Phenol, ethoxylated, esters with acrylic acid

Endpoint summary

Description of key information

The dermal irritation of Phenol, ethoxylated, esters with acrylic acid was investigated in one study, showing mild to slight irritation. Well-defined dermal irritation was observed in two of three animals 4 hours after application, and with the primary irritation index (PII) of 1.2. The CLP-criteria for a classification as skin irritant is therefore not met.

No data was available on eye irritation is available for Phenol, ethoxylated, esters with acrylic acid, therefore read-across has been made to 2-phenoxyethyl acrylate. The eye irritation of 2-phenoxyethyl acrylate was investigated in a rabbit study, showing slight irritation after 48 hours. However, the irritation had disappeared at 72 hours hence it is fully reversible. The criteria for CLP classification as eye irritant is therefore not met. Due to structural and pysico-chemical similarity to Phenol, ethoxylated, esters with acrylic acid, this can also be concluded for Phenol, ethoxylated, esters with acrylic acid as well.

See attached read-across justification in section 13

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

Reliability:

1 (reliable without restriction)

Rationale for reliability incl. deficiencies:

guideline study

Qualifier:

according to guideline

Guideline:

OECD Guideline 404 (Acute Dermal Irritation / Corrosion)

Qualifier:

according to guideline

Guideline:

EU Method B.4 (Acute Toxicity: Dermal Irritation / Corrosion)

Qualifier:

according to guideline

Guideline:

EPA OPPTS 870.2500 (Acute Dermal Irritation)

GLP compliance:

yes (incl. QA statement)

Specific details on test material used for the study:

SOURCE OF TEST MATERIAL
- Source and lot/batch No.of test material: Miramer M142, Lot. No.: 0082301
- Expiration date of the lot/batch: 30 April 2001
- Purity test date: Not specified
- Purity: >95%

STABILITY AND STORAGE CONDITIONS OF TEST MATERIAL
- Storage condition of test material: Room temperature in the dark.
- Stability under test conditions: NA
- Solubility and stability of the test substance in the solvent/vehicle: NA
- Reactivity of the test substance with the solvent/vehicle of the cell culture medium: NA

TREATMENT OF TEST MATERIAL PRIOR TO TESTING
- Treatment of test material prior to testing: administred as supplied by sponsor.
- Preliminary purification step (if any):NA
- Final dilution of a dissolved solid, stock liquid or gel: NA
- Final preparation of a solid:NA

FORM AS APPLIED IN THE TEST (if different from that of starting material)
Exposure scenarios
OTHER SPECIFICS: NA

Species:

rabbit

Strain:

New Zealand White

Details on test animals or test system and environmental conditions:

Weight range beteen 2.8 and 3.8kg bw, Age at least 10weeks prior first treatment. Housed individually in metal cages. Standard laboratory diet, SQC Rabbit Diet and drinking water ad libitum. Temperature 17-21 C, relative humidity 30-70%. Air exchange per hour was not specified. 12 hour/12 hours Light/dark cycle

Type of coverage:

semiocclusive

Preparation of test site:

clipped

Vehicle:

unchanged (no vehicle)

Controls:

no

Amount / concentration applied:

0.5 ml was applied under 25*25mm gauze pads to each intact skin site on each animal.

Duration of treatment / exposure:

3 minutes, 60 minutes and 4 hours

Observation period:

On the day of exposure ( 3 minutres and one hour), 24, 48 and 72 hours

Number of animals:

3 animals

Details on study design:

TEST SITE
- Area of exposure: 25 mm x 25 mm
- % coverage: not specified
- Type of wrap if used: Semi occlusive: Porous gauze pads and Elastoplast elastic adhesive dressing.

REMOVAL OF TEST SUBSTANCE
- Washing (if done): warm water 34-37 oC
- Time after start of exposure: three minutes, one hour and four hours

OBSERVATION TIME POINTS
(indicate if minutes, hours or days) three minutes, one hour and four hours.

SCORING SYSTEM:
- Method of calculation: Primary irritation index (PII) was calculated from the erythema and oedema scores.

Irritation parameter:

primary dermal irritation index (PDII)

Basis:

mean

Time point:

24/48/72 h

Score:

ca. 1.2

Reversibility:

fully reversible within: 96 hours

Irritant / corrosive response data:

Well-defiend erythema with very slight-to-slight oedema was observed in two animals from approximately one hour after bandage removal following the four hours exposure. Reaction had resolved in both animals by Day 4 (96h). No dermal irritation was observed in the remaining animals throughout the study.

Other effects:

No signs of toxicity or ill health

Interpretation of results:

slightly irritating

Remarks:

Migrated information Criteria used for interpretation of results: US CPSC / US FDA

Conclusions:

The skin irritation potential of M142 was tested using semi-occlusive application for four hours in three Rabbits (one male and two females) according to OECD test guideline 404. Dermal irritation was observed in two of three animals 4 hours after application. The primary irritation index (PII) was calculated to be 1.2. Based on the present test M142 was not subject for classification as a skin irritating substance.

Executive summary:

The skin irritation potential of M142 was tested using semi-occlusive application for four hours in three Rabbits (one male and two females) according to OECD test guideline 404.

Dermal observations were made three minutes, one hour, four hours, 24, 48 and 72 hours after removal of the semi-occlusive dressing. Well-defined dermal irritation was observed in two of three animals 4 hours after application. The primary irritation index (PII) was calculated to be 1.2. Mean values of erythema and oedema were below the values triggering CLP classification. Hence, based on the present test M142 was not subject for classification as a skin irritating substance. 

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

Reliability:

1 (reliable without restriction)

Rationale for reliability incl. deficiencies:

other: Standard draize test with no deviations reported

Reason / purpose for cross-reference:

reference to same study

Qualifier:

according to guideline

Guideline:

other: Draize: Appraisal of the safety of chemicals in foods, drugs and cosmetics. In Dermal toxicity p. 46-59 1959

Principles of method if other than guideline:

The eye irritation potential was test as described by Draize; Appraisal of the safety of chemicals in foods, drugs and cosmetics. In dermal toxicity p. 46 -59, 1959: Austin, Tex: Association of food and drug officials of the united states.
The substance was applied to one eye, and irritation score was measured after 1 hour, 24 hours, 48 hours 72 hours and 8 days.

GLP compliance:

not specified

Species:

rabbit

Strain:

Vienna White

Details on test animals or tissues and environmental conditions:

Animals were kept in steel cages, one animal per cage. 20-26C, relative humidity; 30-70%. 12:12 light:dark cycle, light from 0600 to 1800.

Vehicle:

unchanged (no vehicle)

Controls:

no

Amount / concentration applied:

0.1 ml undiluted

Duration of treatment / exposure:

The substance was applied once, and not washed off

Observation period (in vivo):

1 hour, 24 hours, 48 hours, 72 hours and 8 days.

Number of animals or in vitro replicates:

6 animals

Details on study design:

Untreated eye served as control

Irritation parameter:

conjunctivae score

Basis:

mean

Time point:

other: 24 hours

Score:

ca. 1

Max. score:

1

Reversibility:

fully reversible

Irritant / corrosive response data:

After 24 hours no effects were observed in stratum corneum, or iris. All six animals showed light increased redness in conjuctival tissue, without swelling, but two animals showed light secretion. After 48 hours only one animal showed increased redness in conjuctival tissue, no other effetcs were observed. no effects were seen at later time points, the eye irritation effects were therefore fully reversible.

Interpretation of results:

slightly irritating

Remarks:

Migrated information Criteria used for interpretation of results: US CPSC / US FDA

Conclusions:

2-phenoxyethyl acrylate is slightly irritating to the rabbits eye when applied undiluted. The irritating effect were observed as slightly increased redness of conjuctival tissue, and the effect were fully reversible within 48 hours.

Executive summary:

The eye irritation potential of 2 -phenoxyethyl acrylate was investigated in rabbits following the draize test. The substance was shown to be slightly irritating, but fully reversible after 48 hours.

Reference 2

Endpoint:

eye irritation: in vivo

Type of information:

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

Adequacy of study:

key study

Justification for type of information:

Eye irritation test on the read-across substance 2-phenoxyethyl acrylate.
See attached read-across justification in section 13

Reason / purpose for cross-reference:

read-across source

Irritation parameter:

conjunctivae score

Basis:

mean

Time point:

24 h

Score:

1

Max. score:

1

Reversibility:

fully reversible

Executive summary:

No data is available for Phenol, ethoxylated, esters with acrylic acid (T).

The eye irritation potential of 2 -phenoxyethyl acrylate (S1) were investigated in rabbits following the draize test. The substance was shown to be slightly irritating, but fully reversible after 48 hours. Due to structural and pysico-chemical similarity to Phenol, ethoxylated, esters with acrylic acid, a reversible eye irritation potential can be concluded for Phenol, ethoxylated, esters with acrylic acid as well.

See justification for read-across attached in section 13.

Endpoint conclusion

Endpoint conclusion:

adverse effect observed (irritating)

Respiratory irritation

Endpoint conclusion

Endpoint conclusion:

no study available

Additional information

The available experimental data suggest that Phenol, ethoxylated, esters with acrylic acid (M142) is not corrosive, as all observed effects were fully reversible.

The key study on dermal irritation found that two of three animal had dermal reactions, leading to a primary irritation index of 1.2. The major criteria for classification as irritant is therefore not met ( at least two of three animals, with a mean score between 2.3 to 4.0).

The data from a study with the read-across substance 2-phenoxyethyl acrylate (S1) showed that all animals have ligth redness, score 1, which was only persisting in one animal after 48 hours (ligthly increased redness) and fully reversible in all animals after 72 hours.

.

Justification for selection of skin irritation / corrosion endpoint:
OECD TG 404 study in rabbits, performed according to GLP.

Justification for selection of eye irritation endpoint:
No studies were available for Phenol, ethoxylated, esters with acrylic acid. Hence, read-across was made to an in vivo eye irritation study for 2 -phenoxyethyl acrylate.

Effects on skin irritation/corrosion: slightly irritating

Effects on eye irritation: slightly irritating

Justification for classification or non-classification

A skin irritation study (4 hours exposure) found that Phenol, ethoxylated, esters with acrylic acid was slightly irritating but reversible., dermal reactions were observed only in two out of three animals, and with the dermal irritation index of 1.2. The major criteria for a classification as skin irritant is therefor not met.

For classification as an eye irritant the criteria was also not met, as the reactions observed were fully reversible, and mean scores following grading 24, 48, and 72 hours were lower than the criteria set in table 3.3.2 in Regulation (ec) 1272/2008.