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Toxicological information

Acute Toxicity: dermal

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Administrative data

Endpoint:
acute toxicity: dermal
Type of information:
experimental study
Adequacy of study:
key study
Study period:
From 08 April to 06 May 1992
Reliability:
1 (reliable without restriction)
Rationale for reliability incl. deficiencies:
guideline study
Remarks:
Study performed according to EU Method B.3 and in compliance with GLP.

Data source

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

Materials and methods

Test guideline
Qualifier:
according to
Guideline:
EU Method B.3 (Acute Toxicity (Dermal))
Deviations:
no
Principles of method if other than guideline:
not applicable
GLP compliance:
yes (incl. certificate)
Remarks:
UK GLP Compliance Programme (inspected on 1990-06-19/signed on 1990-10-05
Test type:
standard acute method
Limit test:
yes

Test material

Reference
Name:
Unnamed
Type:
Constituent
Type:
Constituent
Test material form:
liquid
Details on test material:
- Name of test material (as cited in study report): ST 02 C 88
- Substance type: pure active substance
- Physical state: colourless liquid
- Lot/batch No.: A/D/33906 (Toxicol reference N°)
- Storage condition of test material: ca. 4°C under nitrogen in the dark

Test animals

Species:
rat
Strain:
other: Crl:CD(SD)BR (VAF plus)
Sex:
male/female
Details on test animals and environmental conditions:
TEST ANIMALS
- Source: Charles River (UK) Limited, Margate, Kent, England
- Age at study initiation: healthy young animals
- Weight at study initiation: 231-248g (males) 216-225g (females)
- Fasting period before study: no
- Housing: Animals were individually housed in grid bottomed cages suspended over cardboard lined excreta trays. Cardboard tray liners were changed as often as necessary to maintain hygiene.
- Diet (e.g. ad libitum): ad libitum, quality certified
- Water (e.g. ad libitum):ad libitum, quality certified
- Acclimation period: at least 5 days


ENVIRONMENTAL CONDITIONS
- Temperature (°C): 19-22 °C
- Humidity (%): 37-51%
- Air changes (per hr): no data, air conditionned
- Photoperiod (hrs dark / hrs light): 12/12

Administration / exposure

Type of coverage:
occlusive
Vehicle:
unchanged (no vehicle)
Details on dermal exposure:
TEST SITE
- Area of exposure: back
- % coverage: no data
- Type of wrap if used: The treated site was covered with a pad of surgical gauze 4 plies thick. This was secured in position by a length of 5.0cm wide 'Elastoplast' elastic adhesive bandage.

REMOVAL OF TEST SUBSTANCE
- Washing (if done): gentle swabbing with cotton wool soaked in warm water.
- Time after start of exposure: 24 hours

TEST MATERIAL
- Amount(s) applied (volume or weight with unit): 2.2 mL/kg bw
- Constant volume or concentration used: yes
Duration of exposure:
24 hours
Doses:
2000 mg/kg bw
No. of animals per sex per dose:
Preliminary range finding study: 1 male + 1 female
Limit test: 5 males + 5 females
Control animals:
not required
Details on study design:
- Duration of observation period following administration: 14 days
- Frequency of observations and weighing: shortly after dosing, after 30 min, after 1, 2 and 4 hours, daily thereafter for 14 consecutive days
- Necropsy of survivors performed: yes
- Other examinations performed: clinical signs, signs of toxicity, body weight,organ weights, histopathology.
Statistics:
None (limit test at one dose level of at least 2000 mg/kg)

Results and discussion

Preliminary study:
A preliminary range finding study was conducted at a dose level of 2000mg/kg bodyweight using one male rat and one female rat.
Following dosing, animals were examined at frequent intervals on the day of dosing and daily thereafter for 7 days. At the end of this period they
were killed and discarded without necropsy. No deaths occurred and both animals appeared throughout the observation period, therefore the main study consisted of a limit test conducted at a dose level of 2000mg/kg bodyweight, using one group of 5 male and 5 female rats.
Effect levelsopen allclose all
Key result
Sex:
male/female
Dose descriptor:
LD50
Effect level:
> 2 000 mg/kg bw
Based on:
test mat.
Remarks on result:
no indication of skin irritation up to the relevant limit dose level
Sex:
male/female
Dose descriptor:
LD0
Effect level:
2 000 mg/kg bw
Based on:
test mat.
Mortality:
There were no deaths
Clinical signs:
There were no signs of systemic toxicity
Body weight:
All animals showed expected gains in bodyweight over the study period
Gross pathology:
The necropsy findings were of low incidence and were considered not to be treatment related.
Other findings:
None

Any other information on results incl. tables

None

Applicant's summary and conclusion

Interpretation of results:
GHS criteria not met
Conclusions:
Dermal LD50Combined > 2000 mg/kg bw. Under the test conditions, the test material is not classified according to the annex VI of the Regulation EC No. 1272/2008 (CLP).
Executive summary:

In a limit acute dermal toxicity study performed according to the EU B.3 test method and in compliance with GLP, young adult Crl:CD(SD)BR (VAF plus) rats were occlusively exposed to undiluted test material for 24 hours at dose of 2000 mg/kg bw. In a preliminary range-finding study, the test material was administered to one male and one female rat. Both of these animals appeared outwardly healthy throughout the 7 day observation period. In the main study, the test material was administered to 5 males and 5 females. After 24 hours, the dressings were removed and the treated sites were washed with warm water. The animals were observed for 14 days and at the end of this period they were killed and necropsied.

No deaths occurred and all animals remained outwardly healthy throughout the study. There was no adverse effect on bodyweight gain in animals of either sex. Necropsy findings were of low incidence and are considered not to be treatment related.

 

Dermal LD50Combined > 2000 mg/kg bw

 

Under the test conditions, the test material is not classified according to the annex VI of the Regulation EC No. 1272/2008 (CLP).

This study is considered as acceptable and satisfies the requirement for acute dermal toxicity endpoint.