Chlorpyrifos Inhibits Intestinal Stem Cell Proliferation and Differentiation at the Acceptable Daily Intake and Disrupts Immune Responses at High Doses

The acceptable daily intake (ADI) and maximum residue limits in food for chlorpyrifos (CPF), a widely used organophosphorus pesticide, may damage the intestine. Here, we evaluated damage to the intestine by CPF at the ADI (0.01 mg/kg bodyweight/day) and at 10 times the ADI (10ADI; 0.1 mg/kg bodyweight/day) in mice after 8 weeks of exposure and evaluated the resulting immune response to an enterotoxigenic Escherichia coli (ETEC) infection. CPF at the ADI dose significantly disrupted the intestinal integrity and intestinal stem cell functionality, which may be associated with reduced indole-3-propionic acid levels. However, mice in the 10ADI group exhibited only elevated pro-inflammatory cell and cytokine levels. During ETEC infection, intestinal mucosal immunity was activated by the 10ADI dose, as indicated by increased regulatory T cells and IL-10 levels, which were associated with decreased fecal butyric acid content. Our study demonstrated that the effects of pesticide residues appear to be dose-specific, bringing attention to the health risk at the ADI level.