Registration Dossier

Administrative data

Endpoint:
acute toxicity: dermal
Type of information:
experimental study
Adequacy of study:
key study
Study period:
1991
Reliability:
1 (reliable without restriction)
Rationale for reliability incl. deficiencies:
other: GLP guideline study

Data source

Reference
Reference Type:
study report
Title:
Unnamed
Year:
1992
Report Date:
1992

Materials and methods

Test guideline
Qualifier:
according to
Guideline:
OECD Guideline 402 (Acute Dermal Toxicity)
GLP compliance:
yes (incl. certificate)
Test type:
fixed dose procedure
Limit test:
yes

Test material

Reference
Name:
Unnamed
Type:
Constituent
Details on test material:
- Batch number: sample no.1
- Purity: 90.5 %
- Before the treatment, the test substance was stored at -20°C and protected from light and was stored at +4 °C during the treatment

Test animals

Species:
rat
Strain:
Sprague-Dawley
Sex:
male/female
Details on test animals and environmental conditions:
TEST ANIMAL
- Source: Iffa Credo (69210 L'Arbresle, France)
- Age: 8 weeks
- Weight at study initiation: 271 ± 7 g (males) and 230 ± 4 g (females)
- Upon their arrival at C.I.T., the animals were acclimatized to the experimental environment for at least 5 days during which they were observed daily.
On the first day of treatment, the adult animals were approximately 8 weeks old, and had a mean weight of 271 ± 7 g for the males and 230 ± 4 g for the females.
- They were individually identified by earmarks or earnotches.

ENVIRONMENTAL CONDITIONS
- Temperature : 22 ± 3°C
- Humidity : 50 ± 20% relative humidity
- Light/dark cycle: 12 hours of light/12 hours of dark
- The air was non-recycled and filtered by absolute filters.
- Food and water: ad libidum

Administration / exposure

Type of coverage:
semiocclusive
Vehicle:
other: none
Details on dermal exposure:
- Area covered: approximately 10%
- Exposure: semi-occlusive
- Concentration in vehicle: undiluted
- Total volume applied: according to the body weight determined on the day of treatment and test substance specific gravity (0.96)
- Removal of test substance: no
- Exposure duration: 24 hours
- Post-dose observation period: 14 days
- The day before treatment, the dorsal area of each animal was clipped with an electric clipper on an area of 6 x 8 cm. Only animals with healthy intact skin were used for the study.
- A hydrophilic gauze patch was applied to the skin
- The test substance and the gauze patch were held in contact with the skin for 24 hours by means of an adhesive hypoallergic aerated semi-occlusive dressing attached to a restraining bandage. This dressing prevented the ingestion of the test substance by the animal. No residual test substance was observed at removal of the dressing.
Duration of exposure:
24 hours
Doses:
2000 mg/kg
No. of animals per sex per dose:
- Number of animals: 5 males + 5 females
Control animals:
no
Details on study design:
- Clinical signs: examined at least once a day
- Mortality: recorded at least twice a day
- Body weight: measured just before administration then on days 5, 8 and 15.
- Necropsy: . macroscopic examination of the main organs: digestive tract, heart, kidneys, liver, lungs, pancreas, spleen and any other organs with obvious abnormalities.
- Microscopic examination: no, due to the absence of macroscopic lesions
Statistics:
NONE

Results and discussion

Effect levels
Sex:
male/female
Dose descriptor:
LD0
Effect level:
>= 2 000 mg/kg bw
Mortality:
No deaths occurred during the observation period.
Clinical signs:
No clinical signs were observed during the study.
Body weight:
Between days 1 and 5, a decrease in the body weight of 2 females (Nos. 01, 02) was noted without subsequent consequence thereafter. The body weight variations recorded within the days following treatment were probably due to the stress caused by the experimental conditions. The body weight gain of the other animals was normal.
Other findings:
NECROPSY FINDINGS: No apparent abnormalities.

Applicant's summary and conclusion

Interpretation of results:
study cannot be used for classification
Remarks:
Migrated information
Conclusions:
The LD0 of the test substance administered by dermal route in rats was higher than 2000 mg/kg. No signs of toxicity were observed at this dose level.
Executive summary:

In an acute toxicity test by dermal route (OECD 402, GLP), the test substance was applied in its original form directly to the skin of 10 Sprague-Dawley rats (5 males and 5 females) at a dose level of 2000 mg/kg, taking into consideration that the specific gravity (SG) of the test substance was 0.96. After 24 hours under a semi-occlusive dressing, no residual test substance was observed.

The mortality, general behaviour and body weight gain of the animals were observed for a period of 14 days after the single application of the test substance. A necropsy was performed on each animal sacrificed at the end of the study.

The general behaviour and body weight gain of the animals were not influenced by the treatment. No deaths occurred at the dose level of 2000 mg/kg.

The macroscopic examination revealed no abnormalities in the animals sacrificed at the end of the study.