Registration Dossier

Administrative data

Endpoint:
skin irritation / corrosion, other
Remarks:
in vivo
Type of information:
experimental study
Adequacy of study:
key study
Study period:
09/01/1991-12/02/1991
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:
OECD Guideline 404 (Acute Dermal Irritation / Corrosion)
Deviations:
no
GLP compliance:
yes (incl. certificate)

Test material

Reference
Name:
Unnamed
Type:
Constituent
Details on test material:
- Name of test material (as cited in study report): phenol 2-(1-methylpropyl)
- Substance type: mono alkylphenol
- Physical state: colourless liquid
- Analytical purity: 99.35 (GC)
- Impurities (identity and concentrations):
- Purity test date: 12/10/1990
- Lot/batch No.: 2-sek-AP/321
- Storage condition of test material: room temperature

Test animals

Species:
rabbit
Strain:
New Zealand White
Details on test animals 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: 2.27-2.55 kg
- Housing: individually housed in suspended metal cages
- Diet (e.g. ad libitum): ad libitum (Rabbit Diet, Preston farmers Limited, New Leake, Boston, Lincolnshire, UK)
- Water (e.g. ad libitum): ad libitum (drinking water)
- Acclimation period: minimum acclimasitation period of five days


ENVIRONMENTAL CONDITIONS
- Temperature (°C): 17-21°C
- Humidity (%): 45-60%
- 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:
unchanged (no vehicle)
Controls:
not required
Amount / concentration applied:
TEST MATERIAL
- Amount(s) applied (volume or weight with unit): 0.5 ml of the test material


Duration of treatment / exposure:
4 hours exposure
3 minute exposure
Observation period:
Approximately 1, 24, 48 and 72 hours, 7 and 14 days following removal of the patches
Number of animals:
3 animals 4 hour exposure
3 animals 3 minute exposure
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, 3 minutes


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 hour
Score:
4
Max. score:
4
Remarks on result:
other: 4 Hours exposure. Haemorrhage of dermal capillaries. Reaction extending beyond the site of application
Irritation parameter:
erythema score
Basis:
animal #1
Time point:
other: 24, 48, 72 hours, 7 days
Max. score:
4
Reversibility:
no data
Remarks on result:
other: 4 hours exposure. Evaluation of erythema not possible due to other adverse reactions
Irritation parameter:
erythema score
Basis:
animal #2
Time point:
other: 1 hour
Score:
4
Max. score:
4
Remarks on result:
other: haemorrhage of dermal capillaries. Reaction extending beyond the site of application
Irritation parameter:
erythema score
Basis:
animal #2
Time point:
other: 24, 48, 72 hours, 7 days
Max. score:
4
Reversibility:
no data
Remarks on result:
other: 4 hours exposure. Evaluation of erythema not possible due to other adverse reactions
Irritation parameter:
erythema score
Basis:
animal #3
Time point:
other: 1 hour
Score:
4
Max. score:
4
Remarks on result:
other: 4 hours exposure. Haemorrhage of dermal capillaries. Light brown discolouration of the epidermis. Reaction extending beyond the site of application
Irritation parameter:
erythema score
Basis:
animal #3
Time point:
other: 24, 48, 72 hours, 7 days
Max. score:
4
Reversibility:
no data
Remarks on result:
other: 4 hours exposure. Evaluation of erythema not possible due to adverse reactions
Irritation parameter:
edema score
Basis:
animal #1
Time point:
other: 1 hour
Score:
4
Max. score:
4
Remarks on result:
other: 4 hours exposure. Reaction extending beyond the site of application
Irritation parameter:
edema score
Basis:
animal #1
Time point:
other: 24, 48, 72 hours, 7 days
Max. score:
4
Reversibility:
no data
Remarks on result:
other: 4 hours exposure. Evaluation of oedema not possible due to adverse reactions
Irritation parameter:
edema score
Basis:
animal #2
Time point:
other: 1 hour
Score:
4
Max. score:
4
Remarks on result:
other: 4 hours exposure. Reaction extending beyond the site of application
Irritation parameter:
edema score
Basis:
animal #2
Time point:
other: 24, 48, 72 hours, 7 days
Max. score:
4
Reversibility:
no data
Remarks on result:
other: 4 hours exposure. Evaluation of oedema not possible due to adverse reactions
Irritation parameter:
edema score
Basis:
animal #3
Time point:
other: 1 hour
Score:
4
Max. score:
4
Remarks on result:
other: 4 hours exposure. Reaction extending beyond the site of application
Irritation parameter:
edema score
Basis:
animal #3
Time point:
other: 24, 48, 72 hours, 7 days
Max. score:
4
Reversibility:
no data
Remarks on result:
other: 4 hours exposure. Evaluation of oedema not possible due to adverse reactions
Irritation parameter:
erythema score
Basis:
animal #4
Time point:
other: 1, 24, 48, 72 hours, 7 & 14 days
Score:
>= 0 - <= 2
Max. score:
4
Reversibility:
not fully reversible within: 14 days
Remarks on result:
other: 3 minute exposure. 14 days: reduced regrowth of fur and desquamation
Irritation parameter:
erythema score
Basis:
animal #5
Time point:
other: 1, 24, 48, 72 hours, 7 & 14 days
Score:
>= 0 - <= 2
Max. score:
4
Reversibility:
not fully reversible within: 14 days
Remarks on result:
other: 3 minute exposure. 14 days: reduced growth of fur and desquamation
Irritation parameter:
erythema score
Basis:
animal #6
Time point:
other: 1, 24, 48, 72 h, 7 & 14 days
Score:
>= 0 - <= 3
Max. score:
4
Reversibility:
not fully reversible within: 14 days
Remarks on result:
other: 3 minute exposure. 14 days: reduce growth of fur and desquamation
Irritation parameter:
edema score
Basis:
animal #4
Time point:
other: 1, 24, 48, 72 h, 7 & 14 days
Score:
>= 0 - <= 4
Max. score:
4
Reversibility:
fully reversible within: 14 days
Remarks on result:
other: 3 minute exposure
Irritation parameter:
edema score
Basis:
animal #5
Time point:
other: 1, 24, 48, 72 h, 7 & 14 days
Score:
>= 0 - <= 3
Max. score:
4
Reversibility:
fully reversible within: 14 days
Remarks on result:
other: 3 minute exposure
Irritation parameter:
edema score
Basis:
animal #6
Time point:
other: 1, 24, 48, 72 h, 7 & 14 days
Score:
>= 0 - <= 4
Max. score:
4
Reversibility:
fully reversible within: 14 days
Remarks on result:
other: 3 minute exposure
Irritant / corrosive response data:
4-hour exposure period:
Severe erythema and oedema was noted at all treated skin sites one after patch removal. The reaction extended up to 4 cm beyond all treatment sites during the study.

3-minute exposure period:
Well-defined or moderate to severe erythema was noted at all treated skin sites one, 24, and 48-hours after patch removal. Well-defined erythema continued to be noted at two treated skin sites at the 72-hour observation.
Moderate to severe oedema was noted at all treated skin sites one hour after patch removal. Slight to severe oedema was noted at the 24-hour observation with very slight to moderate oedema at the 72-hour observation. Very slight to slight oedema was noted at two treated skin sites at the 7-day observation. Ocasionally the reaction extended 2-3 cm beyond the treatment site.
Other effects:
4-hour exposure period:
Evaluation of the erythema and oedema was not possible at the 24, 48, 72-hour and 7 days observations due to other adverse reactions. These included haemorrhage of the dermal capilleries, hardened dark brown/black-coloured scabs, blanching, well-defined or moderate erythema surrounding the treatment site, undulating scabs, scabs lifting at edges to reveal either dried blood or light brown-coloured scabs with small areas of dried blood. These reactions were considered to be indicated of dermal corrosion.

3-minute exposure period:
Evaluation of the erythema and oedema was not possible at one treatment site at the 72-hour observation and at all treatment sites at the 7-day observation due to other adverse reactions. These included haemorrhage of the dermal capilleries, light brown discolouration of the epidermis, loss of skin elasticity, thickening of the skin, hardened dark/black-coloured scab, well-defined erythema surrounding the treatment site, hardened light brown-coloured scab, reduced re-growth of fur and desquamation.

Any other information on results incl. tables

Key to tables:

Hd = haemorrhage of dermal capilleries

St = hardened dark brown/black-coloured scab

Bl = blanching

We = well-defined erythema surrounding other skin reactions

Sw = undulating scab

Sb = scab lifting at edges to reveal dried blood

Sd = scab lifting to reveal further deep scabing

Sd* = dark brown/black-coloured scab has lifted to reveal a light brown-coloured scab with small areas of dried blood

?e = evaluation of erythema not possible due to other adverse reactions

?Od = evaluation of oedema not possible due to other adverse reactions

Br = light brown discolouration of the epidermis

Th = thickening of the skin

Le = loss of skin elasticity

Sp = hardened light brown-coloured scab

Fr = reduced regrowth of fur

D = desquamation

R = reaction extending beyond the site of application

Individual reactions for dermal irritation following 4 -hour exposure

Skin reactions 

Reading 

Individual Scores – Rabbit Number and Sex (Bodyweight Kg)

44 Female

(2.54)

53 Female

(2.55)

55 Female

(2.47)

Erythema/eschar formation 

1 h 

4HdR 

4HdR

4HdBrR

 

24 h 

?eStBlWeR

?eStMeR

?eStMeRBl

 

48 h 

?eStBiWeR 

?eStMeR

?eStMeR 

 

72 h 

?eStWeR 

?eStWeR

?eStWeR 

 

7 days 

?eStSwR

?eStSwSbR

?eSd*R

 

14 days 

-

-

-

Oedema formation 

1 h 

4R

4R

4R 

 

24 h 

?Od

?Od

?Od

 

48 h 

?Od

?Od

?Od

 

72 h 

?Od

?Od

?Od 

 

7 days 

?Od 

?Od 

?Od 

 

14 days 

-

-

-

Individual reactions for dermal irritation following 3 -minute exposure

Skin reactions 

Reading 

Individual Scores – Rabbit Number and Sex (Bodyweight Kg)

40 Female 

(2.30)

41 Female 

(2.40)

43 Female 

(2.27)

Erythema/eschar formation 

1 h 

2Hd 

2Hd 

3Hd 

 

24 h 

2HdBrR 

2HdBr 

3HdBr 

 

48 h 

2HdBrLeR 

2Br 

HdBrLeTh 

 

72 h 

2HdBrThLeR 

2BrLe 

?eStWeR 

 

7 days 

?eSp 

?eSp 

?eSt 

 

14 days 

0FrD 

0FrD 

0FrD 

Oedema formation 

1 h 

 

24 h 

 

48 h 

 

72 h 

?Od 

 

7 days 

?Od 

?Od 

?Od 

 

14 days 

Applicant's summary and conclusion

Interpretation of results:
corrosive
Remarks:
Migrated information Criteria used for interpretation of results: EU
Conclusions:
The test material phenol 2-(1-methylpropyl) was regarded as corrosive according to CLP classification.
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.

A single 4 -hour, semi-occluded application of the test material to the intact skin of three rabbits produced reactions indicative of corrosion. Adverse dermal reactions included haemorrhage of the dermal capillaries, blanching of the skin, scabbing, severe erythema and severe oedema.

A single 3 -minute, semi-occluded application of the test material to an additional group of three rabbits produced well-defined to severe erythema and very slight to severe oedema. Other adverse reactions noted were haemorrhage of the dermal capillaries, light brown discolouration of the epidermis, loss of skin elasticity, thickening of the skin, scabbing, reduced re-growth of fur and desquamation.

The test material phenol 2-(1-methylpropyl) was regarded as corrosive.