Gender-based profiles of developmental immunotoxicity to lead in the rat: Assessment in juveniles and adults

Gender-based differences in immunotoxicity induced by the heavy metal lead (Pb) have been observed both in the juvenile chicken and the adult rat foll owing low-level exposure during embryonic development, To better define the gender-based differences, as related to dose following In utero exposure t o Pb, potential differential sensitivities were examined after exposure of F 344 rats to low concentrations of Pb (0, 50, 700, or 250 ppm Pb) ad libit um throughout gestation. Immune assessment was performed in juveniles (5 wk old) and young adults (13 wk old). At the highest (250 ppm) Pb concentrati on examined, the delayed-type hypersensitivity (DTH) response was depressed in females relative to gender-matched controls at both ages; relative sple en weights and relative neutrophil numbers were increased while relative an d absolute monocyte numbers and relative basophil numbers were decreased at 13 but not 5 wk of age. In contrast, 250 ppm Pb-treated males did not diff er in these endpoints. With in utero exposure to 100 ppm Pb, 13-wk-old fema les again had decreased relative and absolute monocyte numbers and increase d relative neutrophil numbers, although the DTH response was unchanged. Mal es (with 100 ppm Pb) had increased relative neutrophil numbers, decreased r elative lymphocytes, and transiently increased nitrite production seen at 5 , but not 13, wk of age. After gestational exposure to 50 ppm Ph, minimal i mmunotoxic effects were observed in either males or females at either devel opmental age assessed. These results suggest that differential gender-based immunotoxicity profiles exist after gestational Ph exposure depending on t he concentration of Pb administered to the dam. In utero exposure of dams t o 250 ppm Pb results in more profound immunotoxicity in females than males, Males are not more sensitive to lower concentrations of Pb than females. S ince the 50 ppm exposure produced minimal changes, these data may provide i nformation to establish a no-observed-adverse-effect level (NOAEL) for in u tero exposure to Pb. Additionally, white most effects were evident at both juvenile and adult ages, some changes were not fully evident until measured in the adult. Most changes were persistent with only one exception (male n itrite levels at 100 ppm).