2,8,9-Trioxa-5-aza-1-silabicyclo[3.3.3]undecane, 1,1'-(dithiodi-3,1-propanediyl)bis-

Endpoint summary

Description of key information

Oral (OECD 407), subacute, rat (male/female): NOAEL = 200 mg/kg bw/day
Inhalation: no data available
Dermal: no data available

Key value for chemical safety assessment

Repeated dose toxicity: via oral route - systemic effects

Endpoint conclusion

Endpoint conclusion:

adverse effect observed

Dose descriptor:

NOAEL

200 mg/kg bw/day

Study duration:

subacute

Species:

rat

Quality of whole database:

The available information comprises an adequate and reliable study (reliability 1). The information is sufficient for hazard assessment leading to an endpoint conclusion in accordance with Annex VIII, 1.2, of Regulation (EC) No 1907/2006. Therefore, the available information is sufficient to fulfil the standard information requirements set out in Annex VIII, 8.6 of Regulation (EC) No 1907/2006.

Repeated dose toxicity: inhalation - systemic effects

Endpoint conclusion

Endpoint conclusion:

no study available

Repeated dose toxicity: inhalation - local effects

Endpoint conclusion

Endpoint conclusion:

no study available

Repeated dose toxicity: dermal - systemic effects

Endpoint conclusion

Endpoint conclusion:

no study available

Repeated dose toxicity: dermal - local effects

Endpoint conclusion

Endpoint conclusion:

no study available

Additional information

Repeated dose toxicity: via oral route

A reliable key study is available, conducted according to OECD guideline 407 and in compliance with GLP. 5 SD rats per sex per group were daily treated with the test item by oral gavage at doses of 50, 200 and 1000 mg/kg bw/day for 28 consecutive days. Concurrent control animals received the vehicle alone (corn oil). Additional 5 animals per sex were included in the high dose (1000 mg/kg bw/day) and control groups to assess reversibility, persistence, or delayed occurrence of toxic effects. The recovery period consisted of 14 days following the last day of dosing. Based on the results of the present study, obvious toxicity effects to kidneys of male and female SD rats were observed after repeated oral dosing for 28 days with the test substance at a dose of 1000 mg/kg bw/day. Absolute and relative kidney weights were increased in association with histopathological changes. Males showed also in the 200 mg/kg bw/day dose group statistically significant changes in kidney weights (absolute and relative), histopathological changes of kidneys were not significant in this group. At the end of the recovery period, statistically significant changes of kidney weights in high dose males were resolved. Therefore, these effects in males were considered to be reversible. Females showed only in the high dose group a statistically significant increase of kidney weights. At the end of the recovery period, this kidney weight increase was of lower statistical significance when compared with the end of the dosing period, which indicates reversibility of this toxicological effect. Based on the significant increase of kidney weight in high dose females at the end of the recovery period and the histopathological kidney changes in high dose males and females, the NOAEL (No Observed Adverse Effect Level) for the test substance in the rat was determined as follows: male: 200 mg/kg bw/day, female: 200 mg/kg bw/day.

Repeated dose toxicity: via inhalation route

In accordance with Column 1 of REACH Annex VIII, the repeated dose toxicity study via the inhalation route does not need to be conducted as reliable data via the oral route are available.

Repeated dose toxicity: via dermal route

In accordance with Column 1 of REACH Annex VIII, the repeated dose toxicity study via the dermal route does not need to be conducted as reliable data via the oral route are available.

Justification for selection of repeated dose toxicity via oral route - systemic effects endpoint:
The available key study was selected for assessment. The study was conducted according to OECD test guideline 407 and in compliance with GLP.

Justification for selection of repeated dose toxicity inhalation - systemic effects endpoint:
In accordance with Column 1 of REACH Annex VIII, the repeated dose toxicity study via the inhalation route does not need to be conducted as reliable data via the oral route are available.

Justification for selection of repeated dose toxicity inhalation - local effects endpoint:
In accordance with Column 1 of REACH Annex VIII, the repeated dose toxicity study via the inhalation route does not need to be conducted as reliable data via the oral route are available.

Justification for selection of repeated dose toxicity dermal - systemic effects endpoint:
In accordance with Column 1 of REACH Annex VIII, the repeated dose toxicity study via the dermal route does not need to be conducted as reliable data via the oral route are available.

Justification for selection of repeated dose toxicity dermal - local effects endpoint:
In accordance with Column 1 of REACH Annex VIII, the repeated dose toxicity study via the dermal route does not need to be conducted as reliable data via the oral route are available.

Repeated dose toxicity: via oral route - systemic effects (target organ) urogenital: kidneys

Justification for classification or non-classification

The available information on the registered substance is reliable and suitable for classification. The data meet not the criteria for classification for repeated dose toxicity according to Regulation (EC) No 1272/2008 or Directive 67/548/EEC.