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Description of key information

Skin irritation study in vivo:


Three rabbits exposed for 4 hours to 0.5 ml JAU 6476-Chloromethylketone/patch and animal (semi-occlusive condition) showed the following effects: An erythema (grade 2) was observed in all animals 1 and 24 hours after patch removal, the test site was pale and indurated with an approx. 2 cm wide dark-red - brown necrotic strip around the test site from 48 hours until 14 days after patch removal (skin destruction). An oedema (grade 1) was observed in all animals 1 and 24 hours after patch removal and an oedema (grade 2) from 48 hours until 14 days after patch removal. There were no systemic intolerance reactions.

Key value for chemical safety assessment

Skin irritation / corrosion

Link to relevant study records
Reference
Endpoint:
skin irritation: in vivo
Type of information:
experimental study
Adequacy of study:
key study
Study period:
November 3 - 17, 2000
Reliability:
1 (reliable without restriction)
Qualifier:
according to guideline
Guideline:
OECD Guideline 404 (Acute Dermal Irritation / Corrosion)
Version / remarks:
adopted 1992
Deviations:
no
GLP compliance:
yes
Specific details on test material used for the study:
purity 92.11%
no prior stability testing
Species:
rabbit
Strain:
Himalayan
Type of coverage:
semiocclusive
Vehicle:
other: None
Amount / concentration applied:
0.5 ml/ patch
Duration of treatment / exposure:
4 h
Number of animals:
3
Details on study design:
Approximately 24 hours before the test, the fur was removed by shaving from the dorsal area of the trunk of the animals. Care was taken to avoid abrading the skin. Only animals with healthy intact skin were used. A dose of 0.5 ml was applied to the test site (area: approx. 6 cm2). The test substance was applied to the test site and then covered with a gauze patch. The patch was held in contact with the skin by means of a semi-occlusive dressing for the duration of the exposure period. The surrounding untreated skin served as a control. Exposure time was four hours. During the exposure the animals were kept in comfortable restrainers.
Examination of the skin: the skin sites were evaluated immediately before the application of the test substance. After the 4-hour exposure period the patch was removed and the skin sites were evaluated. Scores were taken 60 minutes, 24, 48, 72 hours and 4 - 1 4 days after patch removal. The evaluation of the skin irritation was based on the grading given in the Appendix 1 to this report. Based on most recent guidelines the skin reactions are monitored until the changes observed have completely subsided, however for not more than 14 days after application. Animals that do not reveal any lesions anymore for 24 hours following the first 72 hours of observation are sacrificed.
General criteria: body weight of all animals was measured at the beginning of the study.
Irritation parameter:
erythema score
Basis:
animal #1
Time point:
24/48/72 h
Score:
2
Max. score:
2
Reversibility:
not fully reversible within: 14d
Irritation parameter:
erythema score
Basis:
animal #2
Time point:
24/48/72 h
Score:
2
Max. score:
2
Reversibility:
not fully reversible within: 14d
Irritation parameter:
erythema score
Basis:
animal #3
Time point:
24/48/72 h
Score:
2
Max. score:
2
Reversibility:
not fully reversible within: 14d
Irritation parameter:
edema score
Basis:
animal #1
Time point:
24/48/72 h
Score:
>= 1 - <= 2
Max. score:
2
Reversibility:
not fully reversible within: 14d
Irritation parameter:
edema score
Basis:
animal #2
Time point:
24/48/72 h
Score:
>= 1 - <= 2
Max. score:
2
Reversibility:
not fully reversible within: 14d
Irritation parameter:
edema score
Basis:
animal #3
Time point:
24/48/72 h
Score:
>= 1 - <= 2
Max. score:
2
Reversibility:
not fully reversible within: 14d
Irritant / corrosive response data:
Reversibility of any observed effect: Changes not fully reversible within 14 days
Other effects:
An erythema (grade2) was observed in all animals 1 and 24
hours after patch removal, the test site was pale and
indurated with an approx. 2 cm wide dark-red-brown necrotic
strip around the test site from 48 hours until 14 days after
patch removal (skin destruction).

An oedema (grade 1) was observed in all animals 1 and 24
hours after patch removal and an oedema (grade 2) from 48
hours until 14 days after patch removal.

There were no systemic intolerance reactions.
Interpretation of results:
Category 1 (corrosive) based on GHS criteria
Conclusions:
Based on irreversible findings (skin destruction from 48h until 14d) test compound is corrosive; since since a single exposure period of 4h was investigated no sub-categorization can be applied.
Executive summary:

Under the present test conditions the three rabbits exposed for 4 hours to 0.5 ml JAU 6476-Chloromethylketone/patch and animal (semi-occlusive condition) showed the following effects: An erythema (grade 2) was observed in all animals 1 and 24 hours after patch removal, the test site was pale and indurated with an approx. 2 cm wide dark-red - brown necrotic strip around the test site from 48 hours until 14 days after patch removal (skin destruction). An oedema (grade 1) was observed in all animals 1 and 24 hours after patch removal and an oedema (grade 2) from 48 hours until 14 days after patch removal. There were no systemic intolerance reactions.

Endpoint conclusion
Endpoint conclusion:
adverse effect observed (corrosive)

Eye irritation

Endpoint conclusion
Endpoint conclusion:
no study available

Respiratory irritation

Endpoint conclusion
Endpoint conclusion:
no study available

Additional information

Justification for classification or non-classification

Based on the study results for skin irritation allocation to category 1 (H314) according to Regulation (EC) No. 1272/2008 (CLP), ANNEX I, is warranted.


No further study for eye irritation is therefore required.

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