Comprehensive overview of triclosan neurotoxicity and construction of adverse outcome pathways using a systems toxicology approach: Triclosan-induced attention-deficit hyperactivity disorder as an example

Triclosan (TCS) is widely applied to daily necessities as a chemical bacteriostatic agent. Environmental TCS levels have increased significantly following the coronavirus disease 2019 pandemic, posing a potential threat to humans and ecosystems. Epidemiological investigations and toxicological studies have shown that long-term TCS exposure can damage human tissues and organs and induce neurodevelopmental disorders in offspring. However, studies on the mechanisms underlying its neurotoxicity and toxicity risk assessments are limited. This review summarizes the status of environmental and human TCS exposure and systematically outlines its neurotoxic effects. To further elucidate the mechanisms underlying TCS neurotoxicity, using TCS-induced attention-deficit hyperactivity disorder (ADHD) as an example, we constructed an adverse outcome pathway (AOP) framework based on a systematic toxicology approach. We found that TCS increased the expression of cannabinoid receptor 1, which activates the “neuroactive ligand–receptor interaction” pathway, leading to ADHD-like behaviors, including cognitive, learning, and memory deficits, by modulating chemical synaptic transmission and neurotransmitter levels. The AOP framework was further used to assess the associated neurodevelopmental toxicity risks of TCS, contributing to a better understanding of its characteristics and safety. Thus, future research on the mechanisms underlying TCS toxicity and issues related to its detection and regulation should be emphasized.