Amphibian Metamorphosis Assay (AMA) (OECD TG 231)

311. Modality detected/endpoints: thyroid activity (advanced development; asynchronous development; delayed development in absence of non-specific systemic toxicity; thyroid histopathology), but note that this covers several different modes of action (MOA), including thyroid agonists and antagonists, as well as substances interfering with thyroid hormone synthesis and transport. According to OECD TG 231, there is disagreement about the implications of the different endpoints in this larval development screen. Some experts accept that changes in one of the thyroid-relevant apical endpoints (advanced development; asynchronous development; delayed development in absence of non-specific systemic toxicity) may on their own provide information on thyroid activity, while others will only reach this conclusion if one of the apical endpoints is accompanied by significant thyroid histopathology, such as moderate or severe follicular hypertrophy and/or hyperplasia (OECD, 2007). Note that the AMA is subject to indirect thyroid effects such as those that result from cytochrome P450 induction (e.g. phenobarbital, the model compound for the latter effect, tests positive in the AMA). Therefore, interpretation of the AMA may be complicated.