Registration Dossier

Toxicological information

Skin irritation / corrosion

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Administrative data

Endpoint:
skin irritation: in vivo
Type of information:
experimental study
Adequacy of study:
key study
Study period:
1992-01-16 to 1992-02-12
Reliability:
1 (reliable without restriction)
Rationale for reliability incl. deficiencies:
guideline study

Data source

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

Materials and methods

Test guideline
Qualifier:
according to
Guideline:
OECD Guideline 404 (Acute Dermal Irritation / Corrosion)
GLP compliance:
yes

Test material

Reference
Name:
Unnamed
Type:
Constituent
Specific details on test material used for the study:
For the purpose of this study the test material was used as supplied.

Test animals

Species:
rabbit
Strain:
New Zealand White
Details on test animals and environmental conditions:
TEST ANIMALS
- Source: David Percival Ltd., Moston, Sandbach, Cheshire, U.K.
- Strain: New Zealand White rabbits
- Age: approximately twelve to sixteen weeks old
- Weight at study initiation: 2.10 - 2.32 kg
- Housing: single
- Diet: (Spillers Rabbit Diet, Dalgety Agriculture Ltd., Almondsbury, Bristol), ad libitum
- Water (e.g. ad libitum): tap water
- Acclimation period: at least 5 days

ENVIRONMENTAL CONDITIONS
- Temperature (°C): 17 - 23 °C
- Humidity (%): 42 - 59 %
- Air changes (per hr): approximately 15 changes per hour
- Photoperiod (hrs dark / hrs light): 12 hours daily

Test system

Type of coverage:
semiocclusive
Preparation of test site:
shaved
Vehicle:
unchanged (no vehicle)
Controls:
not required
Amount / concentration applied:
0.5 mL test item
Duration of treatment / exposure:
4 hour and 3 minutes
Observation period:
7 days
Number of animals:
3 and 3
Details on study design:
ADMINISTRATION/EXPOSURE 
- Area of exposure: ca. 6 cm2
- Total volume applied: 0.5 ml
- Type of wrap: The patch was secured in position with a strip of surgical adhesive tape, the trunk o f each rabbit was wrapped in an elasticated corset
- Postexposure period: 7 days
- Removal of test substance: test material removed by gentle swabbing with cotton wool soaked indistilled water.
EXAMINATIONS
- Scoring system: Draize J.H. (1959) Association of Food and Drug Officials of the United States, Austin, Texas, "The Appraisal o f the Safety o f Chemicals in Foods, Drugs and Cosmetics
- Examination time points: 1; 24; 48; 72 hours and 6; 8; 10; 14 days  after removal of patch and test substance

Results and discussion

In vivo

Results
Irritation parameter:
other: signs of necrosis observed
Basis:
other: all animals
Reversibility:
not fully reversible within: 7 days
Remarks on result:
other: scores are not relevant since the material produced dermal necrosis
Irritant / corrosive response data:
4-Hour Exposure Period
Green-coloured dermal necrosis and very slight to severe oedema were noted at all treated skin sites one and 24 hours after patch
removal. Well-defined erythema surrounding other skin reactions was also noted at two treated skin sites at the 24-hour observation. A
hardened, dark brown/black-coloured scab was noted at two treated skin sites at the 48 and 72-hour and 7-day observations. Well -
defined erythema surrounding the scab was also noted a t the 48 and 72-hour observations. Scattered sunken, scabs around the edge of
the treatment site with well-defined erythema over the treatment site was noted at one treated skin site at the 48 and 72-hour observations.
A sunken, hardened, dark brown/bl ack-coloured scab was noted at this treated skin site at the 7-day observation. Adverse reactions prevented accurate evaluation of erythema and oedema at all treated skin sites at the 48 and 72-hour and 7-day observations. The treatment sites were assigned a grade 4 for erythema on the Draize scale due to injuries in depth.
The animals were killed for humane reasons immediately after the 7-day observation i n accordance with current U.K. Home Office guidelines.

Any other information on results incl. tables

3-Minute Exposure Period

Very slight erythema was noted at all treated skin sites one and 24 hours after patch removal and persisted at two treated skin sites at the 48 and 72-hour observations.

Very slight oedema was noted at one treated skin site at the 24-hour observation.

Desquamation was confined to one treated skin site seven days after treatment.

Applicant's summary and conclusion

Conclusions:
Test item is corrosive following a 4-hour semi-occluded exposure.
Executive summary:

The study was performed to assess the irritancy potentia l of the test item following single , semi-occluted applications to the intact rabbit skin for exposure periods o f 4 hours and 3 minutes (Safepharm Standard Method Number OECD 4). The method used followed the recommendations of the OECD Guidelines for Testing of Chemicals (1981) No. 404.

The results may be used as a basis for classification and labeling under Commission Directive 83/467/EEC and the UK Approved Code of Practice " Classification and Labeling of Substances Dangerous for Supply".

The test system was chosen because the rabbit has been shown to be a suitable model for this type of study and is recommended in the test method. The results o f the study are believed to be of value in predicting the likely skin irritancy potential of the test material to man

A single 3-minute, semi-occluded application of the test material to the skin of three rabbits produced very slight erythema. Very slight edema was confined to one treated skin site at the 24-hour observation. Desquamation was confined to one treated skin site seven days after treatment. A single 4-hour, semi-occluded application of the test material to the intact skin of three rabbits produced reactions indicative of dermal corrosion. The reactions included dermal necrosis, slight to severe edema and scabbing.