Registration Dossier

Administrative data

Endpoint:
sub-chronic toxicity: dermal
Type of information:
experimental study
Adequacy of study:
supporting study
Reliability:
1 (reliable without restriction)
Rationale for reliability incl. deficiencies:
test procedure in accordance with generally accepted scientific standards and described in sufficient detail

Data source

Reference
Reference Type:
publication
Title:
Unnamed
Year:
1982

Materials and methods

Test guideline
Qualifier:
no guideline followed
Principles of method if other than guideline:
Standard tox study design
GLP compliance:
yes
Limit test:
no

Test material

Reference
Name:
Unnamed
Type:
Constituent
Test material form:
not specified

Test animals

Species:
rabbit
Strain:
New Zealand White
Sex:
male/female
Details on test animals and environmental conditions:
TEST ANIMALS
- Source: Langshaw Farms, Augusta, Michigan
- Age at study initiation: approx 5 weeks old
- Weight at study initiation: not stated
- Housing: standard stainless steel cages
- Diet: PURINA Rabbit Chow (ad libitum)
- Water: fresh water (ad libitum)
- Acclimation period: 10 days

ENVIRONMENTAL CONDITIONS
- Temperature (°C): 20-24
- Humidity (%): 50-60
- Air changes (per hr): not stated
- Photoperiod (hrs dark / hrs light): not stated

IN-LIFE DATES: From: To: not stated

Administration / exposure

Type of coverage:
occlusive
Vehicle:
unchanged (no vehicle)
Details on exposure:
TEST SITE
- Area of exposure: not stated
- % coverage: not stated
- Type of wrap if used: impervious sleeve of plastic material
- Time intervals for shavings or clippings: at least 24 hours before initial application, as needed thereafter

REMOVAL OF TEST SUBSTANCE
- Washing: lukewarm water
- Time after start of exposure: 6 hours

TEST MATERIAL
- Amount applied (volume or weight with unit): not stated
- Concentration: 100%
- Constant volume or concentration used: not stated

USE OF RESTRAINERS FOR PREVENTING INGESTION: no
Analytical verification of doses or concentrations:
not specified
Duration of treatment / exposure:
6 hours per day
Frequency of treatment:
5 days per week for 3 weeks
Doses / concentrationsopen allclose all
Dose / conc.:
40 mg/kg bw/day (nominal)
Dose / conc.:
200 mg/kg bw/day (nominal)
Dose / conc.:
400 mg/kg bw/day (nominal)
No. of animals per sex per dose:
6
Control animals:
yes, sham-exposed

Examinations

Observations and examinations performed and frequency:
CAGE SIDE OBSERVATIONS: Yes
- Time schedule: at least twice daily after application of test material

DETAILED CLINICAL OBSERVATIONS: No data

DERMAL IRRITATION (if dermal study): No data

BODY WEIGHT: Yes
- Time schedule for examinations: Day 1, 4, 8, 12, 16 and 21

FOOD CONSUMPTION: Yes
- Time schedule for examinations: Day 1, 4, 8, 12, 16 and 21

WATER CONSUMPTION: No

OPHTHALMOSCOPIC EXAMINATION: No

HAEMATOLOGY: Yes
- Time schedule for collection of blood: at termination
- Anaesthetic used for blood collection: Yes (methoxyflurane)
- Animals fasted: No data
- How many animals: All
- Parameters not stated

CLINICAL CHEMISTRY: Yes
- Time schedule for collection of blood: at termination
- Animals fasted: No data
- How many animals: All
- Parameters not stated

URINALYSIS: Yes
- Time schedule for collection of urine: for 16 hours prior to termination
- Metabolism cages used for collection of urine: No data
- Animals fasted: No data
- Parameters not stated

NEUROBEHAVIOURAL EXAMINATION: No
Sacrifice and pathology:
GROSS PATHOLOGY: Yes, performed on all major tissues, organs, orifices, cranial, thoracic, abdominal and pelvic cavities and their viscera.
ORGAN WEIGHT: A complete set of organs and tissues were weighed
HISTOPATHOLOGY: Yes, a complete set of organs and tissues were removed and preserved.
Statistics:
Statistical comparisons between control and test groups were carried out where applicable. The data were analysed by employing Dunnett multiple t-test. Where appropriate, a non-parametric analysis of variance by ranks was used to evaluate these parameters. The 95% (p<0.05) confidence level was used as the criteria of significance.

Results and discussion

Results of examinations

Clinical signs:
effects observed, treatment-related
Description (incidence and severity):
There were no remarkable clinical signs. Three male and 2 females died during the treatment period at 400 mg/kg/day. One female at 200 mg/kg/day died as a result of acute pneumonia.
Dermal irritation:
not specified
Mortality:
mortality observed, treatment-related
Body weight and weight changes:
effects observed, treatment-related
Description (incidence and severity):
Significant reduction in body weight gain was noted for females at 200 and 400 mg/kg/day, similar, but less marked, effects on body weight were noted for males at the same doses.
Food consumption and compound intake (if feeding study):
effects observed, treatment-related
Description (incidence and severity):
Lower food consumption was recorded at 200 and 400 mg/kg/day during the treatment period.
Food efficiency:
not examined
Water consumption and compound intake (if drinking water study):
not examined
Ophthalmological findings:
not examined
Haematological findings:
no effects observed
Description (incidence and severity):
There was no effect of treatment.
Clinical biochemistry findings:
no effects observed
Description (incidence and severity):
Serum alkaline phosphatase activity was significantly lower at 200 or 400 mg/kg/day. Significantly higher serum glutamic-pyruvic transaminase and serum glutamic oxalacetic transaminase were noted in males at 200 or 400 mg/kg/day. For females, only serum glutamic oxalacetic transaminase was higher at 200 mg/kg/day.
Urinalysis findings:
no effects observed
Description (incidence and severity):
There was no effect of treatment.
Behaviour (functional findings):
not examined
Immunological findings:
not examined
Organ weight findings including organ / body weight ratios:
effects observed, treatment-related
Description (incidence and severity):
Relative liver weight was lower in females at all doses and to a lesser extent males.
Gross pathological findings:
no effects observed
Description (incidence and severity):
No remarkable findings.
Histopathological findings: non-neoplastic:
no effects observed
Description (incidence and severity):
No effect of treatment.
Histopathological findings: neoplastic:
no effects observed

Effect levels

Dose descriptor:
NOAEL
Effect level:
40 mg/kg bw/day (nominal)
Based on:
test mat.
Sex:
male/female
Basis for effect level:
other: see 'Remark'

Target system / organ toxicity

Critical effects observed:
not specified

Applicant's summary and conclusion

Conclusions:
Dermal administration of trifluoropropylmethylcyclotrisiloxane to rabbits at 40, 200 or 400 mg/kg/day (5 days a week for 3 weeks) resulted in mortality at 400 mg/kg/day and lower body weight gain, food consumption, serum alkaline phosphatase activity and relative organ weight and increased serum glutamic-pyruvic transaminase and glutamic oxalacetic transaminase at 200 and 400 mg/kg/day. The no-observed-adverse-effect-level was considered to be 40 mg/kg/day.