N,N-dimethylpyridin-4-amine

Skin irritation / corrosion

Administrative data

Endpoint:

skin irritation: in vivo

Type of information:

experimental study

Adequacy of study:

weight of evidence

Study period:

Apr 16-1992 to June 19-1992.

Reliability:

1 (reliable without restriction)

Rationale for reliability incl. deficiencies:

other: Guideline study by GLP

Data source

Reference

Reference Type:

study report

Title:

Unnamed

Year:

1992

Report date:

1992

Materials and methods

Test guideline

Qualifier:

according to guideline

Guideline:

other: US Consumer Protection Safety Commission

Principles of method if other than guideline:

US Consumer Protection Safety Commission 21CFR1500 Guideline, using the Draize Scale

GLP compliance:

yes

Test material

Test material information

Constituent 1

Reference substance name:

N,N-dimethylpyridin-4-amine

EC Number:

214-353-5

EC Name:

N,N-dimethylpyridin-4-amine

Cas Number:

1122-58-3

Molecular formula:

C7H10N2

IUPAC Name:

N,N-dimethylpyridin-4-amine

Test material form:

other: Solid

Details on test material:

- Name of test material: 4-Dimethylaminopyridine
- Physical state: White or off white solid
- Lot/batch No.: 20315AB
- Stability under test conditions: Stable under test conditions
- Storage condition of test material: Room temperature
- Other: Solubility: 7.6 g in 100 ml H2O at 25°C

Test animals

Species:

rabbit

Strain:

New Zealand White

Details on test animals or test system and environmental conditions:

TEST ANIMALS
- Source: Animals were purchased from a registered commercial breeding laboratory (Eastern Rabbit Breeding Laboratories, Taunton, MA).
- Age at study initiation: 10 to 12 weeks
- Weight at study initiation: between 2.0 and 3.0 kilograms
- Housing: Animals were individually housed using suspended stainless steel cages. Hardwood chips (Sani-chips , J.P. Murphy Forest Products, Montvale, NJ) were used as non-contact bedding under the cages. The laboratory and animal rooms were maintained as limited access facilities.
- Diet (e.g. ad libitum): controlled diet of a commercial rabbit ration
- Water (e.g. ad libitum): ad libitum
- Acclimation period: The animals were placed in quarantine for a period of 4 days under the same conditions as for the actual test.
ENVIRONMENTAL CONDITIONS
- Temperature (°C): 20.2 °C i.e. 68+3°F
- Humidity (%): 30-70%
- Air changes (per hr): a minimum of 10 to 13 complete air exchanges per hour
- Photoperiod (hrs dark / hrs light): 12 hour light/dark cycle using full spectrum fluorescent lights.

Test system

Type of coverage:

occlusive

Preparation of test site:

other: Skin was clipped; tested in intact skin and abraded skin on each animal.

Vehicle:

physiological saline

Controls:

other: Test substance was applied to one intact and one abraded site per animal. Seperate animals were not required. Each animal served as its own control.

Amount / concentration applied:

0.5 gram, moistened with 0.5 ml of USP Saline

Duration of treatment / exposure:

Four hours. The patches were applied to one intact site and one abraded site per animal. The test substance was kept in contact with the skin for 4 hours. The skin was wiped following the 4 hour exposure period to remove remaining test substance.

Observation period:

Animals were observed for signs of erythema and edema at 24 and 72 hours post application of the test substance. Observations were scored according to the "Draize Scale for Scoring Skin Reactions"

Number of animals:

Six, three male and three female.

Details on study design:

TEST SITE
- Area of exposure: 2.5 cm x 2.5 cm
- Type of wrap if used: Material was held in place with an impervious bandage (Vetrap, 3M, St.Paul, MN)
REMOVAL OF TEST SUBSTANCE
- Washing: No washing but the skin was wiped following the 4 hour exposure period to remove remaining test substance.
- Time after start of exposure: Four hours

SCORING SYSTEM: 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 (four values). Similarly, the mean values for edema formation at 24 hours and at 72 hours for
intact skin were added to the mean values for abraded skin (four values). The total of the eight values were divided by four to give the Primary Irritation Index.

A test substnce with a PII of 0 was considered a non-irritant. A test substance with an index of 2 or less was considered a mild irritant. Test substances with indices greater than 2 and less than 5 were moderate irritants. Any test substances with an index of 5 or more were considered severe irritants. Those substances that destroy the structure of the intact skin or change it irreversibly were considered corrosive.

Results and discussion

In vivo

Results

Irritation parameter:

primary dermal irritation index (PDII)

Basis:

mean

Time point:

other: 4 hours

Score:

>= 5

Max. score:

5

Reversibility:

not reversible

Remarks on result:

other: All six animals died after 4 hrs. PDII (Test) = Necrosis. PDII (Control) = 0.0

Irritant / corrosive response data:

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.

Other effects:

The gross necropsy indicated signs of hemorrhaging in the lungs and pericardial sac; and the blood had a dark blue color.

Any other information on results incl. tables

Severe necrosis was observed in all rabbits at all test sites, indicating corrosive damage to the skin. None of the control sites of any animal showed signs of erythema or edema, whether the skin was abraded or intact.

Applicant's summary and conclusion

Interpretation of results:

corrosive

Remarks:

Migrated information Necrosis and death in all the test animals Criteria used for interpretation of results: EU

Conclusions:

The test substance is considered a corrosive irritant.

Executive summary:

4-Dimethylaminopyridine was tested in a dermal irritation study according to the U.S. 16 CFR 1500.41 method, under GLP, in New Zealand white rabbits. The material (0.5 g, moistened with saline) was applied to the clipped intact and abraded skin and held in place under occlusive dressing for four hours. All 6 animals died during the test period. No scores of erythema or edema were recorded for he four animals; severe necrosis was observed at all test sites after 4 hours of application indicating corrosive damage to the skin. The material is considered a corrosive irritant.