Registration Dossier

Administrative data

Key value for chemical safety assessment

Effects on fertility

Effect on fertility: via oral route
Dose descriptor:
NOAEL
5 000 mg/kg bw/day
Additional information

No effects on female gonads were observed in the 90 day gavage study on rats at doses up to 5000 mg/kg bw/day (see section repeated dose toxicity). At the high dose level the ratio of testes weight to body weight was significantly increased in males. However, the body weight of male rats was significantly reduced in this dose group. The absolute testes weight was not altered in any treatment group. Furthermore, no changes in the gonads of males and females were observed at histopathological examinations (Angerhofer et al., 1997).


Short description of key information:
A documentation and evaluation of available data on this endpoint is presented in: Thiodiglycol, SIDS Initial Assessment Report for SIAM 19, final version 10/2006.

Effects on developmental toxicity

Description of key information
A documentation and evaluation of available data on this endpoint is presented in: Thiodiglycol, SIDS Initial Assessment Report for SIAM 19, final version 10/2006. Later publications were added in this documentation (see Houpt et al. 2007).
Effect on developmental toxicity: via oral route
Dose descriptor:
NOAEL
400 mg/kg bw/day
Additional information

In a prenatal developmental toxicity study conducted in accordance with OECD guideline 414 (adopted 1981) pregnant Wistar rats (n = 24 per group) received, in a limit test, a dose of 0 or 1000 mg/kg bw/day by gavage on gestation days 6 to 15. The animals were sacrificed on gestation day 20. No maternal toxicity was detected at this dose level. No substance-related differences between the treatment and control group were noted concerning developmental toxicity except a significant increase in dumbbell ossifications of thoracic vertebral bodies was noted (12 % versus 5.2 % in control). This skeletal variation was also outside the laboratory historical control range (BASF 1995). Therefore, a 2nd study was conducted. In this developmental toxicity study pregnant Wistar rats (n = 25 per group) received 0, 100, 400, or 1000 mg/kg bw/day by gavage also on gestation days (GD) 6 to 15 and dams were sacrificed on GD 20. Examination of fetuses did not reveal any obvious substance-related effects except a slight increase in dumbbell ossifications of thoracic vertebral bodies which were also outside the laboratory historical control range concerning litter incidence.This variation was significantly increased in the previously conducted LIMIT Test at the same dose level; a borderline effect due to TS treatment cannot be ruled out. Conclusion for both studies on Wistar rats: The NOAEL for maternal toxicity and developmental toxicity is 400 mg/kg bw/day, the LOAEL is 1000 mg/kg bw/day (reduced body weight in dams and increased skeletal variations in offspring). No teratogenic effects were detected.

In a 3rd developmental toxicity study (comparable to the current OECD Guideline 414; Houpt et al. 2007; not available for OECD SIDS 2006) 25 pregnant Sprague-Dawley rats per dose were gavaged once daily with 0, 430, 1290, 3870 mg/kg bw at gestation day (GD) 5 -19. The study was terminated at GD 20. Maternal body weights were significantly less than controls as well as maternal food consumption at 3870 mg/kg bw/day; food utilization (body weight gain/food consumed) revealed significantly lower values during GDs 5 to 9 and 16 to 20 at 3,870 mg/kg/day. One female at 3870 mg/kg/day died prior to the schedule sacrifice, the cause of death was unknown. No further maternal effects were detected. A statistically significant decrease in average fetal body weights was observed only at 3870 mg/kg bw/day. No further developmental effects were found; also variations and malformations were not increased compared with the concurrent control.

Conclusion: In Sprague-Dawley rats maternal toxicity (reduced food consumption and reduced body weight gain) and a decrease in fetal weights were found at a dose level of 3870 mg/kg bw/day, the NOAEL for maternal and developmental toxicity was 1290 mg/kg bw/day.

Justification for classification or non-classification

In two gavage studies (OECD guideline 414) on the prenatal developmental toxicity in Wistar rats, the NOAEL for maternal and developmental toxicity was 400 mg/kg bw/day. Borderline effects concerning a certain type of skeletal variations (dumbbell ossification of thoracic vertebral bodies) were observed at oral doses of 1000 mg/kg bw/day which resulted also in marginal maternal toxicity.

In accordance with chapter 3.7.2.3.3 of EU Classification, Labelling and Packaging of Substances and Mixtures (CLP) Regulation (EC) No. 1272/2008 and according to the criteria of EU Directive 67/548/EEC, classification is not warranted.