The following abstract presents results of a study conducted by a contract laboratory for the National Toxicology Program. The findings have not been peer reviewed and were not evaluated in accordance with the levels of evidence criteria established by NTP in March 2009. The findings and conclusions for this study should not be construed to represent the views of the NTP or the U.S. Government.
Tetraethyl Lead was selected for immunotoxicological evaluation because of the data in the literature indicating that this chemical has effects on the hematopoietic and immune systems.
Based on probe studies, the doses selected were 0.5, 1.0, and 2.0 mg/kg. Exposure was performed by gastric gavage using corn oil as the vehicle. The mice were exposed daily for 14 consecutive days. The high dose (2.0 mg/kg) produced nervous system toxicity, as seen in tremors which began about day 5 of exposure. Tetraethyl Lead produced dose dependent decreases in erythrocyte number, hematocrit and peripheral blood leukocytes, suggesting the bone marrow as a target. There was a slight but significant increase in BUN, suggesting an effect on the kidney. Histopathological evaluation was negative with respect to the lymphoid tissue, but a mild chronic hepatitis was observed in the middle and high dose groups.
The studies were limited to Tier 1 evaluation because of a lack of effects on the following immune parameters of B6C3F1 mice exposed to Tetraethyl Lead: IgM antibody forming cell response to the T-dependent antigen sheep erythrocytes, mixed lymphocyte response, and delayed hypersensitivity response to keyhole limpet hemocyanin. Serum complement levels, as measured by total hemolytic activity (CH50), were decreased dose dependently. Since decreased serum complement levels have been associated with an increased susceptibility to Streptococcus pneumoniae, this organism was selected as the host resistance model. However, exposure to Tetraethyl Lead did not alter resistance of mice to Streptococcus pneumoniae. One mechanism by which complement is involved with host resistance to Streptococcus pneumoniae is by opsonizing the bacteria with C3 and C3 cleavage products which facilitate phagocytosis by polymorphonuclear leukocytes and macrophages. Serum C3 levels in mice exposed to Tetraethyl Lead were unaffected, explaining the absence of effect on host resistance. Tetraethyl Lead apparently affects some component of complement other than C3.
This is the second metal investigated by the NTP Immunotoxicology Program; cadmium was the first. Both of these metals were reported to be immunotoxic and the studies conducted by the NTP Immunotoxicology Program showed them to lack significant immunotoxic effects.