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Immunotoxicity Studies of Sulfolane Following Developmental Exposure in Hsd:Sprague Dawley SD Rats and Adult Exposure in B6C3F1/N Mice.

K A Shipkowski 1, M C Cora 1, M F Cesta 1, V G Robinson 1, S Waidyanatha 1, K L Witt 1, M K Vallant 1, D M Fallacara 2, M R Hejtmancik 2, S A Masten 1, S D Cooper 3, R A Fernando 3, C R Blystone 1

1Division of the National Toxicology Program, National Institute of Environmental Health Sciences, Research Triangle Park, NC, USA.
2Battelle Memorial Institute, Columbus, OH, USA.
3RTI International, Research Triangle Park, NC, USA.

Note: The PA46 was updated on September 14, 2021 for updates to stats for calculation of % animals with a finding.

Note: M09 was updated for number of spleen cells on September 1, 2021. The new tables contain a correction to a typographical error in the units for the Ig concentrations.

Note: M07 was updated for number of spleen cells on July 22, 2021. The I07 was updated on August 12, 2021 to reflect updated footnotes. The I04G was also updated on August 22, 2021 to reflect updated statistical analysis.

DOI: https://doi.org/10.22427/NTP-DATA-002-03276-0016-0000-7

Related Publications

Waidyanatha S, Black SR, Fennell TR, et al. Toxicokinetics and bioavailability of sulfolane, a ground water contaminant, following oral and intravenous administration in rodents: A dose, species, and sex comparison. Toxicol Appl Pharmacol. 2019;379:114690. doi: https://doi.org/10.1016/j.taap.2019.114690

Waidyanatha S, Black SR, Blystone CR, et al. Disposition and metabolism of sulfolane in Harlan Sprague Dawley rats and B6C3F1/N mice and in vitro in hepatocytes from rats, mice, and humans. Xenobiotica. 2020;50(4):442-453. https://doi.org/10.1080/00498254.2019.1630786

****The 28-day sulfolane comparative studies will be added to this page once accepted for publication (Shipkowski et al, in review) ***



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 wk-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/d. Immune parameters evaluated included measurement of natural killer (NK) cell activity, antibody production to sheep red blood cells (SRBC) and keyhole limpet hemocyanin (KLH), cytotoxic T-cell (CTL) activity, T-cell proliferation, splenic immune cell populations, hematological parameters, and histopathology of immune tissues. The results indicated there was a decrease in NK cell activity in 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, 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/d 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.


Study Tables - Rats

Individual Animal Data - Rats

Study Tables - Mice

Individual Animal Data - Mice