Genotoxic and immunotoxic effects of the organophosphate metabolite diethyldithiophosphate (DEDTP) in Vivo.

Diethyldithiophosphate (DEDTP) is a metabolite produced by the degradation of organophosphorus pesticides and a dialkylphosphate that is chemically synthesized with widespread commercial use. DEDTP is a stable compound, and most studies considered it harmless. However, some studies found adverse effects in vitro, including toxicity in different human cell types. However, there are no in vivo studies characterizing the toxicological effects of DEDTP. Therefore, we investigated the genotoxicity and immunotoxicity of DEDTP in a murine model. We used C57BL/6J and Balb/c mice (6-8-weeks-old) exposed to DEDTP i.p. We established that the medium lethal dose (LD50) of DEDTP was 0.537 g/kg. DEDTP was genotoxic in vivo because it increased the frequency of micronuclei in polychromatic erythrocytes in peripheral blood at 0.05 g/kg. DEDTP showed immunotoxic effects on T and Natural Killer cells and immunomodulatory effects on macrophages, especially M2 type that increased 1000% after 20 days of exposure to 0.01 g/kg. These effects modified the response to a tumoural challenge. DEDTP exposure increased tumour size and reduced the response of lymphocytes to tumoural antigen stimulation. We conclude that exposure to DEDTP produced genotoxic and immunomodulatory effects at environmentally relevant concentrations, which affected the growth of tumours in vivo. These results suggest that DEDTP might reduce the quality of life in exposed individuals, and it exhibits genotoxicity and immunotoxicity despite its stability.