Immunotoxicity of N-butylbenzenesulfonamide: impacts on immune function in adult mice and developmentally exposed rats

• Published in: Toxicological sciences Vol. 196; no. 1; pp. 71 - 84
• Main Authors: Johnson, Victor J, Rider, Cynthia V, Luster, Michael I, Brix, Amy, Burleson, Gary R, Cora, Michelle, Elmore, Susan A, Frawley, Rachel P, Lopez, Franklin R, Mutlu, Esra, Shockley, Keith R, Pierfelice, Jessica, Burback, Brian, Co, Caroll A, Germolec, Dori R
• Format: Journal Article
• Language: English
• Published: United States Oxford University Press 30.10.2023
• Subjects: Animals; Female; Humans; Immunity; Immunotoxicology; Male; Mice; Mice, Inbred Strains; Rats; Rats, Sprague-Dawley; Sulfonamides - toxicity; immunotoxicity testing; T-dependent antibody response; developmental immunotoxicity; natural killer cell activity; butylbenzenesulfonamide; benzosulfonamides; N-butylbenzenesulfonamide
• ISSN: 1096-6080; 1096-0929
• DOI: 10.1093/toxsci/kfad083

Abstract N-butylbenzenesulfonamide (NBBS) is a high-production volume plasticizer that is an emerging contaminant of concern for environmental and human health. To understand the risks and health effects of exposure to NBBS, studies were conducted in adult-exposed mice and developmentally exposed rats to evaluate the potential for NBBS to modulate the immune system. Beginning between 8 and 9 weeks of age, dosed feed containing NBBS at concentrations of 0, 313, 625, 1250, 2500, and 5000 ppm was continuously provided to B6C3F1/N female mice for 28 days. Dosed feed was also continuously provided to time-mated Harlan Sprague Dawley (Sprague Dawley SD) rats at concentrations of 0-, 250-, 500-, and 1000-ppm NBBS from gestation day 6 to postnatal day 28 and in F1 rats until 11–14 weeks of age. Functional assessments of innate, humoral, and cell-mediated immunity were conducted in adult female mice and F1 rats following exposure to NBBS. In female mice, NBBS treatment suppressed the antibody-forming cell (AFC) response to SRBC with small increases in T-cell responses and natural killer (NK)-cell activity. In developmentally exposed rats, NBBS treatment-related immune effects were sex dependent. A positive trend in NK-cell activity occurred in male F1 rats while a negative trend occurred in female F1 rats. The AFC response to SRBC was decreased in female F1 rats but not in male F1 rats. These data provide evidence that oral exposure to NBBS has the potential to produce immunomodulatory effects on both innate and adaptive immune responses, and these effects appear to have some dependence on species, sex, and period of exposure (developmental vs adult).