Species differences in toxicity of 4-hydroxyphenylpyruvate dioxygenase (4-HPPD) inhibitors on the cornea of the eye and molecular layer of the cerebellum

Abstract

The 4-HPPD inhibiting herbicides block tyrosine catabolism and induce hyper tyrosinemia for animals. In order to investigate the species difference of 4-HPPDi-induced toxicity, NTBC was administered for 52 weeks to rats and mice via foods. Mean plasma tyrosine concentrations exceeded over 1000 μmol/L in rats but less than in mice. Histopathologically, keratitis in the eyes and vacuolation of molecular layer in the cerebellum was induced in rats but not in mice. There was a clear species difference in the ocular and brain effects associated with a threshold in plasma tyrosine level.