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Administrative data

Description of key information

The substance oligomerisation and alkylation reaction products of 2-phenylpropene and phenol (OAPP) (previous name phenol, methylstyrenated) is a skin irritant, but it did not produce classifiable eye irritation when instilled into rabbit eyes. There is no data for respiratory irritation. No evidence for corrosivity in skin and eye irritancy testing.

Key value for chemical safety assessment

Skin irritation / corrosion

Link to relevant study records
Reference
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
Qualifier:
according to
Guideline:
OECD Guideline 404 (Acute Dermal Irritation / Corrosion)
Deviations:
no
GLP compliance:
yes
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
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

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
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.

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

 

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.

Endpoint conclusion
Endpoint conclusion:
adverse effect observed (irritating)

Eye irritation

Link to relevant study records
Reference
Endpoint:
eye 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
Qualifier:
according to
Guideline:
OECD Guideline 405 (Acute Eye Irritation / Corrosion)
Deviations:
no
GLP compliance:
yes
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
Species:
rabbit
Strain:
New Zealand White
Details on test animals or tissues and environmental conditions:
TEST ANIMALS
- Source: Broekman Institute, Someren, The Netherlands
- Age at study initiation: 14 - 15 weeks
- Weight at study initiation: 2683 -2763 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

IN-LIFE DATES: From: To:
Vehicle:
unchanged (no vehicle)
Controls:
not required
Amount / concentration applied:
TEST MATERIAL
- Amount(s) applied (volume or weight with unit): 0.1 ml
- Concentration (if solution): 100 %
Duration of treatment / exposure:
24 hours
Observation period (in vivo):
1, 24, 48 and 72 hours
Number of animals or in vitro replicates:
3
Details on study design:
REMOVAL OF TEST SUBSTANCE
- Washing (if done):
- Time after start of exposure: 24 hours

SCORING SYSTEM: OECD 405, Draize et a1. 1944. J. Pharmacal. Exp. Ther. 82; 377-390 and J. Soc. Cosmet. Chem. 13; 281-289

TOOL USED TO ASSESS SCORE: fluorescein

CONTROL
The eye not being treated served as a control
Irritation parameter:
maximum mean total score (MMTS)
Basis:
mean
Score:
4
Reversibility:
fully reversible within: 48 hours
Irritation parameter:
cornea opacity score
Basis:
animal #1
Time point:
24/48/72 h
Score:
0
Max. score:
4
Reversibility:
fully reversible within: 48 hours
Irritation parameter:
iris score
Basis:
animal #1
Time point:
24/48/72 h
Score:
0
Max. score:
2
Reversibility:
fully reversible within: 48 hours
Irritation parameter:
conjunctivae score
Basis:
animal #1
Time point:
24/48/72 h
Score:
0
Max. score:
3
Reversibility:
fully reversible within: 48 hours
Irritation parameter:
chemosis score
Basis:
animal #1
Time point:
24/48/72 h
Score:
0
Max. score:
4
Reversibility:
fully reversible within: 48 hours
Irritation parameter:
cornea opacity score
Basis:
animal #2
Time point:
24/48/72 h
Score:
0
Max. score:
4
Reversibility:
fully reversible within: 48 hours
Irritation parameter:
iris score
Basis:
animal #2
Time point:
24/48/72 h
Score:
0
Max. score:
2
Reversibility:
fully reversible within: 48 hours
Irritation parameter:
conjunctivae score
Basis:
animal #2
Time point:
24/48/72 h
Score:
0.3
Max. score:
3
Reversibility:
fully reversible within: 48 hours
Irritation parameter:
chemosis score
Basis:
animal #2
Time point:
24/48/72 h
Score:
0
Max. score:
4
Reversibility:
fully reversible within: 48 hours
Irritation parameter:
cornea opacity score
Basis:
animal #3
Time point:
24/48/72 h
Score:
0
Max. score:
4
Reversibility:
fully reversible within: 48 hours
Irritation parameter:
iris score
Basis:
animal #3
Time point:
24/48/72 h
Score:
0
Max. score:
2
Reversibility:
fully reversible within: 48 hours
Irritation parameter:
conjunctivae score
Basis:
animal #3
Time point:
24/48/72 h
Score:
0
Max. score:
2
Reversibility:
fully reversible within: 48 hours
Irritation parameter:
chemosis score
Basis:
animal #3
Time point:
24/48/72 h
Score:
0
Max. score:
3
Reversibility:
fully reversible within: 48 hours
Irritant / corrosive response data:
Instillation of 0.1 ml of NECIRES EPX-L into one eye of each of the animals resulted in minimal irritation of the conjunctivae. The irritation consisted of chemosis in two animals (nos. 1941 and 1975) and redness in all three animals, which had completely resolved within 48 hours after instillation. A small amount of discharge was also observed in one animal (no. 1941) 1 hour after instillation. Treatment of the eyes with 2% fluorescein, 24 hours after test substance instillation revealed no corneal epithelial damage in any of the animals.
Other effects:
There was no evidence of ocular corrosion nor was there any peri-ocular staining of tissues by the test substance.
No toxic symptoms were observed in the animals during the test period and nomortality occurred.

INDIVIDUAL OCULAR CHANGES

Time after dosing

Tissue/Finding

Animal 1935 (#1)

Animal 1941 (#2)

Animal 1975 (#3)

1 hour

Corneal opacity

             area

0

0

0

0

0

0

Iris

0

0

0

Conj.: redness

          chemosis

1(A,B,C)

0

1(A,B,C)

1(A)

1(A,B,C)

1(A)

Discharge

0

1

0

24 hours

Corneal opacity

             area

0

0

0

0

0

0

Iris

0

0

0

Conj.: redness

          chemosis

0

0

1(A,C)

0

0

0

Discharge

0

0

0

48 hours

Corneal opacity

             area

0

0

0

0

0

0

Iris

0

0

0

Conj.: redness

          chemosis

0

0

0

0

0

0

Discharge

0

0

0

72 hours

Corneal opacity

             area

0

0

0

0

0

0

Iris

0

0

0

Conj.: redness

          chemosis

0

0

0

0

0

0

Discharge

0

0

0

 

(.) = Score given for: A = Eyelids

                                B = Nictitating membrane

                                C = Sclera      

DRAIZE SCORE CALCULATIONS

Animal no.

Tissue

Hours after application

1 hour

24 hours

48 hours

72 hours

1935 (#1)

Cornea

0

0

0

0

Iris

0

0

0

0

Conjunctivae

2

0

0

0

Subtotal

2

0

0

0

1941 (#2)

Cornea

0

0

0

0

Iris

0

0

0

0

Conjunctivae

6

2

0

0

Subtotal

6

2

0

0

1975 (#3)

Cornea

0

0

0

0

Iris

0

0

0

0

Conjunctivae

4

0

0

0

Subtotal

4

0

0

0

 

Total

12

2

0

0

 

Mean total

4

0.7

0

0

                                   

Interpretation of results:
GHS criteria not met
Conclusions:
Necires EPX-L (phenol, methylstyrenated) is not irritating to eyes acccording to EU/GHS classification criteria as demonstrated in a test according to OECD TG 405.
Executive summary:

Three male rabbits had 0.1 ml phenol, methylstyrenated instilled in their eyes for 24 hours. Following this period, the test substance was washed out, using 2 % fluorescein in water to reveal any signs of irritation. The instillation resulted in minimal irritation of the conjunctivae, irritation of chemosis in two animals and redness in all three animals. In one animal a small amount of dicharge was observed 1 hour after instillation. These symptoms were resolved 48 hours after instillation, and no corneal epithelial damage was seen in any of the animals 24 hours after the instillation. There was no evidence of ocular corrosion nor was there any peri-ocular staining of tissues by the test substance. No toxic symptoms were observed in the animals during the test period, and no mortality occurred. In conclusion, instillation of the test substance into rabbit eyes induced minimal irritation, which was reversible within 48 hours.

Endpoint conclusion
Endpoint conclusion:
no adverse effect observed (not irritating)

Respiratory irritation

Endpoint conclusion
Endpoint conclusion:
no study available

Additional information

Skin irritation

In a GLP compliant primary skin irritation/corrosion study (OECD 404) in the rabbit, the substance oligomerisation and alkylation reaction products of 2-phenylpropene and phenol (previous name phenol, methylstyrenated) was applied to three rabbits. After 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 was observed with a maximum of moderate oedema (grade 3) after 24 hours and of moderate to severe erythema (grades 3-4) 72 hours after exposure. A decrease in the degree of skin irritation was noted from 7 days onwards, reaching score 0 or 1 after 14 days. The irritation had completely resolved within 21 days after exposure in all animals. There was no evidence of any corrosive effects on the skin, nor were there any observed signs of systemic toxicity during the test period.

Eye irritation

A GLP compliant eye irritation/corrosion study (OECD 405) was conducted using the substance oligomerisation and alkylation reaction products of 2-phenylpropene and phenol (OAPP) (previous name phenol, methylstyrenated). The test showed that there was no classifiable eye irritation when using the test substance, nor was there any evidence of eye corrosivity.

Respiratory irritation

There is no data for respiratory irritation.

Effects on skin irritation/corrosion: irritating

Justification for classification or non-classification

The substance oligomerisation and alkylation reaction products of 2-phenylpropene and phenol (previous name phenol, methylstyrenated) induced reversible skin irritation in a skin irritation test according to OECD TG 404. Based on this result, the substance is classified as skin irritating Cat. 2 according to Regulation (EC) No. 1272/2008 (CLP regulation).

Results of an eye irritation test demonstrate that EU classification criteria for eye irritation are not met and that classification for eye irritation is not warranted.

There was no evidence for corrosivity in skin and eye irritancy testing.