METABOLISM, PHARMACOKINETICS, AND TOXICITY OF THE 1ST NONSTEROIDAL ECDYSTEROID AGONIST RH-5849 TO SPODOPTERA-EXEMPTA (WALKER), SPODOPTERA-EXIGUA (HUBNER), AND LEPTINOTARSA-DECEMLINEATA (SAY)

RH 5849 is the first nonsteroidal ecdysteroid agonist which induced prematurely an abnormal and subsequently lethal larval moult in larvae of the two lepidopteran species, Spodoptera exempta and Spodoptera exigua. Mortality in larvae of the coleopteran, Leptinotarsa decemlineata, was scored after inhibition of a normal ecdysis or an evolving abnormal and lethal ecdysis. The toxicity of RH 5849 to the two Spodoptera spp. differed markedly. S. exempta was about 50 times more susceptible than S. exigua larvae: LC50 values in S. exempta larvae of 2nd to 5th and of 6th instar were about 7.5 and 1.8 mg/liter and in S. exigua larvae of 2nd to 4th and of 5th instar 195 and 110 mg/liter. In L. decemlineata, LC50 values were about 5.5 and 1.8 mg/liter for larvae of 1st to 3rd and of 4th instar. To explain such differences in biological activity of RH 5849 in the three insects, its retention, distribution, and metabolism have been measured. Larvae of S. exempta, S. exigua, and L. decemlineata fed [14C]RH 5849 rapidly absorbed the radiolabel. Excretion of absorbed compound was also high, with a 50% excretion time of approximately 3, 2, and 6 hr after intake in the three respective insects. Following the product in the larval body, a total of 9 and 6%, 8 and 13%, 30 and 26% of the applied dose had penetrated 6 hr after intake into the hemolymph and the cuticle of S. exempta, S. exigua, and L. decemlineata, respectively. In the gut, about 8, 5, and 15% of the applied dose had remained at the same time in the three respective species. After intake, the product also seemed to be metabolically quite stable. Six hours after intake, about 11, 14, and 36% was recovered as parent compound in the larval body of S. exempta, S. exempta, and L. decemlineata, respectively. About 3, 12, and 16% of the applied dose was still present as unchanged RH 5849 in the body of the three respective insects 24 hr after intake. The obtained results suggest that the observed differences in biological activity of RH 5849 to S. exempta, S. exigua, and L. decemlineata cannot be attributed to differences in retention, distribution, and metabolic detoxication in the larval body. © 1993 by Academic Press, Inc.