Alteration of toxicity to paraquat in mice fed a purified or cereal-based diet

Toxicity to several compounds is affected by dietary changes that by themselves do not result in nutrient deficiency or toxicity. The herbicide paraquat was tested to determine whether feeding a cereal-based closed formula diet or a purified diet would affect the sensitivity of mice to paraquat. After an intraperitoneal injection of paraquat, 28-day-old male ICR mice, which had been fed a purified diet for periods of 3 to 84 days, had shorter survival times and lower 7-day percent survivals than mice fed a cereal-base closed formula diet. The median lethal dose of paraquat was significantly lower in mice fed the purified diet rather than the closed formula diet. Median effective time to death was also significantly shorter for male ICR mice fed the purified diet rather than the closed formula diet. Female ICR mice and male B6C3F1 mice fed the purified diet for 7 days were more susceptible to paraquat toxicity than similar mice fed the closed formula diet. Male C57BL/6J mice were more sensitive to the effects of paraquat regardless of the type of diet. Modifying the content of lipid, vitamin E, or selenium, or adding butylated hydroxytoluene to the purified diet did not prevent a decrease in 7-day percent survival and survival time compared to male ICR mice fed a closed formula diet. Male ICR mice fed the purified diet with egg-white protein had significantly longer survival times compared to mice fed the purified diet with casein. It is concluded that strictly defined diets must be used in the study of paraquat toxicity to control for any paraquat-diet interactions.