2-Propanone, reaction products with diphenylamine

Skin irritation / corrosion

Administrative data

Endpoint:

skin irritation: in vivo

Type of information:

experimental study

Adequacy of study:

key study

Study period:

9 August 1983 to 12 August 1983

Reliability:

1 (reliable without restriction)

Rationale for reliability incl. deficiencies:

other: Study conducted according to GLP reguations of the FDA effective 20/06/1979.

Data source

Reference

Reference Type:

study report

Title:

Unnamed

Year:

1983

Report date:

1983

Materials and methods

Test guideline

Qualifier:

according to guideline

Guideline:

other: 16 CFR 1500.41

Deviations:

no

GLP compliance:

yes

Test material

Test material information

Constituent 1

Reference substance name:

2-Propanone, reaction products with diphenylamine

EC Number:

270-192-0

EC Name:

2-Propanone, reaction products with diphenylamine

Cas Number:

68412-48-6

Molecular formula:

Variable.

IUPAC Name:

N-cyclohexylcyclohexanamine; propan-2-one

Test material form:

solid: particulate/powder

Remarks:

migrated information: powder

Details on test material:

Source: UNIROYAL, INC.
Date Received: 28/07/1982
Label: Aminox CN 5731
Storage: The test article was stored at ambient room temperature and humidity.
Description of test article: Yellow powder

Test animals

Species:

rabbit

Strain:

New Zealand White

Details on test animals or test system and environmental conditions:

Six healthy albino rabbits were selected for this test from a larger group which had been quarantined at least one week. The animals were received from Nichol as Helf on 23/07/1983 and 30/07/1983.
Animals were identified by cage notation and with a uniquely numbered metal ear tag. The animals were housed 2 per cage in suspended wire mesh cages. Bedding was placed beneath the cages. Fresh Purina Rabbit Chow (Diet #53-21) and water were freely available.
The animal room, reserved exclusively for rabbits on acute tests, was temperature controlled and kept clean and vermin free.

Test system

Type of coverage:

occlusive

Preparation of test site:

clipped

Vehicle:

other: Mazola oil

Controls:

no

Amount / concentration applied:

Six healthy albino rabbits were dosed dermally with Aminox CN 5731 0.5 g of the test article was applied to 1 intact and 1 abraded site on the clipped back for a total dose of 1.0 g/rabbit

Duration of treatment / exposure:

Exposure time: 72 hours

Observation period:

The skin reactions were observed 24 and 72 hours after dosing.

Number of animals:

Six

Details on study design:

Preparation of test site
Prior to application of the test article, the back and sides of each animal were clipped free of hair. The left side of each animal was abraded with a bent tip needle. Three abrasions, approximately 2-3 cm apart, extending the length of the exposure site were made. The abrasions were sufficiently deep to penetrate the stratum corneum, but not deep enough to produce bleeding. The right side of wach animal remained intact.

Experimental design
The test article was applied to two areas, 1 intact and 1 abraded, on the prepared site, on the back of each of the six rabbits. Test substance was applied as 50% weight/volume mixture in a suitable vehicle and dosed by dry weight. 0.5 g/site for a total dose volume of 1.0 g/rabbit. Test article was covered with 2.5 cm square gauze patches which were secured with adhesive tape. The torso was wrapped with plastic which was secured with adhesive tape. The sites were occluded for 24 hours at which time the patches were removed.

Type and frequency of observations
Animals observed for skin reactions at 24 and 72 hours after application of the test article. Erythema and edema were scored according to the numerical Draize technique. Additional signs and general health of the animals was monitored at each observation time.

Analysis of data
The Primary Irritation Index was calculated by adding the mean values (6 rabbits) for erythema/eschar and edema on intact and abraded skin at 24 and 72 hours (a total of 8 values) and dividing the sum by 4.
A primary irritant is defined as a substance which is not corrosive but which results in an empirical score of 5 of more.

Results and discussion

In vivo

Results

Results 1

Irritation parameter:

erythema score

Basis:

animal #1

Time point:

24 h

Score:

1

Max. score:

4

Reversibility:

not specified

Results 2

Irritation parameter:

erythema score

Basis:

animal #1

Time point:

72 h

Score:

2

Max. score:

4

Reversibility:

not specified

Results 3

Irritation parameter:

edema score

Basis:

animal #1

Time point:

24/48/72 h

Score:

0

Max. score:

4

Results 4

Irritation parameter:

erythema score

Basis:

animal #2

Time point:

24/48/72 h

Score:

0

Max. score:

4

Results 5

Irritation parameter:

edema score

Basis:

animal #2

Time point:

24/48/72 h

Score:

0

Max. score:

4

Results 6

Irritation parameter:

erythema score

Basis:

animal #3

Time point:

24 h

Score:

0

Max. score:

4

Results 7

Irritation parameter:

erythema score

Basis:

animal #3

Time point:

72 h

Score:

1

Max. score:

4

Reversibility:

not specified

Results 8

Irritation parameter:

edema score

Basis:

animal #3

Time point:

24/48/72 h

Score:

0

Max. score:

4

Results 9

Irritation parameter:

erythema score

Basis:

animal #4

Time point:

24/48/72 h

Score:

1

Max. score:

4

Reversibility:

not specified

Results 10

Irritation parameter:

edema score

Basis:

animal #4

Time point:

24/48/72 h

Score:

0

Max. score:

4

Results 11

Irritation parameter:

erythema score

Basis:

animal #5

Time point:

24/48/72 h

Score:

1

Max. score:

4

Reversibility:

not specified

Results 12

Irritation parameter:

edema score

Basis:

animal #5

Time point:

24/48/72 h

Score:

0

Max. score:

4

Results 13

Irritation parameter:

erythema score

Basis:

animal #6

Time point:

24/48/72 h

Score:

1

Max. score:

4

Reversibility:

not specified

Results 14

Irritation parameter:

edema score

Basis:

animal #6

Time point:

24/48/72 h

Score:

0

Max. score:

4

Irritant / corrosive response data:

Erythema was minimal at 24 hours and was absent to slight at 72 hours. No odema was observed.

Other effects:

None specified.

Any other information on results incl. tables

 Individual scores

	Rabbit Number						Mean score
	A9707	A9774	A9775	A9777	A9778	A9779
Erythema & Eschar Formation
Intact skin – 24 hours	1^a	0^a	0^a	1^a	1^a	1^a	0.67
Intact skin – 72 hours	2^a	0^a	1^a	1^a	1^a	1^a	1.00
Abraded skin – 24 hours	1^a	0^a	0^a	1^a	1^a	1^a	0.67
Abraded skin – 72 hours	2^a	1^a	1^a	1^a	1^a	1^a	1.17
Edema
Intact skin – 24 hours	0	0	0	0	0	0	0
Intact skin – 72 hours	0	0	0	0	0	0	0
Abraded skin – 24 hours	0	0	0	0	0	0	0
Abraded skin – 72 hours	0	0	0	0	0	0	0
				Sum of mean scores =			3.51
	PRIMARY IRRITATION INDEX = SUM OF MEAN SCORES/4=						0.88

Key:

a = test article remaining on treated site

Applicant's summary and conclusion

Interpretation of results:

not irritating

Remarks:

Migrated information Criteria used for interpretation of results: other: 16 CFR 1500.3(c)(4)

Conclusions:

The Primary Irritation Index is 0.88. Therefore, the test article is a non-irritant as defined in 16 CFR 1500.3(c)(4).

Executive summary:

The objective of the study was to determine the dermal irritation potential of Aminoz CN 5731. Study was conducted in accordance to GLP and test guidline 16 CFR 1500.41. Results of the study concluded that the mean primary irritation idex is 0.88 for the test article. Erythema was minimal at 24 hours and was absent to slight at 72 hours. No odema was observed. Therefore to conclude, the test article is classified as a not irritating under 16 CFR 1500.3(c)(4)