Registration Dossier

Administrative data

Endpoint:
acute toxicity: dermal
Type of information:
experimental study
Adequacy of study:
key study
Study period:
14 December 1995 to 28 December 1995
Reliability:
1 (reliable without restriction)
Rationale for reliability incl. deficiencies:
other: see 'Remark'
Remarks:
Study conducted in compliance with agreed protocols, with no or minor deviations from standard test guidelines and/or minor methodological deficiencies, which do not affect the quality of the relevant results. The study report was conclusive, done to a valid guidelines and the study was conducted under GLP conditions.

Data source

Reference
Reference Type:
study report
Title:
Unnamed
Year:
1996
Report Date:
1996

Materials and methods

Test guidelineopen allclose all
Qualifier:
according to
Guideline:
OECD Guideline 402 (Acute Dermal Toxicity)
Deviations:
no
Qualifier:
according to
Guideline:
EU Method B.3 (Acute Toxicity (Dermal))
Deviations:
no
GLP compliance:
yes
Test type:
fixed dose procedure
Limit test:
yes

Test material

Reference
Name:
Unnamed
Type:
Constituent
Test material form:
solid: particulate/powder
Remarks:
migrated information: powder
Details on test material:
- Substance type: yellow-brown to orange powder.
- Storage condition of test material: at room temperature.

Test animals

Species:
rat
Strain:
Sprague-Dawley
Sex:
male/female
Details on test animals and environmental conditions:
TEST ANIMALS
- Strain: Sprague-Dawley ICO: OFA-SD (IOPS Caw)
- Age at study initiation: ~ 8 weeks old
- Weight at study initiation: Males 296 ± 4 g, females 232 ± 7 g.
- Housing: Individually during treatment in polycarbonate cages (35.5 x 23.5 x 19.3 cm). During acclimatisation animals were housed in groups by sex in polycarbonate cages (48 x 27 x 20 cm).
- Diet (e.g. ad libitum): pelleted diet ad libitum.
- Water (e.g. ad libitum): filtered water ad libitum.
- Acclimation period: At least 5 days.

ENVIRONMENTAL CONDITIONS
- Temperature (°C): 21 ± 2°C
- Humidity (%): 30 to 70 %
- Air changes (per hr): 12 cycles/hour of filtered, non-recycled air.
- Photoperiod: 12 hr light/dark cycle

Administration / exposure

Type of coverage:
semiocclusive
Vehicle:
unchanged (no vehicle)
Details on dermal exposure:
TEST SITE
- Site preparation: The hair was clipped on the day of dosing from an area 6 x 8 cm. Only animals with healthy intact skin were used.
- Area of exposure: 5 x 6 cm for females and 5 x 7 cm for males.
- % coverage: 10 % of the body surface of each animal was treated.
- Type of wrap if used: The test material was applied to a hydrophilic gauze pad, pre-moistened with 2 mL of distilled water. The gauze was held in place using an adhesive hypoallergenic aerated semi-occlusive dressing and a restraining bandage.

REMOVAL OF TEST SUBSTANCE
- Washing: Any residual test material was removed with a gauze pad moistened with water.
- Time after start of exposure: 24 hours.
Duration of exposure:
24 hours
Doses:
2000 mg/kg bw
No. of animals per sex per dose:
5 males and 5 females
Control animals:
no
Details on study design:
- Duration of observation period following administration: 14 days
- Necropsy of survivors performed: yes
- Examinations and frequency of observations:
Clinical signs: Animals were observed frequently in the hours following administration, and then at least once daily thereafter for a period of 14 days. Type, time of onset and duration of clinical signs and local cutaneous reactions were recorded on an individual basis.
Mortality: Animals were checked frequently for mortality and signs of morbidity in the hours following administration and at least once daily thereafter. The time of death was recorded individually in terms of hours after treatment.
Body weight: Animals were weight prior to administration on day 1 and then on days 8 and 15.
Body weight gain of the treated animals was compared to a reference curve created at the test facility, of control animals with the same initial weight.
Necropsy: Animals were euthanized on day 15 and macroscopic examinations were performed.
Examination included; opening of the thoracic and abdominal cavities and examination of the main organs (digestive tract, heart, kidneys, liver, lungs, pancreas, spleen and any with signs of abnormalities).
In the case of macroscopic lesions, organ samples were taken and preserved in 10 % buffered formalin.
No microscopic examinations were performed.

Results and discussion

Effect levels
Sex:
male/female
Dose descriptor:
LD50
Effect level:
> 2 000 mg/kg bw
Based on:
test mat.
Mortality:
No deaths occurred during the observation period.
Clinical signs:
No clinical signs of toxicity were observed during the study.
Slight orange colouration of the test site was observed in all animals on day 2. Crusts were noted in two males and two females on day 3; they persisted up to day 5 in one male and one female.
Body weight:
A slight decrease in body weight gain was noted in females in the first week only. The body weight gain in males was not affected.
Gross pathology:
Macroscopic examination of the main organs revealed no apparent abnormalities.

Any other information on results incl. tables

Table 1: Mean Body Weight and Mean Body Weight Gain (g)

Sex

Body Weight on Days

1

Gain

8

Gain

15

Male

296 (± 4)

37 (± 11)

334 (± 15)

50 (± 5)

384 (± 18)

Female

232 (± 7)

4 (± 4)

235 (± 6)

10 (± 13)

245 (± 15)

(± Standard Deviation)

Applicant's summary and conclusion

Interpretation of results:
not classified
Remarks:
Migrated information Criteria used for interpretation of results: EU
Conclusions:
Under the conditions of the test, no signs of mortality or treatment related toxicity were observed in any of the animals exposed to the test material applied under a semi-occlusive dressing. Therefore the LD50 of the test material was determined to be > 2000 mg/kg bw in both male and female rats.
Executive summary:

The acute dermal toxicity of the test material was determined in a study conducted under GLP conditions in accordance with the standardised guidelines OECD 402 and EU method B.3.

Five male and 5 female Sprague-Dawley rats were exposed to the test material at 2000 mg/kg bw applied in its original form under a semi-occlusive dressing.

Under the conditions of the test, no overt signs of toxicity or mortality were observed in any of the treated animal. Body weight again was slightly decreased in females in the first week only, whereas male body weight gain was not affected. Macroscopic examinations at necropsy revealed no abnormalities.

Based on these observations the LD50 of the test material was determined to be > 2000 mg/kg bw in both male and female rats.