Phenol, C14-18-alkyl derivs.

Eye irritation

Administrative data

Endpoint:

eye irritation: in vivo

Type of information:

experimental study

Adequacy of study:

key study

Study period:

08 September 2014 to 22 September 2014

Reliability:

1 (reliable without restriction)

Rationale for reliability incl. deficiencies:

other: Study conducted to GLP 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.

Data source

Reference

Reference Type:

study report

Title:

Unnamed

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

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: JMAFF, 12 Nousan, Notification No 8147

Deviations:

no

GLP compliance:

yes

Test material

Test material information

Constituent 1

Reference substance name:

C14-16-18 Alkyl phenol

EC Number:

931-468-2

Cas Number:

1190625-94-5

Molecular formula:

For substance information - see Section 1.2

IUPAC Name:

C14-16-18 Alkyl phenol

Test material form:

other: slightly viscous liquid

Details on test material:

- Appearance: Clear amber liquid
- Storage conditions of test material: At room temperature in the dark

Test animals / tissue source

Species:

rabbit

Strain:

New Zealand White

Details on test animals or tissues and environmental conditions:

TEST ANIMALS
- Strain: Albino rabbit, New Zealand White, (SPF-Quality)
- Age at study initiation: 12 to 24 weeks
- Weight at study initiation: At least 1.5 kg
- Housing: Animals were individually housed in cages with perforated floors (67 x 62 x 55 cm) and shelters (40 x 32 x 23 cm).
- Diet: Pelleted diet for rabbits, approximately 100 grams per day; hay and wooden sticks
- Water: ad libitum access to tap water
- Acclimation period: At least 5 days

ENVIRONMENTAL CONDITIONS
- Temperature: 18 to 24 °C
- Humidity: 40 to 70 % (relative)
- Air changes: At least 10/hour
- Photoperiod: 12-hour light/12-hour dark cycle

Test system

Vehicle:

unchanged (no vehicle)

Controls:

other: The other eye remained untreated and served as the reference control.

Amount / concentration applied:

TEST MATERIAL
- Amount(s) applied: 0.1 mL

Duration of treatment / exposure:

Following installation of the test material, the lids were gently held together for about 1 second to prevent loss of the test material.

Observation period (in vivo):

7 days

Number of animals or in vitro replicates:

3 females

Details on study design:

PRE-EMPTIVE PAIN MANAGEMENT
One hour prior to instillation of the test material, buprenorphine (Buprenodale®, Dechra Ltd., Stoke-on-Trent, United Kingdom) 0.01 mg/kg was administered by subcutaneous injection in order to provide a therapeutic level of systemic analgesia.
Five minutes prior to instillation of the test material, two drops of the topical anaesthetic alcaine 0.5 % (SA Alcon-Couvreur NV, Puurs, Belgium) were applied to both eyes.

SCORING SYSTEM
The eyes of each animal were examined approximately 1, 24, 48 and 72 hours and 7 days after instillation of the test material. The irritation scores and a description of all other (local) effects were recorded.
The irritation was assessed according to the numerical scoring system given in Table 1. At each observation, the highest scores given were recorded.

TOOLS USED TO ASSESS SCORE
Where standard lighting was considered inadequate for observing minor effects, eye examinations were performed using an ophthalmic examination lamp. Immediately after the 24-hour observation, a solution of 2 % fluorescein in water (adjusted to pH 7.0) was instilled into both eyes of each animal to quantitatively determine corneal epithelial damage.
Immediately after fluorescein examination on Day 2, in order to provide a continued level of systemic analgesia, buprenorphine 0.01 mg/kg and meloxicam (Metacam®, Boehringer Vetmed GmbH, Ingelheim/Rhein, Germany) 0.5 mg/kg were administered by subcutaneous injection.

OTHER OBSERVATIONS
- Mortality/Viability: Twice daily
- Toxicity At least once daily
- Body Weight: Day of treatment (prior to instillation) and after the final observation.
- Sacrifice: After the final observation, the animals were sacrificed by intra-venous injection of Euthasol® 20 % (AST Farma BV, Oudewater, The Netherlands). No necropsy was performed.

Results and discussion

In vivo

Results

Results 1

Irritation parameter:

conjunctivae score

Basis:

animal #3

Time point:

7 d

Score:

0

Max. score:

0

Reversibility:

not specified

Results 2

Irritation parameter:

conjunctivae score

Basis:

animal #3

Time point:

72 h

Score:

1

Max. score:

1

Reversibility:

fully reversible within: 7d

Results 3

Irritation parameter:

conjunctivae score

Basis:

animal #3

Time point:

48 h

Score:

1

Max. score:

1

Reversibility:

fully reversible within: 7d

Results 4

Irritation parameter:

conjunctivae score

Basis:

animal #3

Time point:

24 h

Score:

2

Max. score:

2

Reversibility:

fully reversible within: 7d

Results 5

Irritation parameter:

conjunctivae score

Basis:

animal #3

Time point:

other: 1h

Score:

1

Max. score:

1

Reversibility:

fully reversible within: 7d

Results 6

Irritation parameter:

conjunctivae score

Basis:

animal #2

Time point:

7 d

Score:

0

Max. score:

0

Reversibility:

not specified

Results 7

Irritation parameter:

conjunctivae score

Basis:

animal #2

Time point:

72 h

Score:

1

Max. score:

1

Reversibility:

fully reversible within: 7d

Results 8

Irritation parameter:

conjunctivae score

Basis:

animal #2

Time point:

48 h

Score:

1

Max. score:

1

Reversibility:

fully reversible within: 7d

Results 9

Irritation parameter:

conjunctivae score

Basis:

animal #2

Time point:

24 h

Score:

2

Max. score:

2

Reversibility:

fully reversible within: 7d

Results 10

Irritation parameter:

conjunctivae score

Basis:

animal #2

Time point:

other: 1h

Score:

1

Max. score:

1

Reversibility:

fully reversible within: 7d

Results 11

Irritation parameter:

conjunctivae score

Basis:

animal #1

Time point:

7 d

Score:

0

Max. score:

0

Reversibility:

not specified

Results 12

Irritation parameter:

conjunctivae score

Basis:

animal #1

Time point:

72 h

Score:

1

Max. score:

1

Reversibility:

fully reversible

Results 13

Irritation parameter:

conjunctivae score

Basis:

animal #1

Time point:

48 h

Score:

1

Max. score:

1

Reversibility:

fully reversible within: 7 d

Results 14

Irritation parameter:

conjunctivae score

Basis:

animal #1

Time point:

24 h

Score:

2

Max. score:

2

Reversibility:

fully reversible within: 7d

Results 15

Irritation parameter:

conjunctivae score

Basis:

animal #1

Time point:

other: 1h

Score:

1

Max. score:

1

Reversibility:

not specified

Results 16

Irritation parameter:

iris score

Basis:

animal #3

Time point:

7 d

Score:

0

Max. score:

0

Reversibility:

not specified

Results 17

Irritation parameter:

iris score

Basis:

animal #3

Time point:

72 h

Score:

0

Max. score:

0

Reversibility:

not specified

Results 18

Irritation parameter:

iris score

Basis:

animal #3

Time point:

48 h

Score:

0

Max. score:

0

Reversibility:

not specified

Results 19

Irritation parameter:

iris score

Basis:

animal #3

Time point:

24 h

Score:

0

Max. score:

0

Reversibility:

not specified

Results 20

Irritation parameter:

iris score

Basis:

animal #3

Time point:

other: 1h

Score:

0

Max. score:

0

Reversibility:

not specified

Results 21

Irritation parameter:

iris score

Basis:

animal #2

Time point:

7 d

Score:

0

Max. score:

0

Reversibility:

not specified

Results 22

Irritation parameter:

iris score

Basis:

animal #2

Time point:

72 h

Score:

0

Max. score:

0

Reversibility:

not specified

Results 23

Irritation parameter:

iris score

Basis:

animal #2

Time point:

48 h

Score:

0

Max. score:

0

Reversibility:

not specified

Results 24

Irritation parameter:

iris score

Basis:

animal #2

Time point:

24 h

Score:

0

Max. score:

0

Reversibility:

not specified

Results 25

Irritation parameter:

iris score

Basis:

animal #2

Time point:

other: 1h

Score:

0

Max. score:

0

Reversibility:

not specified

Results 26

Irritation parameter:

iris score

Basis:

animal #1

Time point:

7 d

Score:

0

Max. score:

0

Reversibility:

not specified

Results 27

Irritation parameter:

iris score

Basis:

animal #1

Time point:

72 h

Score:

0

Max. score:

0

Reversibility:

not specified

Results 28

Irritation parameter:

iris score

Basis:

animal #1

Time point:

48 h

Score:

0

Max. score:

0

Reversibility:

not specified

Results 29

Irritation parameter:

iris score

Basis:

animal #1

Time point:

24 h

Score:

0

Max. score:

0

Reversibility:

not specified

Results 30

Irritation parameter:

iris score

Basis:

animal #1

Time point:

other: 1h

Score:

0

Max. score:

0

Reversibility:

not specified

Results 31

Irritation parameter:

cornea opacity score

Basis:

animal #3

Time point:

7 d

Score:

0

Max. score:

0

Reversibility:

not specified

Results 32

Irritation parameter:

cornea opacity score

Basis:

animal #3

Time point:

72 h

Score:

0

Max. score:

0

Reversibility:

not specified

Results 33

Irritation parameter:

cornea opacity score

Basis:

animal #3

Time point:

48 h

Score:

0

Max. score:

0

Reversibility:

not specified

Results 34

Irritation parameter:

cornea opacity score

Basis:

animal #3

Time point:

24 h

Score:

0

Max. score:

0

Reversibility:

not specified

Results 35

Irritation parameter:

cornea opacity score

Basis:

animal #3

Time point:

other: 1h

Score:

0

Max. score:

0

Reversibility:

not specified

Results 36

Irritation parameter:

cornea opacity score

Basis:

animal #2

Time point:

7 d

Score:

0

Max. score:

0

Reversibility:

not specified

Results 37

Irritation parameter:

cornea opacity score

Basis:

animal #2

Time point:

72 h

Score:

0

Max. score:

0

Reversibility:

not specified

Results 38

Irritation parameter:

cornea opacity score

Basis:

animal #2

Time point:

48 h

Score:

0

Max. score:

0

Reversibility:

not specified

Results 39

Irritation parameter:

cornea opacity score

Basis:

animal #2

Time point:

24 h

Score:

0

Max. score:

0

Reversibility:

not specified

Results 40

Irritation parameter:

cornea opacity score

Basis:

animal #2

Time point:

other: 1h

Score:

0

Max. score:

0

Reversibility:

not specified

Results 41

Irritation parameter:

cornea opacity score

Basis:

animal #1

Time point:

7 d

Score:

0

Max. score:

0

Reversibility:

not specified

Results 42

Irritation parameter:

cornea opacity score

Basis:

animal #1

Time point:

72 h

Score:

0

Max. score:

0

Reversibility:

not specified

Results 43

Irritation parameter:

cornea opacity score

Basis:

animal #1

Time point:

48 h

Score:

0

Max. score:

0

Reversibility:

not specified

Results 44

Irritation parameter:

cornea opacity score

Basis:

animal #1

Time point:

24 h

Score:

0

Max. score:

0

Reversibility:

not specified

Results 45

Irritation parameter:

cornea opacity score

Basis:

animal #1

Time point:

other: 1h

Score:

0

Max. score:

0

Reversibility:

not specified

Results 46

Irritation parameter:

chemosis score

Basis:

animal #3

Time point:

7 d

Score:

0

Max. score:

0

Reversibility:

not specified

Results 47

Irritation parameter:

chemosis score

Basis:

animal #3

Time point:

72 h

Score:

0

Max. score:

0

Reversibility:

not specified

Results 48

Irritation parameter:

chemosis score

Basis:

animal #3

Time point:

48 h

Score:

0

Max. score:

0

Reversibility:

not specified

Results 49

Irritation parameter:

chemosis score

Basis:

animal #3

Time point:

24 h

Score:

1

Max. score:

1

Reversibility:

fully reversible within: 48h

Results 50

Irritation parameter:

chemosis score

Basis:

animal #3

Time point:

other: 1hr

Score:

1

Max. score:

1

Reversibility:

fully reversible within: 48h

Results 51

Irritation parameter:

chemosis score

Basis:

animal #2

Time point:

7 d

Score:

0

Max. score:

0

Reversibility:

not specified

Results 52

Irritation parameter:

chemosis score

Basis:

animal #2

Time point:

72 h

Score:

0

Max. score:

0

Reversibility:

not specified

Results 53

Irritation parameter:

chemosis score

Basis:

animal #2

Time point:

48 h

Score:

0

Max. score:

0

Reversibility:

not specified

Results 54

Irritation parameter:

chemosis score

Basis:

animal #2

Time point:

24 h

Score:

1

Max. score:

1

Reversibility:

fully reversible within: 48h

Results 55

Irritation parameter:

chemosis score

Basis:

animal #2

Time point:

other: 1hr

Score:

1

Max. score:

1

Reversibility:

fully reversible within: 48h

Results 56

Irritation parameter:

chemosis score

Basis:

animal #1

Time point:

other: 1hr

Score:

1

Max. score:

1

Reversibility:

fully reversible within: 7 days

Results 57

Irritation parameter:

chemosis score

Basis:

animal #1

Time point:

24 h

Score:

0

Max. score:

0

Reversibility:

fully reversible within: 48 hours

Results 58

Irritation parameter:

chemosis score

Basis:

animal #1

Time point:

48 h

Score:

0

Max. score:

0

Reversibility:

fully reversible within: 48 hours

Results 59

Irritation parameter:

chemosis score

Basis:

animal #1

Time point:

72 h

Score:

0

Reversibility:

fully reversible

Results 60

Irritation parameter:

chemosis score

Basis:

animal #1

Time point:

7 d

Score:

0

Max. score:

0

Reversibility:

fully reversible

Irritant / corrosive response data:

Instillation of the test material resulted in irritation of the conjunctivae, which consisted of redness, chemosis and discharge. The irritation had completely resolved within 7 days in all animals.
No iridial irritation or corneal opacity were observed, and treatment of the eyes with 2 % fluorescein 24 hours after test substance instillation revealed no corneal epithelial damage.
There was no evidence of ocular corrosion.

Other effects:

No staining of (peri) ocular tissues by the test material was observed. Remnants of the test material were present on the outside of the eyelids of all animals on Days 1, 2 and/or 3.
No symptoms of systemic toxicity were observed in the animals during the test period and no mortality occurred.

Any other information on results incl. tables

Table 1: Individual Eye Irritation Scores

Animal	Time After Dosing	Corneal Opacity	Iris	Conjunctivae
				Redness	Chemosis	Discharge
785	1 hour	0	0	1	1	0
	24 hours	0	0	2	0	1
	8 hours	0	0	1	0	0
	72 hours	0	0	1	0	0
	7 days	0	0	0	0	0
786	1 hour	0	0	1	1	1
	24 hours	0	0	2	1	1
	8 hours	0	0	1	0	0
	72 hours	0	0	1	0	0
	7 days	0	0	0	0	0
787	1 hour	0	0	1	1	1
	24 hours	0	0	2	1	1
	8 hours	0	0	1	0	0
	72 hours	0	0	1	0	0
	7 days	0	0	0	0	0

Applicant's summary and conclusion

Interpretation of results:

not irritating

Remarks:

Migrated information Criteria used for interpretation of results: EU

Conclusions:

Under the conditions of this study, the test material was found to be non-irritating to the eye.

Executive summary:

The potential of the test material to cause acute eye irritation or corrosion was investigated in a study conducted in accordance with the standardised guidelines OECD 405, EU Method B.5, EPA OPPTS 870.2400 and JMAFF, 12 Nousan, Notification No 8147 under GLP conditions.

Single samples of 0.1 mL of the test material were instilled into one eye of each of three New Zealand White rabbits. The other eye remained untreated and served as the reference control. Observations were made 1, 24, 48 and 72 hours and 7 days after instillation.

Instillation of the test material resulted in irritation of the conjunctivae, which consisted of redness, chemosis and discharge. The irritation had completely resolved within 7 days in all animals. No iridial irritation or corneal opacity were observed, and treatment of the eyes with 2 % fluorescein 24 hours after test material instillation revealed no corneal epithelial damage.

Remnants of the test material were present on the outside of the eyelids of all animals on Days 1, 2 and/or 3.

Under the conditions of this study, the test material was found to be non-irritating to the eye.