1,1-dimethylheptanethiol

Endpoint summary

Description of key information

No key repeat dose toxicity data are available for 1,1-dimethylheptanethiol. Following repeated inhalation exposures (28-days) to structural analogue tert-dodecanethiol, mild kidney effects (renal tubular degeneration similar to that seen with branched chain hydrocarbons) were reported in male rats at 26 and 98 ppm, while liver enlargement was reported in rats at 98 ppm and in mice and dogs at 109 ppm. Effects on ovaries were also seen in mice exposed to 109 ppm. Mice and dogs exposed to tert-dodecanethiol at a level of 26 ppm for 28-days did not show any signs of toxicity.

Key value for chemical safety assessment

Repeated dose toxicity: inhalation - systemic effects

Endpoint conclusion

Dose descriptor:

NOAEC

215 mg/m³

Study duration:

subchronic

Species:

rat

Additional information

No key repeat dose inhalation toxicity data are available for 1,1-dimethylheptanethiol. Several criteria justify the use of the read across approach to fill data gaps for 1,1-dimethylheptanethiol using tert-dodecanethiol as an analog. 1,1 -dimethylheptanethiol, like tert-dodecanethiol, is a heavy mercaptan and has similar physiochemical properties. Hence, the toxicological properties of both these substances are also expected to be similar. Key read across data from tert-dodecanethiol was therefore used to evaluate the repeat dose toxicity potential.

In a 4-week inhalation study (comparable to OECD TG 407), rats exposed to nominal concentrations of 0, 26 (0.22 mg/L) and 98 ppm (0.81 mg/L) (the high concentration was a saturated vapour) t-dodecyl mercaptan for six hours/day, five days/week. Body weight reduction in males (98 ppm; 0.81 mg/L) with a corresponding reduction in food consumption was observed. High-dose males showed an increase in creatinine, and liver weights showed an exposure-related increase. Male rats at both concentrations exhibited mild renal tubular degeneration and granular cysts which were consistent with species-specific hydrocarbon nephropathy. Highdose female rats exhibited hydronephrosis. The LOAEC was 26 ppm (0.22 mg/L). Similar exposure to dogs (25 and 109 ppm; 0.22 and 0.90 mg/L, respectively) resulted in increases in alanine aminotransferase and reductions in blood urea nitrogen in females. Both sexes showed increases in alkaline phosphatase and exposure-related increases in liver weights with microscopic hepatocellular hypertrophy observed at the high dose for both sexes. The LOAEC was 25 ppm (0.21 mg/L). Similar exposure to mice (25 and 109 ppm; 0.21 and 0.90 mg/L, respectively) resulted in death of one male and one female at the high concentration. At the high concentration, reductions in erythrocyte counts and hematocrit, and increases in MCH and MCHC levels were observed at termination and females exhibited dermal inflammation, acanthosis, and hyperkeratosis, and showed increases in alanine aminotransferase and blood urea nitrogen, and decreased alkaline

phosphatase values. These females also had decreased ovary weights, and histopathological evaluation revealed either an absence of, or few, corpora lutea. Low-concentration females showed statistically significant increases in blood glucose. Liver weights revealed exposure-related increases; both sexes showed liver enlargement, discoloration and hepatocellular hypertrophy at both concentrations. The LOAEC for systemic toxicity was 25 ppm (0.21 mg/L); the NOAEC was not established.

Justification for classification or non-classification

1,1-dimethylheptanethiol does not meet the criteria for classification and labelling for repeat dose toxicity (STOT-RE) as defined by EU Dangerous Substances Directive 67/548/EEC or CLP EU Regulation 1272/2008.