‘It is the Dose That Makes the Poison’ – A Critical View on Dose Level Setting in Extended-One Generation Reproductive Toxicity (EOGRT) Studies

Abstract

Adequate dose level setting is essential for the evaluation of the toxicity of a substance, meaning that the dose level should not be too low to miss the potential of a substance to exert any toxic effects; it should also not be too high to induce various effects related to systemic toxicity that would hamper a proper evaluation of specific toxicity endpoints such as reproduction and fetal development. This discussion paper is meant to highlight the challenges faced by industry as a result of ECHA’s advice to select high dose levels when conducting EOGRT studies. In our view, in its concern for finding all possible hazards, ECHA is focused on testing at dose levels that may be too high for repeat dose toxicity studies. Such high dose levels may lead to an unethical increase in animal use and animal suffering, an inability to correctly interpret results and unacceptable requests for the repetition of studies leading to an even higher demand for experimental animals.