Di-sec-butylphenol, mixed isomers

Skin irritation / corrosion

Administrative data

Endpoint:

skin irritation: in vivo

Type of information:

experimental study

Adequacy of study:

key study

Study period:

08/07/1992-15/07/1992

Reliability:

1 (reliable without restriction)

Rationale for reliability incl. deficiencies:

other: Guideline study (OECD 404)

Data source

Reference

Reference Type:

study report

Title:

Unnamed

Year:

1992

Materials and methods

Test guideline

Qualifier:

according to guideline

Guideline:

OECD Guideline 404 (Acute Dermal 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

Species:

rabbit

Strain:

New Zealand White

Details on test animals or test system and environmental conditions:

TEST ANIMALS
- Source: David Percival ltd., Moston, Sandbach, Cheshire, UK
- Age at study initiation: twekve to sixteen weeks old
- Weight at study initiation: 2.49-2.78 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): 18-23°C
- Humidity (%): 54-66%
- Air changes (per hr): 15 changes per hour
- Photoperiod (hrs dark / hrs light): 12 hrs dark/12 hrs light


IN-LIFE DATES: From: To:

Test system

Type of coverage:

semiocclusive

Preparation of test site:

other: clipped free of fur

Vehicle:

unchanged (no vehicle)

Controls:

not required

Amount / concentration applied:

TEST MATERIAL
- Amount(s) applied (volume or weight with unit): 0.5 ml

Duration of treatment / exposure:

4 hours

Observation period:

1, 24, 48 and 78 hours and 7 days

Number of animals:

three

Details on study design:

TEST SITE
- Area of exposure: 0.5 ml of the test material was introduced under a 2.5 x 2.5 cm gauze patch and placed in position on the shorn skin
- Type of wrap if used: The patch was secured in position with a strip of surgical adhesive tape (BLENDERM: approximate size 2.5 x 4.0 cm). To prevent the animals interfering with the patches, the trunk of each rabbit was wrapped in an elasticated corset (TUBIGRIP) and the animals were returned to their cages for the duration of the exposure period.


REMOVAL OF TEST SUBSTANCE
- Washing (if done): corset and patches were removed from each animal and any residual test material removed by gentle swabbing with cotton wool soaked in diethyl ether
- Time after start of exposure: four hours


SCORING SYSTEM: according to the scale from 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"

Results and discussion

In vivo

Results

Results 1

Irritation parameter:

erythema score

Basis:

animal #1

Time point:

other: 1, 24, 48, 72 hours & 7 days

Score:

0 - 2

Max. score:

4

Reversibility:

other: 7 days: score 0 but desquamation

Remarks on result:

other: 24, 48, 72 hours: reactions extend up to 5 cm beyond treatment site

Results 2

Irritation parameter:

erythema score

Basis:

animal #2

Time point:

other: 1, 24, 48, 72 hours & 7 days

Score:

0 - 2

Max. score:

4

Reversibility:

other: 7 days: score 0 but crust formation

Remarks on result:

other: 24, 48, 72 hours: reactions extend up to 5 cm beyond treatment site

Results 3

Irritation parameter:

erythema score

Basis:

animal #3

Time point:

other: 1, 24, 48, 72 hours & 7 days

Score:

0 - 2

Max. score:

4

Reversibility:

other: 7 days: score 0 but crust formation

Remarks on result:

other: 24, 48, 72 hours: reactions extend up to 5 cm beyond treatment site

Results 4

Irritation parameter:

edema score

Basis:

animal #1

Time point:

other: 1, 24, 48, 72 hours & 7 days

Score:

0 - 2

Max. score:

4

Reversibility:

fully reversible within: 7 days

Results 5

Irritation parameter:

edema score

Basis:

animal #2

Time point:

other: 1, 24, 48, 72 hours & 7 days

Score:

0 - 2

Max. score:

4

Reversibility:

fully reversible within: 7 days

Results 6

Irritation parameter:

primary dermal irritation index (PDII)

Basis:

other: sum of 24 and 72 hours reading (S), S/6

Score:

4

Max. score:

8

Results 7

Irritation parameter:

erythema score

Basis:

mean

Time point:

other: 24, 48, 72 hours

Score:

2

Max. score:

4

Results 8

Irritation parameter:

edema score

Basis:

mean

Time point:

other: 24, 48, 72 hours

Score:

2

Max. score:

4

Irritant / corrosive response data:

Very slight erythema was noted at two treated skin sites one hour after patch removal. very slight oedema was also noted at one treated skin site at this time. Well-defined erythema and slight oedema were noted at all treated skin sites at the 24, 48 and 72-hour observations. The reactions extended up to 5 cm beyond all treatment sites at the 24, 48 and 72-hours.
Adverse dermal reactions noted at all treated skin sites seven days after treatment were desquamation or crust formation.

Any other information on results incl. tables

Individual skin reactions

Skin reaction	Observation time	Individual Scores – Rabbit Number and Sex (Bodyweight Kg)
		164 Male (2.78)	169 Female (2.49)	177 Female (2.74)	Total
Erythema/eschar formation	1 h	0	1	1	(2)
	24 h	2 R	2 R	2 R	6
	48 h	2 R	2 R	2 R	(6)
	72 h	2 R	2 R	2 R	6
	7 days	0 D	0 Cf	0 Cf	(0)
Oedema formation	1 h	0	0	1	(4)
	24 h	2	2	2	5
	48 h	2	2	2	(5)
	72 h	2	2	2	4
	7 days	0	0	0	(0-4)
Sum of 24 and 72-Hour readings (S): 24
Primary Irritation Index (S/6): 24/6 = 4.0
Classification: Moderate irritant

Cf = crust formation

D = desquamation

R = reactions extend up to 5 cm beyond treatment site

( ) = total values not used for calculation of primary irritation index

Individual daily and individual mean scores

For dermal irritation following 4-hour exposure required for EEC labelling regulations

Skin reaction	Reading (h)	Individual Scores – Rabbit Number and Sex (Bodyweight Kg)
		164 Male (2.78)	169 Female (2.49)	177 Female (2.74)
Erythema/eschar formation	24	2	2	2
	48	2	2	2
	72	2	2	2
Total		6	6	6
Mean Score		2.0+	2.0+	2.0+
Oedema formation	24	2	2	2
	48	2	2	2
	72	2	2	2
Total		6	6	6
Mean Score		2.0+	2.0+	2.0+

+ = positive criteria

Applicant's summary and conclusion

Interpretation of results:

irritating

Remarks:

Migrated information Criteria used for interpretation of results: EU

Conclusions:

The test material produced a primary irritation index of 4.0 and was classified as moderate irritant to rabbit skin according to Draize classification scheme. No corrosive effcts were noted.
The test material produced positive criteria in 3/3 rabbits according to the EEC labelling regulations and was classified as irritant to rabbit skin. The symbol "Xi" and risk phrase R 38 "IRRITATING TO SKIN" are therefore required.

Executive summary:

A study was perform to assess the irritancy potential of the test material to the skin of the New Zealand White rabbit. The method used followed that described in the OECD Guidelines for Testing of Chemicals (1981) No. 404 "Acute Dermal Irritation/Corrosion" referenced as Method B4 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 4 -hour, semi-ocludded application of the test material to the intact skin of three rabbits produced well-defined erythema and slight oedema. Adverse dermal reactions noted seven days after treatment were desquamation or crust formation.

The test material produced a primary irritation index of 4.0 and was classified as moderate irritant to rabbit skin according to Draize classification scheme. No corrosive effects were noted.

The test material was also classified as irritant according to EEC labelling regulations. The symbol "Xi" and risk phrase R 38 "IRRITATING TO SKIN" are therefore required.