Report Date: Sept. 11, 2001
The following abstract presents results of a study conducted by a contract laboratory for the National Toxicology Program. The findings may not have been peer reviewed and were not evaluated in accordance with the levels of evidence criteria established by NTP in March 2009. For more information, see the Explanation of Levels of Evidence for Developmental Toxicity. The findings and conclusions for this study should not be construed to represent the views of NTP or the U.S. Government.
The thioglycolic acids, which include the salt sodium thioglycolate, have a widespread occupational and consumer exposure because of their use in cosmetics and hair-care products. As constituents of those types of products, their use is predominantly focused on the female population. Such a high probability for female exposure expands the potential for the thioglycolic acids to interact with the unborn human. The following study was performed to assess the developmental toxicity of sodium thioglycolate, a representative compound of the thioglycolates, when administered topically to the dorsum of pregnant rats at doses selected from the range-finding study results.
Pregnant Sprague Dawley derived (CD) rats were topically exposed to sodium thioglycolate in vehicle (50, 100, and 200 mg/kg/day) or vehicle alone (95% ethanol:distilled water, 1:1) from gestational day 6 through 19. Twenty-five timed-mated females were assigned to each group and monitored at regular intervals throughout gestation for clinical signs (including dosing site condition), feed and water intake, and body weight. At necropsy on gd 20, the following were recorded: maternal clinical condition; body, liver, and gravid uterine weights; and pregnancy status. The number of ovarian corpora lutea and uterine implantations (resorbed, dead, or live fetuses) was recorded. All live fetuses were counted, weighed, and examined for external alterations, including cleft palate. Approximately 50% of the live fetuses per litter were sexed internally and examined for visceral alterations. These fetuses were decapitated and the heads fixed, decalcified, and examined for soft tissue craniofacial alterations. All fetal carcasses were eviscerated (and fetuses not scheduled for a visceral examination were sexed internally), macerated, and stained with alizarin red S and alcian blue. Intact fetuses (those not decapitated) were examined for ossified and cartilaginous skeletal alterations.
Sodium thioglycolate treatment was associated with one maternal death at 200 mg/kg/day (only clinical observations at the dosing site preceded death). Other effects, dependent on dose and exposure duration, included body weight and weight gain reductions, changes in relative feed and water intake, and discoloration and slight erythema at the application site. Feed consumption in g/kg/day was significantly increased above the control at 50 (5.4%) and 100 (6.1%) mg/kg/day, but not at 200 mg/kg/day (2.2%). Maternal water consumption in g/kg/day was significantly increased at 200 mg/kg/day, (12.7%) and slightly (but not statistically significantly) increased at 50 (3.2%) and 100 (5.1%) mg/kg/day. Maternal body weights and body weight changes were decreased only at 200 mg/kg/day.
At scheduled necropsy, there were no macroscopic indications of organ toxicity. In addition, organ weights and gravid uterine weights were equivalent across groups; maternal body weight was significantly reduced at 200 mg/kg/day.
Prenatal viability was unaffected by maternal exposure to sodium thioglycolate. The incidences of fetal external, visceral, and skeletal alterations were also unaffected. (A significant, dose-related, upward trend was present for % fetuses with skeletal variations per litter, but there were no significant pairwise comparisons to the vehicle control group value.) Body weights of male and female fetuses per litter at 200 mg/kg/day were significantly lower than control values.
In summary, topically applied sodium thioglycolate resulted in toxicity to the dam at 200 mg/kg/day (expressed as reduced body weights and weight gain, increased relative water consumption, observations at the dosing site and one death). Treatment-related increases in feed consumption (and observations at the application site) were also present at 50 and 100 mg/kg/day, in the absence of increased body weights or body weight change. This is an uncommon finding and has been previously observed in rats exposed to sodium thioglycolate, attributed to a block in fatty acid metabolism. Sodium thioglycolate at 200 mg/kg/day also resulted in significantly decreased male and female fetal body weights per litter, with no other evidence of embryofetal toxicity and no evidence of treatment-related teratogenicity. Based on the study findings, a no observed adverse effect level could not be identified for maternal toxicity while for developmental toxicity, 100 mg/kg/day was the NOAEL in rats, under the conditions of this study.