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 when administered topically to the dorsum of pregnant rabbits at doses selected from the range-finding study results.
New Zealand White Rabbits were topically exposed to sodium thioglycolate in vehicle (10, 15, 25, and 65 mg/kg per day ) or vehicle alone (95% ethanol:distilled water, 1:1) from gestational day 6 through 29. Twelve naturally mated females were assigned to each group in a two replicate design for a total of twenty-four does/group and monitored at regular intervals throughout gestation for clinical signs (including dosing site condition), feed intake, and body weight. At necropsy on gestational day 30, the following were recorded: maternal clinical condition; body, liver, kidney (paired) 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. One hundred percent of the live fetuses per litter were sexed internally and examined for visceral alterations. Approximately 50% of the fetuses were decapitated and the heads fixed, decalcified, and examined for soft tissue craniofacial alterations. All fetal carcasses were eviscerated, macerated, and stained with alizarin red S and alcian blue. All fetuses were examined for ossified and cartilaginous skeletal alterations.
No maternal deaths were associated with sodium thioglycolate treatment. One female in the 25 mg/kg per day group delivered early and one doe in the 65 mg/kg per day group was removed due to a preexisting condition (trichobezoar or hairball in the stomach).Clinical observations were almost exclusively limited to effects of treatment on the dosing site. Very slight erythema in few females during the first two days of dosing at greater than or equal to 15 mg/kg per day occurred and progressed to include does at 10 mg/kg per day after 4 days of dosing. Moderate to severe erythema and edema occurred at doses greater than or equal to 15 mg/kg per day and edema occurred in all dose groups by gestational day 16. Petechia at the dosing site and dry skin also was noted in the high dose group as early as gestational day 9 but was also seen in one doe at 25 mg/kg per day. Maternal body weight and body weight gain were equivalent across dose groups for all intervals measured except for body weight gain for gestational days 12-15. There was a trend for decreased body weight gain for this interval which was significant in the high dose group when compared to controls. Absolute feed consumption per rabbit (grams per day) was significantly reduced from gestational days 9-12 in the 10 mg/kg per day group (Replicate II only) and for gestational days 15-18 at 65 mg/kg per day (Replicate II). Relative feed consumption (grams per kilogram per day) was significantly decreased for gestational days 6-9 (65 mg/kg per day, Replicate II), gestational days 9-12 (10 and 65 mg/kg per day , Replicate II), gestational day 12-15 at 15 mg/kg per day (Replicate I), gestational days 15- 18 for 10 and 65 mg/kg per day (Replicate II), and 18-21 at 25 mg/kg per day (Replicate II). Maternal feed consumption in grams per day as well as in grams per kg per day for gestational days 29-30 was significantly reduced at 15 mg/kg per day for Replicate I only. Therefore, there were no consistent treatment related reductions in feed consumption.
At scheduled necropsy, there was no effect of treatment on terminal maternal body weight. In addition, organ weights and gravid uterine weights were equivalent across groups.
Prenatal viability was unaffected by maternal exposure to sodium thioglycolate. The incidences of fetal external, visceral, and skeletal alterations were also unaffected. Body weights of male and female fetuses per litter and percent males and females per litter were equivalent across dose groups.
In summary, topically applied sodium thioglycolate resulted in toxicity to the doe at all dose groups but only at the dosing site; no systemic toxicity was seen at any dose group. There was no evidence of embryo/fetal toxicity in any dose group or treatment related teratogenicity. Therefore, a no observed adverse effect level could not be identified for maternal toxicity based on dosing site observations whereas for developmental toxicity, greater than or equal to 65 mg/kg per day was the NOAEL, in rabbits under the conditions of this study.