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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:
1979
Reliability:
2 (reliable with restrictions)
Rationale for reliability incl. deficiencies:
other: Comparable to guideline study with acceptable deviation (occlusive dressing). Occlusive dressing represents worst case conditions. The study was performed prior to the implementation of GLP.

Data source

Reference
Reference Type:
study report
Title:
Unnamed
Year:
1979
Report date:
1979

Materials and methods

Test guideline
Qualifier:
equivalent or similar to guideline
Guideline:
OECD Guideline 404 (Acute Dermal Irritation / Corrosion)
Principles of method if other than guideline:
Study was performed prior to the implementation of OECD Guidelines and GLP, but is in compliance with the principles described in OECD Guideline 404.
GLP compliance:
no

Test material

Constituent 1
Chemical structure
Reference substance name:
Imidazole
EC Number:
206-019-2
EC Name:
Imidazole
Cas Number:
288-32-4
Molecular formula:
C3H4N2
IUPAC Name:
1H-imidazole
Details on test material:
Imidazole (CAS: 288-32-4), purity approx. 99%

Test animals

Species:
rabbit
Strain:
Vienna White
Details on test animals or test system and environmental conditions:
TEST ANIMALS
- Source: Zuchtbetrieb M. Gauckler, 63065 Offenbach, Germany
- Weight at study initiation: mean 2,7 kg
- Diet (ad libitum): Ssniff K standard diet for rabbits and guinea pigs from IMTERMAST GmbH, Germany
- Water: ad libitum

Test system

Type of coverage:
occlusive
Preparation of test site:
shaved
Vehicle:
water
Controls:
no
Amount / concentration applied:
Concentration: 80 % active substance
Ammounts applied: 0.5 ml
Duration of treatment / exposure:
1 hour (1 h experiment)
4 hour (4 h experiment)
Observation period:
The animals were observed 8 days and skin changes were recorded on working days.
Number of animals:
A total of 6 Vienna White rabbits; 4 animals (1 male, 3 females) in the 1h experiment, 2 females in the 4h experiment.
Details on study design:
- Area of exposure: clipped dorsal skin

REMOVAL OF TEST SUBSTANCE
- Washing (if done): water or a mixture of water/lutrole (1:1 v/v)
- Time after start of exposure: 1h and 4h

SCORING SYSTEM:
Score/Erythema/Oedema
0/not present/not present
1/very slight/very slight
2/mild/mild
3/moderate/moderate
4/severe/severe

Results and discussion

In vivo

Resultsopen allclose all
Irritation parameter:
erythema score
Remarks:
4 h treatment
Basis:
animal #1
Time point:
other: mean of 1, 2 and 8 days
Score:
4
Max. score:
4
Reversibility:
not fully reversible within: 8 d
Remarks on result:
other: comprehensive, parchment like skin necrosis at the end of the observation period
Irritation parameter:
erythema score
Remarks:
4 h treatment
Basis:
animal #2
Time point:
other: mean of 1, 2 and 8 days
Score:
4
Max. score:
4
Reversibility:
not fully reversible within: 8 d
Remarks on result:
other: comprehensive, leathery skin necrosis at the end of the observation period
Irritation parameter:
edema score
Remarks:
4 h treatment
Basis:
animal #1
Time point:
other: mean of 1, 2 and 8 days
Score:
2
Max. score:
4
Reversibility:
not fully reversible within: 8 d
Remarks on result:
other: light edema at the end of the observation period
Irritation parameter:
edema score
Remarks:
4 h treatment
Basis:
animal #2
Time point:
other: mean of 1, 2 and 8 days
Score:
2.33
Max. score:
4
Reversibility:
not fully reversible within: 8 d
Remarks on result:
other: light edema at the end of the observation period
Irritation parameter:
erythema score
Remarks:
1 h treatment
Basis:
animal #1
Time point:
other: mean of 1, 2 and 8 days
Score:
2.67
Max. score:
4
Reversibility:
not fully reversible within: 8 d
Remarks on result:
other: necrotic spots on the skin surface at the end of the observation period
Irritation parameter:
erythema score
Remarks:
1 h treatment
Basis:
animal #2
Time point:
other: mean of 1, 2 and 8 days
Score:
0
Max. score:
4
Remarks on result:
other: desquamation at the end of the observation period
Irritation parameter:
erythema score
Remarks:
1h treatment
Basis:
animal #3
Time point:
other: mean of 1, 2 and 8 days
Score:
1.33
Max. score:
4
Reversibility:
fully reversible within: 8 d
Remarks on result:
other: necrotic spots on the skin surface at the end of the observation period
Irritation parameter:
erythema score
Remarks:
1h treatment
Basis:
animal #4
Time point:
other: mean of 1, 2 and 8 days
Score:
1.67
Max. score:
4
Reversibility:
not fully reversible within: 8 d
Remarks on result:
other: necrotic spots on the skin surface and desquamation at the end of the observation period
Irritation parameter:
edema score
Remarks:
1h treatment
Basis:
animal #1
Time point:
other: mean of 1, 2 and 8 days
Score:
< 1
Max. score:
4
Reversibility:
fully reversible within: 8 d
Irritation parameter:
edema score
Remarks:
1 h treatment
Basis:
animal #2
Time point:
other: mean of 1, 2 and 8 days
Score:
0
Max. score:
4
Reversibility:
fully reversible within: 8 d
Irritation parameter:
edema score
Remarks:
1 h treatment
Basis:
animal #3
Time point:
other: mean of 1, 2 and 8 days
Score:
1.33
Max. score:
4
Reversibility:
fully reversible within: 8 d
Irritation parameter:
edema score
Remarks:
1 h treatment
Basis:
animal #4
Time point:
other: mean of 1, 2 and 8 days
Score:
1.33
Max. score:
4
Reversibility:
fully reversible within: 8 d
Irritant / corrosive response data:
Skin reactions after 1-hr exposure time:
Mild erythema was seen in all (4/4) animals 1 hr after removal of the occlusive dressing. Erythema subsided in one animal overnight. Focal necrosis developed in the other 3 animals within 24 and 48 hr. Findings at the end of the observation period (8 d) were as follows: 2/4 animals showed no erythema but showed desquamation (1/4) and focal necrosis (1/4). Slight erythema, desquamation and extended focal necrosis was seen in the 3rd animal, and severe erythema with superficial necrosis was noted in the 4th animal. Oedema were absent after patch removal but grade 2 oedema were noted in 2/4 and 3/4 animals after 24 and 48 hr, respectively. Oedema had resolved on day 8 of observation.

Skin reactions after 4-hr exposure time:
Well defined, moderate erythema and oedema were seen in both animals after removal of the occlusive dressing. Erythema became severe overnight and rested severe until the end of the observation period. Soft necroses developed overnight in both animals. Leather-like necrosis indicative of full thickness necrosis was noted in both animals and confirmed by pathology after sacrifice of the animals. Oedema started to resolve overnight but rested as grade 2 until day 8.
Other effects:
General toxicity: No signs noted after 1-hr or 4-hr exposure.

Any other information on results incl. tables

On the basis of the results no substance specific destruction of skin tissue, namely, visible necrosis through the epidermis and into the dermis, after exposure up to a 1 hour duration was observed.

Applicant's summary and conclusion

Interpretation of results:
corrosive
Remarks:
Migrated information
Conclusions:
After 4-hr occlusive exposure moderate erythema and oedema were noted within 1 hr. Severe erythema developed overnight and persisted until day 8, the end of the observation period. Soft necroses developed overnight. They hardened and changed into persistent leather-like necroses in both animals as noted on day 8. Slight oedema were noted at the end of the observation period.
No signs of general toxicity were noted but Imidazole was found to be corrosive.
Executive summary:

When imidazole was applied to the intact rabbit skin as a 80% aqueous paste (0.5 ml) for 1 or 4 hours under occlusive dressing skin reactions were noted as early as one hour after removal of the dressing .

After the 4 hour exposure period focal necrosis developed overnight in all animals and was described as leather-like at the end of the observation period when pathology confirmed full thickness necrosis after sacrifice of the animals.

After the 1 hour exposure under occlusive dressing mild erythema was seen in all (4/4) animals. Mild erythema and mild oedema were observed on the following two days of the study. The oedema resolved completely by day 8 of the post-exposure observation period. Residual signs included patchy, superficial necrotic lesions in addition to scaling.

On the basis of the results obtained after 1 hour exposure no substance specific destruction of skin tissue, namely, visible necrosis through the epidermis and into the dermis, was observed.

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