Octamethylcyclotetrasiloxane

Repeated dose toxicity: oral

Administrative data

Endpoint:

short-term repeated dose toxicity: oral

Type of information:

experimental study

Adequacy of study:

supporting study

Study period:

07.11.1989 to 30.01.1990

Reliability:

4 (not assignable)

Rationale for reliability incl. deficiencies:

comparable to guideline study with acceptable restrictions

Remarks:

There were significant restrictions. These restrictions were that no haematology, clinical chemistry, urinalysis or histopathology were conducted.

Data source

Reference

Reference Type:

study report

Title:

Unnamed

Year:

1990

Report date:

1990

Materials and methods

Test guideline

Qualifier:

no guideline followed

Principles of method if other than guideline:

To investigate the potential for repeated dose toxicity.

GLP compliance:

yes

Limit test:

no

Test material

Test material information

Constituent 1

Reference substance name:

Octamethylcyclotetrasiloxane

EC Number:

209-136-7

EC Name:

Octamethylcyclotetrasiloxane

Cas Number:

556-67-2

Molecular formula:

C8H24O4Si4

IUPAC Name:

2,2,4,4,6,6,8,8-octamethyl-1,3,5,7,2,4,6,8-tetroxatetrasilocane

Test animals

Species:

rat

Strain:

Sprague-Dawley

Sex:

male/female

Administration / exposure

Route of administration:

oral: gavage

Vehicle:

other: 0.5% suspension of methocel A4M and distilled water

Analytical verification of doses or concentrations:

no

Duration of treatment / exposure:

Five days per week, for two consecutive weeks

Frequency of treatment:

Daily

Doses / concentrations

Doses / concentrations 1

Dose / conc.:

25 mg/kg bw/day (actual dose received)

Doses / concentrations 2

Dose / conc.:

100 mg/kg bw/day (actual dose received)

Doses / concentrations 3

Dose / conc.:

400 mg/kg bw/day (actual dose received)

Doses / concentrations 4

Dose / conc.:

1 600 mg/kg bw/day (actual dose received)

No. of animals per sex per dose:

8

Control animals:

yes, concurrent vehicle

Results and discussion

Effect levels

Dose descriptor:

NOAEL

Sex:

male/female

Basis for effect level:

other: The biological/toxicological significance of effects observed at the lowest dose (25 mg/kg bw/day) was unclear.

Remarks on result:

not determinable

Remarks:

no NOAEL identified

Target system / organ toxicity

Critical effects observed:

not specified

Any other information on results incl. tables

No overt signs of toxicity or behavioural changes were observed in the animals during the exposure period. Two female animals from the 1600 mg/kg bw/day treatment group died due to dosing error. At terminal sacrifice five animals had lesions consistent with gavage accidents. These five animals had terminal body weights that were slightly to severely below the group means. Two rats had liver lesions that were considered to be spontaneous.

Statistically significant increases in relative liver weight in both males and female animals occurred when the data from the 400 and 1600 mg/kg bw/day treatment groups were compared to controls. Additionally, a statistically significant increase was recorded when the relative liver weights of the females in the 100 mg/kg bw/day was compared to the control values. The absolute liver weight reflected statistically significant increases among those female rats treated with 400 and 1600 mg/kg bw/day. Therefore it is clear that treatment-related liver weight increases were observed at doses of 100 mg/kg bw/day and above. The effects at 25 mg/kg bw/day in both sexes were unclear.

Applicant's summary and conclusion

Conclusions:

In a two-week oral gavage study (DCC, 1990; reliability score 4) a NOAEL could not be determined because the biological/toxicological significance of effects on the liver at the lowest dose was unclear. However, it is the opinion of the current study summary author that the liver effects were adaptive, and that effects on terminal body weight were due to dosing error injuries.