Species difference in protoporphyrin IX accumulation produced by an N-phenylimide herbicide in embryos between rats...

There was a remarkable species difference in developmental toxicity exhibited by S-53482, an N-phenylimide photobleaching herbicide, between rats and rabbits. S-53482 showed embryolethality, teratogenicity, and growth retardation in rats. In contrast, no developmental toxicity was shown in rabbits. The herbicidal activity of S-53482 is due to the photodynamic action of accumulated protoporphyrin IX (PPIX) as a result of inhibition of protoporphyrinogen oxidase (PPO), which is one of the key enzymes in porphyrin biosynthesis common to both plants and animals as part of chlorophyll and heme synthesis. Some plant PPO inhibitors were reported to inhibit mammalian PPO. Therefore, in a search for a possible link between developmental toxicity and enzyme inhibition, PPIX accumulations presumably resulting from PPO inhibition in rat and rabbit embryos were investigated. The results demonstrated that PPIX concentration was increased in rat embryos by 2 orders of magnitude when compared to that of nontreated embryos. On the other hand, no PPIX was accumulated in rabbit embryos even by treatment with a high dose level of S-53482. It was concluded that the species difference in PPIX accumulation corresponded very well to that of the developmental toxicity exhibited by S-53482.