N,N-dimethylpyridin-4-amine

Skin sensitisation

Administrative data

Endpoint:

skin sensitisation: in vivo (non-LLNA)

Type of information:

experimental study

Adequacy of study:

key study

Study period:

April 16-1992 to July 31-1992

Reliability:

1 (reliable without restriction)

Rationale for reliability incl. deficiencies:

other: GLP study according to US guideline protocol (Skin Sensitisation)

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:

EPA OTS 798.4100 (Skin Sensitisation)

Deviations:

no

Test guideline 2

Qualifier:

equivalent or similar to guideline

Guideline:

OECD Guideline 406 (Skin Sensitisation)

Principles of method if other than guideline:

The Buehler protocol for guinea pigs was used, with closed (occlusive) patches.

GLP compliance:

yes

Type of study:

other: closed epicutaneous application

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 white to off white powder

Details on test material:

- Name of test material: 4-Dimethylaminopyridine
- Physical state: Solid
- Lot/batch No.: 20315AB
- Stability under test conditions: Stable
- Storage condition of test material: Room temperature

In vivo test system

Test animals

Species:

guinea pig

Strain:

Hartley

Sex:

male/female

Details on test animals and environmental conditions:

TEST ANIMALS
A total of 28 young healthy animals were used: 14 males and 14 females.
- Source: Elm Hill Breeding Labs, Chelmsford, MA
- Age at study initiation: 21 to 43 days old at the start of the study
- Weight at study initiation: 250 to 400 grams
- Housing: Animals were group housed in stainless steel cages. Hardwood chips (Sani-Chips, JP Murphy Forest Products, Montvale, NJ) were used as contact bedding within the cages.
- Diet: a diet of commercial guinea pig ration (Agway Prolab, Agway, Waverly, NY)
- Water : Ad libitum
- Acclimation period: animals were placed in quarantine for 6 days (Preliminary Irritation Study) and 9 days (Sensitization Study) under the same conditions as for the actual test.

ENVIRONMENTAL CONDITIONS
- Temperature: 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): A 12-hour light/dark cycle using full spectrum fluorescent lights

Study design: in vivo (non-LLNA)

Induction

Induction 1

Route:

epicutaneous, occlusive

Vehicle:

other:

Induction 2

Concentration / amount:

In the Preliminary Irritation Study with four previously unexposed animals, four different concentrations (0.4 ml) were applied by the closed patch technique described above. The concentrations run were 100%, 50%, 25% and 10%.
In the main study, in both Induction and challenge phases, a 50% concentration was used.

Challenge

Challenge 1

Route:

epicutaneous, occlusive

Vehicle:

other:

Challenge 2

Concentration / amount:

In the Preliminary Irritation Study with four previously unexposed animals, four different concentrations (0.4 ml) were applied by the closed patch technique described above. The concentrations run were 100%, 50%, 25% and 10%.
In the main study, in both Induction and challenge phases, a 50% concentration was used.

No. of animals per dose:

5 males and 5 females per dose

Details on study design:

A. INDUCTION EXPOSURE
- No. of exposures: 3
- Exposure period: 6 Hours after which the skin was washed off
- Test groups: 3 exposures for 6 hrs on the side of the animal
- Control group: Positive control group was applied exactly like the test group
- Site: On one side of the animal.
- Frequency of applications: Once a week for three consecutive weeks.
- Duration: 6 hours
- Concentrations: 50%

A gauze pad was applied directly to the skin over the applied test substance, as soon as possible, and kept in place with occlusive bandaging.

B. CHALLENGE EXPOSURE
- No. of exposures: One
- Day(s) of challenge:
- Exposure period: 24 hours
- Test groups: 24 hours exposure
- Control group: 24 hours exposure
- Site: Back of the animal
- Concentrations: 50%. During week 5, the challenge test was performed on freshly clipped skin sites in the same way as the 6 hour closed patch test of the induction phase. The skin was exposed to the test substance for 24 h.
- Evaluation): At 24 hours after application of the challenge dose, the area of the challenge was marked and the whole back shaved. Two hours after shaving, the test site was examined for erythema and edema. Reading of the skin area was repeated 48 hours after the challenge and the skin reactions were graded using BUEHLER TOPICAL CLOSED PATCH SENSITIZATION TEST method.
SCALE:
0.0 = No reaction
0.5 = Very gaint erythema, usually confluent.
1.0 = Faint erythema, usually confluent
2.0 = Moderate erythema
3.0 = Strong erythema with or without edema

Challenge controls:

The day preceding the challenge, a 4 x 3 cm virgin skin site was shaved on the backs of the experimental and control animals.

Positive control substance(s):

yes

Remarks:

Positive Control Article: Dinitrochlorobenzene

Results and discussion

Positive control results:

All 10 animals in the positive control groups exhibited signs of erythema (2.0 - 3.0).
No signs of erythema were observed in any of the test animals. No signs of erythema were evident in the negative control group.

In vivo (non-LLNA)

Results

Results 1

Reading:

1st reading

Hours after challenge:

24

Group:

test chemical

Dose level:

50%

No. with + reactions:

0

Total no. in group:

5

Clinical observations:

No erythema or edema

Remarks on result:

other: Reading: 1st reading. . Hours after challenge: 24.0. Group: test group. Dose level: 50%. No with. + reactions: 0.0. Total no. in groups: 5.0. Clinical observations: No erythema or edema.

Results 2

Reading:

2nd reading

Hours after challenge:

48

Group:

test chemical

Dose level:

50%

No. with + reactions:

0

Total no. in group:

5

Clinical observations:

No erythema

Remarks on result:

other: Reading: 2nd reading. . Hours after challenge: 48.0. Group: test group. Dose level: 50%. No with. + reactions: 0.0. Total no. in groups: 5.0. Clinical observations: No erythema.

Results 3

Reading:

other: 1st and 2nd readings

Hours after challenge:

24

Group:

negative control

Dose level:

0

No. with + reactions:

0

Total no. in group:

5

Remarks on result:

other: Reading: other: 1st and 2nd readings. . Hours after challenge: 24.0. Group: negative control. Dose level: 0. No with. + reactions: 0.0. Total no. in groups: 5.0.

Results 4

Reading:

other: 1st and 2nd readings

Hours after challenge:

24

Group:

positive control

No. with + reactions:

4

Total no. in group:

4

Clinical observations:

erythema (2.0-3.0 severity)

Remarks on result:

other: Reading: other: 1st and 2nd readings. . Hours after challenge: 24.0. Group: positive control. No with. + reactions: 4.0. Total no. in groups: 4.0. Clinical observations: erythema (2.0-3.0 severity).

Any other information on results incl. tables

Positive Control

Observation/Scores for Erythema and Edema

Animal #	24 h 7/17/92)	48 h (07/18/92)
21	2.0	2.0
22	2.0	3.0
23	3.0	3.0
24	3.0	3.0

Combined	Incidence	=	4/4 =	100%
Combined	Severity	(24	hr.)	= 10/4	=	2.50
Combined	Severity	(48	hr.)	= 11/4	=	2.75

Test Group

Erythema and Edema

Animal	24 h (07/17/92)	48 h (07/18/92)
1	0.0	0.0
2	0.0	0.0
3	0.0	0.0
4	0.0	0.0
5	0.0	0.0
6	0.0	0.0
7	0.0	0.0
8	0.0	0.0
9	0.0	0.0
10	0.0	0.0

Combined	Incidence	=	0/10	=	0%
Combined	Severity	(24	hr.)	=	0/10	=	0.0
Combined	Severity	(48	hr.)	=	0/10	=	0.0

Applicant's summary and conclusion

Interpretation of results:

not sensitising

Remarks:

Migrated information Criteria used for interpretation of results: EU

Conclusions:

Under the conditions of this study (Buehler closed patch test in guinea pigs), the test substance (50% concentration) is not considered a skin sensitizer. No signs of erythema or edema were observed in treated animals.