Fluoride Toxicodynamics and Interactions with Co-Contaminants: Mechanistic Insights with Implications for...

Fluoride (F^-) exerts a dual role in agricultural systems, supporting dental mineralization at low levels but inducing multiorgan toxicity under chronic exposure. While the detrimental effects of F^- have been well documented, its interactions with co-occurring micronutrients (e.g., Zn, Se, I) and toxicants (e.g., Al, Cd, As) remain incompletely characterized in the context of food production and animal husbandry. Accumulating evidence indicates that essential micronutrients can attenuate F^- toxicity by potentiating antioxidant defenses and stabilizing metalloenzyme activity, whereas toxicants aggravate F^--mediated injury through synergistic oxidative damage. These multielement interactions modulate F^- bioavailability, tissue distribution, and organ-specific pathology in livestock tissues and food commodities. Critical knowledge gaps persist regarding cumulative exposure thresholds and the practical relevance of animal models for food safety risk assessment. This review synthesizes mechanistic insights into F^--element interactions and discusses emerging mitigation strategies to prevent or ameliorate fluorosis under real-world multicontaminant scenarios in agricultural settings.