Registration Dossier

Administrative data

Key value for chemical safety assessment

Effects on fertility

Description of key information
Additional data is not considered necessary.
Effect on fertility: via oral route
Dose descriptor:
NOAEL
200 mg/kg bw/day
Additional information

In a combined repeated dose/reproductive/developmental toxicity screening test (OECD 422; MHLW, 2006; Klimisch score = 2), groups of male and female Sprague-Dawley rats (12-17/sex/dose) were administered 2 -methylpropane-2 -thiol in corn oil by gavage at 0, 10, 50 or 200 mg/kg bw/day daily for 42-53 days. The animals were dosed daily for 2 weeks prior to mating, during mating and gestation, and the females were dosed for 4 days post-partum after which the adult females and their pups were terminated. 

 

There were no treatment-related effects at any dose on reproductive and developmental parameters including mating index, fertility index, duration of gestation, gestation index, total number of pups born, live birth index, number of pups alive and viability index on day 4 of lactation or sex ratio. Decreases in body weight of live pups on PND 4 were observed in both sexes at 200 mg/kg bw/day. All reproductive organs from adult animals were normal during gross pathology and microscopic evaluations. The NOAEL for reproductive performance and developmental toxicity was 200 mg/kg bw/day and the NOAEL for neonatal toxicity was considered to be 50 mg/kg bw/day.



Short description of key information:
In an OECD Test Guideline 422 study, the NOAEL for reproductive performance and developmental toxicity was 200 mg/kg bw/day and the NOAEL for neonatal toxicity was considered to be 50 mg/kg bw/day.

Effects on developmental toxicity

Description of key information
In the key developmental toxicity/teratogeniticy studies in mice and rats (OECD 414), treatment with 2-methylpropane-2-thiol by whole-body inhalation did not produce developmental effects and the maternal and foetal NOAEC was ≥195 ppm in mice and rats. In an oral combined repeat-dose/reproductive/developmental toxicity study, no treatment-related effects on developmental parameters were observed. The NOAEL for developmental toxicity was determined to be 200 mg/kg bw/day.
Effect on developmental toxicity: via oral route
Dose descriptor:
NOAEL
200 mg/kg bw/day
Effect on developmental toxicity: via inhalation route
Dose descriptor:
NOAEC
721 mg/m³
Additional information

In a key rat developmental toxicity / teratogenicity study (Ulrich, 1982b, OECD 414; Klimisch Score =1), pregnant female Sprague-Dawley rats (COBS CD; 25/concentration) were exposed to analytical concentrations of 0, 11, 99, and 195 ppm (nominal concentrations of 0, 10, 100 and 200 ppm) of 2-methylpropane-2-thiol (CAS # 75-66-1) via whole-body inhalation 6 hrs/day during gestational days 6-19.  All rats survived until study termination. During the in-life portion of the study, there was an increase in the number of rats with hair loss in the treated groups when compared to the control group; however, there were no other signs of maternal toxicity. At necropsy, there were no biologically relevant or statistically significant differences in the mean number of viable foetuses, total implantations, corpora lutea, or foetal sex distribution in the exposed groups as compared to controls. Foetal evaluations did not reveal biologically relevant or statistically significant differences in malformations among the dosed animals as compared to the controls. There were no signs of maternal toxicity or biologically relevant teratogenic effects when 2-methylpropane-2-thiol was administered by whole-body inhalation at or below the 195 ppm actual exposure; therefore, the maternal and foetal NOAEC was ≥ 195 ppm.

 

In a similar key read across mouse developmental toxicity / teratogenicity study (Ulrich, 1982b, OECD 414; Klimisch Score = 1), pregnant female mice (CD-1; 25/group) were exposed to analytical concentrations of 0, 11, 99, and 195 ppm (nominal concentrations of 0, 10, 100 and 200 ppm) of 2-methylpropane-2-thiol via whole-body inhalation 6 hrs/day during gestational days 6-16. All animals survived to scheduled termination. There were no statistically significant differences between the dosed animals and controls with respect to maternal endpoints. Foetal malformations were observed in mice exposed to 99 ppm (litter incidence, 47.8 %) and 195 ppm (litter incidence, 28.6%) when compared to the control group (litter incidence, 16.7%). The particular malformation noted (i. e., vertebral anomaly), however, did not increase in a dose-related pattern and was in the range of historical control data. There were no additional statistically significant differences in treated foetuses when compared to controls. There were no signs of maternal toxicity or biologically relevant teratogenic effects when 2-methylpropane-2-thiol was administered by whole-body inhalation at or below the 195 ppm actual exposure; therefore, the maternal and foetal NOAEC was ≥ 195 ppm. 

 

In a combined repeated dose/reproductive/developmental toxicity screening test (OECD 422; MHLW, 2006; Klimisch score = 2), groups of male and female Sprague-Dawley rats (12 -17/sex/dose) were administered 2 -methylpropane-2 -thiol in corn oil by gavage at 0, 10, 50 or 200 mg/kg bw/day daily for 42-53 days. The animals were dosed daily for 2 weeks prior to mating, during mating and gestation, and the females were dosed for 4 days post-partum after which the adult females and their pups were terminated. There were no treatment-related effects at any dose on reproductive and developmental parameters including mating index, fertility index, duration of gestation, gestation index, total number of pups born, live birth index, number of pups alive and viability index on day 4 of lactation or sex ratio. Decreases in body weight of live pups on PND 4 were observed in both sexes at 200 mg/kg bw/day. All reproductive organs from adult animals were normal during gross pathology and microscopic evaluations. The NOAEL for developmental toxicity was 200 mg/kg bw/day and the NOAEL for neonatal toxicity was considered to be 50 mg/kg bw/day.

Justification for classification or non-classification

One screening reproductive/developmental toxicity study and three teratogenicity studies are available for 2-methylpropane-2-thiol. These studies showed that exposure to 2-methylpropane-2-thiol had no effects on reproductive parameters or development at the highest dose tested. 2-methylpropane-2-thiol is therefore not classified for reproductive or developmental toxicity under the EU Dangerous Substances Directive 67/548/EEC or CLP EU Regulation 1272/2008.

Additional information