Chronotoxicity of dietary acrylamide: insights from circadian neurobiology and translational toxicology

Acrylamide is a well-known neurotoxic and potentially carcinogenic compound formed during high-temperature (>120 °C) food processing via the Maillard reaction between reducing sugars and the amino acid asparagine. Emerging evidence from vertebrate and invertebrate models indicates that dietary acrylamide disrupts circadian rhythmicity—a fundamental biological process governing metabolic and behavioral homeostasis. This review introduces the concept of a “chronotoxin,” defined as a toxicant that disrupts circadian regulation and produces circadian-related toxic effects, and proposes acrylamide as a relevant candidate. We summarize mechanistic insights into acrylamide-driven circadian disruption, focusing on oxidative stress, mitochondrial dysfunction, kinase signaling pathways (ERK/CREB/BDNF), and interactions with melatonin and serotonin systems. Furthermore, we highlight the translational relevance of circadian biomarkers in dietary neurotoxicology and public health monitoring, particularly under chronic, low-dose exposure. In this context, circadian endpoints may be informative for extrapolating findings to dietary exposure scenarios, while acknowledging inherent differences between experimental and dietary conditions. This review advances the concept of chronotoxicity by identifying acrylamide as a model compound for studying circadian disruption, with implications for biomarker development, dietary risk assessment, and public health monitoring, and provides a framework for evaluating circadian aspects of neurotoxicity linked to food-borne chemicals.