Evaluation of the Developmental Toxicity of Sodium Nitrite in Long-Evans Rats

Sodium nitrite administered in the drinking water to Long-Evansrats during pregnancy and lactation severely affected erythropoieticdevelopment, growth, and mortality in their offspring. Pregnantrats were maintained throughout gestation on 0.5, 1, 2, or 3g NaNO₂/liter. There were no significant differences betweentreated and control litters at birth. Thereafter, pups of treateddams on 2 and 3 g NaNO₂/liter gained less weight, progressivelybecame severely anemic, and began to die by the third week postpartum.By the second week postpartum, hemoglobin levels, RBC counts,and mean corpuscular volumes of these pups were all drasticallyreduced compared to controls. Blood smears showed marked anisocytosisand hypochromasia. Gross chylous serum lipemia and fatty liverdegeneration were noted. Histopathology demonstrated cytoplasmicvacuolization of centrilobular hepatocytes and decreased hematopoiesisin bone marrow and spleen. Administration of 1 g NaNO₂/literresulted in hematological effects but did not affect growthor mortality. NaNO₂(0.5 g/liter) was at or near the no observedeffect level. Cross-fostering indicated that treatment dunngthe lactational period was more instrumental in producing lesionsthan treatment during the gestational period. The data presentedare consistent with the lactational induction of severe irondeficiency in the neonate.