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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:
2002
Reliability:
1 (reliable without restriction)
Rationale for reliability incl. deficiencies:
guideline study

Data source

Reference
Reference Type:
study report
Title:
Unnamed
Year:
2002
Report Date:
2002

Materials and methods

Test guideline
Qualifier:
according to
Guideline:
OECD Guideline 404 (Acute Dermal Irritation / Corrosion)
Version / remarks:
1992
Deviations:
no
GLP compliance:
not specified

Test material

Reference
Name:
Unnamed
Type:
Constituent
Type:
Constituent

Test animals

Species:
rabbit
Strain:
New Zealand White
Details on test animals and environmental conditions:
ANIMALS AND ANIMAL HUSBANDRY

- Rabbits were sourced from Kuiper Rabbitry, Gary, Indiana, USA and were approximately 8-10 weeks old.
- Animals were housed individually in stainless steel cages in a temperature, humidity and light controlled room.
- Rabbits were conditioned for at least three days prior to study initiation.
- Purina Rabbit Chow and water were available ad libitum.
- All animals used for the investigation were considered to be in good health at study initiation.

Test system

Type of coverage:
occlusive
Preparation of test site:
not specified
Vehicle:
unchanged (no vehicle)
Controls:
no
Amount / concentration applied:
0.5 mL
Duration of treatment / exposure:
3 minutes, 1 hour and 4 hours
Observation period:
7 days
Number of animals:
6
Details on study design:
COMPOUND ADMINISTRATION

- Three intact sites were prepared on each of the six animals.
- A dose of 0.5 mL of the test article was applied to the occluded sites for contact periods of 3 minutes (site A), 1 hour (site B) and 4 hours (site C).
- At the conclusion of the individual contact periods, any remaining test material was wiped from the site.
- If necrosis was observed at the shorter contact periods the test was considered to be concluded and longer exposure times were not required.

CLINICAL OBSERVATIONS
- Observations for irritation, ulceration and necrosis were performed at the end of each contact period.
- Observations were repeated at 60 minutes for the 3 minute contact time.
- Observations were repeated at 24, 48 and 72 hours following test article application for the 1 and 4-hour contact times.
- Additional readings were continued up to Day 7 to confirm transport packing group
- Corrosion was considered to have resulted if the substance in contact with rabbit skin produced full thickness destruction or irreversible alteration of tissue.
- Tissue destruction was considered to have occurred if ulceration and/or necrosis was observed at any of the readings.
- Tissue destruction did not include merely sloughing of the epidermis, erythema, edema or fissuring.
- Scoring crieria used during evaluation of skin reactions are given in Table 2 (attached).

Results and discussion

In vivo

Resultsopen allclose all
Irritation parameter:
erythema score
Basis:
mean
Time point:
other: 3 min
Score:
0
Max. score:
4
Reversibility:
other: not applicable site A
Remarks on result:
other: Animals 53, 54, 55, 56, 57 and 58
Irritation parameter:
erythema score
Basis:
mean
Remarks:
mean 3 min contact time
Time point:
other: 1 h
Score:
0
Max. score:
4
Reversibility:
other: not applicable site A
Remarks on result:
other: not corrosive after 3 min contact time Animals 53, 54, 55, 56, 57 and 58
Irritation parameter:
erythema score
Basis:
animal #1
Remarks:
1 h contact time
Time point:
24/48/72 h
Score:
2
Max. score:
4
Reversibility:
not reversible
Remarks on result:
other: Animal 53 Necrosis reported at 7 d observation
Irritation parameter:
erythema score
Basis:
animal #2
Remarks:
1 h contact time
Time point:
24/48/72 h
Score:
3
Max. score:
4
Reversibility:
not reversible
Remarks on result:
other: Animal 54 Score unchanged at 7 d observation
Irritation parameter:
erythema score
Basis:
animal #3
Remarks:
I h contact time
Time point:
24/48/72 h
Score:
4
Max. score:
4
Reversibility:
not reversible
Remarks on result:
other: Animal 55 Necrosis reported at 72 h observation
Irritation parameter:
erythema score
Basis:
animal #4
Remarks:
1 h contact time
Time point:
24/48/72 h
Score:
3
Max. score:
4
Reversibility:
not reversible
Remarks on result:
other: Animal 56 Score unchanged at 7 d observation
Irritation parameter:
erythema score
Basis:
animal #5
Remarks:
1 h contact time
Time point:
24/48/72 h
Score:
3
Max. score:
4
Reversibility:
not reversible
Remarks on result:
other: Animal 57 Score unchanged at 7d observation
Irritation parameter:
erythema score
Basis:
animal #6
Remarks:
1 h contact time
Time point:
24/48/72 h
Score:
3
Max. score:
4
Reversibility:
not reversible
Remarks on result:
other: Animal 58 Necrosis reported at 7 d observation
Irritation parameter:
edema score
Basis:
mean
Time point:
24/48/72 h
Remarks on result:
not measured/tested
Irritant / corrosive response data:
- Data showing individual responses of each animal are attached.
- Occluded contact with the test material for three minutes produced no irritation and necrosis was not observed in any of the six animals.
- Occluded contact with the test material for one hour produced severe irritation and necrosis was observed in three of the six animals within 7 days.
- Occluded contact with the test material for four hours caused necrosis in all six animals.

Applicant's summary and conclusion

Interpretation of results:
Category 1B (corrosive) based on GHS criteria
Conclusions:
Occluded contact with the test item for one hour produced severe irritation (erythema scores at 24/4 8/72 hours ≥ 2.3 in 5/6 animals) and necrosis was observed in three of the six animals within 7 days.
On the basis of this study, the test material is found to be corrosive to skin.
Executive summary:

In a study performed in accordance with US D.O.T. regulations and OECD 404, the test item was applied to three prepared skin sites on New Zealand White rabbits under occluded conditions for 3 minutes, 1

hour and 4 hours. After the relevant contact period, any remaining test item was wiped from the site. After removal of patches and 24, 48 and 72 hours later, the test sites were examined for evidence of

primary irritation and scored for erythema. No effects were noted over a period of 60 minutes following contact with the test item for 3 minutes. However, occluded contact with the test item for one hour

produced severe irritation (erythema scores at 24/48/72 hours ≥ 2.3 in 5/6 animals) and necrosis was observed in three of the six animals within 7 days. On the basis of this study, the test material is found

to be corrosive to skin.