Limitations of gross pathology findings to indicate endocrine effects.
•
Historical control data sets establish useful baseline information of pathology findings.
•
Data should not be over interpreted in weight of evidence for potential endocrine effects.
Abstract
The European Chemical Agency and European Food Safety Authority recommend that gross pathology findings, from avian reproduction studies, be used to support assessment of potential endocrine disrupting properties of active pesticidal and biocidal substances. In open literature, little information is available on the utility of gross pathology data for informing endocrine evaluations. Here the gross pathology data from historical control groups of 51 northern bobwhite and 51 mallard reproduction tests is analyzed to evaluate the utility of such information. Incidence of gross morphology findings in untreated birds may aid the interpretation of some gross abnormalities, potentially indicative of an endocrine interaction (e.g. reproductive condition). Statistical analysis of the historical control data indicates that gross pathology is not likely to be useful for detecting endocrine effects as abnormalities with relatively high increases in prevalence (more than 20–30%, depending on prevalence in controls) are reliably interpreted as a treatment response. Gross pathology changes are only indicative and not diagnostic of endocrine interactions making it difficult to distinguish gross pathology abnormalities, due to endocrine-mediated effects, from systemic toxicity. This work demonstrates the utility of using historical control analyses to establish the value and properties of selected endpoints for regulatory applications.
Keywords
Avian reproduction test
Endocrine disruption
Necropsy
Gross pathology
Regulatory toxicology
Abbreviations
ECHA
European Chemical Agency
EFSA
European Food Safety Authority
US-EPA
United States Environmental Protection Agency
EU
European Union
EYP
egg yolk peritonitis
OECD
Organisation for Economic Cooperation and Development
OSCCP
Office of Chemical Safety and Pollution Prevention
WHO/IPCS
World Health Organisation International Programme on Chemical Safety