Repeated Dose 90-Day Oral Toxicity Study in Rodents (OECD TG 408)

Abstract

724. This assay determines the general toxicity of chemicals in rodents after 90 days of oral dosing (by gavage, via the diet or in drinking water). The rat is the preferred species. It provides information on major toxic effects and target organ toxicity likely to arise from the post-weaning period until well into adulthood. OECD TG 408 was adopted in September 1998 and was updated in 2017 to add endocrine disrupter relevant endpoints intended to improve the detection of endocrine activity of test chemicals and mirrors updates to OECD TG 407 (Repeated Dose 28-Day Oral Toxicity Study in Rodents). In the updated version, an emphasis was placed on including additional thyroid parameters that could inform, alone or in combination with other information, on the potential of test chemicals to perturb the thyroid pathway. The update mirrored that of OECD TG 407 and therefore a comparison can be made with validation of the OECD TG 407 (28-Day Oral Toxicity Study) for endocrine endpoints where substances that were moderate and strong endocrine disruptors (EDs) for (anti)estrogenicity and (anti)androgenicity (e.g. ethinylestradiol and flutamide) and weak and strong modulators of thyroid hormone-related effects (e.g. propylthiouracil, T4 and methyl testosterone) were detected (OECD, 2006). Steroidogenesis inhibition was also detected, although only one (potent) chemical was used in the validation study (CGS 18320B). OECD TG 408 is likely to be more sensitive than OECD TG 407 because of the extended dosing period and the larger number of animals per group (ten male and ten female per group compared with five in OECD TG 407).