Immunotoxicity studies of sulfolane following developmental exposure in Hsd:Sprague Dawley SD rats and adult exposure in B6C3F1/N mice

Abstract

Sulfolane is a solvent used in the petrochemical industry and a groundwater contaminant in areas near refineries. The current studies were conducted to assess the impact of oral exposure to sulfolane on the immune system using two models: (1) a perinatal drinking water exposure to 0, 30, 100, 300, or 1000 mg/L from gestation day (GD) 6 until ∼13 weeks-of-age in Harlan Sprague Dawley rats; and, (2) a 90-day gavage exposure of adult female B6C3F1/N mice to 0, 1, 10, 30, 100, or 300 mg/kg/day. Immune parameters evaluated included measurement of antibody production against sheep red blood cells (SRBC) and keyhole limpet hemocyanin (KLH), ex vivo measurements of natural killer (NK) cell activity, cytotoxic T-cell (CTL) activity, and T-cell proliferation, as well as measures of splenic immune cell populations, hematological parameters, and histopathology of immune tissues. A decrease in ex vivo NK cell activity was observed in cells from female - but not male - F1 rats following developmental exposure. In adult female mice, splenic NK cell number was lower than the vehicle controls at doses ≥ 100 mg/kg; however, ex vivo NK cell activity was not affected by sulfolane treatment. In female mice, a decrease in the number of large unstained cells at doses ≥ 30 mg/kg was observed. In F1 rats, effects on white blood cells (WBC) were limited to a decreasing trend in leukocytes in females; no effects were observed in males. Under the conditions of this study, a no-observed-effect level (NOEL) of 3 mg/kg/day was identified based on reduced NK cell activity in female F1 rats. Overall, these findings suggest that oral exposure to sulfolane in rodents had minimal effects on the immune system.

Keywords: Immunotoxicity; NK cells; immune system; immunotoxicology; innate immunity; sulfolane.

Figure 1.

NK cell activity following exposure of adult female B6C3F1/N mice and F1 rats to sulfolane. Cyclophosphamide (CPS) administered via IP intraperitoneal injection at 15 mg/kg (rat) or 50 mg/kg (mice). Arrows indicate significant decreasing trend with increasing sulfolane exposure (p< 0.01 for mice and p< 0.05 for rats). Result is significantly different from vehicle control group (*p< 0.05; **p< 0.01). E:T: effector:target ratio.

Figure 2.

Splenic NK cell numbers following exposure of adult female B6C3F1/N mice and F1 HSD rats to sulfolane. Cyclophosphamide (CPS) administered via IP injection at 15 mg/kg (rat) or 50 mg/kg (mice). Arrows indicate a significant decreasing trend with increasing sulfolane exposure (p< 0.05). Result is significantly different from vehicle control group (*p< 0.05; **p< 0.01).