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

Data source

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

Materials and methods

Test guidelineopen allclose all
Qualifier:
according to guideline
Guideline:
other: US CPSC (16 CFR 1500.41) - Method of testing primary irritant substances.
Deviations:
no
Qualifier:
equivalent or similar to guideline
Guideline:
OECD Guideline 404 (Acute Dermal Irritation / Corrosion)
GLP compliance:
yes

Test material

Constituent 1
Chemical structure
Reference substance name:
2-pyridylamine
EC Number:
207-988-4
EC Name:
2-pyridylamine
Cas Number:
504-29-0
Molecular formula:
C5H6N2
IUPAC Name:
pyridin-2-amine
Test material form:
solid
Details on test material:
STABILITY AND STORAGE CONDITIONS OF TEST MATERIAL
- Storage condition of test material: room temperature
- Stability under test conditions: stable

Test animals

Species:
rabbit
Strain:
New Zealand White
Details on test animals or test system and environmental conditions:
TEST ANIMALS
- Source: Eastern Rabbit Breeding Laboratories, Taunton, MA.
- Age at study initiation: 10-12 wk
- Weight at study initiation: 2.0 - 3.0 kg
- Housing: animals were individually housed using suspended stainless steel cages. Hardwood chips (Sani-chips, JP Murphy Forest Products, Montvale, NJ) were used as non-contact bedding under the cages.
- Diet: controlled diet of a commercial rabbit ration (Agway Prolab, Waverly, NY)
- Water: tap water ad libitum.
- Acclimation period: 4 days.

ENVIRONMENTAL CONDITIONS
- Temperature (°C): 20 ± 1.7
- Humidity (%): 30-70
- Air changes (per hr): 10-13
- Photoperiod (hrs dark / hrs light): 12/12

Test system

Type of coverage:
occlusive
Preparation of test site:
other: The test and control sites were prepared by clipping. One application site on each animal was abraded.
Vehicle:
physiological saline
Controls:
yes, concurrent no treatment
Amount / concentration applied:
TEST MATERIAL
- Amount(s) applied (volume or weight with unit): 0.5 g test item moistened with 0.5 ml of USP 0.9% saline.
- Concentration (if solution): 1g/ml

VEHICLE
- Amount(s) applied (volume or weight with unit): 0.5 ml
- Concentration (if solution): 0.9% saline
- Purity: USP

NEGATIVE CONTROL
- Amount(s) applied (volume or weight):
- Concentration (if solution):

POSITIVE CONTROL
- Amount(s) applied (volume or weight):
- Concentration (if solution):
Duration of treatment / exposure:
4 hours.
Observation period:
72 hours.
Number of animals:
3 males and 3 females.
Details on study design:
TEST SITE
- Area of exposure: 2.5x2.5 cm2
- Type of wrap if used: the test substance was introduced under a gauze patch 2 single layers thick, held in place with an impervious bandage (Vetrap, 3M, St.Paul, MN).

REMOVAL OF TEST SUBSTANCE
- The skin was wiped following the 4 hour exposure period to remove remaining test substance.

OBSERVATION TIME POINTS
Daily observations were made of all clinical manifestations. Animals were observed for signs of erythema and edema at 24 and 72h post application of the test substance.
SCORING SYSTEM:
- Observations were scored according to the 'Draize Scale for Scoring Skin Reactions' (Draize, J. H. 'Dermal Toxicity', appraisal of the Safety of Chemicals in Foods, Drugs and Cosmetics - Dermal Toxicity, pp. 46 -59, Association of Food and Dug Officials of the US., Topeka, Kansas, 1965).
- Method of calculation: A Primary Irritation score was obtained by adding the mean values for erythema and eschar formation at 24 hours and 72 hours for intact skin to the mean values for abraded skin at 24 and 72 hours (4 values). Similarly, the mean values for edema formation at 24 hours and 72 hours for intact skin were aded to the mean values for abraded skin (4 values). The total of the 8 values were divided by 4 to give the Primary Irritation Index. The same procedure was used to obtain the Primary Irritation Index of the control substance. A test substance with a Primary Irritation Index of 0 was considered non-irritant. Substances with indices 2-5 were considered irritants. Any substances with an index of 5 or more were considered severe irritants. Those test substances that destroy the structure of the intact skin or change it irreversibly were considered corrosive.

Results and discussion

In vivo

Resultsopen allclose all
Irritation parameter:
erythema score
Basis:
animal #1
Time point:
24/48/72 h
Remarks on result:
other: severe necrosis, death after 4h.
Irritation parameter:
erythema score
Basis:
animal #2
Time point:
24/48/72 h
Remarks on result:
other: svere necrosis, death after 4h
Irritation parameter:
erythema score
Basis:
animal #3
Time point:
24/48/72 h
Remarks on result:
other: severe necrosis, death after 4h.
Irritation parameter:
erythema score
Basis:
animal #4
Time point:
24/48/72 h
Remarks on result:
other: severe necrosis, death after 4h.
Irritation parameter:
erythema score
Basis:
animal #5
Time point:
24/48/72 h
Remarks on result:
other: severe necrosis, death after 4h.
Irritation parameter:
erythema score
Basis:
animal #6
Time point:
24/48/72 h
Remarks on result:
other: severe necrosis, death after 4h.
Irritation parameter:
edema score
Basis:
animal #1
Time point:
24/48/72 h
Remarks on result:
other: severe necrosis, death after 4h.
Irritation parameter:
edema score
Basis:
animal #2
Time point:
24/48/72 h
Remarks on result:
other: severe necrosis, death after 4h.
Irritation parameter:
edema score
Basis:
animal #3
Time point:
24/48/72 h
Remarks on result:
other: severe necrosis, death after 4h.
Irritation parameter:
edema score
Basis:
animal #4
Time point:
24/48/72 h
Remarks on result:
other: severe necrosis, death after 4h.
Irritation parameter:
edema score
Basis:
animal #5
Time point:
24/48/72 h
Remarks on result:
other: severe necrosis, death after 4h.
Irritation parameter:
edema score
Basis:
animal #6
Time point:
24/48/72 h
Remarks on result:
other: severe necrosis, death after 4h.
Irritant / corrosive response data:
Severe necrosis was observed at all test sites, indicating irreversible corrosive damage to the skin. None of the control sites of any animal at any of the observation periods showed signs of erythema or edema, whether the skin was abraded or intact.
Other effects:
- Other adverse systemic effects: All animals died during the 4 hour application period. Blood was observed around the nose and mouth, and the position of the animals indicated convulsions prior to death. The gross necropsy indicated signs of hemorrhaging in the lungs and pericardial sac and the blood appeared a dark blue color.

Any other information on results incl. tables

Table 1. Body weight and Clinical Observations.

Animal #

Sex

BW (Kg)

06/09/92

Signs of Toxicity

22617

Male

2.39

Death, 4h

22618

Male

2.44

Death, 4h

22619

Male

2.26

Death, 4h

22620

Female

2.40

Death, 4h

22621

Female

2.32

Death, 4h

22622

Female

2.53

Death, 4h

 

Table 2. Skin Examination data: Draize Score (4 hours).

Group

Animal #

Intact

Erythema

Skin

Edema

Abraded

Erythema

Skin

Edema

0.5 g test item

22617

N

N

N

N

22618

N

N

N

N

22619

N

N

N

N

22620

N

N

N

N

22621

N

N

N

N

22622

N

N

N

N

untreated

22617

0

0

0

0

22618

0

0

0

0

22619

0

0

0

0

22620

0

0

0

0

22621

0

0

0

0

22622

0

0

0

0

*N = Severe Necrosis.

Applicant's summary and conclusion

Interpretation of results:
Category 1 (corrosive) based on GHS criteria
Remarks:
EU criteria.
Conclusions:
The test item was found to be corrosive.
Executive summary:

The potential of the test item to produce dermal irritation after a single topical 4h application was studied according to US CPSC (16 CFR 1500.41) - Method of testing primary irritant substances, similar to OECD 404 (GLP study). 0.5 g of test item moistened with 0.5 ml of USP 0.9% saline were applied to 3 male and 3 female New Zealand White rabbits for 4h under a closed patch. All animals died during the 4 hour application period. Blood was observed around the nose and mouth, and the position of the animals indicated convulsions prior to death. The gross necropsy indicated signs of hemorrhaging in the lungs and pericardial sac and the blood appeared a dark blue color. Severe necrosis was observed at all test sites, indicating irreversible corrosive damage to the skin. Based on the test results, the test item was found to be corrosive to the skin.

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