Pesticide toxicological significance

Xenobiotics are frequently metabolized in plants by mechanisms that lead to the incorporation or inclusion of the xenobiotic into biological polymers or tissue residues that are not soluble in commonly used nonreactive solvents. These residues are frequently refered to as bound, insoluble, or nonextractable residues (2 ). Bound residues in plants have most commonly been detected in plant tissues treated with radloactlvely-labeled pesticides. These residues were an important topic of a symposium held in Vail, Colo, in 1975 (17) they have been discussed in mauiy more recent papers (11,154-1577"and they were discussed at a symposium at the l88th ACS National Meeting, 1984 "Non-extractable Pesticide Residues Characteristics, Bioavailability and Toxicological Significance". 

When the products formed by metabolic processes are toxico-logically insignificant and, when this is a known fact, the findings may be valuable in assessing pesticide risk. Contrarily, a number of pesticides yield metabolites known to be highly toxic and these materials may be taken into account in the risk assessment process. Too many times, however, the isolation and identification of pesticide metabolites tell us very little about risks that may be associated with the use of a particular chemical because the information can not be related to in vivo toxicological significance. 

Parathion and Paraoxon. Again, this represents a reaction (the sulfur oxidation of a thiophosphate pesticide) that is familiar to most in the pesticide area. Unlike heptachlor epoxide, paraoxon is not a stable compound and its actual presence in a poisoned animal was very difficult to demonstrate. The oxons of other organo-phosphorothioates are not so elusive. In any event, the paraoxon metabolite is an excellent example of where an understanding of metabolic processes and their potential toxicological significance alerted scientists to the likelihood that such a metabolite existed. Many years of work with similar compounds had established that the insecticidal thiophosphates required oxidation to the P=0 form in order to inhibit the neurotrasmitter acetylcholinesterase, the biochemical basis of their toxic action. Paraoxon was eventually isolated in vivo and now consideration of the oxon is a vital part of the overall risk assessment of this group of pesticides. 

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

Pesticide residues are substances in food, forage, or the environment that are present because of the use of pesticides. Residues include derivatives such as degradation products, metabolites, reaction products, and impurities that may have toxicological significance. 

The most potent interaction of toxicological significance reported to date involves two known animal carcinogens (2). Whether this interaction between chlordecone and CCl results in amplified carcinogenicity has not been tested. The interaction represents a sequential exposure to a halogenated pesticide, chlordecone and a haloalkane, both at individually nontoxic doses (10). 

It is not sufficient to evaluate toxicological significance by monitoring parent compounds alone because many metabolites of OP and CM pesticides have similar or... 

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. 

Depending upon their toxicological significance, pesticide metabolites may or may not be included as components of a... 

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. 

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