A strategy to validate a selection of human effect biomarkers using adverse outcome pathways: Proof of concept for phthalates and reproductive effects
Metadatos
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Baken, Kirsten A.; Mustieles Miralles, Vicente; Rodríguez Carrillo, Andrea; Olea Serrano, NicolásEditorial
Elsevier Inc.
Fecha
2019-05-15Referencia bibliográfica
Baken, K. A., Lambrechts, N., Remy, S., Mustieles, V., Rodríguez-Carrillo, A., Neophytou, C. M., ... & Schoeters, G. (2019). A strategy to validate a selection of human effect biomarkers using adverse outcome pathways: Proof of concept for phthalates and reproductive effects. Environmental research, 175, 235-256.
Patrocinador
This project has received funding from the European Unions' Horizon 2020 research and innovation Programme under grant agreement No 733032 HBM4EUResumen
Human biomonitoring measures the concentrations of environmental chemicals or their metabolites in body
fluids or tissues. Complementing exposure biomarkers with mechanistically based effect biomarkers may further
elucidate causal pathways between chemical exposure and adverse health outcomes. We combined information
on effect biomarkers previously implemented in human observational studies with mechanisms of action reported
in experimental studies and with information from published Adverse Outcome Pathways (AOPs), focusing
on adverse reproductive effects of phthalate exposure. Phthalates constitute a group of chemicals that are
ubiquitous in consumer products and have been related to a wide range of adverse health effects. As a result of a
comprehensive literature search, we present an overview of effect biomarkers for reproductive toxicity that are
substantiated by mechanistic information. The activation of several receptors, such as PPARα, PPARγ, and GR,
may initiate events leading to impaired male and female fertility as well as other adverse effects of phthalate
exposure. Therefore, these receptors appear as promising targets for the development of novel effect biomarkers.
The proposed strategy connects the fields of epidemiology and toxicology and may strengthen the weight of
evidence in observational studies that link chemical exposures to health outcomes.