Sodium thioglycolate: Synthesis, Application and Toxicity Studies

Sodium thioglycolate is one of the salts of thioglycolic acid commonly used in consumer products to wave, straighten, or remove hair, and it may remain applied to the scalp or skin for up to 1 hour. Sodium thioglycolate is also commonly used as an analytical reagent in the preparation of cell culture media. Workers may be exposed through inhalation of aerosols and dermal contact to sodium thioglycolate, especially when applying hair care products to customers. The general population may be exposed through similar routes as workers during home application of hair care products containing sodium thioglycolate.

Synthesis of Sodium thioglycolate

Preparation of Alpha-Kerateine; Human hair was obtained from a local barber shop, cut in to pieces approximately ½ inch in length, washed with mild detergent and warm water, dried in air, washed with ethanol, and dried in air. 10 grams of this clean, degreased, dry hair was reduced in 200 mL of IM sodium thioglycolate at 4° C. for 24 hours. The sodium thioglycolate solution had been prepared by mixing thioglycolic acid with water, adjusting the pH to 10.2 by addition of a saturated solution of sodium hydroxide, and diluting to a final thioglycolic acid concentration of 1 mole per liter. The hair and reduction solution was placed in a 2 L polyethylene jar and shaken on a reciprocating table shaker at 100 rpm. After reduction, the liquid was removed by sieve and the hair rinsed with a copious amount of deionized (DI) water. The reduced hair was extracted with 500 mL of a 0.3M sodium hydroxide solution at 4° C. for 24 hours. The extraction was performed in a 2 L polyethylene jar and shaken on a reciprocating table shaker at 100 rpm. After extraction, residual cuticle was removed by sieve and the liquid recovered. Small particulates were removed by centrifugation at 6,000 rpm for 30 minutes. The alpha-kerateine was precipitated from the resulting liquid by dropwise addition of concentrated HCl to a pH of 4.2. The alpha-kerateine was recovered by centrifugation at 2,000 rpm for 20 minutes and the supernatant retained for future use. The alpha-kerateine was re-dissolved in 20 mM tris base with 20 mM EDTA, re-precipitated by dropwise addition of HCl to a pH of 4.2. The alpha-kerateine was recovered by centrifugation at 2,000 rpm for 20 minutes, re-dissolved in 20 mM tris base with 20 mM EDTA, and dialyzed against DI water using dialysis tubing with a low molecular weight cutoff (LMWCO) of 14,200.[1]

Improved stability of recombinant hemagglutinin using sodium thioglycolate

study was designed to improve the stability of liquid formulations of recombinant influenza hemagglutinin (rHA) and to understand the mechanism of early loss of potency for rHA. The potency of rHA derived from several influenza strains was determined using single radial immunodiffusion (SRID), and the structure of the rHA was characterized using SDS–PAGE and dynamic light scattering. rHA formed disulfide cross-linked multimers, and potency decreased during extended storage. To reduce disulfide-mediated cross-linking and early potency loss, rHA was formulated with sodium thioglycolate (STG) and citrate. Addition of 80 mM STG and 55 mM sodium citrate inhibited disulfide-mediated cross-linking without affecting protein function for each rHA tested. The shelf life of the rHA formulation with STG–citrate, based on potency as determined by SRID, was extended as much as 20-fold, compared to a control formulation without sodium thioglycolate–citrate. sodium thioglycolate–citrate did not have a significant effect on the immunogenicity of H1 A/California/7/2009 rHA in mice.[2]

Toxicity Studies of Sodium Thioglycolate

Sodium thioglycolate was nominated by the National Cancer Institute due to widespread occupational and consumer exposure, most significantly to women through the use of personal care products. NTP studies in rats and mice were conducted using the dermal route because that is the most common exposure route in humans. Animals in the 2-week studies were treated with the highest feasible concentration of sodium thioglycolate based on solubility or toxicity data. Doses for the 3-month studies were selected based on the results of the 2-week studies in mice and rats that showed no systemic toxicity and minimal dermal toxicity at the site of application.[3]

All rats and mice in the 2-week and 3-month studies survived to the end of the study, except for one 360 mg/kg female mouse in the 2-week study. There were increases in kidney weights and decreases in lung weights in the 2-week rat study, but these effects were not observed in the 3-month rat study. Increased kidney and heart weights occurred in the 3-month mouse study, but treatment-related microscopic lesions did not occur in these organs. Liver weights were significantly increased in 180 mg/kg male rats and mild cytoplasmic focal vacuolization of the centrilobular hepatocytes occurred in all groups of dosed males in the 2-week study; no similar changes were observed in the 3-month study. Liver weight increases in the 3-month mouse study occurred without any observed microscopic changes. Feed consumption and clinical chemistry parameters were measured in the 3-month studies based on the findings by others indicating that thioglycolates inhibit fatty acid oxidation and increase food consumption after intraperitoneal injection, especially when the animals are on a medium-to-high fat (above 13%) diet. Contrary to previous findings, in the current dermal studies sodium thioglycolate did not induce significant differences in feed consumption or clinical parameters compared to controls; only small changes in mean body weight (within 10% of controls) were observed. Fat content of the NTP-2000 diet used in these studies in 8%.

Gross and nonneoplastic microscopic lesions were mostly limited to the site of application. All rats and six male mice administered 360 mg/kg sodium thioglycolate for 3 months developed irritation at the site of application. Minimal to mild epidermal hyperplasia occurred at the site of application in rats and mice administered the highest doses of sodium thioglycolate in the 2-week studies. In the 3-month rat and mouse studies, microscopic lesions of minimal to mild severity were observed in the epidermis at the site of application, including hyperkeratosis, hyperplasia, and ulcers. Microscopic lesions were detected at lower doses in 3-month male rats than in females; conversely, microscopic lesions were detected in the 3-month mouse study at lower doses in females than in males. The weak decreased trend in the proportion of female mice with regular cycles in female mice was not considered sufficient to indicate potential for reproductive toxicity because none of the sodium thioglycolate dose groups was significantly different from the vehicle control group.

Sodium thioglycolate was not mutagenic in any of the Salmonella typhimurium strains tested. In chromosomal damage studies in vivo, sodium thioglycolate induced a small but statistically significant increase in micronucleated erythrocytes in female mice following 3 months of dermal application. In contrast, no increases were observed in male mice, and no changes in the percentage of immature polychromatic erythrocytes among total erythrocytes were observed, suggesting no bone marrow toxicity from sodium thioglycolate administration. Although clearly positive results in rodent micronucleus studies are associated with an increased risk for carcinogenicity, weak responses or responses in only one sex are not predictive of carcinogenic potential. 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.

References

[1] WAKE FOREST UNIVERSITY - US2006/51732, 2006, A1

[2] Rhodes DG, Holtz K, Robinson P, Wang K, McPherson CE, Cox MM, Srivastava IK. Improved stability of recombinant hemagglutinin using a formulation containing sodium thioglycolate. Vaccine. 2015 Nov 4;33(44):6011-6.

[3] National Toxicology Program. NTP Technical Report on the Toxicity Studies of Sodium Thioglycolate (CASRN 367-51-1) Administered Dermally to F344/N Rats and B6C3F1/N Mice: Toxicity Report 80 [Internet].

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