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NTP Research Report on Biological Activity of Bisphenol A (BPA) Structural Analogues and Functional Alternatives

Research Report 4

NTP Research Report

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Author Information
Research Triangle Park (NC): National Toxicology Program; .



Recent studies report widespread usage or exposure to a variety of chemicals with structural or functional similarity to bisphenol A (BPA), referred to as BPA analogues or derivatives. These have been detected in foodstuffs, house dust, environmental samples, human urine or blood, and thermal paper. Compared to BPA relatively little is known about potential toxicity of these compounds.


To identify and summarize human, animal, and mechanistic toxicity data for 24 BPA analogues of emerging interest to research and regulatory communities.


The objective was addressed by two efforts: 1) a systematic review of the available research; and 2) analysis of data available from the high throughput screening programs Tox21/ToxCast. We used systematic review methods to identify relevant studies from the published literature. Over 5,100 literature studies were screened for relevance and 166 were considered relevant. Analyses of the high throughput screening data focused on assessing structural and biological similarity among the BPA analogues and between BPA or estradiol (E2).


Reports on 16 of the 24 analogues were found in the published literature. There were no studies of human health effects, animal toxicity or mechanistic studies for 8 of the 24 compounds. The only human health effect that was reported was dermal sensitization to 4,4-BPF, 2,2-BPF or BPS. The majority of the available research was conducted in vitro. Analysis of the Tox21/ToxCast data showed that in general, BPA analogues and derivatives are more structurally and biologically similar to BPA, and to each other, than to E2. Taken together, the published literature and the data available in Tox21/ToxCast demonstrate that many of the BPA analogues that are potential replacements for BPA have biological activity within the range of activity observed for BPA.


The results of these analyses suggest that many of these chemicals may have endocrine activity in vivo. Given that these chemicals have potential widespread use, they should be pursued in further testing and reconsidered as appropriate replacements for BPA in consumer products.

About the Series

NTP Research Report
ISSN (Electronic): 2473-4756
Copyright Notice

This is a work of the US government and distributed under the terms of the Public Domain

Bookshelf ID: NBK538922PMID: 31944638


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