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Toxicological information

Repeated dose toxicity: oral

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Administrative data

Endpoint:
short-term repeated dose toxicity: oral
Type of information:
experimental study
Adequacy of study:
supporting study
Study period:
1989-11-08 to 1989-11-22
Reliability:
1 (reliable without restriction)
Rationale for reliability incl. deficiencies:
other: The study followed a protocol that is comparable to OECD 407, and was conducted in compliance with GLP. It is not considered to be a key study for repeated dose toxicity since the exposure duration was only 14 days.

Data source

Reference
Reference Type:
study report
Title:
Unnamed
Year:
1990
Report Date:
1990

Materials and methods

Principles of method if other than guideline:
No guideline is specified. 14-day gavage study.
GLP compliance:
yes
Limit test:
no

Test material

Reference
Name:
Unnamed
Type:
Constituent

Test animals

Species:
rat
Strain:
Sprague-Dawley
Sex:
male/female

Administration / exposure

Route of administration:
oral: gavage
Vehicle:
other: 0.5% methocel A4M in distilled water
Analytical verification of doses or concentrations:
not specified
Duration of treatment / exposure:
14 days
Frequency of treatment:
daily, 5 days per wk for 2 wk
Doses / concentrations
Remarks:
Doses / Concentrations:
25, 100, 400, 1600 mg/kg bw/day
Basis:
actual ingested
No. of animals per sex per dose:
8
Control animals:
yes
Details on study design:
Post-exposure period: no

Results and discussion

Effect levels

open allclose all
Dose descriptor:
LOAEL
Effect level:
100 mg/kg bw/day (actual dose received)
Sex:
male
Basis for effect level:
other: Based on clear evidence of liver weight increase.
Dose descriptor:
NOAEL
Effect level:
25 mg/kg bw/day (actual dose received)
Sex:
male
Basis for effect level:
other: No clear evidence of liver weight increase
Dose descriptor:
LOAEL
Effect level:
1 600 mg/kg bw/day (actual dose received)
Sex:
female
Basis for effect level:
other: Liver weight increase.
Dose descriptor:
NOAEL
Effect level:
400 mg/kg bw/day (actual dose received)
Sex:
female

Target system / organ toxicity

Critical effects observed:
not specified

Any other information on results incl. tables

The study was designed to investigate whether hexamethylcyclotrisiloxane increases liver weights similar to other oligomeric cyclosiloxanes. No test article-related deaths occurred. There were no clinical signs of toxicity or effects on body weight gains. Clear test article-related increases in the liver weights were seen in the male rats as low as 100 mg/kg/day and in female rats at dosage level in excess of 400 mg/kg/day. There was some slight evidence of liver weight increases in male rats at the lowest tested dose of 25 mg/kg bw/day. No significant changes were noted during gross pathological examination. The biological significance of the liver weight increase was said to be unclear.

Applicant's summary and conclusion

Conclusions:
A 2-wk gavage study in rats, well reported but limited in its range of examinations compared to OECD 407, produced dose-related increases in the liver weight of male rats (clear LOAEL 100 mg/kg bw/day) and liver weight increases in female rats at the highest tested dose of 1600 mg/kg bw/day. This effect was not identified at the lower doses of 25 mg/kg bw/day in males and 400 mg/kg bw/day in females.