A Cross-Species Mode of Action (MOA) Information Assessment: A Case Study of Bisphenol A (BPA)
The cross-species approach assessed the effects and MOA data for a given toxic agent and determined the relationship between MOA and species relatedness (i.e., evolutionary relationships). MOA was defined as the key step in the toxic response after chemical interaction at the target site that is responsible for the physiological outcome or pathology. This case study considers whether species that are more closely related in terms of phylogeny also exhibit a more similar mode of action for reproductive and developmental effects after BPA exposure. And further, this case study considers whether the MOA of related species without data can be predicted. BPA, a component of polycarbonate plastics, epoxy resins, and polyester resins, was selected for the case study because it is a high production volume chemical; data have been identified for both vertebrate and invertebrate species; and the estrogen agonist MOA (i.e., binding and activating the estrogen receptor to transcribe estrogen-responsive genes) has been well described for a number of vertebrate species.
Using only published information on MOA for animal species, reproductive and/or developmental in vivo effects data for BPA were identified for 16 species representing seven animal classes (gastropods, crustaceans, insects, amphibians, fish, birds, and mammals) in three phyla (mollusks, arthopods, and chordates). For the invertebrate species, the data were insufficient to determine the MOA among mollusks and arthropods. For the tested vertebrate species, the data support a relationship between species relatedness and the estrogen agonist MOA. However, while the data strongly support the estrogen agonist MOA for fish and mammals, the data set was less robust for birds and amphibians. Thus, the cross-species MOA approach holds promise for predicting the MOA among species without data, for toxic agents with data for a number of related species.
This approach, in turn, could be applied to make MOA and effects predictions for species without data in an integrated ecological and human health risk assessment, interspecies extrapolation in human health assessments, and chemical screening and toxicity testing prioritization of chemicals. For example, cross-species MOA data may provide useful information for chemical prioritization in the Office of Prevention, Pesticides and Toxic Substances' (OPPTS) Endocrine Disruptor Screening and Testing Program (EDSTP) since the program is concerned with protecting human and wildlife health. Future efforts for 1) developing methods for integrated risk assessment; and 2) using MOA information in human health assessments,can build upon the results of this case study.
- 2002: Draft document was sent to internal/agency peer review.
- 2003: External review draft document was sent to external peer review.
- 2004: EPA revised the report in response to comments.
- 2005: EPA released the final report.
The project is complete.
Endocrine Disruptors Low-Dose Peer Review
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