The life of methylcarbamate insecticides in the animal body is very short. From 70 to 80% of an administered carbamate dose is usually eliminated, primarily in the urine, by 24 hr. The compounds are metabolized by hydrolytic and oxidative mechanisms and the resulting metabolites are excreted largely as sulfate and/or glucuronide conjugates. Some carbamates are reported to be conjugated directly, forming A-glucuronides, and then excreted.Hydrolysis of the carbamic acid ester results in detoxication of the insecticide. Carbamate metabolites formed by oxidation may be more or less toxic than the original compound. The toxicological properties of the conjugate metabolites have not been critically evaluated. This paper reviews recent findings on carbamate metabolism in animals, with particular emphasis on their metabolism by dairy cows and their residues in the milk.The toxicological significance of most foreign compounds entering the animal body is dependent, in part, on the manner in which they are metabolized. Some chemicals, such as strong bases, strong acids, and highly chlorinated hydrocarbons, are highly resistant to metabolism (Williams, 1963). These compounds, if toxic, would tend to retain their toxic action until excreted from the body. Usually, a chemical entering the body does undergo some type of transformation. The new chemical may be more toxic, less toxic, or equal in toxicity to the original compound. All three of these possibilities are known to occur as the result of metabolic transformation of certain carbamate insecticides by animal systems.The carbamate insecticides are esters of carbamic acid and those discussed herein are monomethyl derivatives of such esters. The first insecticidal carbamates synthesized were dimethyl carbamates (Gysin, 1952;Wiesmann, 1951;Wiesmann et al., 1951) but these did not have adequate insecticidal activity, and emphasis on the development of carbamate insecticides was placed on the more effective methylcarbamates (Casida, 1963;Fukuto, 1961;Kolbezen et al., 1954). The structures and chemical and common names of some of these compounds are given below.Although each of the compounds is a monomethyl carbamate, these three materials demonstrate that the carbamate insecticides are highly variable in their chemical makeup. Additional evidence as to the variability of the chemistry of this

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METHAZOLE IN COTTON AND BEANS suggested that five of the minor fecal metabolites were a result of nonmetabolic breakdown of the robenidine which occurred during the extraction process. Chromatography in solvent system I of the radioactivity extracted from the feces with acidified ethanol revealed that all of the radioactivity remained near the origin, while chromatography in solvent system II resolved the radioactivity into ten radioactive spots, none of which was identified. Since more than 60% of the radioactivity found in feces was identified as unmetabolized robenidine, this suggests that robenidine was incompletely absorbed from the digestive tract and does not undergo extensive breakdown in the body of the animal.Tissues. In order to establish the relevance of the urinary metabolites to those occurring in tissues, the radioactivity in selected tissues was isolated by extraction and chromatographed in solvent system I. Benzene extracts of fat and skin, containing 93-95% of the total radioactivity in these tissues, revealed that robenidine was the only compound present. Ethanol extracts of liver, kidney, and muscle containing 87-97% of the total radioactivity in these tissues revealed the presence of p-chlorohippuric acid, p-chlorobenzoic acid, and robenidine as tissue residues. CONCLUSIONSince p-chlorobenzoic acid is excreted as p-chlorohippuric acid in dogs (Novello et al., 1926) and rabbits (Bray et al., 1952) and these compounds have been identified as urinary metabolites of robenidine, this evidence indicates that the scheme shown in Figure 1. represents a major route for the metabolism of robenidine in the rat. No 1amino-3-(p-chlorobenzylidineamino)guanidine, postulated to be a potential metabolite, was found.It is speculated that this aminoguanidine fragment may be a transient metabolite. It could be split by the rat to yield p-chlorobenzoic acid and 1,3-diaminoguanidine, as suggested from the mammalian metabolism of the related aldehyde derivatives of thiosemicarbazide (Williams, 1959). Since there is little literature on the known fate of guanidine in mammalian metabolism, no proposals can be made to suggest the possible fate of the aminoguanidine moiety.ACKNOWLEDGMENT We thank I. J. Morici of the American Cyanamid Company, Princeton, N. J., for conducting the acute toxicology tests. LITERATURE CITED

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Wales who conducted the pathological examination of trout in this study and the Monsanto Chemical Company who provided us with Aroclor 1254. LITERATURE CITED