Immunotoxicity of pyrethroid metabolites in an in vitro model

Risk assessment of man-made chemicals such as pesticides are mainly focused on parent compounds, and relatively little is known about their metabolites, especially with regard to target organ damages such as immunotoxicity. In the present study, the immunotoxicity of five synthetic pyrethroids (SPs) and three common metabolites was evaluated using an in vitro model by 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide (MTT) assay, cytoflow, and enzyme-linked immunosorbent assay (ELISA). Cell viability and apoptosis assays showed that both SPs and their metabolites possessed cytotoxicity to the monocytic cells. The aldehyde and acid derivatives were more effective than the other compounds at cytotoxicity, with inhibition of cell viability by 56.8 and 50.6% at 10⁻⁵ mol L⁻¹, and induction of 8.52 and 8.81% cell apoptosis, respectively. Exposure to SPs and their metabolites also led to changes in the secretion levels of tumor necrosis factor α (TNF α) and interleukins (ILs), and again the metabolites showed stronger effects than the parent compounds. The aldehyde derivative upregulated IL-12p70 level by 1.87-fold, and the alcohol and acid derivative increased the secretion of TNF α 5.88 and 7.96-fold, relative to the control group. In the in vitro model, the common metabolites of SPs clearly exerted greater immunotoxic effects to monocytes than the intact parent compounds. Results from the present study suggested the need for considering metabolites in achieving more comprehensive health risk assessment of man-made chemicals, including target organ toxicities such as immunotoxicity.