Bis(1,2,2,6,6-pentamethyl-4-piperidyl) [[3,5-bis(1,1-dimethylethyl)-4-hydroxyphenyl]methyl]butylmalonate

Immunotoxicity

Additional information

Immunotoxicological parameters were investigated in a 14 -day study in mice (Ciba-Geigy 1987). Toxicological variables evaluated included: (1) body and selected organ wieights; (2) selected hematological parameters; (3) selected serum chemistry levels; (4) the ability to produce antibody to the T-dependent antigen, sheep erythrocytes; (5) the ability to produce a delayed hypersensitivity response to keyhole limpet hemocyanin; (6) the ability of spleen cells to respond to T-cell mitogens and to allogeneic cells; and (7) the ability of spleen cells to respond to a B-cell mitogen (LPS).

The highest tested dose of 70 mg/kg bw did not cause effects on body weight upon 14 -day dermal exposure. The authors of the study indicate that significant oral exposure may have occurred due to preening as the treated site could easily be reached and no special precautions were taken. The vehicle used was acetone/olive oil and it is one that is typically used in the local lymph node assay.Very little difference was noted between abraded and intact abdominal skin.

The substance in acetone/olive oil, administered daily for 14 days to the abraded or non-abraded skin of B6C3F1 female mice produced changes in the lymphoreticular system, as manifested in a decrease in thymus weight, an increase in spleen weight, an increase in the number of polymorphonuclear leukocytes, an increase in humoral- and cell-mediated immune responses, and a decrease in lymphocyte proliferative responses at 70 mg/kg bw. These changes are consistent with an adjuvant effect. There was also a decrease in erythroid elements in one of the studies.

At the next lower dose of 7 mg/kg bw the only parameter that was changed was the responsiveness of spleen cells to LPS stimulation. The lower response to LPS-induced B-cell proliferation in cultivated spleen cells is difficult to interpret. From the subacute oral data, the substance attracts macrophages in the tissue and in serum causes an increase in monocytes and a relative decrease in lymphocytes. plasma. The lower responsiveness to LPS may simply represent the relative decrease in lymphocytes as a lower number of naive B-cells would be present in the tested cell population.