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Toxicological information

Skin irritation / corrosion

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Administrative data

Endpoint:
skin irritation: in vivo
Type of information:
migrated information: read-across from supporting substance (structural analogue or surrogate)
Adequacy of study:
key study
Reliability:
1 (reliable without restriction)
Rationale for reliability incl. deficiencies:
other: The study was conducted in compliance with the Good Laboratory Practices Standards. The study methods were equivalent to OECD Guideline 404.

Data source

Reference
Reference Type:
study report
Title:
Unnamed
Year:
1993
Report Date:
1993

Materials and methods

Test guideline
Qualifier:
equivalent or similar to
Guideline:
OECD Guideline 404 (Acute Dermal Irritation / Corrosion)
Deviations:
yes
Principles of method if other than guideline:
The study methods were equivalent to OECD Guideline 404; however, the test laboratory reported that (1) due to residual test material remaining on
the test sites after patch removal, it was necessary to first remove the residual test material before conducting the first corrosion examination; (2) an
additional dermal observation was conducted on Day 21 of the study; (3) all test sites were collected on Day 22 instead of only those sites exhibiting
dermal irritation on Day 14; and (4) the temperature and humidity conditions in the animal room exceeded the ranges specified by the protocol on 7
days during the study. According to the testing laboratory, these deviations are not considered to have had adverse effect on the outcome of the
study.
GLP compliance:
yes

Test material

Reference
Name:
Unnamed
Type:
Constituent
Details on test material:
Trade name: AS 304
Sample id: C0834-50-7

Test animals

Species:
rabbit
Strain:
New Zealand White
Details on test animals and environmental conditions:
TEST ANIMALS
- Source: Hazleton Research Products, Inc.
- Age at study initiation: Adult
- Weight at study initiation: 2056 to 2318 g.
- Housing: Individually in scren-bottom cages
- Diet: Measured amounts of High Fiber Rabbit Chow #5326, Purina Mills, Inc.
- Water: Ad libitum
- Acclimation period: At least 7 days

ENVIRONMENTAL CONDITIONS
- Temperature (°C): 18-23
- Humidity (%): 55-84
- Air changes (per hr):
- Photoperiod (hrs dark / hrs light):

IN-LIFE DATES: From: To:

Test system

Type of coverage:
semiocclusive
Preparation of test site:
shaved
Vehicle:
unchanged (no vehicle)
Controls:
other: Untreated skin was used for comparison
Amount / concentration applied:
TEST MATERIAL
- Amount(s) applied (volume or weight with unit): 0.5 mL
- Concentration (if solution):

VEHICLE
- Amount(s) applied (volume or weight with unit): None
- Concentration (if solution):
- Lot/batch no. (if required):
- Purity:
Duration of treatment / exposure:
3 minutes, 1 hour, or 4 hours
Observation period:
After approximately 30 minutes after the 3-minute, 1-hour, or 4-hour exposure period, the application site was examined. Subsequent examinations
were made at 24, 48, 72, and 96 hours and Days 7, 14, and 21.
Number of animals:
6
Details on study design:
TEST SITE
- Area of exposure: Animals' backs
- % coverage:
- Type of wrap if used: Gauze patch (two single layers thick) secured with paper tape, loosely overwrapped with Saran Wrap, and secured with
Elastoplast tape.

REMOVAL OF TEST SUBSTANCE
- Washing (if done): Test area was washed using liquid Ivory soap mixed with warm tap water, rinsed with clean tap water, and dried with disposable
paper towels.
- Time after start of exposure: 3 minutes, 1 hour, and 4 hours

SCORING SYSTEM: Primary Dermal Irritation Scoring Scale- Draize Technique

Results and discussion

In vivo

Resultsopen allclose all
Irritation parameter:
primary dermal irritation index (PDII)
Basis:
other: After 3-minute exposure
Time point:
other: 3 minutes, 24, 48, and 72 hours
Score:
2.7
Max. score:
8
Reversibility:
fully reversible within: 21 days
Irritation parameter:
primary dermal irritation index (PDII)
Basis:
other: After 1 hour exposure
Time point:
other: 1, 24, 48, and 72 hours
Score:
4.2
Max. score:
8
Reversibility:
not fully reversible within: 21 days
Irritation parameter:
primary dermal irritation index (PDII)
Basis:
other: After 4 hour exposure
Time point:
other: 4, 24, 48, and 72 hours
Score:
5.6
Max. score:
8
Reversibility:
not fully reversible within: 21 days
Irritant / corrosive response data:
The primary dermal irritation/corrosion potential of AS 304 (C0834-50-7) was evaluated when 0.5 mL was applied to the intact skin of rabbits
under 3-minute, 1-hour, and 4-hour semioccluded conditions. No evidence of corrosion was observed at the test sites receiving a 3-minute
exposure. Evidence of corrosion was observed at all of the test sites receiving the 1- and 4-hour exposures. All irritation cleared by the Day 21
observation in the 3-minute exposure sites, but was still present in the 1- and 4-hour exposure sites. The average of the dermal irritation scores was 2.7 for the 3-minute exposure (3-minute, 24-, 48-, and 72-hour scores), 4.2 for the 1-hour exposure (1-, 24-, 48-, and 72-hour scores),
and 5.6 for the 4-hour exposure (4-, 24-, 48-, and 72-hour scores). The average of the 24-, 48-, and 72-hour scores for the 4-hour exposure
was 3.6 for erythema and 2.3 for edema. The microscopic examination of the collected test sites confirmed the presence of scar tissue at the 1-
and 4-hour exposure sites.
Other effects:
There were no visible macroscopic lesions in any of the animals. At necropsy, gross observations were recorded and sections of skin from four
sites per animal were collected, preserved in formalin, and processed for microscopic examination. The four sites were identified as a control site
and treated sites A, B, and C. Microscopically, the sections of skin from the control site and from treated site A of each animal were unremarkable,
except for a focal area of granulomatous inflammation in the papillary dermis in one section of treated site A from one male. This finding was
considered incidental and unrelated to the test material. All sections of treated site B and C had papillary dermal fibrosis, chronic inflammation, and
epidermal hyperplasia (acanthosis) of variable severity and distribution. These changes were severe enough in some sections to cause atrophy (or
loss) of normal adnexal structures in the skin and are indicative of scar formation. The microscopic findings in treated sites B and C are indicative of a reparative process following severe injury to the epidermis and underlying dermis of the skin.

Applicant's summary and conclusion

Interpretation of results:
Category 1B (corrosive) based on GHS criteria
Remarks:
Migrated information
Conclusions:
Based on the results of this study, this test material, AS 304 (C0834-50-7), is considered to be corrosive to the skin of rabbits under 1- and 4-hour
semioccluded conditions.
Executive summary:

The primary dermal irritation/corrosion potential of AS 304 (C0834-50-7) was evaluated when 0.5 mL was applied to the intact skin of six rabbits under 3-minute, 1-hour, and 4-hour semioccluded conditions. No evidence of corrosion was observed at the test sites receiving a 3-minute exposure. Evidence of corrosion was observed at all of the test sites receiving the 1 - and 4-hour exposures. The test material produced well-defined to moderate-to severe erythema and very slight to moderate edema reactions with subcutaneous hemorrhaging, blanching, desquamation, and fissuring at the test sites receiving the 3-minute exposure. Severe erythema and slight edema reactions with subcutaneous hemorrhaging, blanching, possible necrotic areas, and possible scar tissue were observed at the test sites receiving the 1-hour exposure. Severe erythema and slight to moderate edema reactions with subcutaneous hemorrhaging, blanching, desquamation, exfoliation, possible necrotic areas, and possible scar tissue were observed at the test sites receiving the 4-hour exposure. All irritation cleared by the Day 21 observation in the 3-minute exposure sites, but was still present at the 1- and 4-hour exposure sites. The microscopic examination of the collected test sites confirmed the presence of scar tissue at the 1- and 4-hour exposure sites. The average of the dermal irritation scores was 2.7 for the 3-minute exposure (3-minute, 24-, 48-, and 72-hour scores), 4.2 for the 1-hour exposure (1-, 24-, 48-, and 72 -hour scores), and 5.6 for the 4-hour exposure (4-, 24-, 48-, and 72-hour scores). The average of the 24-, 48-, and 72-hour scores for the 4 -hour exposure was 3.6 for erythema and 2.3 for edema. This test material is considered to be corrosive to the skin of rabbits after 1- and 4 -hour semioccluded exposures.