Toxicological significance of pesticide

Dorough, H.W., Toxicological significance of pesticide conjugates, J. Toxicol. Clin. Toxicol.,... 

Pesticide metabolism studies are, without question, very important components in the evaluation of the toxicological significance of pesticides to man. The rate, extent, mechanisms, and products of metabolism are inevitably linked to the expression of toxic action, and a clear definition of pesticide biotransformation is often a necessary prerequisite to understanding mechanisms of toxicity and to the formulation of approaches for assessment and management of potentially undesired toxic effects. 

Species variations that may seriously affect the validity of laboratory animal metabolism studies as predictive models for man are a problem without apparent solution. For proper evaluation of the toxicological significance of pesticides to man, metabolism... 

We must always recognize that pesticide metabolism studies cannot be considered as an end in themselves but rather, they are a means toward an end. For the ultimate value of a metabolism study, be it in microorganisms, plants, birds, laboratory mammals, or v atever, is its yield of data valuable toward further assessment of the toxicological significance of the pesticide in question to lower organisms (i.e., its environmental impact) or, more importantly, to assess toxicological significance to man himself. 

The detection of pesticide metabolites in the urine of workers indicates prior exposure. However, it is difficult to relate this level of urinary metabolite to the actual worker exposure, and it is equally difficult to Interpret the toxicological significance of the level. A preliminary study conducted in rats exposed dermally to 100, 200 and 400 ug of azinphos-methyl showed a significant linear correlation between the dermal dosage and the urinary alkyl phosphate metabolite levels (19). Further studies are being conducted in other species to determine whether a similar type of relationship occurs and to develop a standard curve in which urinary metabolite levels could be utilized to estimate the amount of dermal exposure. 

The rate and extent of pesticide metaboHsm can vary dramatically, depending on chemical stmcture, the number of specific pesticide-degrading microorganisms present and their affinity for the pesticide, and environmental parameters. The extent of metaboHsm can vary from relatively minor transformations which do not significantly alter the chemical or toxicological properties of the pesticide, to mineralisation, ie, degradation to CO2, H2O, NH" 4, Cf, etc. The rate of metaboHsm can vary from extremely slow (half-life of years) to rapid (half-life of days). 

The question of pesticide residues and their environmental implications must be considered in the context of the active ingredient and its accompanying trace materials. The lUPAC definition of a pesticide residue is "any substance or mixture of substances in or on any substrate resulting from the use of a pesticide and includes any derivatives, such as degradation and conversion products, metabolites, reaction products and impurities (11). The significance of that residue depends on the toxicological properties of the substance and the degree of exposure. Thus, by definition, materials associated with the pesticide in the formulation must necessarily be considered as "pesticide residues". 

---