Registration Dossier

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

Constituent 1
Chemical structure
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 / concentrationsopen allclose all
Dose / conc.:
96 mg/kg bw (total dose)
Remarks:
0.1 ml/kg bw
Dose / conc.:
190 mg/kg bw (total dose)
Remarks:
0.3 ml/kg bw
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).