Phenol, mono- + distyrenated (MSP+DSP)

Endpoint summary

Description of key information

The supporting substance Necires EPX-L (phenol, methylstyrenated) has been demonstrated to be irritating to skin but not to eyes (studies according to OECD TG 404 and 405). These results are adopted for the target substance phenol, styrenated (LS 500).

Key value for chemical safety assessment

Skin irritation / corrosion

Link to relevant study records

Reference

Reference 1

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:

other: The study was conducted according to GLP and OECD 404 without deviations

Qualifier:

according to guideline

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
- Lot/batch No.: 9356059
- Expiration date of the lot/batch: 1995/02/01
- Stability under storage conditions: stable
- Storage condition of test material: at room temperature in the dark

Species:

rabbit

Strain:

New Zealand White

Details on test animals or test system 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 according to 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:

other: severely irritating

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 of 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 of 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 Necires EPX-L (phenol, methylstyrenated) meets EU classification criteria for skin irritation.

Executive summary:

In a primary skin irritation/corrosion study in the rabbit (4 hours semi-occlusive application), 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 of 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 of 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, nor were there any observed signs of systemic toxicity during the test period. In conclusion, application of phenol, methylstyrenated to intact rabbit skin results in severe irritation, and as such phenol, methylstyrenated is be classified as a skin irritant (Cat.2) according to EU criteria.

Reference 2

Endpoint:

skin irritation: in vivo

Type of information:

read-across from supporting substance (structural analogue or surrogate)

Adequacy of study:

weight of evidence

Justification for type of information:

REPORTING FORMAT FOR THE ANALOGUE APPROACH

1. HYPOTHESIS FOR THE ANALOGUE APPROACH
The source substance Necires EPX-L (Oligomerisation and alkylation reaction products of 2-phenylpropene and phenol, previous name phenol, methylstyrenated) is produced by the same process as LS 500 (phenol, mono- & distyrenated, target substance). In both cases, one reactant is phenol. The second reactant is different being 2-phenylpropene and just styrene for Necires EPX-L and LS 500 respectively.
During the manufacturing process (acid catalysed alkylation reaction), the starting monomeric reactants form di- or higher substituted/condensed products. Reaction products are on the one hand the alkylation products mono- and disubstituted phenol (LS 500 1-phenylethyl and Necires EPX-L 1-methyl-1-phenylethyl substituents, respectively). On the other hand, manufacture of Necires EPX-L results, in addition to the 1-methyl-1-phenylethyl substituted phenols, also in di-/oligomerisation reaction products of the olefinic reaction component. Substituted phenol components of Necires EPX-L and LS 500 differ only in one methyl group that in case of Necires EPX-L is additionally attached to the bridging carbon atom, the substituents being 1-methyl-1-phenylethyl- (Necires EPX-L) and 1-phenylethyl- (LS 500), respectively.

2. SOURCE AND TARGET CHEMICAL(S) (INCLUDING INFORMATION ON PURITY AND IMPURITIES)
Main difference between Necires EPX-L and LS 500 is, that the production of Necires EPX-L results in dimers and oligomers of 2-phenylpropene (olefinic reaction component) in addition to substituted phenols. These di/oligomers are purely alkylaromatic substances with no phenol moiety present. They are composed of an alkyl chain (C5 or longer) that carries two or more phenyl-rings (benzene moieties). Ratio of non-phenolic to phenolic substances in Necires EPX-L is > 0.5.

3. ANALOGUE APPROACH JUSTIFICATION
Summarise here based on available experimental data how these results verify that the read-across is justified]
Use of Necires EPX-L as supporting substance for LS 500 is justified because both substances contain very similar components (substituted phenols), which differ only in one methyl substituent at the bridging carbon chain. In addition, components with the same degree of condensation (equal number of aromatic rings) (either alkylated or di-/oligomerised products) are quite similar in size and have similar spatial arrangements of structural elements. Structural elements are basically the same for both substances, as components are comprised of aromatic rings (benzene and phenol or purely benzene) and of a smaller aliphatic chain, to which the aromatic moieties are attached. Due to the similarity of the structural elements, metabolism and biotransformation will proceed in a similar way. There will be attack at the aliphatic chain resulting in hydroxylated products that subsequently are transformed to aldehydes and carboxylic acids. Metabolism of the aromatic rings will also result in hydroxylated products. Thus, similar metabolites are formed for Necires EPX-L and LS 500. Based on these grounds, it is justified to adopt results of toxicity tests obtained with the source substance Necires EPX-L (phenol, methylstyrenated) for the target substance LS 500 (phenol, mono- & distyrenated).

Reason / purpose for cross-reference:

read-across source

Principles of method if other than guideline:

Read-across to the preceding entry:
Source substance: Phenol, methylstyrenated (Necires EPX-L)
Reference: Pels Rijcken WR 1994

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

Interpretation of results:

Category 2 (irritant) based on GHS criteria

Conclusions:

The supporting substance Necires EPX-L (phenol, methylstyrenated) was determined to be skin irritating Cat. 2 in a test acording to OECD TG 404. Results are adopted for the target substance phenol, styrenated (LS 500).

Endpoint conclusion

Endpoint conclusion:

adverse effect observed (irritating)

Eye irritation

Link to relevant study records

Reference

Reference 1

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:

other: The study was conducted according to GLP and OECD 405 without deviations

Qualifier:

according to guideline

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): Necrires EPX-L
- Lot/batch No.: 9356059
- Expiration date of the lot/batch: 1995/02/01
- Stability under storage 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:

3

Reversibility:

fully reversible within: 48 hours

Irritation parameter:

chemosis score

Basis:

animal #3

Time point:

24/48/72 h

Score:

0

Max. score:

4

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 (methyl styrenated) instilled in their eyes for 24 hours. Following this period the test substance was washed out using 2 % fluroescein 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.

Reference 2

Endpoint:

eye irritation: in vivo

Type of information:

read-across from supporting substance (structural analogue or surrogate)

Adequacy of study:

weight of evidence

Justification for type of information:

REPORTING FORMAT FOR THE ANALOGUE APPROACH

1. HYPOTHESIS FOR THE ANALOGUE APPROACH
The source substance Necires EPX-L (Oligomerisation and alkylation reaction products of 2-phenylpropene and phenol, previous name phenol, methylstyrenated) is produced by the same process as LS 500 (phenol, mono- & distyrenated, target substance). In both cases, one reactant is phenol. The second reactant is different being 2-phenylpropene and just styrene for Necires EPX-L and LS 500 respectively.
During the manufacturing process (acid catalysed alkylation reaction), the starting monomeric reactants form di- or higher substituted/condensed products. Reaction products are on the one hand the alkylation products mono- and disubstituted phenol (LS 500 1-phenylethyl and Necires EPX-L 1-methyl-1-phenylethyl substituents, respectively). On the other hand, manufacture of Necires EPX-L results, in addition to the 1-methyl-1-phenylethyl substituted phenols, also in di-/oligomerisation reaction products of the olefinic reaction component. Substituted phenol components of Necires EPX-L and LS 500 differ only in one methyl group that in case of Necires EPX-L is additionally attached to the bridging carbon atom, the substituents being 1-methyl-1-phenylethyl- (Necires EPX-L) and 1-phenylethyl- (LS 500), respectively.

2. SOURCE AND TARGET CHEMICAL(S) (INCLUDING INFORMATION ON PURITY AND IMPURITIES)
Main difference between Necires EPX-L and LS 500 is, that the production of Necires EPX-L results in dimers and oligomers of 2-phenylpropene (olefinic reaction component) in addition to substituted phenols. These di/oligomers are purely alkylaromatic substances with no phenol moiety present. They are composed of an alkyl chain (C5 or longer) that carries two or more phenyl-rings (benzene moieties). Ratio of non-phenolic to phenolic substances in Necires EPX-L is > 0.5.

3. ANALOGUE APPROACH JUSTIFICATION
Use of Necires EPX-L as supporting substance for LS 500 is justified because both substances contain very similar components (substituted phenols), which differ only in one methyl substituent at the bridging carbon chain. In addition, components with the same degree of condensation (equal number of aromatic rings) (either alkylated or di-/oligomerised products) are quite similar in size and have similar spatial arrangements of structural elements. Structural elements are basically the same for both substances, as components are comprised of aromatic rings (benzene and phenol or purely benzene) and of a smaller aliphatic chain, to which the aromatic moieties are attached. Due to the similarity of the structural elements, metabolism and biotransformation will proceed in a similar way. There will be attack at the aliphatic chain resulting in hydroxylated products that subsequently are transformed to aldehydes and carboxylic acids. Metabolism of the aromatic rings will also result in hydroxylated products. Thus, similar metabolites are formed for Necires EPX-L and LS 500. Based on these grounds, it is justified to adopt results of toxicity tests obtained with the source substance Necires EPX-L (phenol, methylstyrenated) for the target substance LS 500 (phenol, mono- & distyrenated).

Reason / purpose for cross-reference:

read-across source

Principles of method if other than guideline:

Read-across to the preceding entry:
Source substance: Phenol, methylstyrenated (Necires EPX-L)
Reference: Pels Rijcken WR 1994

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:

3

Reversibility:

fully reversible within: 48 hours

Irritation parameter:

chemosis score

Basis:

animal #3

Time point:

24/48/72 h

Score:

0

Max. score:

4

Reversibility:

fully reversible within: 48 hours

Interpretation of results:

GHS criteria not met

Conclusions:

The supporting substance 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. Results are adopted for the target substance phenol, styrenated (LS 500).

Endpoint conclusion

Endpoint conclusion:

no adverse effect observed (not irritating)

Respiratory irritation

Endpoint conclusion

Endpoint conclusion:

no study available

Justification for classification or non-classification

Based on results of a skin irritation test according to OECD TG 404 with the supporting substance Necires EPX-L (phenol, methylstyrenated), phenol, mono- & distyrenated (LS 500) 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.