N,N-bis(2-hydroxyethyl)-3-[(C16-18)alkoxy]-1-propanamine

Skin irritation / corrosion

Administrative data

Endpoint:

skin irritation: in vivo

Type of information:

experimental study

Adequacy of study:

key study

Study period:

October 27, 1987 to February 26, 1988

Reliability:

2 (reliable with restrictions)

Rationale for reliability incl. deficiencies:

study well documented, meets generally accepted scientific principles, acceptable for assessment

Data source

Reference

Reference Type:

study report

Title:

Unnamed

Year:

1988

Report date:

1988

Materials and methods

Test guideline

Qualifier:

equivalent or similar to guideline

Guideline:

other: Not reported

Deviations:

not applicable

Principles of method if other than guideline:

The primary skin irritation potential of the test material was evaluated following its application to the clipped backs of 6 New Zealand White rabbits. The test material was administered as a single 0.5 g dose introduced under a gauze patch, moistened with saline and secured with tape. The patch was loosely held in contact with the skin by means of an occlusive dressing. The dressing remained in place for 4 hours. After exposure was completed, the dressing and gauze were removed and the test site was graded for erthema, edema and other signs of dermal irritation at 45 m, 24, 48 and 72 h following patch removal. Dermal readings were also made on Day 7. All dermal scoring was made according to the Draize Method of scoring.

GLP compliance:

not specified

Test material

Test material information

Constituent 1

Reference substance name:

N,N-bis(2-hydroxyethyl)-3-[(C16-18)alkoxy]-1-propanamine

EC Number:

930-859-5

Molecular formula:

C23-25H49-53NO3

IUPAC Name:

N,N-bis(2-hydroxyethyl)-3-[(C16-18)alkoxy]-1-propanamine

Test material form:

solid

Remarks:

Amber solid

Specific details on test material used for the study:

SOURCE OF TEST MATERIAL
- Source and lot/batch No.of test material: Batch No. 1

STABILITY AND STORAGE CONDITIONS OF TEST MATERIAL
- Storage condition of test material: Room temperature

OTHER SPECIFICS: The test material was a waxy off-white solid which was assumed to be 100 % pure for the purpose of dosing.

Test animals

Species:

rabbit

Strain:

New Zealand White

Details on test animals or test system and environmental conditions:

TEST ANIMALS
- Source: Hazelton Reserach Products, Inc., Denver, Pennsylvania
- Age at study initiation: Approximately 13 weeks
- Weight at study initiation: 2.29 to 3.15 kg
- Housing: Individually in suspended stainless steel caging
- Diet (e.g. ad libitum): ad libitum
- Water (e.g. ad libitum): ad libitum
- Acclimation period: 22 d

ENVIRONMENTAL CONDITIONS
- Temperature (°F): 65 to 70
- Humidity (%): 40 to 60
- Photoperiod (hrs dark / hrs light): 12/12 by automatic timer

IN-LIFE DATES: From: October 27, 1987 To: November 3, 1987

Test system

Type of coverage:

occlusive

Preparation of test site:

clipped

Vehicle:

unchanged (no vehicle)

Controls:

no

Amount / concentration applied:

TEST MATERIAL
- Amount(s) applied (volume or weight with unit): 0.5 g

Duration of treatment / exposure:

4 h

Observation period:

7 d

Number of animals:

3 males, 3 females

Details on study design:

- Preparation of animals: The day prior to topical administration of the test material, the hair of each rabbit on the dorsal surface from the shoulder region to the lumbar region was closely clipped with an electric clipper. The skin was left intact. Elizabethan-type collares were placed around the neck of each rabbit at this time to acclimate them to wearing collars. Animals were reclipped as needed for dermal evaluations.
- Administration of test material: The test material was administered as a single 0.5 g dose, moistened with 0.5 mL saline and introduced under a gauze patch which was loosely held in contact with the skin by means of an occlusive dressing for the duration of the exposure period. After approximately 4 h exposure, the dressing and gauze patch were removed. Residual test material was removed using distilled water and paper towels. Collars were removed after the exposure period.
- Experimental evaluation: The animals were examined for viability twice daily on weekdays and once daily on weekends. Dermal responses were evaluated approximately 45 minutes, 24, 48 and 72 h following patch removal, and on Day 7. All scoring was made according to the Draize Method of Scoring. Body weights were recorded on the day of dosing (Day 0) and on Day 7. After the Day 7 observations and terminal weighings, all rabbits were sacrified and discarded without further examination.

Results and discussion

In vivo

Results

Results 1

Irritation parameter:

primary dermal irritation index (PDII)

Basis:

other: All animals

Score:

4.5

Remarks on result:

probability of moderate irritation

Results 2

Irritation parameter:

erythema score

Basis:

other: mean score for animal 1, 2 and 6

Time point:

24/48/72 h

Score:

2.66

Results 3

Irritation parameter:

erythema score

Basis:

other: mean score for animal 3

Time point:

24/48/72 h

Score:

2

Results 4

Irritation parameter:

erythema score

Basis:

other: mean score for animal 4

Time point:

24/48/72 h

Score:

2.33

Results 5

Irritation parameter:

erythema score

Basis:

other: mean score for animal 5

Time point:

24/48/72 h

Score:

3

Results 6

Irritation parameter:

edema score

Basis:

other: mean score for animal 1, 2 and 6

Time point:

24/48/72 h

Score:

1.66

Results 7

Irritation parameter:

edema score

Basis:

other: mean score for animal 3 and 4

Time point:

24/48/72 h

Score:

1

Results 8

Irritation parameter:

edema score

Basis:

other: mean score for animal 6

Time point:

24/48/72 h

Score:

2

Irritant / corrosive response data:

Topical application of the test item elicited erythema in all animals. Erythema was noted as very slight in all animals at the 45 Minute observations and increased as the study progressed. Severe erythema was noted in 5 animals at the 72 Hour observation while the remaining animal was noted with well-define erythema. Severe erythema was observed in all animals at the Day 7 observations.

Edema scores at the 45 Minute observations were limited to 2 animals who exhibited very slight edema. Edema scores increased during the test period and by termination were substantially increased. Edema was noted as very slight in 1 animal, slight in 4 animals and moderate in the remaining animal.

Supplemental dermal observations were noted in all animals during the study and included eschar, necrosis, desquamation, atonia and leathery skin. Supplemental dermal observations were limited to the 72 Hour and Day 7 observations.

Any other information on results incl. tables

Please see attached:

Table 1: Individual dermal irritation scores for all animals

Table 2: Supplemental dermal observations

Table 3: Individual animal body weights by weighing period

Appendix A: The Draize Method of Scoring used for evaluation of dermal irritation.

Applicant's summary and conclusion

Interpretation of results:

Category 1C (corrosive) based on GHS criteria

Remarks:

We have concluded that there is enough evidence to consider the test substance to be classified as a skin corrosive, category 1C.

Conclusions:

The primary skin irritation potential of the test material was evaluated following its application to the clipped backs of 6 New Zealand White rabbits. The test material was administered as a single 0.5 g dose introduced under a gauze patch, moistened with saline and secured with tape. The patch was loosely held in contact with the skin by means of an occlusive dressing. The dressing remained in place for 4 hours. After exposure was completed, the dressing and gauze were removed and the test site was graded for erthema, edema and other signs of dermal irritation at 45 m, 24, 48 and 72 h following patch removal. Dermal readings were also made on Day 7. All dermal scoring was made according to the Draize Method of scoring. Topical application of the test item elicited erythema in all animals. Erythema was noted as very slight in all animals at the 45 Minute observations and increased as the study progressed. Severe erythema was noted in 5 animals at the 72 Hour observation while the remaining animal was noted with well-define erythema. Severe erythema was observed in all animals at the Day 7 observations. Edema scores at the 45 Minute observations were limited to 2 animals who exhibited very slight edema. Edema scores increased during the test period and by termination were substantially increased. Edema was noted as very slight in 1 animal, slight in 4 animals and moderate in the remaining animal. Supplemental dermal observations were noted in all animals during the study and included eschar, necrosis, desquamation, atonia and leathery skin. Due to visible nerosis was seen in at least one animal, the substance is classified as a Category 1C skin corrosive.

Executive summary:

Due to necrosis being seen in at least 1 animal, we have concluded that there is enough evidence to consider the test substance to be classified as a skin corrosive, category 1C.