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Toxicological information

Skin irritation / corrosion

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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

Constituent 1
Chemical structure
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

Resultsopen allclose all
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
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
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
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
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
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
Irritation parameter:
edema score
Basis:
animal #1
Time point:
other: 1, 24, 48, 72 hours
Score:
2 - 3
Max. score:
4
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
Irritation parameter:
edema score
Basis:
animal #2
Time point:
other: 1, 24, 48, 72 hours
Score:
0 - 1
Max. score:
4
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
Irritation parameter:
edema score
Basis:
animal #3
Time point:
other: 1, 24, 48, 72 hours
Score:
1 - 2
Max. score:
4
Irritation parameter:
edema score
Basis:
animal #3
Time point:
other: 7, 14 days
Score:
0
Max. score:
4
Reversibility:
fully reversible within: 7 days
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
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
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

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

5

 

7 days 

?Od 

?Od 

(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

 Total

12 

12 

10 

 Mean Score

4.0+

4.0+

3.3+ 

 Oedema formation 

24

21

2

 

48

1

 

72

2

 Total

 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.