Integrated evidence-based assessment of in vitro and in vivo data supports that the effects of phenmedipham in Xenopus laevis are consistent with generalised toxicity rather than thyroid disruption.

Phenmedipham (PMP), an herbicide registered for various crops across different geographies, is under re-approval in Europe and should be evaluated for potential endocrine-disrupting properties according to the current legislation on pesticide active substances. This paper describes an evidence-based assessment of potential thyroid-mediated effects of PMP in Xenopus laevis as model species for thyroid modality. As an indication of thyroid activity, rat thyroperoxidase inhibition was reported in a single in vitro assay in the US-EPA ToxCast database. The results of a 27-day Extended Amphibian Metamorphosis Assay with X. laevis showed very little evidence of the consequences of potential thyroperoxidase inhibition in vivo. A minor non-statistically significant delay of 0.76 days in the mean time to reach metamorphic climax was estimated for tadpoles from the highest treatment group (0.5 mg/L) which reached the metamorphic climax at a significantly lower rate over time compared to control. As it is within the historical control data variability (± 2.72 days), the estimated developmental delay of 0.76 days is not adverse for individuals, and no population-level impact is therefore expected in field. Other statistically significant low-magnitude effects (e.g. ≤ 4.2 % for reduced survival and growth) were observed at the highest PMP concentration at study termination. Minor statistically significant histopathological changes in the thyroid of tadpoles from the highest treatment group could be explained by the effects on developmental timing. Overall, the response pattern observed in X. laevis was consistent with generalised toxicity and thus, PMP does not meet the endocrine disruption identification criteria for thyroid modality.