2-Propenoic acid, methyl ester, reaction products with 2-ethyl-1-hexanamine and sodium hydroxide

Eye irritation

Administrative data

Endpoint:

eye irritation: in vivo

Type of information:

experimental study

Adequacy of study:

key study

Study period:

24 September -02 October 2007

Reliability:

1 (reliable without restriction)

Rationale for reliability incl. deficiencies:

guideline study

Cross-reference

Reason / purpose for cross-reference:

read-across: supporting information

Reference

Endpoint:

eye irritation: in vivo

Type of information:

read-across from supporting substance (structural analogue or surrogate)

Adequacy of study:

key study

Justification for type of information:

REPORTING FORMAT FOR THE ANALOGUE APPROACH

1. HYPOTHESIS FOR THE ANALOGUE APPROACH
The read-across hypothesis is based on “different compounds which have similar properties”.

2. SOURCE AND TARGET CHEMICAL(S) (INCLUDING INFORMATION ON PURITY AND IMPURITIES)
- The source substance is identified as Sodium N-(2-carboxyethyl)-N-(2-ethylhexyl)-β-alaninate, also known as Sodium 3-[(2-carboxyethyl)(2-ethylhexyl)amino]propanoate (CAS no. 94441-92-6 | EC no. 305-318-6). It is a UVCB substance whose major constituent is sodium 2-ethylhexylimino-di-propionate. Minor constituents are sodium 2-ethylhexylimino-mono-propionate, unreacted acrylic acid and unreacted 2-ethylhexylamine.
- The target substance is identified as Propenoic acid, methyl ester, reaction products with 2-ethyl-1-hexanamine and sodium hydroxide (methanol free) (CAS no. 68610-44-6| EC no. 271-865-1). It is a UVCB substance whose major constituents are sodium 2-ethylhexylimino-mono-propionate and sodium 2-ethylhexylimino-di-propionate. Minor constituents are unreacted acrylic acid and unreacted 2-ethylhexylamine.

3. ANALOGUE APPROACH JUSTIFICATION
The target and source substances are essentially the same: both are UVCB substances composed of the exact same constituents with the exact same functional groups (i.e. carboxylic acid groups and secondary/tertiary amine groups). They are expected to have the same ADME profile and to share common mode of action and breakdown products. The target and source substances only differ in the overlapping ranges of their constituents, the content of sodium 2-ethylhexylimino-mono-propionate being especially higher in the target substance. This difference is expected to have no or very limited impact on the potency of effects exerted on exposed living organisms.

4. DATA MATRIX
Cf. read-across justification document attached in §13. Assessment reports.

Reason / purpose for cross-reference:

read-across source

Irritation parameter:

conjunctivae score

Basis:

animal: Mean of animals 1, 2 and 3 / Individual scores not specified in the report

Time point:

24/48/72 h

Score:

ca. 1.8

Max. score:

3

Reversibility:

fully reversible within: 8 days

Irritation parameter:

chemosis score

Basis:

animal: Mean of animals 1, 2 and 3 / Individual scores not specified in the report

Time point:

24/48/72 h

Score:

ca. 0.8

Max. score:

4

Reversibility:

fully reversible within: 6 days

Irritation parameter:

iris score

Basis:

animal: Mean of animals 1, 2 and 3 / Individual scores not specified in the report

Time point:

24/48/72 h

Score:

ca. 0

Max. score:

2

Reversibility:

other: Not applicable

Irritation parameter:

cornea opacity score

Basis:

animal: Mean of animals 1, 2 and 3 / Individual scores not specified in the report

Time point:

24/48/72 h

Score:

ca. 0

Max. score:

4

Reversibility:

other: Not applicable

Interpretation of results:

GHS criteria not met

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)

Test guideline 2

Qualifier:

according to guideline

Guideline:

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

GLP compliance:

yes (incl. QA statement)

Test material

Test material information

Constituent 1

Reference substance name:

Sodium N-(2-carboxyethyl)-N-(2-ethylhexyl)-β-alaninate

EC Number:

305-318-6

EC Name:

Sodium N-(2-carboxyethyl)-N-(2-ethylhexyl)-β-alaninate

Cas Number:

94441-92-6

Molecular formula:

C14H26NO4.Na

IUPAC Name:

sodium 3-[(2-carboxyethyl)(2-ethylhexyl)amino]propanoate

Constituent 2

Reference substance name:

Water

EC Number:

231-791-2

EC Name:

Water

Cas Number:

7732-18-5

Molecular formula:

H2O

IUPAC Name:

Water

Test material form:

liquid

Details on test material:

- Name of test material:sodium N-(2-carboxyethyl)-N-(2-ethylhexyl)-β-alaninate
- Physical state: liquid (colorless)
- Analytical purity: confidential information
- Composition of test material, percentage of components: confidential information
- Lot/batch No.: confidential information
- Expiration date of the lot/batch: confidential information
- Storage condition of test material: Room temperature, in the dark, container: plastic flask.
- Other: Date received 10 September 2007

Test animals / tissue source

Species:

rabbit

Strain:

New Zealand White

Details on test animals or tissues and environmental conditions:

TEST ANIMALS
- Source: Elevage de Gérome, Linxe
- Age at study initiation: 18 weeks
- Weight at study initiation: 3.20-3.84 kg
- Housing: Individual box
- Diet (e.g. ad libitum): ad libitium
- Water (e.g. ad libitum): ad libitium
- Acclimation period: 5 days
- Other: Albino rabbits (male)

ENVIRONMENTAL CONDITIONS
- Temperature (°C): 20-25 °C
- Humidity (%): 36-70 %
- Photoperiod (hrs dark / hrs light): (12/12)

Test system

Vehicle:

unchanged (no vehicle)

Controls:

no

Amount / concentration applied:

0,1 mL of test item was instilled into conjunctival sac of one eye, the other eye remained untreated as control.

Duration of treatment / exposure:

Single dose.

Observation period (in vivo):

1, 24, 48, and 72 hours following treatment and daily thereafter up to 8 days after treatment

Number of animals or in vitro replicates:

3

Details on study design:

SCORING SYSTEM: In accordance with OECD 405

Results and discussion

In vivo

Results

Results 1

Irritation parameter:

conjunctivae score

Remarks:

redness

Basis:

animal: Mean of animals 1, 2 and 3 / Individual scores not specified in the report

Time point:

24/48/72 h

Score:

ca. 1.8

Max. score:

3

Reversibility:

fully reversible within: 8 days

Results 2

Irritation parameter:

chemosis score

Basis:

animal: Mean of animals 1, 2 and 3 / Individual scores not specified in the report

Time point:

24/48/72 h

Score:

ca. 0.8

Max. score:

4

Reversibility:

fully reversible within: 6 days

Results 3

Irritation parameter:

iris score

Basis:

animal: Mean of animals 1, 2 and 3 / Individual scores not specified in the report

Time point:

24/48/72 h

Score:

ca. 0

Max. score:

2

Reversibility:

other: not applicable

Results 4

Irritation parameter:

cornea opacity score

Basis:

animal: Mean of animals 1, 2 and 3 / Individual scores not specified in the report

Time point:

24/48/72 h

Score:

ca. 0

Max. score:

4

Reversibility:

other: not applicable

Irritant / corrosive response data:

The conjunctiva reactions observed during the study have been moderate, and totally reversible in the three animals: a moderate redness, noted 24 hours after the test item instillation and totally reversible between day 6 and day 8, associated with a moderate chemosis, noted 1 hour after the test item instillation and totally reversible between day 3 and day 6.

Other effects:

No other effects were observed

Applicant's summary and conclusion

Interpretation of results:

GHS criteria not met

Conclusions:

The eye irritating potential of Amphotensid EH was investigated in an acute eye irritation study, which was performed according to OECD 405 and under GLP conditions. Based on the results, the test item does not need to be classified according to the criteria outlined in Annex I of 67/548/EEC and Annex VI of 1272/2008, under the conditions of this study.

Executive summary:

The eye irritating potential of Amphotensid EH was investigated in an acute eye irritation study, which was performed according to OECD 405 and under GLP conditions. Three male albino New Zealand White rabbits were administered a single ocular dose of 0.1 ml of the test substance and observed up to eight days after instillation. Moderate conjunctiva reactions (redness and chemosis) were observed, which were totally reversible within 8 days. Based on these results, the test item does not need to be classified according to the criteria outlined in Annex I of 67/548/EEC and Annex VI of 1272/2008, under the conditions of this study.