N-(2-hydroxyethyl)-N-[2-[(1-oxooctyl)amino]ethyl]-β-alanine

Eye irritation

Administrative data

Endpoint:

eye irritation: in vivo

Type of information:

experimental study

Adequacy of study:

key study

Study period:

2007-07-09 to 2007-09-03

Reliability:

1 (reliable without restriction)

Rationale for reliability incl. deficiencies:

guideline study

Data source

Reference

Reference Type:

study report

Title:

Unnamed

Year:

2007

Report date:

2007

Materials and methods

Test guideline

Test guideline 1

Qualifier:

according to guideline

Guideline:

OECD Guideline 405 (Acute Eye Irritation / Corrosion)

Version / remarks:

2002

Deviations:

no

Test guideline 2

Qualifier:

according to guideline

Guideline:

EU Method B.5 (Acute Toxicity: Eye Irritation / Corrosion)

Version / remarks:

2004

Deviations:

no

GLP compliance:

yes

Test material

Test material information

Constituent 1

Reference substance name:

N-(2-hydroxyethyl)-N-[2-[(1-oxooctyl)amino]ethyl]-β-alanine

EC Number:

264-761-2

EC Name:

N-(2-hydroxyethyl)-N-[2-[(1-oxooctyl)amino]ethyl]-β-alanine

Cas Number:

64265-45-8

Molecular formula:

C15H30N2O4

IUPAC Name:

N-(2-hydroxyethyl)-N-[2-[(1-oxooctyl)amino]ethyl]-β-alanine

Test material form:

liquid

Details on test material:

- Physical state: liquid
- Analytical purity: 97.0%

Test animals / tissue source

Species:

rabbit

Strain:

New Zealand White

Details on test animals or tissues and environmental conditions:

TEST ANIMALS
- Age at study initiation: >/= 9 weeks
- Weight at study initiation: 2.165 - 2.757 kg
- Housing: individually
- Diet (e.g. ad libitum): pelleted diet for rabbits (K-H from SSNIFF Spezialdiäten)
- Water (e.g. ad libitum): tap water, ad libitum
- Acclimation period: at least 5 d

ENVIRONMENTAL CONDITIONS
- Temperature (°C): 21.0±3 (actual range: 21.0-22.4°C)
- Humidity (%): 30-70 (actual range: 42-78%)
- Air changes (per hr): approx. 15
- Photoperiod (hrs dark / hrs light): 12/12

Test system

Vehicle:

unchanged (no vehicle)

Controls:

yes, concurrent no treatment

Amount / concentration applied:

TEST MATERIAL
- Amount(s) applied (volume or weight with unit): 0.1 mL of the test item was instilled in the conjunctival sac of one eye

Duration of treatment / exposure:

24 h

Observation period (in vivo):

14 d

Number of animals or in vitro replicates:

3 (started by treatment of a single rabbit (sentinel); the two other animals were treated 6 weeks later, after considering the degree of eye irritation observed in the first animal)

Details on study design:

REMOVAL OF TEST SUBSTANCE
- Washing (if done): no; at the 24 h observation, a solution of 2% fluorescein in water (adjusted to pH 7.0) was instilled into both eyes of each animal to quantitatively determine corneal epithelial damage.

SCORING SYSTEM: according to OECD TG 405 (Draize scale)

TOOL USED TO ASSESS SCORE: hand-slit lamp / fluorescein

Results and discussion

In vivo

Results

Results 1

Irritation parameter:

cornea opacity score

Basis:

animal: #1, 2, 3

Time point:

24/48/72 h

Score:

1

Max. score:

4

Reversibility:

fully reversible within: 7 d

Results 2

Irritation parameter:

iris score

Basis:

animal: #1, 3

Time point:

24/48/72 h

Score:

0.3

Max. score:

2

Reversibility:

fully reversible within: 72 h

Results 3

Irritation parameter:

iris score

Basis:

animal #2

Time point:

24/48/72 h

Score:

0.7

Max. score:

2

Reversibility:

fully reversible within: 7 d

Results 4

Irritation parameter:

conjunctivae score

Basis:

animal: #1, 3

Time point:

24/48/72 h

Score:

2.7

Max. score:

3

Reversibility:

fully reversible within: 14 d

Results 5

Irritation parameter:

conjunctivae score

Basis:

animal #2

Time point:

24/48/72 h

Score:

3

Max. score:

3

Reversibility:

fully reversible within: 14 d

Results 6

Irritation parameter:

chemosis score

Basis:

animal: #1, 3

Time point:

24/48/72 h

Score:

1.7

Max. score:

4

Reversibility:

fully reversible within: 7 d

Results 7

Irritation parameter:

chemosis score

Basis:

animal #2

Time point:

24/48/72 h

Score:

1.3

Max. score:

4

Reversibility:

fully reversible within: 14 d

Irritant / corrosive response data:

Instillation of 0.1 mL of the test item into one eye of each of three rabbits resulted in effects on the cornea, iris and conjunctivae. The corneal injury consisted of opacity (maximum grade 1) and epithelial damage (maximum 75 or 50% of the corneal area). The corneal injury had resolved within 7 days. Iridial irritation grade 1 was observed and had resolved within 48 hours, 72 hours or 7 days. The irritation of the conjunctivae consisted of redness, chemosis and discharge and had completely resolved within 14 days.
There was no evidence of ocular corrosion.
No staining of (peri) ocular tissues by the test substance was observed and no test substance remnants were seen.

Other effects:

No symptoms of systemic toxicity were observed in the animals during the test period and no mortality occurred.

Any other information on results incl. tables

Irritant/corrosive response data for each animal at each observation time up to removal of each animal from the test

Score at time point	Cornea	Iris	Conjunctivae	Chemosis
	Max. score: 4	Max. score: 2	Max. score: 3	Max. score: 4
1 h	1/1/1	1/1/1	2/2/2	2/3/3
24 h	1/1/1	0/1/1	2/3/2	2/2/3
48 h	1/1/1	1/0/0	3/3/3	2/1/1
72 h	1/1/1	0/1/0	3/3/3	1/1/1
Average 24h, 48h, 72h	1/1/1	0.3/0.7/0.3	2.7/3.0/2.7	1.7/1.3/1.7
7 d	0/0/0	0/0/0	1/2/1	0/1/0
14 d	0/0/0	0/0/0	0/0/0	0/0/0

 

 

Applicant's summary and conclusion

Interpretation of results:

Category 2 (irritating to eyes) based on GHS criteria

Conclusions:

In this study, of Amphopropionate C8 (97% a.i.) is irritating to the eye (Category 2).

Executive summary:

In a primary eye irritation study according to OECD Guideline 405 (2002) and EU method B.5 (2004) 0.1 mL of Amphopropionate C8 (97% a.i.) was instilled into the conjunctival sac of one eye of 3 male young adult New Zealand White rabbits. At the 24 h observation, a solution of 2% fluorescein in water was instilled into both eyes of each animal to quantitatively determine corneal epithelial damage. Animals then were observed for 14 days. Irritation was scored by the method of Draize.

Instillation of 0.1 mL of the test item into one eye of each of three rabbits resulted in effects on the cornea, iris and conjunctivae. The corneal injury consisted of opacity (maximum grade 1) and epithelial damage (maximum 75 or 50% of the corneal area). The corneal injury had resolved within 7 days. Iridial irritation grade 1 was observed and had resolved within 48 hours, 72 hours or 7 days. The irritation of the conjunctivae consisted of redness, chemosis and discharge and had completely resolved within 14 days. There was no evidence of ocular corrosion.

In this study, Amphopropionate C8 (97% a.i.) is irritating to the eye (Category 2) based on conjunctival redness scores >/= 2.