Decamethylcyclopentasiloxane

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:

11.07.1988 to 12.03.1990

Reliability:

1 (reliable without restriction)

Rationale for reliability incl. deficiencies:

comparable to guideline study

Data source

Reference

Reference Type:

study report

Title:

Unnamed

Year:

1990

Report date:

1990

Materials and methods

Test guideline

Qualifier:

equivalent or similar to guideline

Guideline:

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

Deviations:

yes

Remarks:

Limited haematology

GLP compliance:

yes

Limit test:

no

Test material

Test material information

Constituent 1

Reference substance name:

Decamethylcyclopentasiloxane

EC Number:

208-764-9

EC Name:

Decamethylcyclopentasiloxane

Cas Number:

541-02-6

Molecular formula:

C10H30O5Si5

IUPAC Name:

2,2,4,4,6,6,8,8,10,10-decamethyl-1,3,5,7,9,2,4,6,8,10-pentoxapentasilecane

Test animals

Species:

rat

Strain:

Sprague-Dawley

Sex:

male/female

Details on test animals or test system and environmental conditions:

TEST ANIMALS
- Source: Charles Rivers Breeding Laboratories, Portage, Michigan
- Age at study initiation: 'young'
- Weight at study initiation: males: 259-286 g; females: 215-263 g
- Fasting period before study: No data
- Housing: Individually in standard stainless steel wire mesh cages of conventional design
- Diet (e.g. ad libitum): Ad libitum
- Water (e.g. ad libitum): Ad libitum
- Acclimation period: Seven days


ENVIRONMENTAL CONDITIONS
- Temperature (°C): 22 ±3
- Humidity (%): 30-70
- Air changes (per hr): No data
- Photoperiod (hrs dark / hrs light): 12/12


IN-LIFE DATES: From: To:

Administration / exposure

Type of coverage:

occlusive

Vehicle:

unchanged (no vehicle)

Details on exposure:

TEST SITE
- Area of exposure: Dorsal area
- % coverage: approx. 10%
- Type of wrap if used: Occluded with plastic wrap
- Time intervals for shavings or clippings: as needed


REMOVAL OF TEST SUBSTANCE
- Washing (if done): No

TEST MATERIAL
- Amount(s) applied (volume or weight with unit): No data
- Constant volume or concentration used: No data


USE OF RESTRAINERS FOR PREVENTING INGESTION: no

Analytical verification of doses or concentrations:

not specified

Duration of treatment / exposure:

28 days

Frequency of treatment:

Once daily for 6 hr/day, 7d/week, for 28 days

Doses / concentrations

Doses / concentrations 1

Dose / conc.:

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

Doses / concentrations 2

Dose / conc.:

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

Doses / concentrations 3

Dose / conc.:

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

No. of animals per sex per dose:

10 per sex in main study groups, 5 per sex in the 2 satellite groups.

Control animals:

other: occluded with plastic wrap, but without test material

Details on study design:

- Dose selection rationale: No data
- Rationale for animal assignment (if not random): random
- Rationale for selecting satellite groups: reversibility of adverse effects (control and 1600 mg/kg bw/day groups)
- Post-exposure recovery period in satellite groups: 28 days

Positive control:

None

Examinations

Observations and examinations performed and frequency:

CAGE SIDE OBSERVATIONS: Yes
- Time schedule: Daily for all groups

DETAILED CLINICAL OBSERVATIONS: No

DERMAL IRRITATION (if dermal study): No

BODY WEIGHT: Yes
- Time schedule for examinations: study initiation, weekly throughout the study and at termination, including the post-exposure rest period.

FOOD CONSUMPTION:
- Food consumption for each animal determined and mean daily diet consumption calculated as g food/kg body weight/day: Yes


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: Yes
- Time schedule for examinations: study initiation and termination
- Dose groups that were examined: control and high dose group animal

HAEMATOLOGY: Yes
- Time schedule for collection of blood: At study termination
- Anaesthetic used for blood collection: Yes (ketamine HCl)
- Animals fasted: Yes
- How many animals: All animals
- Parameters checked in table 1 were examined.


CLINICAL CHEMISTRY: Yes
- Time schedule for collection of blood: At study termination
- Animals fasted: Yes
- How many animals: All animals
- Parameters checked in table 1 were examined


URINALYSIS: Yes
- Time schedule for collection of urine: At study termination
- Metabolism cages used for collection of urine: Yes
- Animals fasted: Yes
- 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

Statistics:

Body weight, food consumption, hematology, clinical chemistry, urinalysis, organ weights analysed by 1-way ANOVA.
Group means compared with controls using Dunnett's multiple T-test or non-parametric analysis of variance by ranks
where appropriate.

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:

not examined

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

not examined

Ophthalmological findings:

no effects observed

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:

• Body weight: No significant differences were found.
• Food/water consumption: No significant differences were found.
• Description, severity, time of onset and duration of clinical signs: No significant clinical observations or
behavioural changes were reported.
• Ophthalmologic findings incidence and severity: No adverse effects observed.
• Hematological findings incidence and severity: No significant changes were reported.
• Clinical biochemistry findings incidence and severity: No significant changes were reported for clinical chemistry or
urinalysis results.
• Mortality and time to death: No unscheduled early deaths occurred during this study.
• Gross pathology incidence and severity: There were no apparent treatment-related effects noted at gross necropsy.
• Organ weight changes: No significant changes were reported
• Histopathology incidence and severity: No significant dose-related findings were reported for either terminal or
recovery group sacrifices.

Effect levels

1

Dose descriptor:

NOAEL

Effect level:

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

Based on:

test mat.

Sex:

male/female

Basis for effect level:

other: No systemic effects observed.

2

Dose descriptor:

NOAEL

Effect level:

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

Based on:

test mat.

Sex:

male/female

Basis for effect level:

other: No local effects observed.

Target system / organ toxicity

Critical effects observed:

no

Applicant's summary and conclusion

Conclusions:

Dermal administration of undiluted D5 under occlusive conditions over a 28-day period at doses up to and including 1600 mg/kg bw/day resulted in no adverse effects on survival, body weight, food consumption, clinical observations, clinical pathology, hematology, ophthalmoscopy, organ weights, or gross or microscopic pathology (study reliability score 1).