Isomeric stability of indaziflam and major degradation products in the environment

Abstract

Understanding the isomeric behavior of active ingredients in the soil and water environment is the first and a major part of deriving an exposure assessment. Whilst a variety of approaches have been taken previously, with the new regulatory framework for the risk assessment of isomeric plant protection compounds recently published by EFSA, (European Food Safety Authority) there will in future be a more consistent approach which has been taken here. For indaziflam (IAF), the alkylazine, cross spectrum residual herbicide which has a cellulose biosynthesis inhibition mode of action, there was no published data on the isomeric degradation behavior in soil and water. The results of measuring the isomeric stability of [14C]-radiolabeled 437-IAF, the major stereoisomer of indaziflam (AE 1170437, [1R,2S,6R] configuration) during its degradation in an aerobic soil metabolism study with four EU soils, an aerobic aquatic metabolism study with two natural water/sediment test systems, as well as an aqueous photolysis study are reported. To sum up, it was shown that in the different environmental conditions under abiotic as well as biotic degradation processes, indaziflam was not subject to isomeric interconversion to diastereoisomers 435-IAF (RRR), 438-IAF (RSS), or 439-IAF (SSR). Thus, all three chiral centers of indaziflam can be considered isomerically stable. In addition, no isomeric interconversion was observed at the 1-fluoroethyl position for the major degradation products IAF-indanone and IAF-carboxylic acid to the RSS-configuration as well as IAF-diaminotriazine from the R- to the S-configuration.