Sodium methanethiolate

Endpoint summary

Description of key information

In a combined repeated-dose/reproductive/developmental toxicity screening study (OECD TG 422) in rats, the NOAEL and the LOAEL of sodium methanethiolate in rats were considered to be 15 and 45  mg/kg bw/day, respectively, based on a regenerative anemia.
In a 13-week inhalation toxicity study on the analogue and degradation product methanethiol, the authors concluded that the NOAEC and  LOAEC were considered to be 17 (0.033 mg/L) and 57 (0.118 mg/L) ppm, respectively.

Key value for chemical safety assessment

Repeated dose toxicity: via oral route - systemic effects

Endpoint conclusion

Dose descriptor:

NOAEL

15 mg/kg bw/day

Additional information

Oral study on sodium methanethiolate

In a combined repeated-dose/reproductive/developmental toxicity screening study (OECD TG 422), Sprague-Dawley rats (10/sex/dose) were administered 0, 5, 15 or 45 mg/kg bw/day of sodium methanethiolate in water by gavage daily for 8-9 weeks at a volume of 5 ml/kg (Gaoua, 2005). There was no mortality or changes in blood biochemistry values or urinalysis parameters. There were no clinical signs of toxicity or body weight or food consumption effects observed in the 5 or 15 mg/kg bw/day groups. At 45 mg/kg bw/day, clinical signs observed included transient low muscle tone in males and females, incoordination of muscles in four males and one female at weeks 5 or 6 and excessive salivation in most males and females beginning a few days into the study and continuing though the end of dosing. The group mean body weight gain of the males in the 45 mg/kg bw/day group was significantly lower (19%) during the first week of dosing and remained marginally reduced during the dosing period relative to the control group. In the females exposed to 45 mg/kg bw/day, the mean group body weights were marginally reduced during premating and significantly reduced during the first week of gestation in comparison to the control group. The food consumption values were marginally reduced throughout the study for the 45 mg/kg bw/day males but not the females. Decreased hemoglobin concentration was observed in the males and females of the 45 mg/kg/day dose group. This was associated with reduced mean cell volume in the males and with decreased mean cell hemoglobin concentration, red blood cell count and packed cell volume in the females. At necropsy, there were no macroscopic treatment-related effects observed in any dose group. There were no organ weight effects or microscopic effects observed in the 5 or 15 mg/kg bw/day dose groups. Higher absolute and relative spleen weights were observed for the male (22 and 33% increased, respectively) and female (49 and 57% increased, respectively) rats exposed to 45 mg/kg bw/day. Increased incidence and/or severity of extramedullary hematopoiesis and hemosiderosis in the spleen of both male and female rats and sinusoidal ectasia in the male rats was observed at 45 mg/kg bw/day (p<0.01). In the 45  mg/kg bw/day females, a higher incidence of extramedullary hematopoiesis in the liver was observed that was associated with greenish pigment in a few Kupffer’s cells. The NOAEL and the LOAEL of sodium methanethiolate in rats were considered to be 15 and 45  mg/kg bw/day, respectively.

Inhalation study on the analogue and degradation product methanethiol

In a 3-month inhalation toxicity study, Sprague-Dawley rats (31 males/concentration) were exposed (whole body) to methanethiol at 0, 2, 17 or 57 ppm (0, 0.0039, 0.033 or 0.118 mg/L, respectively) for seven hours per day, five days per week (Tansy et al., 1981). There were no deaths, clinical signs of toxicity, food intake or fecal weight effects or organ weight changes observed. During actual exposures the rats tended to huddle in groups of 5 or 6 toward the periphery of the chamber with noses pointed outward from the chamber's vertical axis. This behavior was not observed in the sham group but was markedly obvious at 57 ppm. Average terminal body weights were lower in all treated groups and statistically significant (p<0.05) in the 57 ppm group indicating a statistically significant dose-related trend. Significant changes in organ weights (spleen and adrenals) were not considered relevant by the study authors. Average total serum proteins were significantly higher for all exposed groups but no dose-response relationship was evident. Average albumin concentration was significantly lower for all exposed groups. The authors noted that these changes in blood chemistry could indicate liver damage but also might indicate dehydration. In addition, statistically-significant reductions in inorganic phosphate (2 and 17 ppm groups), slightly elevated cholesterol (2 ppm group) and elevated total bilirubin (2 and 17 ppm groups) were observed but these were not considered treatment-related because of the lack of effect at 57 ppm (i.e. no dose response). Blood urea nitrogen was significantly lowered in the 57 ppm group and lactate dehydrogenase was significantly lower in all exposed groups (only increases in these parameters are generally considered of toxicological relevance). It can be concluded with 95% confidence that there were no dose-related trends in any clinical chemistry parameters. There were no exposure-related histopathological effects (including kidneys) observed in this study. All animals at all concentrations had inflammatory cells in their livers and possibly enlarged bile ducts; these effects were not seen in the controls. One hepatic carcinoma was seen in a rat in the 17 ppm exposure group. The authors of the study report concluded that the NOAEC and LOAEC were considered to be 17 (0.033 mg/L) and 57 (0.118 mg/L) ppm, respectively. 

Justification for classification or non-classification

According to REGULATION (EC) No 1272/2008 and DIRECTIVE 67/548/EEC criteria and in the absence of any marked toxic effects, the substance should not be classified for repeated dose toxicity.