Butanedioic acid, 2-hydroxy-, 1,4-bis[5,7,7-trimethyl-2-(1,3,3-trimethylbutyl)octyl] ester

Eye irritation

Administrative data

Endpoint:

eye irritation: in vitro / ex vivo

Type of information:

experimental study

Adequacy of study:

key study

Study period:

2015-05-05 to 2015-09-02

Reliability:

1 (reliable without restriction)

Rationale for reliability incl. deficiencies:

other: see 'Remark'

Remarks:

The Enucleated Eye Test with isolated eyes of chickens has been recognized as a valuable alternative to the Draize eye irritation test regarding ocular corrosivity or severe eye irritancy testing, because it represents a test system nearest to the in vivo test, without the need to use live animals

Data source

Reference

Reference Type:

study report

Title:

Unnamed

Year:

2015

Report date:

2015

Materials and methods

Test guideline

Qualifier:

according to guideline

Guideline:

OECD Guideline 438 (Isolated Chicken Eye Test Method for Identifying Ocular Corrosives and Severe Irritants)

Deviations:

no

GLP compliance:

yes (incl. QA statement)

Test material

Test material information

Constituent 1

Reference substance name:

1,4-bis[2-(4,4-dimethylpentan-2-yl)-5,7,7-trimethyloctyl] 2-hydroxybutanedioate

EC Number:

807-422-1

Cas Number:

66918-01-2

Molecular formula:

C40H78O5

IUPAC Name:

1,4-bis[2-(4,4-dimethylpentan-2-yl)-5,7,7-trimethyloctyl] 2-hydroxybutanedioate

Results and discussion

In vitro

Results

Results 1

Irritation parameter:

percent corneal swelling

Run / experiment:

Mean maximum corneal swelling at up to 75 min

Value:

ca. -0.5

Vehicle controls validity:

not applicable

Negative controls validity:

valid

Positive controls validity:

valid

Remarks on result:

no indication of irritation

Remarks:

ICE Class I

Results 2

Irritation parameter:

percent corneal swelling

Run / experiment:

Mean maximum corneal swelling at up to 240 min

Value:

ca. -0.5

Vehicle controls validity:

not applicable

Negative controls validity:

valid

Positive controls validity:

valid

Remarks on result:

no indication of irritation

Remarks:

ICE Class I

Results 3

Irritation parameter:

cornea opacity score

Run / experiment:

Mean maximum corneal opacity

Value:

ca. 0.17

Vehicle controls validity:

not applicable

Negative controls validity:

valid

Positive controls validity:

valid

Remarks on result:

no indication of irritation

Remarks:

ICE Class I

Results 4

Irritation parameter:

fluorescein retention score

Run / experiment:

Mean fluorescein retention

Value:

ca. 0.5

Vehicle controls validity:

not applicable

Negative controls validity:

valid

Positive controls validity:

valid

Remarks on result:

no indication of irritation

Remarks:

ICE Class I

Other effects / acceptance of results:

Other observations: None
Overall ICE Class: 3 x I

Any other information on results incl. tables

Corneal swelling was calculated and small negative numbers for swelling (0 to -5%) following application are evaluated as class I. Large negative numbers (>12% below control) are probably due to erosion and indicate a severe effect (scored as class IV). Cases of values of -5% to -12% are evaluated on a case by case basis but in the absence of other findings do not indicate a severe effect (class II). Cornea opacity was calculated and Fluorescein retention were also calculated.

The mean values of the treated eyes for maximum corneal thickness change, corneal opacity change and fluorescein retention change are given below. The conclusion on eye irritancy was based on the OECD guideline quantitative assessments. The mean maximum corneal swelling up to 240 min, the mean maximum corneal opacity and the mean fluorescein retention ICE classes are used for EC and GHS classification.

Observation	Value	ICE Class
Mean maximum corneal swelling at up to 75 min	-0.5%	I
Mean maximum corneal swelling at up to 240 min	-0.5%	I
Mean maximum corneal opacity	0.17	I
Mean fluorescein retention	0.50	I
Other Observations	None
Overall ICE Class

Based on this in vitro eye irritation in the isolated chicken eyes test with Bis[2-(4,4-dimethylpentan-2-yl)-5,7,7-trimethyloctyl] malate, the test item is not irritant, UN GHS Classification: Non-classified.

The positive control Benzalkonium chloride was classified as severely irritating, UN GHS Classification: Category 1.

The negative control Physiological saline was classified as non-irritating, UN GHS Classification: Non-classified.

The results from all eyes used met the quality control standards. The negative control and positive control results were in line with historic data. This experiment was considered to be valid.

Applicant's summary and conclusion

Interpretation of results:

not irritating

Remarks:

Migrated information Criteria used for interpretation of results: OECD GHS

Conclusions:

Based on this in vitro eye irritation assay in the isolated chicken eyes with Bis[2-(4,4-dimethylpentan-2-yl)-5,7,7-trimethyloctyl] malate, the test item is not irritant to eye, UN GHS Classification: Non-classified.

Executive summary:

An in vitro eye irritation study of the test item was performed in isolated chicken’s eyes. The irritation effects of the test item were evaluated according to the OECD No. 438 guideline (26 July 2013).

After the zero reference measurements, the eye was held in horizontal position and 30 μL of test item was applied onto the centre of the cornea such that the entire surface of the cornea was covered. After 10 seconds, the surface was rinsed with physiological saline. The positive control eyes were treated with 30 μL Benzalkonium chloride solution. The negative control eye was treated with 30 μL of physiological saline (Salsol solution, 0.9% (w/v) NaCl solution). In the study, three test item treated eyes, three positive control treated eyes and one negative control treated eye were examined.

The results from all eyes used in the study met the quality control standards. The negative control and positive control results were in good correlation with the historical control data. Thus, the experiment was considered to be valid.

No significant corneal swelling was observed during the four-hour observation period on test item treated eyes. Fluorescein retention change (severity 0.5) was noted on three eyes. Cornea opacity change (severity 0.5) was noted on one eye.

Based on this in vitro eye irritation assay in the isolated chicken eyes with Bis[2-(4,4-dimethylpentan-2-yl)-5,7,7-trimethyloctyl] malate, the test item is not irritant to eye, UN GHS Classification: Non-classified.