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ICCVAM Biennial Report 2020-2021

Biennial Progress Report 2020-2021 Interagency Coordinating Committee on the Validation of Alternative Methods

Investigation of Environmental Determinants of Pubertal Timing in Girls

Over the past decade, there has been a worldwide trend toward earlier breast development in girls. The rapid pace of this trend suggests the involvement of environmental factors. While some studies (e.g., Bandera et al. 2011) have suggested a relationship between the presence of endocrine-disrupting chemicals in girls and pubertal timing, more evidence is needed to develop clear associations. Scientists at NIEHS and NCATS are examining the potential effects of endocrine-disrupting chemicals on important components of the biochemical pathway responsible for pubertal timing. Chemicals in the Tox21 10K collection are being tested in human cell-based assays that measure activation or inhibition of the gonadotropin-releasing hormone receptor and kisspeptin receptor. These receptors are expressed in the hypothalamus and are important players in the control of pubertal timing. Chemicals that exhibit activity will be tested further in cell-based assays or possibly in animals to confirm the biological relevance of the identified activity and determine the chemical’s mechanism of action.