4-tert-butylphenol

Skin irritation / corrosion

Administrative data

Endpoint:

skin irritation: in vivo

Type of information:

experimental study

Adequacy of study:

key study

Study period:

22/01/91 - 5/02/91

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:

1991

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:

4-tert-butylphenol

EC Number:

202-679-0

EC Name:

4-tert-butylphenol

Cas Number:

98-54-4

Molecular formula:

C10H14O

IUPAC Name:

4-tert-butylphenol

Details on test material:

- Name of test material (as cited in study report): para-tertiary butylphenol, UCAR Butylphenol 4T-Flake (para tert-Butyl Phenol), PTBP.
- Physical state: White flakes.
- Analytical purity: Not reported.
- Lot/batch No.: Charge No. 496500; BRRC Sample No. 48-186.
- Expiration date of the lot/batch: Not reported.
- Stability under test conditions: Not reported.
- Storage condition of test material: Not reported.

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, U.K.
- Age at study initiation: twelve to sixteen weeks old
- Weight at study initiation: 2.63-2.69 kg
- Housing: individually housed in suspended metal cages
- Diet (e.g. ad libitum): ad libitum (Spillers Rabbit Diet, Dalgety Agriculture Ltd., Almondsbury, Bristol)
- Water (e.g. ad libitum): ad libitum (drinking water)
- Acclimation period: minimum acclimasitation period of five days


ENVIRONMENTAL CONDITIONS
- Temperature (°C): 17-22°C
- Humidity (%): 49-61%
- Air changes (per hr): approximately 15 changes/hour
- Photoperiod (hrs dark / hrs light): 12 hrs dark / 12 hrs light

Test system

Type of coverage:

semiocclusive

Preparation of test site:

other: clipped

Vehicle:

other: moistened with distilled water

Controls:

not required

Amount / concentration applied:

TEST MATERIAL
- Amount(s) applied (volume or weight with unit): 0.5 g of the test material, moistened with 0.5 ml of distilled water, was introduced under a 2.5 x 2.5 cm gauze patch and placed in position on the shorn skin

Duration of treatment / exposure:

Four hours

Observation period:

1, 24, 48 and 72 hours

Number of animals:

3

Details on study design:

TEST SITE
- Area of exposure: 0.5 g of the test material, moistened with 0.5 ml of distilled water, 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 distilled water
- 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

Score:

2 - 4

Max. score:

4

Remarks on result:

other: 24, 48, 72 hr: small areas, approximately 5 mm x 5 mm, of white-coloured necrosis. Well-defined erythema surrounding scabs

Results 2

Irritation parameter:

erythema score

Basis:

animal #1

Time point:

other: 7, 14 days

Score:

0

Max. score:

4

Reversibility:

other: reversible within 14 days

Remarks on result:

other: reduced re-growth of fur

Results 3

Irritation parameter:

erythema score

Basis:

animal #2

Time point:

other: 1, 24, 48, 72 hours

Score:

1 - 4

Max. score:

4

Remarks on result:

other: 24, 48, 72 hr: small areas, approximately 5 mm x 5 mm, of white-coloured necrosis. Well-defined erythema surrounding scabs

Results 4

Irritation parameter:

erythema score

Basis:

animal #2

Time point:

other: 7, 14 days

Score:

0

Max. score:

4

Reversibility:

other: reversible within 14 days

Remarks on result:

other: reduced re-growth of fur

Results 5

Irritation parameter:

erythema score

Basis:

animal #3

Time point:

other: 1, 24, 48, 72 hours

Score:

1 - 4

Max. score:

4

Remarks on result:

other: 24, 48 hr: small areas, approximately 5 mm x 5 mm, of white-coloured necrosis. Well-defined erythema surrounding scabs

Results 6

Irritation parameter:

erythema score

Basis:

animal #3

Time point:

other: 7, 14 days

Score:

0

Max. score:

4

Reversibility:

fully reversible within: 14 days

Remarks on result:

other: 7 days: crust formation

Results 7

Irritation parameter:

edema score

Basis:

animal #1

Time point:

other: 1, 24, 48, 72 hours

Score:

2 - 3

Max. score:

4

Results 8

Irritation parameter:

edema score

Basis:

animal #1

Time point:

other: 7, 14 days

Score:

0

Max. score:

4

Reversibility:

fully reversible within: 14 days

Remarks on result:

other: 7 days: adverse reactions prevent accurate evaluation of edema

Results 9

Irritation parameter:

edema score

Basis:

animal #2

Time point:

other: 1, 24, 48, 72 hours

Score:

0 - 1

Max. score:

4

Results 10

Irritation parameter:

edema score

Basis:

animal #2

Time point:

other: 7, 14 days

Score:

0

Max. score:

4

Reversibility:

fully reversible within: 14 days

Remarks on result:

other: 7 days: adverse reactions prevent accurate evaluation of edema

Results 11

Irritation parameter:

edema score

Basis:

animal #3

Time point:

other: 1, 24, 48, 72 hours

Score:

1 - 2

Max. score:

4

Results 12

Irritation parameter:

edema score

Basis:

animal #3

Time point:

other: 7, 14 days

Score:

0

Max. score:

4

Reversibility:

fully reversible within: 7 days

Results 13

Irritation parameter:

primary dermal irritation index (PDII)

Basis:

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

Time point:

other: 24 and 72 hours

Score:

5.5

Max. score:

8

Results 14

Irritation parameter:

erythema score

Basis:

mean

Time point:

other: 24, 48, 72 hours

Score:

3.3 - 4

Max. score:

4

Remarks on result:

other: positive criterion

Results 15

Irritation parameter:

edema score

Basis:

mean

Time point:

other: 24, 48, 72 hours

Score:

1 - 2.3

Max. score:

4

Remarks on result:

other: positive criterion

Irritant / corrosive response data:

Very slight to well-defined erythema was noted at all treated skin sites one hour after patch removal. Severe erythema, small areas of white-coloured necrosis (approximately 5 mm x 5 mm) and well-defined erythema surrounding scabs were noted at all treated skin sites at the 24 and 48 hour observations and at two treated skin sites at the 72-hour observation.
Very slight to slight oedema was noted at two treated skin sites one hour after patch removal. Very slight to moderate oedema was noted at all treated skin sites at the 24-hour observation with very slight to slight oedema at the 48 and 72-hour observation.

Other effects:

Hardened light brown-coloured scabs and thickening of the skin were noted at two treated skin sites at the 7-day observation. Adverse reactions prevented accurate evaluation of erythema and oedema at these treated skin sites at the 7-day observation. Reduced re-growth of fur was noted at these treated skin sites at the 14-day observation. Well-defined erythema was noted at one treated skin site at the 72-hour observation with crust formation at the 7-day observation.

Any other information on results incl. tables

Key to table:

Cf = crust formation

Fr = reduced re-growth of fur

N = small areas, approximately 5 mm x 5 mm, of white-coloured necrosis

Sp = hardened light brown-coloured scab

Th = thickening of skin

We = well-defined erythema surrounding scabs

?e = adverse reactions prevent accuarte evaluation of erythema

Od = adverse reactions prevent accurate evaluation of oedema

Individual skin reactions

Skin reactions	Observation time	Individual Scores ¿ Rabbit Number and Sex (Bodyweight Kg)
		146 Male (2.64)	147 Female (2.69)	162 Female (2.63)	Total
Erythema/eschar formation	1 h	2	1	1	(4)
	24 h	4NWe	4NWe	4NWe	12
	48 h	4NWe	4NWe	4NWe	(12)
	72 h	4NWe	4NWe	2	10
	7 days	?eSpTh	?eSpTh	0Cf	(0-8)
	14 days	0Fr	0Fr	0	(0)
Oedema formation	1 h	2	0	1	(3)
	24 h	3	1	2	6
	48 h	2	1	1	(4)
	72 h	2	1	2	5
	7 days	?Od	?Od	0	(0-8)
	14 days	0	0	0	(0)
Sum of 24 and 72-Hour readings (S): 33
Primary Irritation Index (S/6):  33/6 = 5.5
Classification: Severe irritant

( ) = 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 reactions	Reading (h)	Individual Scores ¿ Rabbit Number and Sex (Bodyweight Kg)
		146 Male (2.64)	147 Female  (2.69)	162 Female  (2.63)
Erythema/eschar formation	24	4	4	4
	48	4	4	4
	72	4	4	2
Total		12	12	10
Mean Score		4.0+	4.0+	3.3+
Oedema formation	24	3	21	2
	48	2	1	1
	72	2	1	2
Total		7	3	5
Mean Score		2.3+	1.0	1.7

+ = positive criterion

Applicant's summary and conclusion

Interpretation of results:

Category 2 (irritant) based on GHS criteria

Conclusions:

The test material produced a primary irritation index of 5.5 and was classified as a severe irritant to rabbit skin according to the Draize classification scheme. No corrosive effects were noted.
The test material was also classified as irritant according to EEC labeling regulations. The symbol "Xi" and risk phrase R38 "IRRITATING TO SKIN" are therefore required.

Executive summary:

A study was performed 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 basis for classification and labelling under Annex VI of Council Directive 67/548/EEC (as adapted to technical progress by Commission Directive 83/467/EEC).

A single 4 -hour, semi-occluded application of the test material to the intact skin of three rabbits produced severe erythema and very slight to moderate oedema. Other adverse skin reactions noted were small areas of white-colored necrosis, well-defined erythema surrounding scabs, hardened light brown-coloured scab, thickening of the skin, crust formation and reduced re-growth of fur.

The test material produced a primary irritation index of 5.5 and was classified as a severe irritant to rabbit skin according to the Draize classification scheme. No corrosive effects were noted.

The test material was also classified as irritant according to EEC labeling regulations. The symbol "Xi" and risk phrase R38 "IRRITATING TO SKIN" are therefore required.