Different effects of an N-phenylimide herbicide on heme biosynthesis between human and rat erythroid cells

Kawamura, Satoshi; Otani, Mitsuhiro; Miyamoto, Taiki; Abe, Jun; Ihara, Ryo; Inawaka, Kunifumi; Fantel, Alan G.

doi:10.1016/j.reprotox.2020.11.007

Cited by 5 publications

(2 citation statements)

References 77 publications

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“…For further evaluation of the effect of species difference in dynamics on the downstream outcome of heme biosynthesis inhibition, we investigated the impact of flumioxazininduced PPO inhibition on heme biosynthesis in human and rat erythroid cells. 22) Treatment with flumioxazin led to dosedependent accumulation of PPIX in both human erythroleukemia (K562) cells and rat erythroleukemia (REL) cells; however, differences in heme biosynthesis were observed between species. As presented in Fig.…”

Section: Human Safety Assessment Of the Herbicide Flumioxazinmentioning

confidence: 99%

Researches on the evaluation of pesticide safety in humans using a pharmacokinetic approach

Abe

2021

J. Pestic. Sci.

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Similar to the pharmaceutical compounds, pesticides require human safety assessment for their registration and distribution; however, it is absolutely impossible to assess human safety by dosing humans with pesticides. Thus, how to appropriately evaluate the safety of pesticides in humans remains a great subject of debate. In this article, we present some examples of pesticide toxicity studies that identify species differences in toxicity and evaluate human safety by applying combinations of novel in vivo, in vitro, and in silico techniques to separately assess the key toxicodynamic (i.e., sensitivity) and/or toxicokinetic (i.e., exposure) factors. Because it is scientifically sound, the safety assessment strategy illustrated for three compounds in this article is expected to play an important role in the human safety assessment of agricultural compounds.

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Section: Human Safety Assessment Of the Herbicide Flumioxazinmentioning

confidence: 99%

Researches on the evaluation of pesticide safety in humans using a pharmacokinetic approach

Abe

2021

J. Pestic. Sci.

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“…On the other hand, it is generally known that species differences in toxicity occur when significant variations in dynamics and kinetics arise among species. [8][9][10][11] Thus, it was considered very important to evaluate the species differences in the dynamics and kinetics of PPO inhibition separately to precisely assess the risk to humans.…”

Section: Introductionmentioning

confidence: 99%

Comparative hepatotoxicity of a herbicide, epyrifenacil, in humans and rodents by comparing the dynamics and kinetics of its causal metabolite

et al. 2021

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A new herbicide, epyrifenacil (S-3100), inhibits protoporphyrinogen oxidase (PPO) in plants. Repeated administration of epyrifenacil in laboratory animals led to some toxicological changes related to PPO inhibition, e.g., hepatotoxicity caused by porphyrin accumulation and anemia caused by the inhibition of heme biosynthesis. In vitro studies revealed that an ester-cleaved metabolite, S-3100-CA, is predominant in mammals, exhibits PPO-inhibitory activity, and thus is the cause of epyrifenacil-induced toxicity. To assess the human risk, the effects of species differences on the dynamics (PPO inhibition) and kinetics (liver uptake) of epyrifenacil were evaluated separately. The results of in vitro assays revealed an approximately tenfold weaker inhibition of PPO by S-3100-CA in humans than in rodents and six-to thirteen-fold less hepatic uptake of S-3100-CA in humans than in mice. Finally, it was suggested that humans are less sensitive to the toxicity of epyrifenacil than are rodents, although further mechanistic research is highly anticipated.

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Prediction of the human pharmacokinetics of epyrifenacil and its major metabolite, S-3100-CA, by a physiologically based pharmacokinetic modeling using chimeric mice with humanized liver

Hirasawa

Abe

Nagahori

et al. 2022

Toxicology and Applied Pharmacology

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Different effects of an N-phenylimide herbicide on heme biosynthesis between human and rat erythroid cells

Cited by 5 publications

References 77 publications

Researches on the evaluation of pesticide safety in humans using a pharmacokinetic approach

Researches on the evaluation of pesticide safety in humans using a pharmacokinetic approach

Comparative hepatotoxicity of a herbicide, epyrifenacil, in humans and rodents by comparing the dynamics and kinetics of its causal metabolite

Prediction of the human pharmacokinetics of epyrifenacil and its major metabolite, S-3100-CA, by a physiologically based pharmacokinetic modeling using chimeric mice with humanized liver

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