## EDSP Tier 1 Screening: Assay and Battery Performance Summary

Office of Chemical Safety and Pollution Prevention U.S. Environmental Protection Agency

# Summary: Purpose of Review

 Evaluate how well each Tier 1 assay test guideline can be consistently executed based on defined performance criteria and to highlight any issues associated with interpretation of responses within each assay;

 Evaluate the complementary relationships among responses within the assays; and,

 Evaluate the redundancy of responses across the Tier 1 battery

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# Summary: Purpose of Review

 

### Review also considered whether or not a modified number of assays within the battery, could reduce animal usage and lower costs, while adequately ensuring the identification of potential interactions with the E, A or T hormonal pathways

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# Summary: Case Studies

 

### Subsample of 21 chemicals out of 52

• Represented range of chemical classes, physico
chemical properties

• Represented range of biological activities

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# Summary: Study Performance

 

### With respect to whether Tier 1 assay test guideline can be consistently executed based on defined performance criteria

• Laboratory performance of each Tier 1 assay typically consistent

• Some performance criteria were not met, but deviations were not considered significant; did not impact the interpretation or reliability of the data

• Assays provide information useful for evaluating potential interaction with E, A and T signaling pathways

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# Summary: Challenges

 

### With respect to issues identified with the performance of individual assays

• Dose selection and overt toxicity were issues associated with performance of in vivo assays

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# Summary

 

### With respect to whether complementarity was demonstrated within assays and redundancy was demonstrated across assays, based on a qualitative assessment:

• Individual assay results demonstrated complementarity, i.e ., concordance of endpoints within an assay

• Battery of assays demonstrated redundancy, i.e ., the concordance of endpoints across assays, relative to E, A or T pathways

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# Summary

 

### For the E and A pathways, there were complementary responses with two or more endpoints responding in the pubertal assays and in the fish short
- term reproduction assay (FSTRA)

 

### In some case studies, the male and female pubertal assays and/or the FSTRA identified endpoint responses along with endpoint responses in the relevant in vitro assays for E and A

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# Summary

 

### There were also cases in which assay concordance was not observed between the in vivo and in vitro tests

• Emphasizes the importance of multi
- parameter in vivo assays as a component of the battery to evaluate HPG alterations; and,

• Potential differences between taxa

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# Summary

 

### With respect to the T pathway, less complementarity and redundancy were observed within and across assays

• Design of battery

• Emphasizes the need for AMA and rat pubertal assays

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# Conclusions

 

### Current analysis illustrated both complementarity within assays and redundancy across assays and generally supported the importance of the designed complementarity and redundancy in the battery for evaluating potential interactions with the E, A, or T signaling pathways across taxa

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# Conclusions and Notes

 

### With respect to the extent of redundancy and whether the battery of assays could be modified

• Chemicals that elicited a response in the Hershberger also elicited a response in the male pubertal assay and/or FSTRA

• Uterotrophic assay never showed a response with the subset of chemicals used to evaluate battery performance

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