Fatty acids, C18-unsatd., reaction products with diethylenetriamine, acetates

Eye irritation

Administrative data

Endpoint:

eye irritation: in vivo

Type of information:

experimental study

Adequacy of study:

key study

Study period:

Experimental start date: 27 March 2012, Experimental termination date: 17 April 2012

Reliability:

1 (reliable without restriction)

Rationale for reliability incl. deficiencies:

other: see 'Remark'

Remarks:

Study conducted in compliance with agreed protocols, with no or minor deviations from standard test guidelines and/or minor methodological deficiencies, which do not affect the quality of the relevant results. The study report was conclusive, done to a valid guideline and the study was conducted under GLP conditions.

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

GLP compliance:

yes (incl. QA statement)

Test material

Test material information

Constituent 1

Reference substance name:

Fatty acids, C18 unsaturated, reaction products with diethylenetriamine, acetate salts

EC Number:

938-649-5

Cas Number:

1469982-92-0

Molecular formula:

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

IUPAC Name:

Fatty acids, C18 unsaturated, reaction products with diethylenetriamine, acetate salts

Details on test material:

Sponsor's identification: Fatty acids, C18 unsaturated, reaction products with diethylenetriamine, acetate salts
CAS number : 68140-11-4
Description : Translucent amber semi-solid
Batch number : LE012569
Date received : 26 Jan 2012
Storage conditions: room temperature and humidity

Test animals / tissue source

Species:

rabbit

Strain:

New Zealand White

Details on test animals or tissues and environmental conditions:

TEST ANIMALS
- Source: New Zealand White rabbits were received from Covance Research Products, Inc., Denver, PA on 14 Mar 2012
- Age at study initiation: The animals were born on 19 Nov 2011 (approximately 16 weeks old at study initiation).
- Weight at study initiation: The pretest body weight range was 2.5 - 2.7 kg.
- Housing: The animals were housed 1 per cage in suspended cages. Absorbent paper bedding was placed beneath the cages and changed at least three times per week.
- Diet (e.g. ad libitum): Fresh PMI Rabbit Chow was provided daily.
- Water (e.g. ad libitum): Water was available ad libitum.
- Acclimation period:

ENVIRONMENTAL CONDITIONS
- Temperature (°C): The animal room was temperature controlled.
- Photoperiod (hrs dark / hrs light): 12-hour light/dark cycle.

Test system

Vehicle:

unchanged (no vehicle)

Controls:

yes, concurrent no treatment

Amount / concentration applied:

TEST MATERIAL
The test article (0.1 ml) was placed by syringe into the conjunctival sac that was formed by gently pulling the lower eyelid away from the eye. After installation, the lids were held together for approximately one second to insure adequate distribution of the test article. One eye of each rabbit was dosed.

Duration of treatment / exposure:

Single application.

Observation period (in vivo):

21 days

Number of animals or in vitro replicates:

3

Details on study design:

Type and Frquency of Observations:
Using a Mini-Maglite flashlight equipped with a high intensity bulb, the treated eye of each rabbit was examined ofr irritation of the cornea, iris and conjunctiva at 1, 24, 48 and 72 hours and again on Days 7, 14 and 21. The control eyes were observed at the same time periods. Sodium flurescein dye procedures were used 24-hour observation interval up to Day 21. The eye was examined with the aid of an ultra-violet light source.

Ocular reactions were graded according to the numerical Draize technique (see attached background material for Draize scale). Additional signs were described.

Body weights were recorded pretest and at termination.

Observations for toxicity and pharmacological effects were recorded daily. All animals were humanely sacrificed using CO2 following study termination.

Results and discussion

In vivo

Results

Results 1

Irritation parameter:

cornea opacity score

Basis:

mean

Remarks:

(Animal 1 - H5089/F)

Time point:

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

Score:

2

Max. score:

4

Reversibility:

not fully reversible within: 21 days

Remarks on result:

other: Score of 2 at 7, 14 and 21 day observations

Results 2

Irritation parameter:

cornea opacity score

Basis:

mean

Remarks:

(Animal 2 - H5090/F)

Time point:

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

Score:

2

Max. score:

4

Reversibility:

not fully reversible within: 21 days

Remarks on result:

other: Score of 2 at 7 day observation, scores of 3 at 14 and 21 day observation

Results 3

Irritation parameter:

cornea opacity score

Basis:

mean

Remarks:

(Animal 3 - H5091/F)

Time point:

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

Score:

2

Max. score:

4

Reversibility:

not fully reversible within: 21 days

Remarks on result:

other: Score of 2 at 7 day observation, scores of 3 at 14 and 21 day observation

Results 4

Irritation parameter:

iris score

Basis:

mean

Remarks:

(Animal 1 - H5089/F)

Time point:

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

Score:

1

Max. score:

2

Reversibility:

fully reversible within: 7 days

Results 5

Irritation parameter:

iris score

Basis:

mean

Remarks:

(Animal 2 - H5090/F)

Time point:

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

Score:

1

Max. score:

2

Reversibility:

fully reversible within: 21 days

Remarks on result:

other: Scores were unable to be determined because of chemosis at 24 and 48 hour observations. Score of 1 at 72 hour observation.

Results 6

Irritation parameter:

iris score

Basis:

mean

Remarks:

(Animal 3 - H5091/F)

Time point:

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

Score:

1

Max. score:

2

Reversibility:

fully reversible within: 7 days

Results 7

Irritation parameter:

conjunctivae score

Remarks:

(redness)

Basis:

mean

Remarks:

(Animal 1 - H5089/F)

Time point:

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

Score:

2.7

Max. score:

3

Reversibility:

fully reversible within: 21 days

Results 8

Irritation parameter:

conjunctivae score

Remarks:

(redness)

Basis:

mean

Remarks:

(Animal 2 - H5090/F)

Time point:

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

Score:

2.7

Max. score:

3

Reversibility:

not fully reversible within: 21 days

Remarks on result:

other: Scores of 3 at 7 and 14 day observations, score of 2 at 21 day observation

Results 9

Irritation parameter:

conjunctivae score

Remarks:

(redness)

Basis:

mean

Remarks:

(Animal 3 - H5091/F)

Time point:

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

Score:

2.7

Max. score:

3

Reversibility:

not fully reversible within: 21 days

Remarks on result:

other: Scores of 2 at 7, 14 and 21 day observations

Results 10

Irritation parameter:

chemosis score

Basis:

mean

Remarks:

(Animal 1 - H5089/F)

Time point:

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

Score:

3.3

Max. score:

4

Reversibility:

not fully reversible within: 21 days

Remarks on result:

other: Scores of 2 at 7 day observation, scores of 1 at 14 and 21 day observations

Results 11

Irritation parameter:

chemosis score

Basis:

mean

Remarks:

(Animal 2 - H5090/F)

Time point:

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

Score:

4

Max. score:

4

Reversibility:

not fully reversible within: 21 days

Remarks on result:

other: Scores of 3 at 7 and 14 days observations, score of 2 at 21 day observation.

Results 12

Irritation parameter:

chemosis score

Basis:

mean

Remarks:

(Animal 3 - H5091/F)

Time point:

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

Score:

4

Max. score:

4

Reversibility:

not fully reversible within: 21 days

Remarks on result:

other: Scores of 3 at 7, 14 and 21 day observations

Irritant / corrosive response data:

OCULAR FINDINGS:
Corneal opacity and conjunctival irritation, noted in three out of three eyes, persisted to Day 21.
Iritis, noted in three out of three eyes, cleared in two eyes by Day 7 and in one eye by Day 21.

See attached background material for Table 1 - Ocular findings, body weights and systemic observations.

Other effects:

SYSTEMIC OBSERVATIONS AND BODY WEIGHTS:
There were no abnormal physical signs noted during the observation period.
All animals gained weight.

See attached background material for Table 1 - Ocular findings, body weights and systemic observations.

Any other information on results incl. tables

According to OECD and OPPTS the test item is corrosive.

According to Kay & Calandra, the test item is severely irritating.

According to EU CLP classification, the test item should be classified as, Category 1 - Irreversible effects on the eye.

Applicant's summary and conclusion

Interpretation of results:

Category 1 (irreversible effects on the eye)

Remarks:

Migrated information Criteria used for interpretation of results: EU

Conclusions:

According to EU CLP classification, the test item should be classified as, Category 1 - Irreversible effects on the eye.

Executive summary:

Objective:

To determine the irritant or corrosive effects of the test item, Fatty acids, C18 unsaturated, reaction products with diethylenetriamine, acetate salts. The study was designed to comply with the standards set forth in OECD Guidelines For Testing Chemicals, Number 405, adopted April 24, 2002, US EPA OPPTS Series 870.2400, fnal guideline, August 1998, and method B5 Acute Toxicity (Eye Irritation) of Commision Regulation (EC) No. 440/2008.

Method:

Three healthy New Zealand White rabbits (females), free from evidence of ocular irritation and corneal abnormalities, were dosed with Fatty acids, C18 unsaturated, reaction products with diethylenetriamine, acetate salts. The test article (0.1 ml) was placed into the conjunctival sac of one eye of each rabbit. The eyes were examined pretest and scored by the Draize technique at 1, 24, 48 and 72 hours and again on Days 7, 14 and 21. The control eyes were observed at the same time periods. Sodium fluorescein dye procedures were used at the 24 -hour observation interval up to Day 21. Observations for toxicity and pharmacological effects were recorded at each ocular observation period and mortality observations were performed daily. The mean total scores were calculated by adding the total score for each time period and dividing by the number of animals. The degree of irritation was determined according to Kay & Calandra and classified according to the Official Journal of the European Union, on Classification, Labeling and Packaging of substances and mixtures. Body weights were recorded pretest and at termination.

Summary:

Corneal opacity and conjunctival irritation, noted in three out of three eyes, persisted to Day 21. Iritis, noted in three out of three eyes, cleared in two eyes by Day 7 and in one eye by Day 21.

The control eyes appeared normal at all observation periods.

All animals gained weight.

Conclusions:

According to OECD and OPPTS the test item is corrosive.

According to Kay & Calandra, the test item is severely irritating.

According to EU CLP classification, the test item should be classified as, Category 1 - Irreversible effects on the eye.