In vitro myelotoxic effects of cypermethrin and mancozeb on human hematopoietic progenitor cells

In the past two decades, hematologic and immunologic disorders in humans have been increasingly reported as a result of pesticide exposures. Therefore, safety assessment is required to assess the effects on hematopoiesis and thus on the immune system in addition to routine toxicity evaluation. Currently, the data available on effects of pesticides on hematopoiesis in humans is limited. In the study here, cypermethrin and mancozeb were evaluated for their possible effects on hematopoiesis in vitro. Hematopoietic stem or progenitor cells from human cord blood were isolated and then exposed for 14 days to cypermethrin or mancozeb at non-cytotoxic doses (0.9-16 mu M), and the effect on hematopoiesis screened via a methylcellulose-based clonogenic assay. Results indicated there were significant concentration-related decreases in clonogenic potentials of erythroid and granulocyte-macrophage colony formation. The inhibitory concentration (IC50) value with erythroid progenitors for cypermethrin was 8.7 [+/- 0.2 mu M; mean [+/- SE]) and for mancozeb 6.2 [+/- 0.2] mu M. Similarly, IC50 values with granulocyte-macrophage progenitors for cypermethrin and mancozeb were 19.2 [+/- 1.0] and 8.1 [+/- 0.2] mu M, respectively. These data suggest that erythroid progenitors are perhaps more sensitive to these pesticides. Still, further studies are needed to understand the functional significance of these in vitro findings. For now, these data, albeit preliminary, emphasize the need to include an expanded battery of tests to understand effects on immune parameters in pre-clinical safety studies with pesticides. This study also emphasizes the utility of human cord blood in assessing potential effects on hematopoiesis in vitro.