Close link between protoporphyrin IX accumulation and developmental toxicity induced by N-phenylimide herbicides in rats.

  title={Close link between protoporphyrin IX accumulation and developmental toxicity induced by N-phenylimide herbicides in rats.},
  author={S. Kawamura and Terushige Kato and A. Fantel},
  journal={Birth defects research. Part B, Developmental and reproductive toxicology},
  volume={101 6},
BACKGROUND S-53482, 7-fluoro-6-[(3,4,5,6-tetrahydro)phthalimido]-4-(2-propynyl)-1,4-benzoxazin-3(2H)-one (flumioxazin), is an N-phenylimide herbicide and developmentally toxic to rats, but not to rabbits. The day of greatest sensitivity to S-53482 is gestational day (GD) 12 in rats. There is a compound-specific difference in developmental toxicity among structurally similar compounds including S-23121 (N-[4-chloro-2-fluoro-5-[(1-methyl-2-propynyl)oxy]phenyl]-3,4,5,6-tetrahydrophthalimide… Expand
Different Effects of an N-Phenylimide Herbicide on Heme Biosynthesis between Human and Rat Erythroid Cells.
It is suggested that the rat would be an inappropriate model for assessing the developmental toxicity of S-53482 in humans as rats are specifically sensitive to PPO inhibition by the herbicide. Expand
Flumioxazin metabolism in pregnant animals and cell‐based protoporphyrinogen IX oxidase (PPO) inhibition assay of fetal metabolites in various animal species to elucidate the mechanism of the rat‐specific developmental toxicity
The species difference in the developmental toxicity was concluded to be due to the difference in sensitivity of PPO to flumioxazin, and rats were confirmed to be the most sensitive of these species. Expand
Mechanism of Developmental Effects in Rats Caused by an N-Phenylimide Herbicide: Transient Fetal Anemia and Sequelae during Mid-to-Late Gestation.
Developmental toxicity results from PPO inhibition in primitive erythroblasts, causing transient fetal anemia followed by death, and inhibition of PPO in rats, rabbits, and humans by the herbicides in vitro is proposed. Expand
Species-specific developmental toxicity in rats and rabbits: Generation of a reference compound list for development of alternative testing approaches.
A retrospective data analysis was conducted to identify compounds for which species sensitivity differences between rats and rabbits are not caused by maternal toxicity or toxicokinetic differences, and could be useful to identify mechanisms leading to species differences. Expand


In vitro mode of action of N-Phenylimide photobleaching herbicides
Abstract The effect of N-Phenylimide photobleaching herbicides on in vitro synthesis of protoporphyrin was examined. The N-phenylimide photobleaching herbicide S-23142Expand
Species difference in protoporphyrin IX accumulation produced by an N-phenylimide herbicide in embryos between rats and rabbits.
The species difference in PPIX accumulation corresponded very well to that of the developmental toxicity exhibited by S-53482, an N-phenylimide photobleaching herbicide between rats and rabbits. Expand
Difference in developmental toxicity among structurally similar N-phenylimide herbicides in rats and rabbits.
The mechanism of action of developmental toxicity by S-53482 should account for the compound-specific difference as well as species difference between rats and rabbits and the difference in developmental toxicity in rats was striking among N-phenylimide herbicides. Expand
Dermal developmental toxicity of N-phenylimide herbicides in rats.
Dermal exposure of rats to S-53482 and S-23121 produced patterns of developmental toxicity similar to those resulting from oral exposure as well as teratogenic when administered dermally to pregnant rats as were the compounds administered orally. Expand
Species Difference in Developmental Toxicity of an N‐Phenylimide Herbicide between Rats and Rabbits and Sensitive Period of the Toxicity to Rat Embryos
It is likely that there is a common mechanism for the three types of developmental toxicity and that S‐53482 does not produce VSD by its direct damage to embryonic heart tissue. Expand
Protoporphyrinogen oxidase inhibition by three peroxidizing herbicides: Oxadiazon, LS 82‐556 and M&B 39279
Three chemically unrelated peroxidizing molecules, namely oxadiazon, LS 82‐556, M&B 39279 and 5‐amino‐4‐cyano‐1‐(2,6‐dichloro‐ 4‐trifluoromethylphenyl)pyrazol, are potent inhibitors of plant, yeast and mouse protoporphyrinogen oxidase. Expand
Protoporphyrinogen oxidase as a molecular target for diphenyl ether herbicides.
The results lead to propose protoporphyrinogen oxidase as a cellular target for diphenyl ether herbicides. Expand
Protoporphyrinogen oxidase inhibitor: an ideal target for herbicide discovery.
The structures of PPOs from plants, human, and bacteria; the interactions between P POs and inhibitors; the quantitative structure-activity relationships of P PO inhibitors; and the molecular design of new PPO inhibitors are summarized. Expand
Effects of diphenyl ether herbicides on porphyrin accumulation by cultured hepatocytes.
It is suggested that diphenyl ether treatment can cause uroporphyrin accumulation similar to that induced by other cytochrome P450-inducing chemicals such as polyhalogenated aromatic hydrocarbons in the chick hepatocyte system. Expand
Herbicide safety relative to common targets in plants and mammals.
  • D. Shaner
  • Biology, Medicine
  • Pest management science
  • 2004
Most modern herbicides have low mammalian toxicity due to rapid metabolism and/or excretion of the herbicide from mammalian systems. Expand