Fatty acids, C18-unsatd., esters with triethanolamine

Eye irritation

Administrative data

Endpoint:

eye irritation: in vivo

Type of information:

experimental study

Adequacy of study:

key study

Study period:

Study performed between 12 September 2011 and 23 September 2011

Reliability:

1 (reliable without restriction)

Rationale for reliability incl. deficiencies:

other: Study conducted to GLP and in compliance with agreed protocols, with no or minor deviations from standard test guidelines and/or minor methodological deficiencies, which do no effect the quality of the relevant results.

Data source

Reference

Reference Type:

study report

Title:

Unnamed

Year:

2012

Report date:

2012

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

Test guideline 3

Qualifier:

according to guideline

Guideline:

EPA OPPTS 870.2400 (Acute Eye Irritation)

Deviations:

no

Test guideline 4

Qualifier:

according to guideline

Guideline:

other: Japanese Ministry of Agriculture, Forestry and Fisheries (JMAFF), Testing Guidelines for Toxicology Studies, 12 NohSan No. 8147, amended 10 December 2002

Deviations:

no

Test guideline 5

Qualifier:

according to guideline

Guideline:

other: Japanese Ministry of Health and Welfare, 1992

Deviations:

no

GLP compliance:

yes (incl. QA statement)

Test material

Test material information

Constituent 1

Reference substance name:

Esterification products of Fatty acids C18 unsaturated and triethanolamine

EC Number:

939-649-8

Cas Number:

1474044-69-3

Molecular formula:

Not applicable (a generic molecular formula cannot be provided for this specific UVCB substance)

IUPAC Name:

Esterification products of Fatty acids C18 unsaturated and triethanolamine

Test material form:

liquid: viscous

Test animals / tissue source

Species:

rabbit

Strain:

New Zealand White

Details on test animals or tissues and environmental conditions:

TEST ANIMALS
- Source: Three New Zealand White (Hsdlf:NZW) strain rabbits were supplied by Harlan Laboratories UK Ltd.
- Age at study initiation: Twelve to twenty weeks old.
- Weight at study initiation: 2.48 to 2.82 kg.
- Fasting period before study: None.
- Housing: The animals were individually housed in suspended cages.
- Diet (e.g. ad libitum): Free access to food (2930 Teklad Global Certified Rabbit diet) was allowed throughout the study.
- Water (e.g. ad libitum): Free access to mains drinking water was allowed throughout the study.
- Acclimation period: At least five days.

ENVIRONMENTAL CONDITIONS
- Temperature (°C): Set to achieve limits of 17 to 23°C
- Humidity (%): Set to achieve limits of 30 to 70%
- Air changes (per hr): At least fifteen changes per hour
- Photoperiod (hrs dark / hrs light): lighting was controlled by a time switch to give twelve hours continuous light (06:00 to 18:00) and twelve hours darkness.

Test system

Vehicle:

unchanged (no vehicle)

Controls:

yes, concurrent no treatment

Amount / concentration applied:

A volume of 0.1 ml of the test item was placed into the conjunctival sac of the right eye.

Duration of treatment / exposure:

Single application.

Observation period (in vivo):

72 hours

Number of animals or in vitro replicates:

3

Details on study design:

MEASUREMENT OF PH:
The pH of the test item was determined prior to commencement of the study and found to be as follows:
Undileted as supplied: pH approximately 7.7 (immediately)
90% v/v aqueous preparation of the test item: pH approximately 8.8 (immediately)
: pH approximately 8.8 (after 10 minutes)

PROCEDURE:
Immediately before the start of the test, both eyes of the provisionally selected test rabbits were examined for evidence of ocular irritation or defect with the aid of a light source from a standard ophthalmoscope. Only animals free of ocular damage were used.

Initially, a single rabbit was treated. A volume of 0.1 ml of the test item was placed into the conjunctival sac of the right eye, formed by gently pulling the lower lid away from the eyeball. The upper and lower eyelids were held together for about one second immediately after treatment, to prevent loss of the test item, and then released. The left eye remained untreated and was used for control purposes. Immediately after administration of the test item, an assessment of the initial pain reaction was made according to the six point scale shown in Appendix 1 (see attached background material; Appendix 1 - Initial Pain Reaction).

After consideration of the ocular responses produced in the first treated animal, two additional animals were treated.

SCORING SYSTEM:
Assessment of ocular damage/irritation was made approximately 1 hour and 24, 48 and 72 hours following treatment, according to the numerical Draize Scale for Scoring Ocular Irritation (see Appendix 2 - attached background material).

Any other ocular effects were also noted.

TOOL USED TO ASSESS SCORE: Examination of the eye was facilitated by the use of the light source from a standard ophthalmoscope.

Other:
Any clinical signs of toxicity, if present, were also recorded.

Individual bodyweights were recorded on Day 0 (the day of dosing) and at the end of the observation period.

Results and discussion

In vivo

Results

Results 1

Irritation parameter:

cornea opacity score

Basis:

mean

Remarks:

(Animal 70933 - male)

Time point:

other: Mean of scores at 24, 48 and 72 hours

Score:

0

Max. score:

4

Remarks on result:

other: No effects observed at any time point

Results 2

Irritation parameter:

cornea opacity score

Basis:

mean

Remarks:

(Animal70989 - male)

Time point:

other: Mean of scores at 24, 48 and 72 hours

Score:

0

Max. score:

4

Remarks on result:

other: No effects observed at any time point

Results 3

Irritation parameter:

cornea opacity score

Basis:

mean

Remarks:

(Animal 70990 - male)

Time point:

other: Mean of scores at 24, 48 and 72 hours

Score:

0

Max. score:

4

Remarks on result:

other: No effects observed at any time point

Results 4

Irritation parameter:

iris score

Basis:

mean

Remarks:

(Animal 70933 - male)

Time point:

other: Mean of scores at 24, 48 and 72 hours

Score:

0

Max. score:

2

Remarks on result:

other: No effects observed at any time point

Results 5

Irritation parameter:

iris score

Basis:

mean

Remarks:

(Animal 70989 - male)

Time point:

other: Mean of scores at 24, 48 and 72 hours

Score:

0

Max. score:

2

Remarks on result:

other: No effects observed at any time point

Results 6

Irritation parameter:

iris score

Basis:

mean

Remarks:

(Animal 70990 - male)

Time point:

other: Mean of scores at 24, 48 and 72 hours

Score:

0

Max. score:

2

Remarks on result:

other: No effects observed at any time point

Results 7

Irritation parameter:

conjunctivae score

Remarks:

(redness)

Basis:

mean

Remarks:

(Animal 70933 - male)

Time point:

other: Mean of scores at 24, 48 and 72 hours

Score:

0.33

Max. score:

3

Reversibility:

fully reversible within: 48 hours

Results 8

Irritation parameter:

conjunctivae score

Remarks:

(redness)

Basis:

mean

Remarks:

(Animal 70989 - male)

Time point:

other: Mean of scores at 24, 48 and 72 hours

Score:

0.33

Max. score:

3

Reversibility:

fully reversible within: 48 hours

Results 9

Irritation parameter:

conjunctivae score

Remarks:

(redness)

Basis:

mean

Remarks:

(Animal 70990 - male)

Time point:

other: Mean of scores at 24, 48 and 72 hours

Score:

0.33

Max. score:

3

Reversibility:

fully reversible within: 48 hours

Results 10

Irritation parameter:

chemosis score

Basis:

mean

Remarks:

(Animal 70933 - male)

Time point:

other: Mean of scores at 24, 48 and 72 hours

Score:

0

Max. score:

4

Reversibility:

fully reversible within: 24 hours

Remarks on result:

other: Score of 1 at 1 hour observation

Results 11

Irritation parameter:

chemosis score

Basis:

mean

Remarks:

(Animal 70989 - male)

Time point:

other: Mean of scores at 24, 48 and 72 hours

Score:

0

Max. score:

4

Reversibility:

fully reversible within: 24 hours

Remarks on result:

other: Score of 1 at 1 hour observation

Results 12

Irritation parameter:

chemosis score

Basis:

mean

Remarks:

(Animal 70990 - male)

Time point:

other: Mean of scores at 24, 48 and 72 hours

Score:

0

Max. score:

4

Reversibility:

fully reversible within: 24 hours

Remarks on result:

other: Score of 1 at 1 hour observation

Irritant / corrosive response data:

Individual and group mean scores for ocular irritation are given in Table 1 and Table 2.

Pale yellow coloured staining of the fur was noted around all treated eyes during the study.

No corneal or iridial effects were noted during the study.

Minimal conjunctival irritation was noted in all treated eyes one and 24 hours after treatment.

All treated eyes appeared normal at the 48-Hour observation.

Other effects:

Bodyweight
Individual bodyweights and bodyweight changes are given in Table 3.
All animals showed expected gain in bodyweight during the study.

Any other information on results incl. tables

Table 1              Individual Scores and Individual Total Scores for Ocular Irritation

Rabbit Number and Sex	70933Male				70989Male				70990Male
	IPR= 2				IPR = 2				IPR = 2
Time After Treatment	1 Hour	24 Hours	48 Hours	72 Hours	1 Hour	24 Hours	48 Hours	72 Hours	1 Hour	24 Hours	48 Hours	72 Hours
CORNEA
E = Degree of Opacity	0	0	0	0	0	0	0	0	0	0	0	0
F = Area of Cornea Involved	0	0	0	0	0	0	0	0	0	0	0	0
Score (E x F) x 5	0	0	0	0	0	0	0	0	0	0	0	0
IRIS
D	0	0	0	0	0	0	0	0	0	0	0	0
Score (D x 5)	0	0	0	0	0	0	0	0	0	0	0	0
CONJUNCTIVAE
A = Redness	1Sf	1	0	0	1Sf	1	0	0	1Sf	1Sf	0Sf	0
B = Chemosis	1	0	0	0	1	0	0	0	1	0	0	0
C = Discharge	1	0	0	0	1	0	0	0	1	0	0	0
Score (A + B + C) x 2	6	2	0	0	6	2	0	0	6	2	0	0
Total Score	6	2	0	0	6	2	0	0	6	2	0	0

IPR=  Initial pain reaction

Sf =     Pale yellow coloured staining of the fur

Table 2              Individual Total Scores and Group Mean Scores for Ocular Irritation

Rabbit Number and Sex	Individual Total Scores At:
	1 Hour	24 Hours	48 Hours	72 Hours
70933Male	6	2	0	0
70989Male	6	2	0	0
70990Male	6	2	0	0
Group Total	18	6	0	0
Group Mean Score	6.0	2.0	0.0	0.0

Table 3              Individual Bodyweights and Bodyweight Changes

Rabbit Number and Sex	Individual Bodyweight (kg)		Bodyweight Change (kg)
	Day 0	Day 3
70933Male	2.48	2.50	0.02
70989Male	2.67	2.71	0.04
70990Male	2.82	2.87	0.05

Applicant's summary and conclusion

Interpretation of results:

not classified

Remarks:

Migrated information minimal irritant Criteria used for interpretation of results: EU

Conclusions:

The test item produced a maximum group mean score of 6.0 and was classified as a minimal irritant (Class 3 on a 1 to 8 scale) to the rabbit eye according to a modified Kay and Calandra classification system.
The test item does not meet the criteria for classification according to the Classification, Labelling and Packaging Regulation or the Globally Harmonised Classification System.

Executive summary:

Introduction.

The study was performed to assess the irritancy potential of the test item to the eye of the New Zealand White rabbit. The method was designed to be compatible with the following:

- OECD Guidelines for the Testing of Chemicals No. 405 “Acute Eye Irritation/Corrosion” (adopted 24 April 2002)

- Method B5 Acute Toxicity (Eye Irritation) of Commission Regulation (EC) No. 440/2008

- United States Environmental Protection Agency Health Effects Test Guidelines OPPTS 870.2400 Acute Eye Irritation August 1998

- Japanese Ministry of Agriculture, Forestry and Fisheries (JMAFF), Testing Guidelines for Toxicology Studies, 12 NohSan No. 8147, amended 10 December 2002

- Japanese Ministry of Health and Welfare, 1992

Result.

A single application of the test item to the non-irrigated eye of three rabbits produced minimal conjunctival irritation. All treated eyes appeared normal at the 48‑Hour observation.

Conclusion.

The test item produced a maximum group mean score of 6.0 and was classified as a minimal irritant (Class3 on a 1 to 8 scale) to the rabbit eye according to a modified Kay and Calandra classification system.

The test item does not meet the criteria for classification according to the Classification, Labelling and Packaging Regulation or the Globally Harmonised Classification System.