Exploring Biological Read Across of Endocrine-Mediated Effects Between Birds and Other Vertebrates

Regulation 1107/2009 states that for approval, pesticide active substances require a consideration of endocrine disrupting (ED) properties for humans and non-target organisms. Currently, environmental safety testing for endocrine properties include tests in mammals, fish and amphibians (OECD, 2018). The available test for avian species is limited to the one generation avian reproduction study (OECD TG 206), which includes only apical endpoints. The US EPA’s avian 2-generation toxicity test in Japanese quail has not been validated by the OECD as it was considered unresponsive for EATS (estrogen, androgen, thyroid and steroidogenesis) modalities. In addition, it is unclear from available guidance whether these studies would be sufficient to draw a conclusion on ED potential in birds. As there are various anatomical and hormonal differences between birds and other vertebrates (e.g. different body temperatures, the production of cleidoic eggs, production of uric acid to void nitrogenous waste, different sexual differentiation mechanism) it is necessary to understand how responses of birds to endocrine active chemicals compare to better studied vertebrates. There is also the regulatory requirement to avoid unnecessary animal testing. Here we review the evidence for biological extrapolation of endocrine-mediated effects between birds and other vertebrates for which agreed test methods exist (mammals, amphibians and fish). We consider the usefulness of existing methodologies/study guidelines and guidance in the identification and evaluation of potential endocrine-mediated effects in birds. We also briefly compare the hormone systems and ADME (absorption, distribution, metabolism and excretion) processes of birds and other vertebrates. Through a review of published in vivo case studies with known ED chemicals targeting the EATS modalities, we compare observed effects in birds with those in other vertebrates. We discuss the question of whether potential ED chemicals for birds are likely to be captured by existing tests on non-avian vertebrates. Our assessment suggests there is a good basis for biological read across between birds and other vertebrate taxa, and also provides some suggestions for future research.

The poster is available for free download.