bis(branched-alkyl) 2-{[(1-phenylethyl)amino]methyl}alkanedioate

Eye irritation

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Administrative data

Endpoint:

eye irritation: in vivo

Type of information:

experimental study

Adequacy of study:

key study

Study period:

09 January 2015 to 23 April 2015

Reliability:

1 (reliable without restriction)

Rationale for reliability incl. deficiencies:

other: GLP guideline study.

Data source

Reference

Reference Type:

study report

Title:

Unnamed

Year:

2015

Report date:

2015

Materials and methods

Test guideline

Test guideline 1

Qualifier:

according to guideline

Guideline:

OECD Guideline 405 (Acute Eye Irritation / Corrosion)

Deviations:

no

Test guideline 2

Qualifier:

according to guideline

Guideline:

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

Deviations:

no

GLP compliance:

yes

Test material

Test material information

Details on test material:

- Physical state: Pale amber liquid
- Analytical purity: 100 %
- Expiration date of the lot/batch: 08 January 2017
- Storage condition of test material: Approximately 4 °C in the dark

Test animals / tissue source

Species:

rabbit

Strain:

New Zealand White

Details on test animals or tissues and environmental conditions:

ANIMALS AND ANIMAL HUSBANDRY
- Two New Zealand White (Hsdlf:NZW) strain rabbits were supplied by Harlan Laboratories UK Ltd, Leicestershire, UK.
- At the start of the study the animals weighed 2.37 or 2.62 kg and were 12 to 20 weeks old.
- After an acclimatisation period of at least 5 days each animal was given a number, unique within the study, which was written with a black indelible marker-pen on the inner surface of the ear and on the cage label.
- The animals were individually housed in suspended cages.
- Free access to mains drinking water and food (2930C Teklad Global Rabitt diet supplied by Harlan Laboratories Ltd, Oxon, UK) was allowed throughout the study.
- The diet and drinking water were considered not to contain any contaminant of a level that might have affected the purpose or integrity of the study.
- Temperature and relative humidity were set to achieve limits of 17 to 23 °C and 30 to 70 % respectively.
- Rate of air exchange was at least 15 changes per hour.
- Lighting was controlled by a time switch to give 12 hours continuous light (06:00 to 18:00) and 12 hours darkness.
- The animals were provided with environmental enrichment items, which were considered not to contain any contaminant of a level that might have affected the purpose or integrity of the study.

Test system

Vehicle:

unchanged (no vehicle)

Controls:

no

Amount / concentration applied:

0.1 mL of test item

Duration of treatment / exposure:

Single application

Observation period (in vivo):

7 days

Number of animals or in vitro replicates:

Two

Details on study design:

TEST ITEM FORMULATION AND EXPERIMENTAL PREPARATION
- The test item was used as supplied.
- Absorption of the test material was not determined.

Results and discussion

In vivo

Results

Results 1

Irritation parameter:

cornea opacity score

Remarks:

opacity

Basis:

animal #1

Remarks:

mean score

Time point:

24/48/72 h

Score:

0

Max. score:

4

Reversibility:

other: not applicable

Remarks on result:

other: 74924 male

Results 2

Irritation parameter:

iris score

Basis:

animal #1

Remarks:

mean score

Time point:

24/48/72 h

Score:

0

Max. score:

2

Reversibility:

other: not applicable

Remarks on result:

other: 74924 male

Results 3

Irritation parameter:

conjunctivae score

Remarks:

redness

Basis:

animal #1

Remarks:

mean score

Time point:

24/48/72 h

Score:

1.67

Max. score:

3

Reversibility:

fully reversible within: 7 d

Remarks on result:

other: 74924 male

Results 4

Irritation parameter:

chemosis score

Basis:

animal #1

Remarks:

mean score

Time point:

24/48/72 h

Score:

1.33

Max. score:

4

Reversibility:

fully reversible within: 7 d

Remarks on result:

other: 74924 male

Results 5

Irritation parameter:

cornea opacity score

Remarks:

opacity

Basis:

animal #2

Remarks:

mean score

Time point:

24/48/72 h

Score:

0

Max. score:

4

Reversibility:

other: not applicable

Remarks on result:

other: 74945 male

Results 6

Irritation parameter:

iris score

Basis:

animal #2

Remarks:

mean score

Time point:

24/48/72 h

Score:

0

Max. score:

2

Reversibility:

other: not applicable

Remarks on result:

other: 74945 male

Results 7

Irritation parameter:

conjunctivae score

Remarks:

redness

Basis:

animal #2

Remarks:

mean score

Time point:

24/48/72 h

Score:

1.33

Max. score:

3

Reversibility:

fully reversible within: 7 d

Remarks on result:

other: 74945 male

Results 8

Irritation parameter:

chemosis score

Basis:

animal #2

Remarks:

mean score

Time point:

24/48/72 h

Score:

1

Max. score:

4

Reversibility:

fully reversible within: 72 h

Remarks on result:

other: 74945 male

Irritant / corrosive response data:

- Individual and group mean scores for occular irritation are given in Table 1 and Table 2 (attached).
- No corneal effects were noted during the study.
- Iridial inflammation was noted in both treated eyes 1 hour after application of the test material.
- Moderate conjunctival irritation was noted in both treated eyes at 1 and 24 hours after application of the test item.
- Moderate conjunctival irritation was noted in one treated eye with minimal conjunctival irritation noted in the other treated eye at the 48 hour observation.
- Minimal conjunctival irritation waas noted in both treated eyes at the 72 hour observation.
- Both treated eyes appeared normal at the 7 day observation.

Other effects:

BODY WEIGHT
- Individual body weights are given in Table 3 (attached).
- Both animals showed expected gain in body weight during the study.

Any other information on results incl. tables

MEASUREMENT OF pH

- Test item undiluted as supplied: pH 5

- Aqueous preparation of test item (90 % v/v): pH 5 immediately; pH 10 after 10 minutes; pH 10 after 20 minutes

Applicant's summary and conclusion

Interpretation of results:

not classified

Remarks:

Migrated information Criteria used for interpretation of results: EU

Conclusions:

The test item produced a maximum group mean score of 16.0 and was considered to be a moderate irritant (Class 5 on a 1 to 8 scale) to the rabbit eye according to a modified Kay and Calandra system. However, the test material is not classified under the terms of Regulation (EC) No 1272/2008.

Executive summary:

GUIDELINE

The study was performed to assess the irritancy potential of the test item to the eye of the New Zealand White rabbit using a procedure designed to be compatible with OECD Guideline for the Testing of Chemicals No 405 "Acute Eye Irritation/Corrosion" (adopted 02 October 2012) and EU Method B.5 Acute Toxicity (Eye Irritation) of Commission Regulation (EC) No 440/2008.

RESULTS

A single application of the test item to the non-irrigated eye of two rabbits produced iridial inflammation and moderate conjunctival irritation. Both eyes appeared normal at the 7 day observation.

CONCLUSION

The test item produced a maximum group mean score of 16.0 and was considered to be a moderate irritant (Class 5 on a 1 to 8 scale) to the rabbit eye according to a modified Kay and Calandra system. However, the test material is not classified under the terms of Regulation (EC) No 1272/2008 because the mean scores for two animals calculated using data from 24, 48 and 72 hour observations were below the stated limits for corneal opacity, iritis, conjunctival redness and chemosis.