Hexamethyldisiloxane

Toxicity to reproduction: other studies

Administrative data

Endpoint:

toxicity to reproduction: other studies

Type of information:

experimental study

Adequacy of study:

supporting study

Study period:

No data

Reliability:

4 (not assignable)

Rationale for reliability incl. deficiencies:

other: 4b The result is sourced from secondary literature (HPV IUCLID 2008 data set). The original reference was not available for review and no further information is available.

Data source

Reference

Reference Type:

secondary source

Title:

Potential estrogenic and antiestrogenic activity of the cyclic siloxane octamethylcyclotetrasiloxane (D4) and the linear siloxane Hexamethyldisiloxane (HMDS) in immature rats using the uterotrophic assay.

Author:

McKim Jr., J. M., Wilga, P. C., Breslin, W. J., Plotzke, K. P., Gallavan, R. H., and Meeks, R.G.

Year:

2001

Bibliographic source:

Toxicol Sci. 63, 37-46.

Materials and methods

Test guideline

Qualifier:

equivalent or similar to guideline

Guideline:

other: OECD 440

GLP compliance:

yes

Type of method:

in vivo

Test material

Test material information

Constituent 1

Reference substance name:

Hexamethyldisiloxane

EC Number:

203-492-7

EC Name:

Hexamethyldisiloxane

Cas Number:

107-46-0

Molecular formula:

C6H18OSi2

IUPAC Name:

trimethyl[(trimethylsilyl)oxy]silane

Test animals

Species:

rat

Strain:

Sprague-Dawley

Sex:

female

Details on test animals or test system and environmental conditions:

immature females: 18 days old at the initiation of the study

Administration / exposure

Route of administration:

oral: gavage

Vehicle:

other: sesame oil

Analytical verification of doses or concentrations:

not specified

Duration of treatment / exposure:

Four days

Frequency of treatment:

Daily

Duration of test:

Four days

Doses / concentrations

Remarks:

Doses / Concentrations:
600 and 1200 mg/kg bw/day
Basis:
actual ingested

No. of animals per sex per dose:

12

Control animals:

other: yes, ethinyl estradiol

Details on study design:

All pups were acclimated to the laboratory conditions from their time of arrival (7 to 11 days of age) to the start of dosing at 18 days of age. The pups were weighed and only pups weighing 35-50 g were included in the study. Dosing solutions of HMDS and ethinyl estradiol (EE), a positive control were prepared once for use throughout the study by mixing known weights of test compound with a known volume of sesame oil. All compounds were administered once per day for 4 consecutive days by oral gavage in a volume of 5 ml/kg. The gavage apparatus consisted of a 5.0 French Polyurethane umbilical vessel catheter placed over the base of a 19-guage blunt hypodermic needle attached to a 1 cc syringe. HMDS was administered at doses of 0 (sesame oil), 600 or 1200 mg/kg/day. EE was given at 3 µg/kg/day. All animals were euthanized the morning after the last dose by carbon dioxide inhalation followed by exsanguination via the abdominal aorta. Uteri were removed and weighed. The left uterine horn with cervix from six pups in each dose group were fixed in Bouin's fixative and processed to paraffin blocks. The tissues were then sectioned, placed on glass slides, and stained with hematoxylin and eosin using standard techniques. The slides were then evaluated microscopically for changes in uterine epithelial cell height along the endometrial surface lining. To evaluate the anti-estrogenic potential of the test compound, a combination of HMDS (1200 mg/kg/day) and EE (3 µg/kg/day) was given by oral gavage once a day for 4 consecutive days and the animals necropsied at the completion of the dosing.

Results and discussion

Effect levels

Dose descriptor:

NOAEL

Effect level:

>= 1 200 mg/kg bw/day (actual dose received)

Sex:

female

Observed effects

HMDS at 600 and 1200 mg/kg/day showed no treatment-related clinical abnormalities. There was also no dose-related changes in body weight. HMDS had no effect on uterine weight at either of the doses tested. In this study EE was evaluated at a single dose of 3 µg/kg/day, which produced a statistically significant increase in uterine weight. When HMDS was co-administered with EE, there was a small but statistically significant reduction in uterine weight compared to EE alone.

Applicant's summary and conclusion

Conclusions:

Using the Rat Uterotrophic Assay (reliability score 4) as an indicator of estrogenic potential, HMDS administration did not result in an estrogenic response in the Sprague Dawley rat. When HMDS was co-administered with EE there was a small but statistically significant reduction in uterine weight gain. The biological ramification of this could not be assessed in the present study.