Registration Dossier

Administrative data

Key value for chemical safety assessment

Effects on fertility

Effect on fertility: via oral route
Endpoint conclusion:
no study available
Effect on fertility: via inhalation route
Endpoint conclusion:
adverse effect observed
Dose descriptor:
NOAEC
9 837 mg/m³
Study duration:
subacute
Species:
rat
Effect on fertility: via dermal route
Endpoint conclusion:
no study available
Additional information

In a combined Repeated Dose Toxicity Study with the Reproduction/Developmental Toxicity Screening Test conducted using a protocol comparable to OECD 422 and to GLP (Harlan, 2012)lower corpora lutea counts were recorded at 3000/2000 ppm. As a consequence, a lower implantation rate and a lower number of living pups at first litter check were noted. Although the differences to the control values were not statistically significant, they were below the range of the historical control values and were therefore considered to be related to the treatment2,4,6,8-tetramethylcyclotetrasiloxane. These effects occurred at the dose level at which severe maternal toxicity was noted early on in the study and therefore may be secondary to the maternal toxicity. Because the reduction of corpora lutea could be a specific effect of the test item or as an effect secondary to the maternal toxicity, this, and the consequent reduction in the number of pups was considered to be adverse. No further indication of a test item related effect on reproduction was observed at any dose level; mating performance, fertility, duration of gestation as well as pre- and post-implantation loses in dose groups were similar to the control values.

Based on the reduction of corpora lutea number and consequent reduction of the number of pups observed at the dose level of 3000/2000 ppm, the NOAEC (no observed adverse effect concentration) for reproduction was considered to be 1000 ppm (9837 mg/m3).

An extended one-generation reproductive toxicity study according to OECD 443 is planned.


Short description of key information:
There is a reliable OECD 422 screening study available for 2,4,6,8-tetramethylcyclotetrasiloxane. There are no other studies relating to reproductive toxicity. In the toxicity assessment part of the study the reproductive organs were weighed and were the subject of histopathological examinations, and there were no adverse findings.

Justification for selection of Effect on fertility via inhalation route:
The selected study is the only available reproductive toxicity study for the registered substance. It was conducted in accordance with an appropriate OECD test guideline and in compliance with GLP.

Effects on developmental toxicity

Description of key information
There is a reliable OECD 422 screening study available for 2,4,6,8-tetramethylcyclotetrasiloxane. There are no other studies relating to developmental toxicity.
Effect on developmental toxicity: via oral route
Endpoint conclusion:
no study available
Effect on developmental toxicity: via inhalation route
Endpoint conclusion:
no adverse effect observed
Dose descriptor:
NOAEC
19 674 mg/m³
Study duration:
subchronic
Species:
rat
Effect on developmental toxicity: via dermal route
Endpoint conclusion:
no study available
Additional information

In a combined Repeated Dose Toxicity Study with the Reproduction/Developmental Toxicity Screening Test conducted using a protocol comparable to OECD 422 and to GLP Harlan, 2012) no effects on development were noted and the NOAEC for developmental toxicity was 3000/2000 ppm (19674 mg/m3)


Justification for selection of Effect on developmental toxicity: via inhalation route:
The selected study is the only available developmental toxicity study for the registered substance. It was conducted in accordance with an appropriate OECD test guideline and in compliance with GLP.

Justification for classification or non-classification

Based on the available OECD 422 screening study, 2,4,6,8-tetramethylcyclotetrasiloxane is not classified for effects on reproduction or development under Regulation (EC) No 1272/2008 as the concentrations at which effects on corpora lutea count and number of live pups were noted and at which the NOAEC was defined, are considerably in excess of the maximum concentration generally required.