2-amino-2-ethylpropanediol

Eye irritation

Administrative data

Endpoint:

eye irritation: in vivo

Type of information:

experimental study

Adequacy of study:

key study

Study period:

3 - 24 November, 1980

Reliability:

2 (reliable with restrictions)

Rationale for reliability incl. deficiencies:

comparable to guideline study with acceptable restrictions

Data source

Reference

Reference Type:

study report

Title:

Unnamed

Year:

1982

Report date:

1982

Materials and methods

Test guideline

Qualifier:

equivalent or similar to guideline

Guideline:

OECD Guideline 405 (Acute Eye Irritation / Corrosion)

GLP compliance:

not specified

Test material

Test material information

Constituent 1

Reference substance name:

2-amino-2-ethylpropanediol

EC Number:

204-101-2

EC Name:

2-amino-2-ethylpropanediol

Cas Number:

115-70-8

Molecular formula:

C5H13NO2

IUPAC Name:

2-amino-2-ethylpropane-1,3-diol

Constituent 2

Reference substance name:

2-Amino-2-ethyl-1,3-propanediol

IUPAC Name:

2-Amino-2-ethyl-1,3-propanediol

Details on test material:

AEPD (P-1050)
Liquid

Specific details on test material used for the study:

- Lot No. NPP-41344
- Purity: 85.34%
- By-products
- Methanol: 1.48%
- Monomethyl amino butanol: 10.92%
- Water: 1.89%

Test animals / tissue source

Species:

rabbit

Strain:

New Zealand White

Details on test animals or tissues and environmental conditions:

Animals purchased at least 1 week prior to study and allowed to acclimatise. Healthy animlas free of disease were selected for the study. 24 hours prior to test, animals examined for eye injury. Those with no injury were used in test. Animals were fed Purina Certified Rabbit Chow, ad libitum, certified free of contaminants by supplier.Animals were given tap water ad libitum. Water was tested to ensure levels of contaminants are equivalent to or less than recommended levels as per the primary drinking water regulations.

Test system

Vehicle:

unchanged (no vehicle)

Controls:

other: right eye of each animal served as control

Amount / concentration applied:

0.1 ml of AEPD

Duration of treatment / exposure:

In 6 animals, the test compound was administered into the left eye. No washing of test compound out of eye took place. In three animals, the test compound was washed fromt he eye using water, 20 to 30 seconds after administration.

Observation period (in vivo):

Observation period 21 days. At 24 hours, 7, 14 and 21 days after treatment, the eyes were examined using fluorescein stain to assess corneal damage under UV light.

Number of animals or in vitro replicates:

9

Details on study design:

0.1 ml of AEPD was instilled into the lower conjunctival sac of the left eye. Six rabbits had their treated eyes unwashed while three had there treated eyes irrigated with water at 20 to 30 seconds following treatment. Eyes were examined at 24, 48 and 72 hours for damage and irritation. Additionally, at 24 hours, and then 7, 14 and 21 days, the eyes were examined using Fluorescein and UV light to assess corneal damage.

Results and discussion

In vivo

Results

Results 1

Irritation parameter:

cornea opacity score

Remarks:

unwashed

Basis:

mean

Time point:

24 h

Score:

2.17

Max. score:

4

Reversibility:

not reversible

Remarks on result:

probability of severe irritation

Results 2

Irritation parameter:

cornea opacity score

Remarks:

washed

Basis:

mean

Time point:

24 h

Score:

1.33

Max. score:

2

Results 3

Irritation parameter:

iris score

Remarks:

unwashed

Basis:

mean

Time point:

24 h

Score:

1.17

Max. score:

2

Results 4

Irritation parameter:

iris score

Remarks:

washed

Basis:

mean

Time point:

24 h

Score:

0.33

Max. score:

1

Results 5

Irritation parameter:

chemosis score

Remarks:

unwashed

Basis:

mean

Time point:

24 h

Score:

4

Max. score:

4

Results 6

Irritation parameter:

chemosis score

Remarks:

washed

Basis:

mean

Time point:

24 h

Score:

4

Max. score:

4

Results 7

Irritation parameter:

conjunctivae score

Remarks:

redness/unwashed

Basis:

mean

Time point:

24 h

Score:

3

Max. score:

3

Results 8

Irritation parameter:

conjunctivae score

Remarks:

redness/washed

Basis:

mean

Time point:

24 h

Score:

2.67

Max. score:

3

Results 9

Irritation parameter:

cornea opacity score

Remarks:

unwashed

Basis:

mean

Time point:

48 h

Score:

2.5

Max. score:

4

Reversibility:

not reversible

Remarks on result:

probability of severe irritation

Results 10

Irritation parameter:

cornea opacity score

Remarks:

washed

Basis:

mean

Time point:

48 h

Score:

1.33

Max. score:

2

Results 11

Irritation parameter:

iris score

Remarks:

unwashed

Basis:

mean

Time point:

48 h

Score:

1.17

Max. score:

2

Results 12

Irritation parameter:

iris score

Remarks:

washed

Basis:

mean

Time point:

48 h

Score:

0.33

Max. score:

1

Results 13

Irritation parameter:

chemosis score

Remarks:

unwashed

Basis:

mean

Time point:

48 h

Score:

4

Max. score:

4

Results 14

Irritation parameter:

chemosis score

Remarks:

washed

Basis:

mean

Time point:

48 h

Score:

4

Max. score:

4

Results 15

Irritation parameter:

conjunctivae score

Remarks:

redness/unwashed

Basis:

mean

Time point:

48 h

Score:

3

Max. score:

3

Results 16

Irritation parameter:

conjunctivae score

Remarks:

redness/washed

Basis:

mean

Time point:

48 h

Score:

2.67

Max. score:

3

Results 17

Irritation parameter:

cornea opacity score

Remarks:

unwashed

Basis:

mean

Time point:

72 h

Score:

3

Max. score:

4

Results 18

Irritation parameter:

cornea opacity score

Remarks:

washed

Basis:

mean

Time point:

72 h

Score:

1.33

Max. score:

2

Results 19

Irritation parameter:

iris score

Remarks:

unwashed

Basis:

mean

Time point:

72 h

Score:

1.17

Max. score:

2

Results 20

Irritation parameter:

iris score

Remarks:

washed

Basis:

mean

Time point:

72 h

Score:

0.33

Max. score:

1

Results 21

Irritation parameter:

chemosis score

Remarks:

unwashed

Basis:

mean

Time point:

72 h

Score:

4

Max. score:

4

Reversibility:

not reversible

Results 22

Irritation parameter:

chemosis score

Remarks:

washed

Basis:

mean

Time point:

72 h

Score:

3.67

Max. score:

4

Results 23

Irritation parameter:

conjunctivae score

Remarks:

redness/unwashed

Basis:

mean

Time point:

72 h

Score:

3

Max. score:

3

Results 24

Irritation parameter:

conjunctivae score

Remarks:

redness/washed

Basis:

mean

Time point:

72 h

Score:

3

Max. score:

3

Results 25

Irritation parameter:

cornea opacity score

Remarks:

unwashed

Basis:

mean

Time point:

7 d

Score:

3

Max. score:

4

Reversibility:

not specified

Results 26

Irritation parameter:

cornea opacity score

Remarks:

washed

Basis:

mean

Time point:

7 d

Score:

2

Max. score:

3

Results 27

Irritation parameter:

iris score

Remarks:

unwashed

Basis:

mean

Time point:

7 d

Score:

1.5

Max. score:

4

Results 28

Irritation parameter:

iris score

Remarks:

washed

Basis:

mean

Time point:

7 d

Score:

1.33

Max. score:

2

Results 29

Irritation parameter:

chemosis score

Remarks:

unwashed

Basis:

mean

Time point:

7 d

Score:

3.83

Max. score:

4

Results 30

Irritation parameter:

chemosis score

Remarks:

washed

Basis:

mean

Time point:

7 d

Score:

1.67

Max. score:

3

Results 31

Irritation parameter:

conjunctivae score

Remarks:

redness/unwashed

Basis:

mean

Time point:

7 d

Score:

2.83

Max. score:

3

Results 32

Irritation parameter:

conjunctivae score

Remarks:

redness/washed

Basis:

mean

Time point:

7 d

Score:

2

Max. score:

3

Results 33

Irritation parameter:

other: rabbits with unwashed eyes were sacrificed at day 14. All animals showed keratinitis.

Time point:

14 d

Remarks on result:

other: rabbits with unwashed eyes were sacrificed at day 14. All animals showed keratinitis.

Results 34

Irritation parameter:

cornea opacity score

Remarks:

washed

Basis:

mean

Time point:

14 d

Score:

0.67

Max. score:

1

Results 35

Irritation parameter:

iris score

Remarks:

washed

Basis:

mean

Time point:

14 d

Score:

0.67

Max. score:

1

Results 36

Irritation parameter:

chemosis score

Remarks:

washed

Basis:

mean

Time point:

14 d

Score:

0.33

Max. score:

1

Results 37

Irritation parameter:

conjunctivae score

Remarks:

redness/washed

Basis:

mean

Time point:

14 d

Score:

0

Max. score:

0

Reversibility:

fully reversible within: 14 days

Results 38

Irritation parameter:

cornea opacity score

Remarks:

washed

Basis:

mean

Time point:

21 d

Score:

0

Max. score:

0

Reversibility:

fully reversible within: 21 days

Results 39

Irritation parameter:

iris score

Remarks:

washed

Basis:

mean

Time point:

21 d

Score:

0

Max. score:

0

Reversibility:

fully reversible within: 21 days

Results 40

Irritation parameter:

chemosis score

Remarks:

washed

Basis:

mean

Time point:

21 d

Score:

0

Max. score:

0

Reversibility:

fully reversible within: 21 days

Irritant / corrosive response data:

At 24 hours, all the animals’ corneas showed lesions and the eyes were severely irritated. The eye of the unwashed group of animals never recovered and by day 14 were completely keratinized. The eyes of the washed group of rabbits were completely normal by day 21.

Applicant's summary and conclusion

Interpretation of results:

Category 2A (irritating to eyes) based on GHS criteria

Remarks:

Criteria used for interpretation of results: EU

Conclusions:

Undiluted AEPD was found to be severly irritating to eyes. The unwashed eyes were permenently damaged by day 14. Washing the material from the eye prevented irreversible damage (eyes normal at day 21), however the material was still severly irritating. The substance needs to be classified as Category 2a (H319, severe eye irritation) under the CLP/GHS Regulation (EC) No 1272/2008.

Executive summary:

2-Amino-2-ethyl-1,3-propanediol or AEPD (P-1050) was tested in rabbits to determine the eye irritation potential of the product. At 24 h, all the animals’ corneas showed lesions and the eyes were severely irritated. The eyes of the unwashed group of animals never recovered and by day 14 were completely keratitised, and the animals were sacrificed. The organs in all the animals were normal. The eyes of the washed group of animals showed improvement by day 14 and were completely normal by day 21. One of the rabbits in the unwashed group died on day 8 of the test, and the post mortem examination showed that the animal was suffering from severe diarrhea; the death was not related to the treatment.

In conclusion, undiluted AEPD was found to be severly irritating to eyes. The unwashed eyes were permenently damaged by day 14. Washing the material from the eye prevented irreversible damage (eyes normal at day 21), however the material was still severly irritating. The substance needs to be classified as Category 2a (H319, severe eye irritation) under the CLP/GHS Regulation (EC) No 1272/2008.