title: Evaluation of N-butylbenzenesulfonamide (NBBS) neurotoxicity in Sprague-Dawley male rats following 27-day oral exposure.
abstract: N-Butylbenzenesulfonamide (NBBS) is widely used as a plasticizer in polyacetals, polyamides, and polycarbonates and has been found in ground water and effluent from wastewater treatment sites. The compound is lipophilic and distributes rapidly to the brain but also clears rapidly and shows little evidence of accumulation. Limited studies in the literature report neurotoxicity of NBBS in rabbits and rats. Adult Sprague-Dawley male rats (Harlan) received corn oil vehicle or NBBS (100, 200, or 400mg/kg/d) via oral gavage (5 ml/kg bwt) daily/5d/week for 27 d. Deaths were observed in the 400mg/kg/d dose group in the first 5d and dosing was decreased to 300 mg/kg/d. No alterations were observed in gait, locomotor activity, and rearing behavior. No histological lesions were observed in the testis, seminal vesicles, coagulating gland, epididymis, and prostate. In the liver, minimal centrilobular hypertrophy was evident in all rats of the high dose group. Contrary to previous reports, there was no evidence of peripheral nerve lesions or gliosis in the hippocampus or cerebellum. mRNA levels for glial fibrillary acidic acid protein, interferon gamma, CXCR-3, intracellular adhesion molecule-1, and CD11b were not altered in the hippocampus while Iba-1 levels were decreased. These data do not support previous reports of neurotoxicity for NBBS within a 4-week exposure regimen; however, neuropathological injury occurring over an extended period of exposure cannot be ruled out and given the potential for human exposure requires further examination.
authors: Toxicology Branch, National Toxicology Program, NIEHS, United States.
authors: C V
authors: CV
authors: Rider
authors: lntegrated Laboratory Systems Inc., RTP, NC, United States.
authors: K S
authors: KS
authors: Janardhan
authors: lntegrated Laboratory Systems Inc., RTP, NC, United States.
authors: D
authors: D
authors: Rao
authors: Charles River Pathology Associates, 4025 Stirrup Creek Drive, Suite 150, Durham, NC 27703, United States.
authors: J P
authors: JP
authors: Morrison
authors: NTP Laboratory, NIEHS, RTP, NC 27709, United States.
authors: C A
authors: CA
authors: McPherson
authors: NTP Laboratory, NIEHS, RTP, NC 27709, United States. Electronic address: harry@niehs.nih.gov.
authors: G J
authors: GJ
authors: Harry
mesh_terms: D000284:Administration, Oral; D000818:Animals; D001522:Behavior, Animal / Q000187:drug effects; D015415:Biomarkers / Q000378:metabolism; D004305:Dose-Response Relationship, Drug; D005786:Gene Expression Regulation / Q000187:drug effects; D005837:Genitalia, Male / Q000187:drug effects / Q000473:pathology; D006624:Hippocampus / Q000187:drug effects* / Q000378:metabolism / Q000473:pathology; D008099:Liver / Q000187:drug effects / Q000473:pathology; D008297:Male; D009043:Motor Activity / Q000187:drug effects; D020258:Neurotoxicity Syndromes / Q000209:etiology* / Q000235:genetics / Q000378:metabolism / Q000473:pathology / Q000503:physiopathology / Q000523:psychology; D010968:Plasticizers / Q000008:administration & dosage / Q000633:toxicity*; D012333:RNA, Messenger / Q000378:metabolism; D051381:Rats; D017207:Rats, Sprague-Dawley; D060888:Real-Time Polymerase Chain Reaction; D018570:Risk Assessment; D012737:Sex Factors; D013449:Sulfonamides / Q000008:administration & dosage / Q000633:toxicity*; D013997:Time Factors; D018675:Toxicity Tests; D014874:Water Pollutants, Chemical / Q000008:administration & dosage / Q000633:toxicity*; D000096926:Benzenesulfonamides
chemical_list: D015415:Biomarkers; D010968:Plasticizers; D012333:RNA, Messenger; D013449:Sulfonamides; D014874:Water Pollutants, Chemical; C065565:N-butylbenzenesulfonamide; D000096926:Benzenesulfonamides