Di-sec-butylphenol, mixed isomers

Eye irritation

Administrative data

Endpoint:

eye irritation: in vivo

Type of information:

experimental study

Adequacy of study:

key study

Study period:

23/07/1992-30/07/1992

Reliability:

1 (reliable without restriction)

Rationale for reliability incl. deficiencies:

other: Guideline study (OECD 405)

Data source

Reference

Reference Type:

study report

Title:

Unnamed

Year:

1992

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:

Di-sec-butylphenol, mixed isomers

EC Number:

226-854-6

EC Name:

Di-sec-butylphenol, mixed isomers

Cas Number:

5510-99-6

Molecular formula:

C14H22O

IUPAC Name:

2,6-bis(butan-2-yl)phenol

Details on test material:

Name of test material (as cited in study report): Phenol 2,6-bis(1-methylpropyl)
- Substance type: Di-alkylphenol
- Physical state: dark straw-coloured liquid
- Analytical purity: 98.7% GC
- Purity test date: 04/02/1992
- Lot/batch No.: 20204010
- Expiration date of the lot/batch:
- Storage condition of test material: room temperature

Test animals / tissue source

Species:

rabbit

Strain:

New Zealand White

Details on test animals or tissues and environmental conditions:

EST ANIMALS
- Source: David Percival ltd., Moston, Sandbach, Cheshire, UK
- Age at study initiation: twekve to sixteen weeks old
- Weight at study initiation: 2.74-3.30 kg
- Housing: individually housed in suspended metal cages.
- Diet (e.g. ad libitum): ad libitum (Spillers Rabbit Dite, Dalgety Agriculture Ltd., Almondsbury, Bristol, UK
- Water (e.g. ad libitum): ad libitum (drinking water)
- Acclimation period: a minimum acclimatisation period of 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.

ENVIRONMENTAL CONDITIONS
- Temperature (°C): 19-24°C. On occassions the temperature was above the limit specified in the protocol (23°C). This was considered not to have affected the purpose or integrity of the study.
- Humidity (%): 55-67%
- Air changes (per hr): 15 changes per hour
- Photoperiod (hrs dark / hrs light): 12 hrs dark/12 hrs light

Test system

Vehicle:

unchanged (no vehicle)

Controls:

other: left eye remained untreated for control purposes

Amount / concentration applied:

TEST MATERIAL
- Amount(s) applied (volume or weight with unit): 0.1 ml

Duration of treatment / exposure:

1 second

Observation period (in vivo):

1, 24, 48, 72 hours

Number of animals or in vitro replicates:

3

Details on study design:

The test material was instilled 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 application, to prevent loss of the test material, and then released. The left eye remain untreated and was used for control purposes. Immediately after administration of the test material, an assessment of the initial pain reaction was made.

SCORING SYSTEM: Assessment of ocular damage/irritation was made according to the numerical evaluation given by Draize J. H. 1959, Association of Food and Drug Officials of the United states, Austin, Texas, "The Appraisal of the Safety of Chemicals in Foods, Drugs and Cosmetics"

Any other adverse ocular effects were also noted.

TOOL USED TO ASSESS SCORE: Examination of the eye was falicitated by use of the light source from a standard ophthalmoscope

Results and discussion

In vivo

Results

Results 1

Irritation parameter:

cornea opacity score

Basis:

animal: #1, #2, #3

Time point:

other: 1, 24, 48, 72 hours

Score:

0

Max. score:

4

Results 2

Irritation parameter:

iris score

Basis:

animal #1

Time point:

other: 1, 24, 48, 72 hours

Score:

0 - 5

Max. score:

10

Reversibility:

fully reversible within: 48 hours

Remarks on result:

other: (D x 5)

Results 3

Irritation parameter:

iris score

Basis:

animal #2

Time point:

other: 1, 24, 48, 72 hours

Score:

0

Max. score:

10

Remarks on result:

other: (D x 5)

Results 4

Irritation parameter:

iris score

Basis:

animal #3

Time point:

other: 1, 24, 48, 72 hours

Score:

0 - 5

Max. score:

10

Reversibility:

fully reversible within: 24 hours

Remarks on result:

other: (D x 5)

Results 5

Irritation parameter:

conjunctivae score

Basis:

animal #1

Time point:

other: 1, 24, 48, 72 hours

Score:

0 - 12

Max. score:

20

Reversibility:

fully reversible within: 72 hours

Remarks on result:

other: (A + B + C) x 2

Results 6

Irritation parameter:

conjunctivae score

Basis:

animal #2

Time point:

other: 1, 24, 48, 72 hours

Score:

0 - 6

Max. score:

20

Reversibility:

fully reversible within: 24 hours

Remarks on result:

other: (A + B + C) x 2

Results 7

Irritation parameter:

conjunctivae score

Basis:

animal #3

Time point:

other: 1, 24, 48, 72 hours

Score:

0 - 8

Max. score:

20

Reversibility:

fully reversible within: 48 hours

Remarks on result:

other: (A + B + C) x 2

Irritant / corrosive response data:

No adverse corneal effects were oberved during the study.
Iridial inflammation was noted in two treated eyes one hour after treatment and in one treated eye at the 24-hour observation. No other adverse iridial effects were noted.
Minimal to moderate conjunctival irritation was noted an all treated eyes one hour after treatment and in two treated eyes at the 24-hour observation. Minimal conjunctival irritation was noted in one treated eye at the 48-hour observation. Hemorrhage of the nictitating membrane was also noted in one treated eye one and 24 hours after treatment.
Treated eyes appeared normal 24, 48 or 72 hours after treatment.

Any other information on results incl. tables

Individual scores and individual total scores for ocular irritation

Rabbit number and sex               (bodyweight Kg)	IPR = 3   68 Female (3.06)				IPR = 0 + 25 Female (2.74)				IPR = 0 + 73 Male (3.30)
Time after treatment	1 hr	24 hr	48 hr	72 hr	1 hr	24 hr	48 hr	72 hr	1 hr	24 hr	48 hr	72 hr
CORNEA
E = degree of opacity	0	0	0	0	0	0	0	0	0	0	0	0
F = area of opacity	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	1	1	0	0	0	0	0	0	1	0	0	0
Score (D x 5)	5	5	0	0	0	0	0	0	5	0	0	0
CONJUNCTIVAE
A = redness	2	2	1	0	1	0	0	0	2H	1H	0	0
B = chemosis	2	2	1	0	1	0	0	0	1	1	0	0
2 = discharge	2	0	0	0	1	0	0	0	1	0	0	0
Score (A + B + C) x 2	12	8	4	0	6	0	0	0	8	4	0	0
Total score	17	13	4	0	6	0	0	0	13	4	0	0

hr = hour(s)

IPR = initial pain reaction

H = haemorrhage of the nictitating membrane

+ = one drop of ophthaine instilled into each eye 1 -2 minutes before dosing

Individual total scores and group mean scores for ocular irritation

Rabbit number and sex	Individual total scores at:
	1 hr	24 hr	48 hr	72 hr
68 Female	17	13	4	0
25 Female	6	0	0	0
73 Male	13	4	0	0
Group total	36	17	4	0
Group mean score	12.0 1 hr	5.7 24 hr	1.3 48 hr	0.0 72 hr

Individual & mean scores for cornea, iris & conjunctivae required for EEC labelling regulations

Rabbit number and sex               (bodyweight Kg)	Time after treatment	Corneal opacity	Iridial inflammation	Conjunctival redness	Conjunctival chemosis
68 Female (3.06)	24 hr	0	1	2	2
	48 hr	0	0	1	1
	72 hr	0	0	0	0
Total		0	1	3	3
Mean		0.0	0.3	1.0	1.0
25 Female (2.74)	24 hr	0	0	0	0
	48 hr	0	0	0	0
	72 hr	0	0	0	0
Total		0	0	0	0
Mean		0.0	0.0	0.0	0.0
73 Male (3.30)	24 hr	0	0	1	1
	48 hr	0	0	0	0
	72 hr	0	0	0	0
Total		0	0	1	1
Mean		0.0	0.0	0.3	0.3

Applicant's summary and conclusion

Interpretation of results:

not irritating

Remarks:

Migrated information Criteria used for interpretation of results: EU

Conclusions:

The test material produced a maximum group mean score of 12.0 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.
The test material did not produce positive criteria in any rabbit according to the EEC labelling regulations and was classified as non-irritant to the rabbit eye. No symbol and risk phrase are therefore required.

Executive summary:

A study was performed to assess the irritancy potential of the test material to the eye of the New Zealand White rabbit. The method used followed that described in the OECD Guidelines for testing of Chemicals (1987) No. 405 "Acute Eye Irritation/Corrosion" referenced as Method B5 in Commission Directive 84/449/EEC (which constitutes Annex V of Council Directive 67/548/EEC).

The results may be used as a basis for classification and labelling under Annex VI of Council Directive 67/548/EEC (as adapted to technical progress by Commission Directive 91/325/EEC).

A single instillation of the test material to the non-irrigated eye of three rabbits produced iridial inflammation and/or minimal to moderate conjunctival irritation. Haemorrhage of the nictitating membrane was noted in one treated eye one and 24 hours after treatment. Treated eyes appeared normal 24, 48 or 72 hours after treatment.

The test material produced a maximum group mean score of 12.0 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.

The test material was also classified as non-irritant according to the EEC labelling regulations. No symbol and risk phrase are required.