2-pyridylamine

Skin irritation / corrosion

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 guideline

Test guideline 1

Qualifier:

according to guideline

Guideline:

other: US CPSC (16 CFR 1500.41) - Method of testing primary irritant substances.

Deviations:

no

Test guideline 2

Qualifier:

equivalent or similar to guideline

Guideline:

OECD Guideline 404 (Acute Dermal Irritation / Corrosion)

GLP compliance:

yes

Test material

Test material information

Constituent 1

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

Results

Results 1

Irritation parameter:

erythema score

Basis:

animal #1

Time point:

24/48/72 h

Remarks on result:

other: severe necrosis, death after 4h.

Results 2

Irritation parameter:

erythema score

Basis:

animal #2

Time point:

24/48/72 h

Remarks on result:

other: svere necrosis, death after 4h

Results 3

Irritation parameter:

erythema score

Basis:

animal #3

Time point:

24/48/72 h

Remarks on result:

other: severe necrosis, death after 4h.

Results 4

Irritation parameter:

erythema score

Basis:

animal #4

Time point:

24/48/72 h

Remarks on result:

other: severe necrosis, death after 4h.

Results 5

Irritation parameter:

erythema score

Basis:

animal #5

Time point:

24/48/72 h

Remarks on result:

other: severe necrosis, death after 4h.

Results 6

Irritation parameter:

erythema score

Basis:

animal #6

Time point:

24/48/72 h

Remarks on result:

other: severe necrosis, death after 4h.

Results 7

Irritation parameter:

edema score

Basis:

animal #1

Time point:

24/48/72 h

Remarks on result:

other: severe necrosis, death after 4h.

Results 8

Irritation parameter:

edema score

Basis:

animal #2

Time point:

24/48/72 h

Remarks on result:

other: severe necrosis, death after 4h.

Results 9

Irritation parameter:

edema score

Basis:

animal #3

Time point:

24/48/72 h

Remarks on result:

other: severe necrosis, death after 4h.

Results 10

Irritation parameter:

edema score

Basis:

animal #4

Time point:

24/48/72 h

Remarks on result:

other: severe necrosis, death after 4h.

Results 11

Irritation parameter:

edema score

Basis:

animal #5

Time point:

24/48/72 h

Remarks on result:

other: severe necrosis, death after 4h.

Results 12

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.