title: NTP Toxicology and Carcinogenesis Studies of Technical Grade Sodium Xylenesulfonate (CAS No. 1300-72-7) in F344/N Rats and B6C3F1 Mice (Dermal Studies).
abstract: Sodium xylenesulfonate is used as a hydrotrope, an organic compound that increases the ability of water to dissolve other molecules. Sodium xylenesulfonate is a component in a variety of widely used shampoos and liquid household detergents where it can constitute up to 10% of the total solution. Because of its widespread use, the potential for human exposure to sodium xylenesulfonate is great. Male and female F344/N rats and B6C3F1 mice were administered sodium xylenesulfonate in water or 50% ethanol dermally for 17 days, 14 weeks, or 2 years. Genetic toxicology studies were conducted in Salmonella typhimurium, L5178Y mouse lymphoma cells, and cultured Chinese hamster ovary cells. 17-DAY STUDY IN RATS: Groups of five male and five female rats were administered 300 mL of 0, 5, 15, 44, 133, or 400 mg/mL sodium xylenesulfonate in distilled water by dermal application 5 days per week for 17 days. All rats survived to the end of the study. Final mean body weights and body weight gains of dosed rats were similar to those of the control groups. Dermal applications of 300 mL of 5, 15, 44, 133, and 400 mg/mL delivered average daily doses of approximately 10, 30, 90, 260, and 800 mg sodium xylenesulfonate/kg body weight to males and 13, 40, 120, 330, and 1,030 mg/kg to females. Clinical findings generally involved the skin of dosed animals and included tan or brown skin discoloration and crusty white deposits (presumed to be dried chemical) at the site of application. Neither of these observations were considered significant findings. The relative liver weights of 133 and 400 mg/mL male and female rats were significantly greater than those of the control groups, but the absolute liver weights were not increased and the biological significance of the relative differences in liver weight was unclear. In males and females, the few lesions observed grossly and microscopically were generally attributed to repeated clipping and were not considered related to chemical administration. 17-DAY STUDY IN MICE: Groups of five male and five female mice were administered 100 mL of 0, 5, 15, 44, 133, or 400 mg/mL sodium xylenesulfonate in distilled water by dermal application 5 days per week for 17 days. All mice survived to the end of the study. Final mean body weights and body weight gains of dosed mice were similar to those of the controls. Dermal applications of 5, 15, 44, 133, and 400 mg/mL delivered average daily doses of approximately, 20, 60, 190, 540, and 1,600 mg sodium xylenesulfonate/kg body weight to males and 26, 80, 220, 680, and 2,000 mg/kg to females. Clinical findings included crusty white deposits (presumed to be dried chemical) at the site of application in two 133 mg/mL males and in all 400 mg/mL males and females. The absolute and relative liver weights of 15 and 44 mg/mL males and 400 mg/mL males and females were significantly greater than those of the control groups, but the biological significance of these differences was unclear. The few skin lesions observed grossly and microscopically in males and females were generally attributed to repeated clipping and were not considered related to chemical administration. 14-WEEK STUDY IN RATS: Groups of 10 male and 10 female rats were administered 300 mL of 0, 5, 15, 44, 133, or 400 mg/mL sodium xylenesulfonate in 50% ethanol by dermal application for 14 weeks. For special hematology and clinical pathology studies, additional groups of 10 male and 10 female rats were administered 0, 5, 15, 44, 133, or 400 mg/mL sodium xylenesulfonate in 50% ethanol by dermal application for 14 weeks. All rats survived to the end of the study. Final mean body weights and body weight gains of dosed male and female rats were similar to those of the control groups. Dermal applications of 5, 15, 44, 133, and 400 mg/mL delivered average daily doses of approximately 6, 20, 60, 170, and 500 mg sodium xylenesulfonate/kg body weight to males and 10, 30, 90, 260, and 800 mg/kg to females. The only notable clinical finding was brown discoloration of the skin at the site of application in dosed animals. Hemaation in dosed animals. Hematology and clinical chemistry parameters of dosed groups of males and females were significantly different from those of the controls in several instances, but these differences were sporadic and did not demonstrate a treatment relationship. The absolute and relative liver weights of males receiving 44, 133, or 400 mg/mL were significantly less than those of the control group, but the biological significance of these differences was unclear, and there were no treatment-related histopathologic effects in the liver. There were no significant differences in liver weights in female rats. Minimal hyperplasia of the epidermis at the site of application occurred in both male and female rats in the control group as well as most dosed groups. The incidence of epidermal hyperplasia in 400 mg/mL males was possibly chemical related. 14-Week Study in Mice: Groups of 10 male and 10 female mice were administered 100 mL of 0, 5, 15, 44, 133, or 400 mg/mL sodium xylenesulfonate in 50&percnt; ethanol by dermal application for 14 weeks. There were no chemical-related deaths. The mean body weight gain of the 400 mg/mL males was significantly greater than that of the control group. Dermal applications of 5, 15, 44, 133, and 400 mg/mL delivered average daily doses of approximately 17, 40, 140, 440, and 1,300 mg sodium xylenesulfonate/kg body weight to males and 20, 60, 170, 530, and 1,630 mg/kg to females. There were no clinical findings related to sodium xylenesulfonate administration. Epidermal hyperplasia occurred in one 44 mg/mL female, two 133 mg/mL males, five 400 mg/mL males, and four 400 mg/kg females. Hyperplasia of the epidermis in 400 mg/mL males and females was probably related to chemical administration. Chronic inflammation of the skin occurred primarily in the control groups of males and females. These lesions consisted of mononuclear inflammatory cells in the dermis. 2-YEAR STUDY IN RATS: Groups of 50 male and 50 female rats were dermally administered 0, 60, 120, or 240 mg sodium xylenesulfonate/kg body weight in 50&percnt; ethanol for 104 weeks. Survival, Body Weights, and Clinical Findings: Survival of dosed males and females was similar to that of the control groups. Mean body weights of dosed males and females were similar to those of the controls throughout the study. In male groups, there were no clinical findings considered treatment related. In females, clinical findings were limited to irritation at the site of application in one control female, four 120 mg/kg females, and two 240 mg/kg females. Pathology Findings: There were no neoplasms at any site (including the skin) that were considered treatment related.Low incidences of hyperplasia of the epidermis at the site of application occurred in males in the 60, 120, and 240 mg/kg groups. Low incidences of hyperplasia of the epidermis at the site of application also occurred in females in the 120 and 240 mg/kg groups, and they occurred with a significant positive trend. Low incidences of hyperplasia of the sebaceous gland occurred in control and 60 mg/kg males and in control, 120 mg/kg, and 240 mg/kg females. 2-YEAR STUDY IN MICE: Groups of 50 male and 50 female mice were dermally administered 0, 182, 364, or 727 mg sodium xylenesulfonate/kg body weight in 50&percnt; ethanol for 104 to 105 weeks. Survival, Body Weights, and Clinical Findings: Survival of dosed males and females was similar to that of the control groups. Mean body weights of dosed males and females were generally similar to those of the controls throughout the study; however, the mean body weights of 727 mg/kg females were greater than those of the control group from week 85 to week 97. With the exception of irritation at the site of application in one 364 mg/kg female, there were no clinical findings related to sodium xylenesulfonate administration. Pathology Findings: There were no neoplasms at any site (including the skin) that were considered treatment related.Hyperplasia of the epidermis occurred in control,364 mg/kg, and 727 mg/kg males and in control and dosed females. In male mice, the incidences occurred with a significant positive trend. Focal ulceration occurred in one 727 mg/kg male and in one female in each dose group. In males and females from control and dosed groups, the incidences of hepatocellular adenoma, hepatocellular carcinoma, and hepato- cellular adenoma or carcinoma (combined) were generally higher than those expected by spontaneous occurrence. The incidences of hepatocellular neoplasms in some groups of males and females exceeded the NTP historical control range. Male mice had a pattern of nonneoplastic liver lesions along with silver stained positive helical organisms within the liver which suggests an infection with Helicobacter hepaticus. The findings in this study of sodium xylenesulfonate were not considered to have been significantly impacted by the infection with H. hepaticus or its associated hepatitis. GENETIC TOXICOLOGY: Sodium xylenesulfonate was not mutagenic in Salmonella typhimurium strain TA98, TA100, TA1535, or TA1537 with or without induced liver S9. Equivocal results were obtained in a mutation assay with mouse lymphoma cells in the presence of induced S9; no evidence of mutagenicity was noted without S9 in this assay. In cytogenetic tests with sodium xylenesulfonate in cultured Chinese hamster ovary cells, significant increases in sister chromatid exchanges were observed in the absence of S9 only, and no increases in chromosomal aberrations were observed with or without S9. CONCLUSIONS: Under the conditions of these 2-year dermal studies, there was no evidence of carcinogenic activity of sodium xylenesulfonate in male or female F344/N rats administered 60, 120, or 240 mg/kg or in male or female B6C3F1 mice administered 182, 364, or 727 mg/kg. Increased incidences of epidermal hyperplasia in female rats and male mice may have been related to exposure to sodium xylenesulfonate. Synonyms: Benzenesulfonic acid, dimethyl-, sodium salt; xylenesulfonic acid, sodium salt; sodium dimethylbenzenesulfonate; xylenesulfonic acid, sodium salt Trade names: Conco SXS; Cyclophil; SXS 30; Eletesol SX 30; Naxonate; Naxonate G; Richonate SXS; Stepanate SXS; Stepanate X; SXS 40; Ultrawet 40SX