Octane-1-thiol

Endpoint summary

Key value for chemical safety assessment

Effects on fertility

Description of key information

No additional data is considered necessary. 

Additional information

One key guideline study was identified to evaluate the reproductive toxicity potential of octane-1-thiol.

In a key guideline (OECD 422) reproduction/developmental toxicity screening study (MHLW, 2004; Klimisch score = 1), groups of male and female Sprague-Dawley rats (Crj: CD(SD) IGS, SPF; 12/sex/dose) were administered 0, 10, 50 or 250 mg/kg bw/day of octane-1-thiol (CAS Number 111-88-6) by gavage in olive oil daily for 35 days in males and from 14 days before mating to day 4 of lactation for females. The animals were sacrificed on the 36thday for the males and on the 5thday post-partum/after birth for the females and pups respectively.

 

No treatment-related mortality occurred during the study. There were no treatment-related effects at any dose on reproductive parameters for males. For females, there was an extension of the mean estrous cycle and gestation length as well as a low delivery index at 250 mg/kg bw/day. Necropsy revealed significant maternal toxicity effects to the stomach, spleen, and thymus in females at 50 and 250 mg/kg bw/day. Females also showed an absolute and relative increase in weight of the spleen, liver, adrenal, a relative weight increase in the kidney, and a decrease in absolute and relative weight in the thymus in 250 mg/kg bw. There were no treatment-related effects at any dose on offspring. 

 

The NOAEL for reproductive toxicity was 250 and 50 mg/kg bw/day for males and females respectively. The NOAEL for maternal toxicity was 10 mg/kg bw/day. The NOAEL for the offspring was 250 mg/kg bw/day.  

Short description of key information:
One key guideline study was identified to evaluate the reproductive toxicity potential of octane-1-thiol. No treatment-related effects on reproductiveparameters were observed in male rats. An extension of the mean estrous cycle and gestation length, as well as a low delivery index was observed in female rats dosed at 250 mg/kg bw/day. There was also significant maternal toxicity effects in the stomach, spleen, and thymus of female rats dosed at 50 and 250 mg/kg bw/day. The NOAEL for reproductive toxicity was 250 and 50 mg/kg bw/day for males and females respectively. The NOAEL for maternal toxicity is 10 mg/kg bw/day. The NOAEL for the offspring was determined to be 250 mg/kg bw/day. 

Effects on developmental toxicity

Description of key information

No treatment-related developmental effects were seen with octane-1-thiol in a rat reproductive/developmental toxicity screening study. Furthermore, no developmental effects were seen in a pre-natal developmental toxicity study conducted on dodecane-1-thiol, a structural analogue of octane-1-thiol. The NOAEL for developmental toxicity was 250 mg/kg/day for octane-1-thiol and 7.4 ppm (61 mg/m3) for dodecane-1-thiol.

Effect on developmental toxicity: via oral route

Dose descriptor:

NOAEL

250 mg/kg bw/day

Effect on developmental toxicity: via inhalation route

Dose descriptor:

NOAEC

61 mg/m³

Additional information

In a key guideline (OECD 422) reproduction/developmental toxicity screening study (MHLW, 2004; Klimisch score = 1), groups of male and female Sprague-Dawley rats (Crj: CD(SD) IGS, SPF; 12/sex/dose) were administered 0, 10, 50 or 250 mg/kg bw/day of octane-1-thiol (CAS Number 111-88-6) by gavage in olive oil daily for 35 days in males and from 14 days before mating to day 4 of lactation for females. The animals were sacrificed on the 36thday for the males and on the 5thday post-partum/after birth for the females and pups respectively. There were significant maternal toxicity effects to the stomach, spleen, and thymus in females at 50 and 250 mg/kg bw/day. Females also showed an absolute and relative increase in weight of the spleen, liver, adrenal, a relative weight increase in the kidney, and a decrease in absolute and relative weight in the thymus in 250 mg/kg bw. There were no treatment-related effects at any dose on the offspring. The NOAELs for maternal and developmental toxicity for this study are 10 and 250 mg/kg/day.

A pre-natal rat developmental toxicity study (TG 414) has been conducted on dodecane-1-thiol (Schardein, 1983), a structural analogue of octane-1-thiol. In the range-finding study (Schardein, 1983), pregnant Sprague-Dawley rats (5/dose) were exposed by inhalation to 0, 10-12 ppm (0.083-0.099 mg/L , 0.83, and 4.1 mg/L for 6 hours/day during GD 6-19. Due to early signs of toxicity, the 2 highest dose levels were reduced to 0.30 and 2.0 mg/L. All 5 females exposed to 2.0 mg/L died on GD 9 or 10, and all 5 females exposed to 0.30 mg/L were sacrificed in extremis on GD 12 or 13. All animals in the control group and those exposed to 10-12 ppm survived to scheduled termination. Clinical observations included ocular irritation and nasal discharge at 10-12 ppm (0.083-0.099 mg/L). Females at 10-12 ppm (0.083-0.099 mg/L), showed a slight increase in implantation loss as compared to the controls; however, the values were within the range of the historical control data and not considered biologically significant. The NOAEC for maternal and developmental toxicity was 10-12 ppm (0.083-0.099 mg/L) based on maternal mortality at higher doses.

 

In the definitive prenatal developmental toxicity study (Schardein, 1983), pregnant Charles River COBS CD rats (25/dose) were exposed via the inhalation route (whole body) to dodecane-1-thiol (CAS number 112-55-0) at concentrations of 0, or 0. 061 mg/L (7.4 ppm) for 6 hrs/day from days 6 through 19 of gestation. Animals were sacrificed on day 19 of gestation and organs such as ovaries and uterine content were examined in addition to the foetuses. Survival was unaffected by exposure. Signs of maternal toxicity included unkept coat, matter in the vagina, ptosis of the eyelids, thinness, body weight decrease and a moribund appearance. The majority of animals also showed hair loss, reddened conjunctiva, dry matter around the nose, and dry peeling skin around the ears. There were no biologically meaningful or statistically significant differences in the total incidence of malformation in foetuses. The developmental NOAEC was therefore determined to be >7.4 ppm (61 mg/m^{3 or 0.061mg/L}).

 

Based on the data available, octane-1-thiol is not a developmental toxicant.

Read across justification

The use of the read across approach was used to fill the data gaps for octane-1-thiol using dodecane-1-thiol as an analog. Dodecane-1-thiol has similar physiochemical properties to octane-1-thiol and thus the toxicological properties of both substances are expected to be similar.

Justification for classification or non-classification

According to the available data and the criteria for classification of REGULATION (EC) No 1272/2008 and the EU DSD Directive Dir 67/548/EEC, no classification is warranted for reproductive and developmental toxicity.