Partially hydrogenated β-3,7,11-trimethyldodeca-1,3,6,10-tetraene, reaction products with linear C8-C16 alpha olefin, hydrogenated.

Eye irritation

Administrative data

Endpoint:

eye irritation: in vivo

Type of information:

experimental study

Adequacy of study:

key study

Study period:

11 to 28 November 2013

Reliability:

1 (reliable without restriction)

Rationale for reliability incl. deficiencies:

other: GLP study conducted in accordance with current OECD guidelines.

Data source

Reference

Reference Type:

study report

Title:

Unnamed

Report date:

2014

Materials and methods

Test guideline

Qualifier:

according to guideline

Guideline:

OECD Guideline 405 (Acute Eye Irritation / Corrosion)

Deviations:

no

GLP compliance:

yes (incl. QA statement)

Test material

Test material information

Constituent 1

Reference substance name:

Partially hydrogenated β-3,7,11-trimethyldodeca-1,3,6,10-tetraene, reaction products with linear C8-C16 alpha olefin, hydrogenated.

EC Number:

939-894-0

Molecular formula:

Variable - substance is a UVCB

IUPAC Name:

Partially hydrogenated β-3,7,11-trimethyldodeca-1,3,6,10-tetraene, reaction products with linear C8-C16 alpha olefin, hydrogenated.

Test material form:

liquid: viscous

Details on test material:

Identification: NovaSpec 450Batch: TS8837Purity: 100% (UVCB)Expiry Date: Not suppliedStorage 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 2.35 to 2.73 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. Any occasional deviations from these targets were considered not to have affected the purpose or integrity of the study. 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:

no

Amount / concentration applied:

0.1 mL of the test item

Duration of treatment / exposure:

7 days

Observation period (in vivo):

7 days

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 approximately 60 minutes prior to test item application to provide a therapeutic level of systemic analgesia. Approximately 5 minutes prior to test item application, a pre-dose anaesthesia of ocular anesthetic (two drops of 0.5% tetracaine hydrochloride) was applied to each eye.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.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).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 in one treated eye on Day 7 to assess the reversibility of the ocular effects.Individual body weights were recorded on Day 0 (the day of dosing) and at the end of the observation period.Interpretation of ResultsThe numerical values corresponding to each animal, tissue and observation time were recorded. The data relating to the conjunctivae were designated by the letters A (redness), B (chemosis) and C (discharge), those relating to the iris designated by the letter D and those relating to the cornea by the letters E (degree of opacity) and F (area of cornea involved). For each tissue the score was calculated as follows:Score for conjunctivae = (A + B + C) x 2Score for iris = D x 5Score for cornea = (E x F) x 5Using the numerical data obtained a modified version of the system described by Kay J.H. and Calandra J.C. (1962) was used to classify the ocular irritancy potential of the test item. This was achieved by adding together the scores for the cornea, iris and conjunctivae for each time point for each rabbit. The group means of the total scores for each observation were calculated. The highest of these group means (the maximum group mean score) together with the persistence of the reactions enabled classification of the eye irritancy potential of the test item.

Results and discussion

In vivo

Results

Results 1

Irritation parameter:

cornea opacity score

Basis:

mean

Time point:

other: 72 hours

Score:

0

Max. score:

0

Reversibility:

fully reversible

Results 2

Irritation parameter:

iris score

Basis:

mean

Time point:

other: 72 hours

Score:

0

Max. score:

0

Reversibility:

fully reversible

Results 3

Irritation parameter:

conjunctivae score

Basis:

animal #1

Time point:

other: 72 hours

Score:

1

Max. score:

3

Reversibility:

fully reversible within: 7 days

Results 4

Irritation parameter:

chemosis score

Basis:

animal #1

Time point:

other: 72 hours

Score:

1

Max. score:

4

Reversibility:

fully reversible within: 7 days

Results 5

Irritation parameter:

conjunctivae score

Basis:

animal #2

Time point:

other: 48 hours

Score:

1

Max. score:

3

Reversibility:

fully reversible within: 72 hours

Results 6

Irritation parameter:

chemosis score

Basis:

animal #2

Time point:

other: 24 hours

Score:

1

Max. score:

4

Reversibility:

fully reversible within: 48 hours

Results 7

Irritation parameter:

conjunctivae score

Basis:

animal #3

Time point:

other: 48 hours

Score:

1

Max. score:

3

Reversibility:

fully reversible within: 72 hours

Results 8

Irritation parameter:

chemosis score

Basis:

animal #3

Time point:

other: 24 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 below.No corneal effects were noted during the study.Iridial inflammation was noted in one treated eye one hour after treatment. No effects were noted at 24 hours.Minimal conjunctival irritation was noted in all treated eyes one hour after treatment and at the 24 and 48-Hour observations and in one treated eye at the 72-Hour observation.Two treated eyes appeared normal at the 72-Hour observation and one treated eye appeared normal at the 7-Day observation.

Other effects:

Body Weight
Individual body weights and body weight change are given in Table 3 below.One animal showed expected gain in body weight during the study. No gain in body weight was noted in one animal and one animal showed body weight loss during the study.

Any other information on results incl. tables

Table1  Individual Scores and Individual Total Scores for Ocular Irritation

Rabbit Number and Sex	73717Male					73758Male				73759Male
	IPR= 0					IPR = 0				IPR = 0
Time After Treatment	1 Hour	24 Hours	48 Hours	72 Hours	7 Days	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	0
F = Area of Cornea Involved	0	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	0
IRIS
D	1	0	0	0	0	0	0	0	0	0	0	0	0
Score (D x 5)	5	0	0	0	0	0	0	0	0	0	0	0	0
CONJUNCTIVAE
A = Redness	1	1	1	1	0	1	1	1	0	1	1	1	0
B = Chemosis	1	1	1	1	0	1	1	0	0	1	1	1	0
C = Discharge	1	0	0	0	0	1	1	0	0	1	1	0	0
Score (A + B + C) x 2	6	4	4	4	0	6	6	2	0	6	6	4	0
Total Score	11	4	4	4	0	6	6	2	0	6	6	4	0

 

Table2  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		7 Days
73717Male		11		4		4		4		0
73758Male		6		6		2		0		-
73759Male		6		6		4		0		-
Group Total		23		16		10		0		0
Group Mean Score		7.7		5.3		3.3		1.3		0.0

 

Table3  Individual Body Weights and Body Weight Change

Rabbit Number and Sex	Individual Body Weight (kg)		Body Weight Change (kg)
73717 Male	Day 0	Day 7	0.14
	2.73	2.87
73758 Male	Day 0	Day 3	0.00
	2.36	2.36
73759 Male	Day 0	Day 3	-0.01
	2.35	2.34

IPR=Initial pain reaction

- =         Observation not required - considered to be zero for calculation of Group Mean Score

Applicant's summary and conclusion

Interpretation of results:

not classified

Remarks:

Migrated information Criteria used for interpretation of results: EU

Conclusions:

The test item produced a maximum group mean score of 7.7 and was classified as a mild irritant (Class 4 on a 1 to 8 scale) to the rabbit eye according to a modified Kay and Calandra classification system.

Executive summary:

An assessment in vitro was not conducted. This is because OECD Guideline 438 is not a full test for eye irritation, and only provides information on whether a substance is a severe eye irritant. A negative finding would need to be followed by an in vivo study. Equivalent information on irritancy information can be obtained from the in-vitro skin corrosivity study. As this study was negative , severe eye irritation was not anticipated as the substance was not corrosive. It was considered appropriate to proceed directly to an in vivo test on these grounds.

The test item produced a maximum group mean score of 7.7 and was classified as a mild irritant (Class 4 on a 1 to 8 scale) to the rabbit eye according to a modified Kay and Calandra classification system.

No classification is applicable.