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Toxicological information

Toxicity to reproduction: other studies

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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:
other: OECD 440
GLP compliance:
yes
Type of method:
in vivo

Test material

Reference
Name:
Unnamed
Type:
Constituent

Test animals

Species:
rat
Strain:
Sprague-Dawley
Sex:
female
Details on test animals 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.