Current risk assessment policies typically focus on an individual chemical-by-chemical approach that fails to identify interactions between chemical and nonchemical stressors and to address the impact of environmentally relevant chemical mixtures during neuronal development. Speakers and researchers of the Workshop Session “This is Your Brain on Mixtures: Neurodevelopmental Effects of Combined Exposures” during the 2022 SOT Annual Meeting and ToxExpo discussed the importance of implementing tools to assess mixtures risk for evaluating developmental neurotoxicity.
Dr. Elaine Faustman from the University of Washington provided insights on the exposome in the context of neurodevelopmental pesticide. The exposome is defined as the entirety of an individual exposure from conception to death and can be used to investigate lifetime environmental exposure and to provide a more accurate assessment of toxicological endpoints. Assessing neurodevelopmental toxicity of mixtures is critical, and the neurodevelopmental pesticide exposome represents a useful tool to investigate neurodevelopmental processes in children.
Dr. David Herr from the US EPA focused on the neurological effects of combined exposure to a neurotoxicant and nonchemical stressors during the perinatal period. In the study presented during his talk, pregnant rats and pups were exposed to manganese through drinking water and subjected to pre- and postnatal stressors (e.g., noise, predator odor, restricted movement). The results presented showed that effects of manganese alone or in combination with nonchemical stressors varied between sexes and tests. Interestingly, more changes were reported in tests that required training compared with untrained behaviors.
Dr. Kristen Ryan from NIEHS discussed new methodologies to evaluate the neurodevelopmental toxicity of complex mixtures and presented some of the new approach methodologies (NAMs) available for developmental neurotoxicity screening batteries. While NAMs are promising tools to screen for neurodevelopmental toxicity, further development and refinement are needed to facilitate integration and interpretation of complex data.
Dr. Anna Bal-Price from the European Commission Joint Research Centre presented how adverse outcome pathways (AOP), critical developmental processes, and key events could be used to build a useful framework to evaluate mixtures. Mixture effects of heterogeneous chemicals known to cause cognitive impairment included endpoints that also are observed in the brains of children with autism spectrum disorder. As chemicals at low concentrations showed neurotoxicity in mixtures, it is pivotal to further develop and characterize these methods and frameworks to incorporate data collected from various sources and to better predict mixtures’ effects during neurodevelopment.
Dr. Devon Payne-Sturges from the University of Maryland introduced the concept of system dynamics and explained how these systems could be used to assess cumulative environmental neurodevelopmental risks and to study the combined effects of exposure to multiple developmental toxicants and to nonchemical stressors. Importantly, these models are useful to assess environmental health inequities and population-level disparities and assist in regulatory and policy decisions.
Even if the five talks discussed the neurodevelopmental effects of combined exposures from different angles, several common factors were highlighted by all the speakers. These common aspects included the importance of implementing the current “single-chemical” regulatory policies that underestimate the impact that environmental mixtures exposure has on the developing brain. Neurodevelopmental mixture risk assessment is certainly not trivial and there are still several challenges to address to refine and improve these methods in the light of regulatory relevance. Leaving the Workshop Session, I realized that while the pathway has been traced, the best is certainly yet to come.
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