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Chlorpyrifos (CPF) [O, O-diethyl-O-3, 5, 6-trichloro-2-pyridyl phosphorothioate] is an organophosphate insecticide widely used for agricultural and urban pest control. Trichloropyridinol (TCP; 3,5,6-trichioro2-pyridinol), the primary metabolite of CPF, is often used as a generic biomarker of exposure for CPF and related compounds. Human embryonic kidney 293 (HEK 293) cells were exposed to CPF and TCP with varying concentrations and exposure periods. Cell cultures enable the cost-effective study of specific biomarkers to help determine toxicity pathways to predict the effects of chemical exposures without relying on whole animals. Both CPF and TCP were found to induce cytotoxic effects with CPF being more toxic than TCP with EC50 values of 68.82 mu g/mL and 146.87 mu g.ml(-1) respectively. Cell flow cytometric analyses revealed that exposure to either CPF or TCP leads to an initial burst of apoptotic induction followed by a slow recruitment of cells leading towards further apoptosis. CPF produced a strong induction of IL6, while TCP exposure resulted in a strong induction of IL1 alpha. Importantly, the concentrations of CPF and TCP required for these cytokine inductions were higher than those required to induce apoptosis. These data suggest CPF and TCP are cytotoxic to HEK 293 cells but that the mechanism may not be related to an inflammatory response. CPF and TCP also varied in their effects on the HEK 293 proteome with 5 unique proteins detected after exposure to CPF and 31 unique proteins after TCP exposure. Published by Elsevier Ltd.