Developmental Neurotoxicity of Endocrine Disruptor Chemicals: A Challenge for Behavioral Toxicology

Abstract

Abstract The brain develops over an extended period of time during which it is extremely sensitive to environmental influences and to endogenous hormones that modulate brain plasticity and behavior. Endocrine disrupting chemicals (EDCs) interfere with physiological endocrine actions by a variety of mechanisms including epigenetic modification. In common with known neurotoxicants EDCs induce neurobehavioral alterations in the developing organisms that may not become apparent until later in life. The scientific criteria for proper risk assessment of EDCs are still the subject of intense debate among scientists and regulators worldwide: major issues concern the definition of endocrine function and relative adverse effects, the existence of thresholds, the significance of non-monotonic dose–response relationships. A growing number of chemicals are reported to cause behavioral changes at low-dose developmental exposure by previously unsuspected hormone-like activity. The variety of EDC action on brain and behavior development makes extremely complicated to select endpoints representing the whole spectrum of potential effects of these chemicals in humans. Predictive biomarkers of exposure and effects are needed to trace EDC health effects in a shorter period of time in epidemiological studies. In a developmental perspective, prospective animal cohorts integrated by updated in vitro and in silico models may identify candidate biomarkers anchored to the behavioral phenotype and pinpoint sex and life stage vulnerability to address the EDC issue in large prospective human studies.