
Lewalter
G
G
Leng
D004237:Diuron / Q000009:adverse effects / Q000493:pharmacokinetics; D006801:Humans; D016273:Occupational Exposure; D010575:Pesticides / Q000009:adverse effects* / Q000493:pharmacokinetics; D011110:Polymorphism, Genetic; D001074:Propoxur / Q000009:adverse effects / Q000493:pharmacokinetics; D014227:Triazines / Q000009:adverse effects / Q000493:pharmacokinetics
D010575:Pesticides; D014227:Triazines; D004237:Diuron; D001074:Propoxur; C004855:dyrene