Oxidative Metabolism of Pyrethrins in Mammals

THE natural pyrethrins present in pyrethrum flowers ( Chrysanthemum cinerariaefolium ) have attracted attention for more than a century because they are powerful insecticides yet have very low toxicity to mammals 1,2 . Concern about the persistence of some insecticides in mammals and in the environment has stimulated a consideration of the degradability of widely used compounds, both old and new. The two principal insecticidal constituents of pyrethrum, pyrethrins I and II (Fig. 1), do not persist in the environment because they are unstable when exposed to light and air 3 . There is some information about the metabolism of pyrethrin I and related compounds in houseflies 4,5 , but little is known of the fate of pyrethrum constituents in mammals 6,7 even though man is often exposed to pyrethrins from household aerosols and other sources. We therefore examined the degradation of pyrethrin I and of pyrethrin II in rats fed separately with large amounts of pure tritium-labelled pyrethrins I and II, prepared with high specific activities by a new procedure involving a direct exchange reaction on (+)-pyrethrolone 8 . The metabolites were isolated in milligram quantities from urine; nuclear magnetic resonance (NMR) and mass spectrometry (MS) showed that each of the principal metabolites retains the cyclopropane ester linkage and is formed by modification of both the acid and alcohol moieties. The oxidation of the acid side chain is similar in type to that encountered previously in other systems 4,5 , but the establishment of attack on the alcohol part is new and involves the unsaturated side chain as detailed below.