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

Eye irritation

Administrative data

Endpoint:

eye irritation: in vivo

Type of information:

experimental study

Adequacy of study:

disregarded due to major methodological deficiencies

Study period:

November 30, 1987 to April 8, 1988

Reliability:

3 (not reliable)

Rationale for reliability incl. deficiencies:

significant methodological deficiencies

Remarks:

Due to the inconsistency of effects between animals and the scoring, this study is not considered reliable for classification purposes.

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 ocular irritation of the test item was evaluated following a single 0.1 mL instillation to the right eye of 6 rabbits. The treated eyes of all animals remained unwashed. Observations for signs of ocular irritation and toxicity were made at 1, 4, 24, 48 and 72 hours post-instillation and once per days 4 and 7. Ocular reactions were graded according to the Draize Scale for Scoring Ocular Lesions.

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: 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 purposes of dosing.

Test animals / tissue source

Species:

rabbit

Strain:

New Zealand White

Details on test animals or tissues and environmental conditions:

TEST ANIMALS
- Source: Hazelton Research Products, Inc., Denver, Pennsylvania
- Age at study initiation: Approximately 9 weeks
- Weight at study initiation: 1.54 to 2.14 kg; Protocol deviation: The weight range for this study was 2.0 to 3.0 kg. This deviation did not appear to have affected the study results.
- Housing: Individually housed in suspended stainless steel caging.
- Diet (e.g. ad libitum): ad libitum
- Water (e.g. ad libitum): ad libitum
- Acclimation period: 14 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: November 30, 1987 To: December 7, 1987

Test system

Vehicle:

unchanged (no vehicle)

Controls:

no

Amount / concentration applied:

0.1 mL

Duration of treatment / exposure:

7 days

Observation period (in vivo):

Observations of signs of ocular irritation were made at 1, 4, 24, 48 and 72 hours post-instillation and once per day on Days 4 and 7.

Number of animals or in vitro replicates:

3 males, 3 females

Details on study design:

REMOVAL OF TEST SUBSTANCE
- Washing (if done): The treated eyes of all animals remained unwashed.

SCORING SYSTEM: Draize scale

TOOL USED TO ASSESS SCORE: 2 % sodium fluorescein dye was used to confirm the presence or absence of corneal ulceration in treated eyes starting with the 24 hour observation and at each subsequent observation until there was no dye retention for 2 consecutive observations.

Results and discussion

In vivo

Results

Results 1

Irritation parameter:

iris score

Basis:

other: mean score for all animals

Time point:

24/48/72 h

Score:

0

Results 2

Irritation parameter:

cornea opacity score

Basis:

other: mean score for all animals

Time point:

24/48/72 h

Score:

0

Results 3

Irritation parameter:

conjunctivae score

Remarks:

Redness

Basis:

other: mean score for animal 1

Time point:

24/48/72 h

Score:

1.33

Results 4

Irritation parameter:

conjunctivae score

Remarks:

Redness

Basis:

other: mean score for animal 2

Time point:

24/48/72 h

Score:

0.67

Results 5

Irritation parameter:

conjunctivae score

Remarks:

Redness

Basis:

other: mean score for animal 3

Time point:

24/48/72 h

Score:

3

Results 6

Irritation parameter:

conjunctivae score

Remarks:

Redness

Basis:

other: mean score for animal 4

Time point:

24/48/72 h

Score:

0.33

Results 7

Irritation parameter:

conjunctivae score

Remarks:

Redness

Basis:

other: mean score for animal 5

Time point:

24/48/72 h

Score:

1.33

Results 8

Irritation parameter:

conjunctivae score

Remarks:

Redness

Basis:

other: mean score for animal 6

Time point:

24/48/72 h

Score:

3

Results 9

Irritation parameter:

chemosis score

Basis:

other: mean score for animals 1, 2 and 4

Time point:

24/48/72 h

Score:

0

Results 10

Irritation parameter:

chemosis score

Basis:

other: mean score for animal 3

Time point:

24/48/72 h

Score:

1.67

Results 11

Irritation parameter:

chemosis score

Basis:

other: mean score for animal 5

Time point:

24/48/72 h

Score:

0.33

Results 12

Irritation parameter:

chemosis score

Basis:

other: mean score for animal 6

Time point:

24/48/72 h

Score:

1.33

Irritant / corrosive response data:

All animals were clear of irritation at the Day 7 observations and the study was terminated.

Other effects:

- Redness was observed in all animals at the 1, 4 and 24 Hour observations. One animal was clear of redness after the 24 Hour observation, while the remaining 5 animals still exhibited redness at the 48 Hour and Day 4 observations. Two of these animals were clear of redness at the 72 Hour observations.
- Chemosis was observed in 4 animals at the 1 Hour observations and in all animals at the 4 Hours observations. at the 24 Hour observations chemosis was displayed by 3 test animals. Two animals continued to display chemosis at the 72 Hour observations and by Day 4 chemosis was limited to 1 animal.
- Discharge/ white or red discharge was observed in 5 animals during the test period. White discharge was note in 4 animals. One animal exhibited red discharge at the 1 Hour observation and was noted with dry red material on the fur of the treated eye at the next interval (4 Hours).
- Necrosis of the conjunctiva was observed in 2 animals and conjunctival ulceration was noted in 3 animals during the test period.
- Other observations included blistered conjunctiva, dye retention of the conjunctiva and residual test material in the eye.
- An iridial response was observed in 1 animal at the 1 and 4 Hour observations.
- Corneal responses were not noted during the test period.
- All animals survived to study termination.

Applicant's summary and conclusion

Interpretation of results:

study cannot be used for classification

Conclusions:

The ocular irritation of the test item was evaluated following a single 0.1 mL instillation to the right eye of 6 rabbits, 3 male and 3 female. The treated eyes of all animals remained unwashed. Observations for signs of ocular irritation and toxicity were made at 1, 4, 24, 48 and 72 hours post-instillation and once per days 4 and 7. Ocular reactions were graded according to the Draize Scale for Scoring Ocular Lesions.

Executive summary:

Due to the inconsistency of effects between animals and the scoring, with some animals showing slight redness and chemosis and some animals showing necrosis and ulceration which appears to reverse by day 7, this study is not considered reliable for classification purposes.