Abstract

Sodium thioglycolate is a white powder with a melting point greater than 300°C. It appears as hygroscopic crystals with an unpleasant odor characteristic of the sulfhydryl group (mercaptans). Thioglycolic acid can be prepared by the action of sodium sulfhydrate on sodium chloroacetate and by electrolysis of dithioglycollic acid from sodium sulfide and sodium chloroacetate. It is also formed by heating chloroacetic acid with potassium hydrogen sulfide. Thioglycolic acid and its salts and glyceryl esters are not known to occur naturally. Sodium thioglycolate is used in the cosmetic industry as an antioxidant, depilating agent, hair waving/straightening agent, and reducing agent. Its primary cosmetic use is in depilatories. Sodium thioglycolate is also used as an analytical reagent and in bacteriology for the preparation of thioglycolate media. Sodium thioglycolate was nominated by the National Cancer Institute for toxicology studies due to its high production volume and widespread occupational and consumer exposure to thioglycolic acid and its salts and esters, including significant female exposure in personal care products. Male and female F344/N rats and B6C3F1/N mice were administered sodium thioglycolate (approximately 99% pure) in a vehicle of 95% ethanol:deionized water (1:1) by application to shaved dorsal skin for 16 (rats) or 17 (mice) days or for 3 months. Genetic toxicology studies were conducted in Salmonella typhimurium and mouse peripheral blood erythrocytes.

In the 2-week study in rats, groups of five males and five females were dermally administered 0, 11.25, 22.5, 45, 90, or 180 mg sodium thioglycolate/kg body weight in 95% ethanol:deionized water (1:1) 5 days per week for 16 days. All rats survived to the end of the study. Mean body weights of dosed groups were similar to those of the vehicle control groups. On day 17, all 180 mg/kg males, two 90 mg/kg females, and two 180 mg/kg females had irritation at the site of application. Kidney and liver weights were significantly increased in 180 mg/kg males. Lung weights were significantly decreased in all groups of dosed males. Minimal epidermal hyperplasia occurred in male and female rats administered 45 mg/kg or greater. Mild cytoplasmic focal vacuolization of the centrilobular hepatocytes occurred in all groups of dosed males.

In the 2-week study in mice, groups of five males and five females were dermally administered 0, 22.5, 45, 90, 180, or 360 mg/kg sodium thioglycolate in 95% ethanol:deionized water (1:1) 5 days per week for 17 days. One 360 mg/kg female was found dead on day 5. The mean body weight gain of 180 mg/kg males was significantly greater than that of the vehicle control group. Minimal to mild epidermal hyperplasia occurred in male mice administered 90 mg/kg or greater and in female mice administered 45 mg/kg or greater.

In the 3-month study in rats, groups of 10 males and 10 females were dermally administered 0, 11.25, 22.5, 45, 90, or 180 mg/kg sodium thioglycolate in 95% ethanol:deionized water (1:1) 5 days per week for 3 months. Additional clinical pathology groups of 10 male and 10 female rats were administered the same doses for 22 days. All rats survived to the end of the study; mean body weights of 90 and 180 mg/kg males were significantly less than those of the vehicle controls. All sodium thioglycolate dosed rats developed irritation at the site of application. Thickening of the skin in 90 and 180 mg/kg males and 45 mg/kg or greater females and ulceration of the skin in 90 and 180 mg/kg males and females were observed at the site of application. Chemical-related nonneoplastic lesions occurred at the site of application and included minimal to mild epidermal hyperplasia, hyperkeratosis, sebaceous gland hypertrophy, and ulcers.

In the 3-month study in mice, groups of 10 males and 10 females were dermally administered 0, 22.5, 45, 90, 180, or 360 mg/kg sodium thioglycolate in 95% ethanol:deionized water (1:1) 5 days per week for 3 months. All mice survived to the end of the study; mean body weights of dosed groups were similar to those of the vehicle control groups. Six 360 mg/kg males developed irritation at the site of application. Heart weights were significantly increased in 180 and 360 mg/kg males and 360 mg/kg females. Liver weights were significantly increased in 180 and 360 mg/kg males and 45 mg/kg or greater females. Nonneoplastic lesions were limited to the site of application and included minimal to mild epidermal hyperplasia, hyperkeratosis, sebaceous gland hypertrophy, and inflammation.

Sodium thioglycolate was not mutagenic in S. typhimurium strains TA98, TA100, TA1535, or TA1537 when tested with or without liver S9 activation enzymes. Dermal exposure to sodium thioglycolate for 3 months resulted in a small but significant increase in micronucleated normochromatic erythrocytes in peripheral blood of female mice; results in male mice were negative.

In summary, sodium thioglycolate caused minimal to mild nonneoplastic lesions at the site of application in rats and mice after 3 months of exposure through the skin. The no-observed-effect level (NOEL) for site of application lesions in female rats was 11.25 mg/kg. The NOEL for site of application lesions in male mice was 90 mg/kg. There was no NOEL for male rats or female mice.

Synonyms: Mercaptoacetic acid monosodium salt; mercaptoacetic acid, sodium salt; monosodium mercaptoacetate; sodium 2-mercaptoethanoate; sodium mercaptoacetate; sodium thioglycollate; thioglycolate sodium; thioglycolic acid, sodium salt; thioglycollic acid, sodium salt

Trade names: Erhavit D, Mollescal SF

Contents

• Foreword
• Collaborators
• Contributors
• Peer Review
• Publication Details
• Introduction
  • Chemical and Physical Properties
  • Production, Use, and Human Exposure
  • Regulatory Status
  • Absorption, Distribution, Metabolism, and Excretion
  • Toxicity
  • Reproductive and Developmental Toxicity
  • Carcinogenicity
  • Genetic Toxicity
  • Study Rationale
• Materials and Methods
  • Procurement and Characterization
  • Preparation and Analysis of Dose Formulations
  • Two-week Studies
  • Three-month Studies
  • Statistical Methods
  • Quality Assurance Methods
  • Genetic Toxicology
• Results
  • Rats
  • Mice
  • Genetic Toxicology
• Discussion
• References
• Appendix A. Summary of Neoplasms and Nonneoplastic Lesions in Rats and Mice
• Appendix B. Genetic Toxicology
• Appendix C. Clinical Pathology Results
• Appendix D. Organ Weights and Organ-Weight-to-Body-Weight Ratios
• Appendix E. Reproductive Tissue Evaluations and Estrous Cycle Characterization
• Appendix F. Chemical Characterization and Dose Formulation Studies
• Appendix G. Feed Consumption
• Appendix H. Ingredients, Nutrient Composition, and Contaminant Levels in NTP-2000 Rat and Mouse Ration
• Appendix I. Sentinel Animal Program