1,6,10-Dodecatriene, 7,11-dimethyl-3-methylene-, (6E)-, hydrogenated

Eye irritation

Administrative data

Endpoint:

eye irritation: in vivo

Type of information:

experimental study

Adequacy of study:

key study

Study period:

14 July 2014 to 24 July 2014

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:

2014

Report date:

2014

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:

1.25H Farnesene

IUPAC Name:

1.25H Farnesene

Test material form:

other: liquid

Details on test material:

A Certificate of Analysis supplied by the Sponsor is given in Appendix 4 (attachment 1)

Identification: 1.25H Farnesene
Batch: RV-752-153-2
Purity: 98.92%
Physical state / Appearance: clear, colorless liquid
Expiry date: 01 March 2015
Storage Conditions: room temperature in the dark

Test animals / tissue source

Species:

rabbit

Strain:

New Zealand White

Details on test animals or tissues and environmental conditions:

Three 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 2.20 to 2.64 kg and were twelve to twenty weeks old. After an acclimatization period of at least five 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 Rabbit diet supplied by Harlan Laboratories UK 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.

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 twelve hours continuous light (06:00 to 18:00) and twelve 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:

other: The left eye remained untreated and was used for control purposes.

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:

Up to 1 hour

Observation period (in vivo):

Approximately 1 hour and 24, 48 and 72 hours following treatment

Number of animals or in vitro replicates:

3

Details on study design:

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% tetracaine hydrochloride) was applied to each eye.

Up to 1 hour 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.

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, two additional animals were 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) given in Appendix 2.

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.

Individual body weights 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:

animal: 74501 Female

Time point:

other: Highest score at 1, 24, 48 and 72 hours

Score:

0

Max. score:

4

Reversibility:

other: No effects observed

Results 2

Irritation parameter:

cornea opacity score

Basis:

animal: 74539 Male

Time point:

other: Highest score at 1, 24, 48 and 72 hours

Score:

0

Max. score:

4

Reversibility:

not specified

Remarks:

No effects observed

Results 3

Irritation parameter:

cornea opacity score

Basis:

animal: 74540 Male

Time point:

other: Highest score at 1, 24, 48 and 72 hours

Score:

0

Max. score:

4

Reversibility:

other: No effects observed

Results 4

Irritation parameter:

iris score

Basis:

animal: 74501 Female

Time point:

other: Highest score at 1, 24, 48 and 72 hours

Score:

0

Max. score:

2

Reversibility:

other: No effects observed

Results 5

Irritation parameter:

iris score

Basis:

animal: 74539 Male

Time point:

other: Highest score at 1, 24, 48 and 72 hours

Score:

0

Max. score:

2

Reversibility:

other: No effects observed

Results 6

Irritation parameter:

iris score

Basis:

animal: 74540 Male

Time point:

other: Highest score at 1, 24, 48 and 72 hours

Score:

0

Max. score:

2

Reversibility:

other: No effects observed

Results 7

Irritation parameter:

other: redness

Basis:

animal: 74501 Female

Time point:

other: Highest score at 1, 24, 48 and 72 hours

Score:

1

Max. score:

3

Reversibility:

fully reversible within: 48 hours

Results 8

Irritation parameter:

other: redness

Basis:

animal: 74539 Male

Time point:

other: Highest score at 1, 24, 48 and 72 hours

Score:

2

Max. score:

3

Reversibility:

fully reversible within: 48 hours

Results 9

Irritation parameter:

other: redness

Basis:

animal: 74540 Male

Time point:

other: Highest score at 1, 24, 48 and 72 hours

Score:

2

Max. score:

3

Reversibility:

fully reversible within: 48 hours

Results 10

Irritation parameter:

chemosis score

Basis:

animal: 74501 Male

Time point:

other: Highest score at 1, 24, 48 and 72 hours

Score:

1

Max. score:

4

Reversibility:

fully reversible within: 24 hours

Results 11

Irritation parameter:

chemosis score

Basis:

animal: 74539 Male

Time point:

other: Highest score at 1, 24, 48 and 72 hours

Score:

1

Max. score:

4

Reversibility:

fully reversible within: 48 hours

Results 12

Irritation parameter:

chemosis score

Basis:

animal: 74540 Male

Time point:

other: Highest score at 1, 24, 48 and 72 hours

Score:

1

Max. score:

4

Reversibility:

fully reversible within: 48 hours

Irritant / corrosive response data:

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

No corneal or iridial effects were noted during the study.

Moderate conjunctival irritation was noted in one treated eye and minimal conjunctival irritation was noted in two treated eyes 1 hour after treatment with minimal conjunctival irritation noted in all treated eyes at the 24-Hour observation.

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

Other effects:

Body Weight
Individual body weights and body weight change are given in Table 3.

One animal showed body weight loss and two animals showed expected gain in body weight 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	74501 Female				74539 Male				74540 Male
	IPR= 0				IPR = 0				IPR = 0
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	1	1	0	0	2	1	0	0	2	1	0	0
B = Chemosis	1	0	0	0	1	1	0	0	1	1	0	0
C = Discharge	1	0	0	0	0	0	0	0	1	0	0	0
Score (A + B + C) x 2	6	2	0	0	6	4	0	0	8	4	0	0
Total Score	6	2	0	0	6	4	0	0	8	4	0	0

IPR=Initial pain reaction

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
74501 Female	6	2	0	0
74539 Male	6	4	0	0
74540 Male	8	4	0	0
Group Total	20	10	0	0
Group Mean Score	6.7	3.3	0.0	0.0

Table 3     Individual Body Weights and Body Weight Change

Rabbit Number and Sex	Individual Body Weight (kg)		Body Weight Change (kg)
	Day 0	Day 3
74501 Female	2.64	2.65	0.01
74539 Male	2.20	2.22	0.02
74540 Male	2.44	2.42	-0.02

Applicant's summary and conclusion

Interpretation of results:

Category III

Remarks:

Migrated information Criteria used for interpretation of results: OECD GHS

Conclusions:

The test item produced a maximum group mean score of 6.7 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 Globally Harmonized System of Classification and Labelling of Chemicals

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 three rabbits produced minimal to moderate conjunctival irritation. All treated eyes appeared normal at the 48‑Hour observation.

  

Conclusion

The test item produced a maximum group mean score of 6.7 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 Globally Harmonized Systemof Classification and Labelling of Chemicals