Evaluation of reproductive toxicology studies according the OECD Guideline 443 – Claim and reality

The ECHA's work aims to establish uniform procedures for the authorization or restriction of the use of chemicals in the European Union. Studies conducted in accordance with OECD Guideline 443, in which, among others, the evaluation of pituitary and thyroid hormones and fertility under high-dose exposure are used as read-out parameters. Since 2022, ECHA has been compiling such extended one-generation reproductive toxicity (EOGRT) study data and publishing its assessments with regard to design, study conduct and toxicological results. Based on this, since then the authority has made demands on EOGRT study performers that are excessive, sometimes contra productive, may hamper data interpretation and lead neither to an improved validity of the studies nor to better animal welfare. Here, we explicitly address the physiological variability of pituitary hormone values and the interaction of reproductive toxicity with high dose exposure scenarios. ●Critical review of ECHA requirements for EOGRT studies conducted in accordance with OECD GD 443.●Considerations on high biological variability of the thyroid-stimulating hormone (TSH) in humans and rats.●Disproportional high dose settings requested by ECHA, aggravate qualified results and bear risk of enhanced animal distress.●Appeal to ECHA and scientists to collaborate for valid study parameters and optimized animal welfare concerns.