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Description of key information

Skin Irritation:

The minimum mean dermal irritation score at any observation was 0.0 (Maximum possible score is 8.0).No animal showed any indication of dermal irritation.

Thus, it was considered that 4 methoxy phenylacetic acid (MPAA) was not irritating to skin.

Eye Irritation:

The maximum mean irritation score was 71.2 (of 110 possible maximum) which occurred on day 3.

4-MethoxyphenyIacetic Acid (MPAA) was considered to be a very severe irritant to the eye of albino rabbits under the conditions of these studies causing effects which were not reversed within 21 days of treatment. Immediate washing of the eyes resulted in reduced irritation and more rapid recovery.

4-MethoxyphenyIacetic Acid (MPAA) may be classified under the category of eye irritant.

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:
weight of evidence
Reliability:
4 (not assignable)
Rationale for reliability incl. deficiencies:
secondary literature
Justification for type of information:
Data is from NTIS study report.
Qualifier:
no guideline available
Principles of method if other than guideline:
Skin irritation study was carried out to test the effects of 4 methoxy phenylacetic acid (MPAA) on New Zealand rabbits at concentration of 0.5gms.
GLP compliance:
not specified
Specific details on test material used for the study:
- Name of test material (as cited in study report):4 methoxy phenylacetic acid (MPAA)
- Molecular formula : C9H10O3
- Molecular weight : 166.175g/mol
- Smiles notation: c1(ccc(OC)cc1)CC(O)=O
- InChl : 1S/C9H10O3/c1-12-8-4-2-7(3-5-8)6-9(10)11/h2-5H, 6H2, 1H3, (H,10,11)
- Substance type: Organic
- Physical state: Solid
Species:
rabbit
Strain:
New Zealand White
Details on test animals or test system and environmental conditions:
No data available
Type of coverage:
other: Gauze patch and adhesive tape
Preparation of test site:
clipped
Vehicle:
water
Controls:
not specified
Amount / concentration applied:
0.5gms
Duration of treatment / exposure:
4 hours
Observation period:
1 hrs after removal of cover and 1,2,3 days after removal
Number of animals:
6 animals
Details on study design:
TEST SITE
- Area of exposure: 6 square cms of clipped skin
- Type of wrap if used: Gauze patch

REMOVAL OF TEST SUBSTANCE
- Washing (if done): Skin wiped free of excess test material with absorbant pad
- Time after start of exposure: 4 hours

SCORING SYSTEM: Draize scoring system approx 1 hr after removal of cover and 1,2 3 days after removal.



Irritation parameter:
other: maximum mean dermal irritation score
Basis:
mean
Time point:
other: 1 hr,1,2 and 3 days
Score:
0
Max. score:
8
Reversibility:
not specified
Remarks on result:
no indication of irritation
Irritant / corrosive response data:
not irritating to skin of rabbits
Interpretation of results:
other: not irritating
Conclusions:
4 methoxy phenylacetic acid (MPAA) was considered to be not irritating under test conditions of this study.
Executive summary:

A skin irritation study was carried out to test the effects of 4 methoxyphenyl acetic acid on New Zealand rabbits. Six New Zealad White rabbits were treated with 0.5 gm of test substance moistened with water.The Area of exposure was 6 square cm of clipped skin and the wrap used was Gauze patch. The cover was removed after 4 hours of exposure and the skin was wiped free of excess test material with absorbant pad.The skin reactions in the rabbits were observed and evaluated according to Draize method after 1 hr of removal of cover and 1, 2,3 days after removal . The minimum mean dermal irritation score at any observation was 0.0 (Maximum possible score is 8.0). No animal showed any indication of dermal irritation.

Thus, it was considered that 4 methoxy phenylacetic acid (MPAA) was not irritating to skin.

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

Eye irritation

Link to relevant study records
Reference
Endpoint:
eye irritation: in vivo
Type of information:
experimental study
Adequacy of study:
weight of evidence
Reliability:
4 (not assignable)
Rationale for reliability incl. deficiencies:
secondary literature
Justification for type of information:
Data is from NTIS study report.
Qualifier:
no guideline available
Principles of method if other than guideline:
The eye irritation potential of 4-methoxyphenylacetic acid was assessed in rabbits according to the Draize method.
GLP compliance:
not specified
Specific details on test material used for the study:
- Name of test material (as cited in study report): 4-methoxyphenylacetic acid
- Molecular formula : C9H10O3
- Molecular weight : 166.175g/mol
- Smiles notation : c1(ccc(OC)cc1)CC(O)=O
- InChl : 1S/C9H10O3/c1-12-8-4-2-7(3-5-8)6-9(10)11/h2-5H, 6H2, 1H3, (H,10,11)
- Substance type: Organic
- Physical state: Solid
Species:
rabbit
Strain:
New Zealand White
Details on test animals or tissues and environmental conditions:
No data available
Vehicle:
physiological saline
Controls:
not specified
Amount / concentration applied:
0.1gm
Duration of treatment / exposure:
21 days
Observation period (in vivo):
1hr ,1,2, 3,4 ,7,14and 21 days
Duration of post- treatment incubation (in vitro):
no data available
Number of animals or in vitro replicates:
9 animals (one animal and 8 additional animals)
Details on study design:
TEST SITE: Right eye
REMOVAL OF TEST SUBSTANCE
- Washing (if done): Yes with room temperature saline solution 30 seconds after application of test material.
Irritation parameter:
overall irritation score
Basis:
mean
Time point:
other: 3 days
Score:
71.2
Max. score:
110
Reversibility:
not reversible
Remarks on result:
probability of severe irritation
Irritant / corrosive response data:
Discharge ,swelling ,redness between one hr and 3 days Cornal opacity, iritis and conjunctival irritation.
Interpretation of results:
Category 2 (irritating to eyes) based on GHS criteria
Conclusions:
4-MethoxyphenyIacetic Acid (MPAA) was considered to be a very severe irritant to the eye of New Zealand White rabbits under the conditions of these studies causing effects which were not reversed within 21 days of treatment. Immediate washing of the eyes resulted in reduced irritation and more rapid recovery.
4-MethoxyphenyIacetic Acid (MPAA) may be classified under the category 2 (irritating to eyes).
Executive summary:

The eye irritation potential of 4-methoxyphenylacetic acid was assessed in rabbits according to the Draize method. The test was conducted on New Zealand White rabbits.

Test is first performed on one rabbit with 0.1gm of test substance, the treated eye showed moderate irritation, Thereafter 8 additional animals were tested and subjected to rinsing with normal saline after 30 seconds of administration .Ocular lesions were scored approx 1 hr, 1 day upto 21 days. Even 21 days after treatment, un-rinsed eyes in 5/6 treated animals displayed corneaI opacity, iritis and conjunctival irritation. The maximum mean irritation score was 71.2 (of 110 possible maximum) which occurred on day 3, the rinsed eyes showed milder effects; however, serious adverse effects persisted to day 21. 4-MethoxyphenyIacetic Acid (MPAA) was considered to be a very severe irritant to the eye of albino rabbits under the conditions of these studies causing effects which were not reversed within 21 days of treatment. Immediate washing of the eyes resulted in reduced irritation and more rapid recovery.

4-MethoxyphenyIacetic Acid (MPAA) may be classified under the category 2 (irritating to eyes).

Endpoint conclusion
Endpoint conclusion:
adverse effect observed (irritating)

Respiratory irritation

Endpoint conclusion
Endpoint conclusion:
no study available

Additional information

Skin Irritation:

For evaluation of dermal irritation potential of 4-MethoxyphenyIacetic Acid (MPAA),4 studies of target chemical along with read across substance are summarized as follows:

Study 1:

A skin irritation study was carried out by NTIS (1991), to test the effects of 4 methoxyphenyl acetic acid on New Zealand rabbits. Six New Zealand White rabbits were treated with 0.5 gm of test substance moistened with water. The Area of exposure was 6 square cm of clipped skin and the wrap used was Gauze patch. The cover was removed after 4 hours of exposure and the skin was wiped free of excess test material with absorbant pad. The skin reactions in the rabbits were observed and evaluated according to Draize method after 1 hr of removal of cover and 1, 2, 3 days after removal . The minimum mean dermal irritation score at any observation was 0.0 (Maximum possible score is 8.0).No animal showed any indication of dermal irritation.

Thus, it was considered that 4 methoxy phenylacetic acid (MPAA) was not irritating to skin.

Studies 2, 3 are estimated data for 4-methoxy phenylacetic acid (MPAA)

Study 2:

The dermal irritation potential of 4-methoxyphenylacetic acid (MPAA) was predicted using the OECD QSAR toolbox version 3.4 with log kow as the primary descriptor and considering the five closest read across substances.

4 -methoxy phenylacetic acid(MPAA) was estimated to be not irritating to the skin of New Zealand White rabbits.

On the basis of the estimated result, 4 -methoxy phenylacetic acid (MPAA) can be considered to be not irritating to skin and can be classified under the category "Not Classified" as per CLP regulation.

Study 3:

Skin irritation effects were estimated by four different models i.e, Battery, leadscope, SciQSAR and CASE Ultra used within Danish QSAR database for chemical 4-methoxy phenylacetic acid.

Based on estimation, no severe skin irritation effect were known when test chemical, 4 -methoxy phenylacetic acid was exposed to rabbit skin.

The estimated results of Studies 2, 3 are in agreement with the experimental data (Study 1)

Study 4:

A pre-screen test for a human maximization study was conducted (Food and Chemical Toxicology 50 (2012) S134–S139) to evaluate the irritation potential of the similar substance 105-13-5 (4-methoxybenzyl alcohol).

5% anisyl alcohol in petrolatum (3450 microgram/cm2) was applied under occlusion to the normal skin of seven subjects for 48 h and the effects were observed.

No irritation was observed in all the volunteers after 48 hours.

Hence, 4 -methoxybenzyl alcohol can be considered as not irritating to skin.

The read across study also supports to the possibility of 4 methoxy phenylacetic acid (MPAA) being not irritating to skin.

Therefore, by applying the weight of evidence approach, 4 methoxyphenylacetic acid (MPAA) can be considered to be not irritating to skin. It can be classified under the category "Not Classified" as per CLP regulation.

Eye Irritation:

For evaluation of ocular irritation potential of 4-MethoxyphenyIacetic Acid (MPAA), 3 studies of target chemical along with relevant read across substances are summarized as follows:

Study 1:

The eye irritation potential of 4-methoxyphenylacetic acid was assessed (NTIS;1991) in rabbits according to the Draize method. The test was conducted on New Zealand White rabbits.

Test is first performed on one rabbit with 0.1gm of test substance, the treated eye showed moderate irritation, Thereafter 8 additional animals were tested and subjected to rinsing with normal saline after 30 seconds of administration .Ocular lesions were scored approx 1 hr 1 day upto 21 days. Even 21 days after treatment, un-rinsed eyes in 5/6 treated animals displayed corneaI opacity, iritis and conjunctival irritation. The maximum mean irritation score was 71.2 (of 110 possible maximum) which occurred on day 3, the rinsed eyes showed milder effects; however, serious adverse effects persisted to day 21. 4-MethoxyphenyIacetic Acid (MPAA) was considered to be a very severe irritant to the eye of albino rabbits under the conditions of these studies causing effects which were not reversed within 21 days of treatment. Immediate washing of the eyes resulted in reduced irritation and more rapid recovery.

4-MethoxyphenyIacetic Acid (MPAA) may be classified under the category of eye irritant.

Studies 2, 3 are the experimental data for the relevant read across substances.

Study 2:

A rabbit eye irritation study was performed (SAX (Sax's Handbook of Dangerous Industrial Materials), 2007) to assess the irritation potential of the similar substance 111-27-3 (hexan-1-ol).

250 g of hexan-1-ol instilled into rabbit eye and effects were observed till 72 hours and reactions were scored. The maximum score was 10. Scores over 5 were considered to cause severe eye injury.

Hexan-1-ol was graded 9/10 after 72 hours. Based on the scores, Hexan-1-ol can be considered as a severe eye irritant with a possibility to cause injury to rabbit eyes.

Study 3

Acute toxicity studies were carried out (American Industrial Hygiene Association Journal, (1973), 34:11, 493-499) to estimate the toxicity of the similar substance 112-70-9 (tridecyl alcohol).

A single application of 0.1 ml of undiluted tridecyl alcohol was made into the conjunctival sac of the left eye of each of six rabbits. The untreated eye served as the control. The treated eye was closed for 30 seconds and eyes were not washed. Observations for irritancy and possible systemic toxicity were made at 1, 4, and 24 hours and at 2, 3, 4, and 7 days. Where positive effects persisted, observations were continued initially and at termination the eyes were examined following instillation of 2 % sodium fluorescein solution to detect any corneal lesions if not otherwise visible. Grading scale is slight-moderate-marked and severe. Signs of irritation exposure were graded and scored according to the method of Draize.

Tridecyl alcohol caused little irritation in most of the animals, but persistent corneal opacity in one caused the classification as moderate. Tridecyl alcohol can be considered as moderately irritating to eyes.

The read across studies also supports to the possibility of 4 methoxy phenylacetic acid (MPAA) being irritating to eyes.

Therefore, by applying the weight of evidence approach, 4 methoxy phenylacetic acid (MPAA) can be considered to be irritating to eyes. It can be classified under the category "Category 2 (irritating to eyes)" as per CLP regulation.

Justification for classification or non-classification

Available studies for 4 methoxyphenylacetic acid (MPAA) indicate that it is not irritating to skin but irritating to eyes.

4-methoxyphenylacetic acid (MPAA) can be classified under the category "Not Classified" for Skin Irritation, and “Category 2 (irritating to eyes)" for Eye Irritation as per CLP regulation.