Soybean oil, maleated, ester with triethanolamine

Eye irritation

Administrative data

Endpoint:

eye irritation: in vivo

Remarks:

Acute Eye Irritation in the Rabbit

Type of information:

experimental study

Adequacy of study:

key study

Study period:

Experimental start date 15 November 2016 Experimental completion date 06 December 2016

Reliability:

1 (reliable without restriction)

Rationale for reliability incl. deficiencies:

guideline study

Data source

Reference

Reference Type:

study report

Title:

Unnamed

Year:

2017

Report date:

2017

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 (incl. QA statement)

Test material

Test material information

Constituent 1

Reference substance name:

Soybean oil, maleated, ester with triethanolamine

EC Number:

285-107-2

EC Name:

Soybean oil, maleated, ester with triethanolamine

Cas Number:

85029-82-9

Molecular formula:

C63H113NO12 to C67H123NO12

IUPAC Name:

Soybean oil, maleated, ester with triethanolamine

Test material form:

other: Clear amber viscous liquid

Details on test material:

100% product
Physical state/Appearance: Clear amber viscous liquid
Expiry Date: 24 June 2018
Storage Conditions: Room temperature in the dark

Specific details on test material used for the study:

Identification: Test item
Physical state/Appearance: Clear amber viscous liquid
Purity: 100% wt - (UVCB)
Expiry Date: 24 June 2018
Storage Conditions: Room temperature, in the dark

Test animals / tissue source

Species:

rabbit

Strain:

New Zealand White

Remarks:

Two New Zealand White (Hsdlf:NZW)

Details on test animals or tissues and environmental conditions:

The study was designed and conducted to cause the minimum suffering or distress to the animals consistent with the scientific objectives and in accordance with the Envigo - Shardlow policy on animal welfare and the requirements of the United Kingdom's Animals (Scientific Procedures) Act 1986 Amendment Regulations 2012. The conduct of the study may be reviewed, as part of the Envigo - Shardlow Ethical Review Process.

The study was conducted in accordance with the UK Home Office Guidance document on Regulatory Toxicology and Safety Evaluation Studies and the OECD guidance document on recognition, assessment and use of clinical signs as humane endpoints for experimental animals used in safety evaluation.

Animal Information
Two New Zealand White (Hsdlf:NZW) strain rabbits were supplied by Envigo RMS (UK) Limited, Leicestershire, UK. At the start of the study the animals weighed 3.55 or 4.26 kg and were 12 to 52 weeks old. After an acclimatization 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.
Animal Care and Husbandry
The animals were individually housed in suspended cages. Free access to mains drinking water and food (2930C Teklad Global Rabbit diet supplied by Envigo RMS (UK) Limited, 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.
The temperature and relative humidity were set to achieve limits of 17 to 23 °C and 30 to 70% respectively. The rate of air exchange was at least fifteen changes per hour and the lighting was controlled by a time switch to give 12 hours continuous light 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)

Remarks:

For the purpose of the study the test item was used as supplied.

Controls:

yes, concurrent no treatment

Amount / concentration applied:

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 subcutaneous injection of buprenorphine 0.01 mg/kg was administered 60 minutes prior to test item application to provide a therapeutic level of systemic analgesia. Five minutes prior to test item application, a pre-dose anesthesia of ocular anesthetic (two drops of 0.5% proxymetacaine hydrochloride) was applied to each eye.
A volume of 0.1 mL of the test item was placed into the conjunctiva! 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 Annex 2.

Eight hours after test item application, a subcutaneous injection of post-dose analgesia, buprenorphine 0.01 mg/kg and meloxicam 0.5 mg/kg, was administered to provide a continued therapeutic level of systemic analgesia. The treated animal was checked for signs of pain and suffering approximately 12 hours later. No further analgesia was required.

After consideration of the ocular responses produced in the first treated animal, a second animal was similarly treated.

Assessment of ocular damage/irritation was made approximately 1 hour and 24, 48 and 72 hours following treatment, according to the numerical evaluation (Draize, J.H, 1977)
Any other ocular effects were also noted. Examination of the eye was facilitated by the use of the light source from a standard ophthalmoscope.
Any clinical signs of toxicity, if present, were also recorded.
An additional observation was made on Day 7 to assess the reversibility of the ocular effects.
Individual body weights were recorded on Day O (the day of dosing) and at the end of the observation period.

Duration of treatment / exposure:

A volume of 0.1 mL of the test item was placed into the conjunctiva! 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.

Observation period (in vivo):

Assessment of ocular damage/irritation was made approximately 1 hour and 24, 48 and 72 hours following treatment, according to the numerical evaluation (Draize, J.H, 1977)

Number of animals or in vitro replicates:

2

Details on study design:

The pH of the test item was determined prior to commencement of the study and found to be as follows:


Preparation pH Measurement*
immediately after 10 minutes
Undiluted as Supplied 6 not applicable
90% v/v aqueous preparation of the test item 7 7
* = pH paper used

Results and discussion

In vivo

Results

Results 1

Irritation parameter:

cornea opacity score

Basis:

mean

Time point:

24/48/72 h

Score:

0

Max. score:

0

Reversibility:

fully reversible

Remarks on result:

no indication of irritation

Results 2

Irritation parameter:

iris score

Basis:

mean

Time point:

24/48/72 h

Score:

0

Max. score:

0

Reversibility:

fully reversible

Remarks on result:

no indication of irritation

Results 3

Irritation parameter:

conjunctivae score

Basis:

mean

Time point:

24/48/72 h

Score:

1.3

Max. score:

2

Reversibility:

fully reversible

Remarks on result:

probability of mild irritation

Results 4

Irritation parameter:

chemosis score

Basis:

mean

Time point:

24/48/72 h

Score:

1

Max. score:

1

Reversibility:

fully reversible

Remarks on result:

probability of mild irritation

Irritant / corrosive response data:

Individual and group mean scores for ocular irritation are given in Appendix 1 The mean scores for corneal opacity, iridial inflammation and conjunctiva! redness and chemosis are given in Appendix 2.

No corneal or iridial effects were noted during the study.

Moderate conjunctiva! irritation was noted in both treated eyes 1 hour after treatment. Moderate conjunctiva! irritation was noted in one treated eye with minimal conjunctiva! irritation noted in the other treated eye at the 24-Hour observation. Minimal conjunctiva! irritation was noted in both treated eyes at the 48 and 72-Hour observations.

Both treated eyes appeared normal at the 7-Day observation.

Other effects:

Individual body weights and body weight change are given in Appendix 3. Both animals showed expected gain in body weight during the study.

Applicant's summary and conclusion

Interpretation of results:

other: Not clasified under CLP

Remarks:

 The test item produced a maximum group mean score of 12.0 out of a possible maximum of 110 and was considered to be a mild irritant (Class 4 on a 1 to 8 scale) to the rabbit eye according to a modified Kay and Calandra system.

Conclusions:

The test item produced individual mean scores of 0.0 for corneal opacity, 0.0 for iritis, 1.3 for conjunctiva / redness and 1.0 for conjunctiva / chemosis.

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.

Results

A single application of the test item to the non-irrigated eye of two rabbits produced moderate conjunctiva! irritation. Both treated eyes appeared normal at the 7-Day observation.

Conclusion

The test item produced individual mean scores of 0.0 for corneal opacity, 0.0 for iritis, 1.3 for conjunctiva / redness and 1.0 for conjunctiva / chemosis.