Octamethylcyclotetrasiloxane

Repeated dose toxicity: dermal

Administrative data

Endpoint:

short-term repeated dose toxicity: dermal

Type of information:

experimental study

Adequacy of study:

key study

Study period:

October to November 1984

Reliability:

2 (reliable with restrictions)

Rationale for reliability incl. deficiencies:

guideline study with acceptable restrictions

Remarks:

The restrictions were that the report was in German, and a proper translation could not be performed, therefore some details are not presented.

Data source

Reference

Reference Type:

study report

Title:

Unnamed

Year:

1988

Report date:

1988

Materials and methods

Test guideline

Qualifier:

equivalent or similar to guideline

Guideline:

OECD Guideline 410 (Repeated Dose Dermal Toxicity: 21/28-Day Study)

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:

rabbit

Strain:

New Zealand White

Sex:

male/female

Details on test animals or test system and environmental conditions:

TEST ANIMALS
- Source: Züchter Hacking Churchill, Huntingdon, England.
- Age at study initiation: No data
- Weight at study initiation: Males: 3.2 kg; Females: 3.1 kg.
- Fasting period before study: No data
- Housing: Conventional cages
- Diet (e.g. ad libitum):Ad libitum
- Water (e.g. ad libitum): Ad libitum
- Acclimation period: 14 days


ENVIRONMENTAL CONDITIONS
- Temperature (°C): 22± 2
- Humidity (%): approximately 50%
- Air changes (per hr): approximately 10
- Photoperiod (hrs dark / hrs light): 12/12


IN-LIFE DATES: From: 15th October 1984 To: November 1984

Administration / exposure

Type of coverage:

open

Vehicle:

unchanged (no vehicle)

Details on exposure:

TEST SITE
- Area of exposure: Flanks (shaven intact skin)
- % coverage: No data
- Type of wrap if used: No wrap, open exposure
- Time intervals for shavings or clippings: as required


REMOVAL OF TEST SUBSTANCE
- Washing (if done): yes, with water
- Time after start of exposure: six hours


TEST MATERIAL
- Amount(s) applied (volume or weight with unit): 0.1, 0.3 and 1.0 ml/kg bw/day.
- Constant volume or concentration used: various volumes of neat test substance applied.

USE OF RESTRAINERS FOR PREVENTING INGESTION: yes

Analytical verification of doses or concentrations:

not specified

Duration of treatment / exposure:

3 weeks

Frequency of treatment:

5 days/week

Doses / concentrations

Doses / concentrations 1

Dose / conc.:

96 mg/kg bw (total dose)

Remarks:

0.1 ml/kg bw

Doses / concentrations 2

Dose / conc.:

190 mg/kg bw (total dose)

Remarks:

0.3 ml/kg bw

Doses / concentrations 3

Dose / conc.:

960 mg/kg bw (total dose)

Remarks:

1 ml/kg bw

No. of animals per sex per dose:

Five

Control animals:

yes

Details on study design:

- Dose selection rationale: No data (might have been missed in translation)
- Rationale for animal assignment (if not random): Random
- Rationale for selecting satellite groups: To investigate the reversibility of effects.
- Post-exposure recovery period in satellite groups: Two weeks for highest dose group.

Positive control:

None

Examinations

Observations and examinations performed and frequency:

CAGE SIDE OBSERVATIONS: Yes
- Time schedule: Twice daily on week days, and once daily at weekends and holidays.

DETAILED CLINICAL OBSERVATIONS: Yes
- Time schedule: Once per week

DERMAL IRRITATION (if dermal study): Yes
- Time schedule for examinations: Daily, and scored according to the Draize scoring system.

BODY WEIGHT: Yes
- Time schedule for examinations: Needs translation

FOOD CONSUMPTION:
- Food consumption was measured once per week, by calculating the amount of food not eaten by the animals. Food consumption per seven days was calculated for each week.


FOOD EFFICIENCY:
- Body weight gain in kg/food consumption in kg per unit time X 100 calculated as time-weighted averages from the consumption and body weight gain data: No


WATER CONSUMPTION: No


OPHTHALMOSCOPIC EXAMINATION: No


HAEMATOLOGY: Yes
- Time schedule for collection of blood: At the end of the treatment period, and at the end of the observation period.
- Anaesthetic used for blood collection: No data
- Animals fasted: No
- How many animals: All animals (except only 4 and 3 males in 0.1 and 0.3 ml/kg groups, respectively)
- Parameters checked in table 1 were examined.


CLINICAL CHEMISTRY: Yes
- Time schedule for collection of blood: At the end of the treatment period, and at the end of the observation period.
- Animals fasted: No
- How many animals: All animals (except only 4 and 3 males in 0.1 and 0.3 ml/kg groups, respectively)
- Parameters checked in table 1 were examined.


URINALYSIS: Yes
- Time schedule for collection of urine: At the end of the exposure period and observation period (16 hour collection period).
- Metabolism cages used for collection of urine: No data
- Animals fasted: No
- Parameters checked in table 1 were examined.


NEUROBEHAVIOURAL EXAMINATION: No

Sacrifice and pathology:

GROSS PATHOLOGY: Yes (see table 2)
HISTOPATHOLOGY: Yes (see table 2)

Other examinations:

None reported.

Statistics:

NEEDS TRANSLATION

Results and discussion

Results of examinations

Clinical signs:

no effects observed

Dermal irritation:

no effects observed

Mortality:

no mortality observed

Body weight and weight changes:

no effects observed

Food consumption and compound intake (if feeding study):

no effects observed

Food efficiency:

no effects observed

Water consumption and compound intake (if drinking water study):

not examined

Ophthalmological findings:

not examined

Haematological findings:

no effects observed

Clinical biochemistry findings:

no effects observed

Urinalysis findings:

no effects observed

Behaviour (functional findings):

not examined

Organ weight findings including organ / body weight ratios:

no effects observed

Gross pathological findings:

no effects observed

Histopathological findings: non-neoplastic:

no effects observed

Histopathological findings: neoplastic:

not examined

Details on results:

There were no treatment-related effects.

Effect levels

Dose descriptor:

NOAEL

Effect level:

>= 1 other: ml/kg bw

Based on:

test mat.

Sex:

male/female

Basis for effect level:

other: No adverse effects observed.

Remarks on result:

other: NOAEL was ≥ 1 ml/kg bw (equivalent to 960 mg/kg bw/day).

Target system / organ toxicity

Critical effects observed:

no

Applicant's summary and conclusion

Conclusions:

In a three-week dermal exposure study in rabbits conducted using a protocol similar to OECD 410 and GLP (reliability score 2), there were no adverse effects and therefore the dermal NOAEL was ≥ 1 ml/kg bw/day (equivalent to 960 mg/kg bw/day).