Registration Dossier

Toxicological information

Skin irritation / corrosion

Currently viewing:

Administrative data

Endpoint:
skin irritation: in vivo
Type of information:
experimental study
Adequacy of study:
key study
Study period:
1994
Reliability:
1 (reliable without restriction)
Rationale for reliability incl. deficiencies:
guideline study

Data source

Reference
Reference Type:
study report
Title:
Unnamed
Year:
1994
Report Date:
1994

Materials and methods

Test guideline
Qualifier:
according to
Guideline:
OECD Guideline 404 (Acute Dermal Irritation / Corrosion)
Deviations:
no
GLP compliance:
yes

Test material

Reference
Name:
Unnamed
Test material form:
liquid: viscous
Details on test material:
- Manufacturers identification: Novares LA 300
- Substance type: organic
- Test material is 'Oligomerisation and alkylation reaction products of 2-phenylpropene and phenol' (OAPP), EC list number 700-960-7 (assigned manually to validated substances from inquiries by ECHA). Originally the substance phenol, methylstyrenated, CAS No. 68512-30-1, EC No. 270-966-8 was submitted for registration. Subsequent to substance validation, the identity of the substance was changed by ECHA.
- for additional information see respective study record
Specific details on test material used for the study:
- Name of test material (as cited in study report): Necires EPX-L (phenol, methylstyrenated)
- Impurities (identity and concentrations): None
- Purity test date: Unknown
- Lot/batch No.: 9356059
- Expiration date of the lot/batch: 2005/02/01
- Stability under test conditions: Stable
- Storage condition of test material: At room temperature in the dark

Test animals

Species:
rabbit
Strain:
New Zealand White
Details on test animals and environmental conditions:
TEST ANIMALS
- Source: Broekman Institute, Someren, The Netherlands
- Age at study initiation: approx. 13 weeks
- Weight at study initiation: 2410 -2603 grams
- Housing: Individually in labelled cages with perforated floors and equipped with an automatic drinking system (ITl, Bergen, The Netherlands).
- Diet (e.g. ad libitum): Standard laboratory rabbit diet (LKK-20, pellet diameter 4mm, Hope Farms, Woerden, The Netherlands) approx. 100 gram per day. In addition, hay (BMI, Helmond, the Netherlands) was provided once a week.
Certificates of analysis were examined and retained in the NOTOX archives.
- Water (e.g. ad libitum): ad libitum
- Acclimation period: Acclimatisation period was at least 5 days before start of treatment under laboratory conditions

ENVIRONMENTAL CONDITIONS
- Temperature (°C): 21
- Humidity (%): 50
- Air changes (per hr): 15
- Photoperiod (hrs dark / hrs light): 12 hours dark/12 hours light

Test system

Type of coverage:
semiocclusive
Preparation of test site:
shaved
Vehicle:
unchanged (no vehicle)
Controls:
not required
Amount / concentration applied:
TEST MATERIAL
- Amount(s) applied (volume or weight with unit): 0.5 ml
- Concentration (if solution): 100%

Duration of treatment / exposure:
4 hours
Observation period:
21 days
Number of animals:
3
Details on study design:
TEST SITE
- Area of exposure: 2 x 3 cm
- % coverage: Unknown
- Type of wrap if used: Surgical gauze

REMOVAL OF TEST SUBSTANCE
- Washing (if done): Water
- Time after start of exposure: 4 hours

SCORING SYSTEM: OECD 404: Grading of skin reactions and Draize et. al. (1944) J.Pharmacol. Exp. 82, 377.

CONTROL
- A similar patch (without test substance) was applied to the contralateral flank to act as a procedural control.

OBSERVATIONS
- Viability/mortality/toxicity: Twice dailiy
- Body weight: Day of treatment (prior to application)
- Irritation: 1, 24, 48 and 72 hours and 7, 14 and 21 days

Results and discussion

In vivo

Resultsopen allclose all
Irritation parameter:
primary dermal irritation index (PDII)
Basis:
mean
Remarks:
over 3 animals and two time points: total of individual scores for erythema and oedema divided by 6
Time point:
other: 24 + 72 hours
Score:
5.7
Max. score:
8
Reversibility:
fully reversible within: 21 days
Remarks on result:
probability of severe irritation
Irritation parameter:
erythema score
Basis:
animal #1
Time point:
24/48/72 h
Score:
3.3
Max. score:
4
Reversibility:
fully reversible within: 21 days
Remarks on result:
other: fissuring of treated skin noted at 72 hours
Irritation parameter:
edema score
Basis:
animal #1
Time point:
24/48/72 h
Score:
2.7
Max. score:
4
Reversibility:
fully reversible within: 21 days
Irritation parameter:
erythema score
Basis:
animal #2
Time point:
24/48/72 h
Score:
3
Max. score:
4
Reversibility:
fully reversible within: 21 days
Remarks on result:
other: scattered erythema noted at 72 hours
Irritation parameter:
edema score
Basis:
animal #2
Time point:
24/48/72 h
Score:
2.3
Max. score:
4
Reversibility:
fully reversible within: 21 days
Irritation parameter:
erythema score
Basis:
animal #3
Time point:
24/48/72 h
Score:
3
Max. score:
4
Reversibility:
fully reversible within: 21 days
Remarks on result:
other: scattered erythema noted at 24 and 72 hours
Irritation parameter:
edema score
Basis:
animal #3
Time point:
24/48/72 h
Score:
2.3
Max. score:
4
Reversibility:
fully reversible within: 21 days
Irritant / corrosive response data:
One hour after 4 hours exposure to 0.5 ml of NECIRES EPX-L well defined or moderate to severe erythema (grades 2-3) and slight oedema (grade 2) were observed in the treated skin areas of the three animals. An increase in the degree of erythema and oedema were observed at the following observations, with a maximum of moderate oedema (grade 3) after 24 hours and of moderate to severe erythema (grades 3-4) 72 hours after exposure. Fissuring of the treated skin was also observed in one animal (no. 1964) after 72 hours. A decrease in the degree of skin irritation was noted from 7 days onwards, and the irritation had completely resolved within 21 days after exposure in all animals. Scaliness was observed on the treated skin in all animals after 7 days and persisted in two animals (nos. 1964 and 1976) at 14 days after exposure.

There was no evidence of a corrosive effects on the skin.
Other effects:
Colouration: Remnants of the test substance were noted in the treated skin-area of all three animals on day 1.

Toxicity symptoms/mortality: No symptoms of systemic toxicity were observed in the animals during the test period, and no mortality occurred.

Any other information on results incl. tables

numerical skin grades at 1, 4, 24, 48 and 72 hours

 

Time (hours)

Animal

1964 (#1)

1972 (#2)

1976 (#3)

Erythema

Oedema

Erythema

Oedema

Erythema

Oedema

1

2

2

3

2

3

2

24

3

3

3

3

2

3

48

3

3

3

2

3

2

72

4

2

3

2

4

2

 

delayed grading scores at 7 to 21 days

 

Time (days)

Animal

1964 (#1)

1972 (#2)

1976 (#3)

Erythema

Oedema

Erythema

Oedema

Erythema

Oedema

7

2

2

2

1

3

1

14

1

1

1

0

1

0

 21  0  0  0  0  0  0

 

Applicant's summary and conclusion

Interpretation of results:
Category 2 (irritant) based on GHS criteria
Conclusions:
The test substance meets EU classification criteria for skin irritation.
Executive summary:

In a primary skin irritation/corrosion study in the rabbit (4-hour semi-occlusive application), oligomerisation and alkylation reaction products of 2-phenylpropene and phenol (phenol, methylstyrenated) was applied (0.5 ml via surgical gauze) to a 2 x 3 cm patch on three shaved New Zealand White rabbits. One hour after 4 hours exposure, well defined or moderate to severe erythema (grades 2-3) and slight oedema (grade 2) were observed in the treated skin areas of the three animals. An increase in the degree of erythema and oedema were observed at the following observations, with a maximum of moderate oedema (grade 3) after 24 hours and of moderate to severe erythema (grades 3-4) 72 hours after exposure. Fissuring of the treated skin was also observed in one animal (no. 1964) after 72 hours. A decrease in the degree of skin irritation was noted from 7 days onwards, and the irritation had completely resolved within 21 days after exposure in all animals.Scalinesswas observed on the treated skin in all animals after 7 days and persisted in two animals at 14 days after exposure. There was no evidence of a corrosive effects on the skin, nor were there any observed signs of systemic toxicity during the test period. In conclusion, application of phenol, methyl styrenated to intact rabbit skin results in severe irritation, and as such phenol, methylstyrenated should be classified as a skin irritant.