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Description of key information

Acute toxicity – oral

LD50 was considered to be > 2000 mg/kg bw and < 5000 mg/kg bw when rat were treated with (4-methoxyphenyl) acetic acid orally.

Acute toxicity – dermal

LD50 was considered to be > 2000 mg/kg bw when New Zealand White male and female rabbits were treated with 4-methoxyphenylacetic acid under an occlusive wrapping for 24 hours.

Key value for chemical safety assessment

Acute toxicity: via oral route

Link to relevant study records
Reference
Endpoint:
acute toxicity: oral
Type of information:
experimental study
Adequacy of study:
weight of evidence
Study period:
23/08/1990 to 24/10/9090
Reliability:
4 (not assignable)
Rationale for reliability incl. deficiencies:
secondary literature
Justification for type of information:
Toxicity study data from Hoechst Celanese corporation
Qualifier:
according to guideline
Guideline:
other: AOOECDL-001
Principles of method if other than guideline:
Acute oral toxicity study of 4-methoxyphenylacetic acid in rats.
GLP compliance:
yes
Test type:
standard acute method
Limit test:
no
Specific details on test material used for the study:
- Name of test material (as cited in study report): (4-methoxyphenyl) acetic acid
- Molecular formula:C9H10O3
- Molecular weight:166.175 g/mole
- Substance type:Organic
- Physical state:White powder or flakes, sliqht odour
- Purity-100%
Species:
rat
Strain:
Sprague-Dawley
Sex:
male/female
Details on test animals or test system and environmental conditions:
Source: Healthy animals were obtained from SASCO Inc., Omaha, Nebraska.
- Age at study initiation: Males: Approx. 9 week of mle and 12 week of female
- Weight at study initiation: Approximately 190-350 gram at pre-fast. Animal weights fell within 20% of the group mean.
- Fasting period before study: The animals were fasted the night immediately prior to dosing.
-Housing: Animals were housed Individually, separate from other species, in Stainless Steel, wire mesh bottom cages and Each animal was assigned a unique and individual nuaber. This nuaber was peraanently indicated on the aniaal with an ear tag.
Diet (e.g. ad libitum): Fresh certified Agway rodent feed was provided ad libitum, except feed was withheld the night prior to dosing.
- Water (e.g. ad libitum): Fresh potable water was provided ad libitum.
- Acclimation period: 8 days

ENVIRONMENTAL CONDITIONS
- Temperature (°C): Within protocol limits of 77.7- 26.1 °C
- Humidity (%):Within protocol limits of 30 – 70%
- Air changes (per hr):No data
- Photoperiod (hrs dark / hrs light): 12/12 hour, light/dark cycle
Route of administration:
oral: gavage
Vehicle:
corn oil
Details on oral exposure:
VEHICLE
- Concentration in vehicle: 0,2000 and 5000 mg/kg
- Amount of vehicle (if gavage): 1 ml/100 g fasted body weight
- Justification for choice of vehicle: Corn oil
- Lot/batch no. (if required): 19F0038
- Purity: No Data

MAXIMUM DOSE VOLUME APPLIED:5000mg/kg

DOSAGE PREPARATION (if unusual): Test article, homogenized in corn oil at 0,2000 and 5000 mg/kg

CLASS METHOD (if applicable)
- Rationale for the selection of the starting dose: No Data
Doses:
0,2000 and 5000 mg/kg
No. of animals per sex per dose:
Total: 30
0 mg/kg bw 5 male and 5 female
2000 mg/kg bw 5 male and 5 female
5000 mg/kg bw 5 male and 5 female
Control animals:
yes
Details on study design:
- Duration of observation period following administration: 14 days
- Frequency of observations and weighing: hourly for the firlt 4 hour immediately after dosing and twice daily (am. and pm ) for the next 13 and 14 days
- Necropsy of survivors performed: yes
- Other examinations performed: MortalityClinical signs, body weight and gross pathology were examined.
Statistics:
No details
Preliminary study:
No data available
Sex:
male/female
Dose descriptor:
LD50
Effect level:
> 2 000 - < 5 000 mg/kg bw
Based on:
test mat.
Remarks on result:
other: Effect on survival, body weights, Organ weights and gross pathology
Mortality:
When treated with 5000 mg/kg, 90% mortality was observed in treated male and female rats as compared to control.
When treated with 2000 mg/kg, 10% mortality was observed in treated male and female rats as compared to control
l.
Clinical signs:
When treated with 5000 mg/kg, oral discharge, nasal discharge, tremors, ataxia abnormal stool, lethargy, Stained coat, alopecia, hunched posture, necrosis, unthriftinees and anal discharge were observed in treated male and female rats as compared to control.
Body weight:
When treated with 5000 mg/kg, decrease in weight was observed in surviving one animal at end of the study.
When treated with 2000 mg/kg, weight gain were observed and All of the control animals also gained weight through the study period.
Gross pathology:
Liver lesions were observed in all the treated rats at 5000 mg/kg dose group.
Increased incidences of liver lesions relative to control were observed in 2000 mg/kg bw treated male and female rats considered to be treatment related.
Other findings:
No data available

MORTALITY DATA SUMMARY (DOSE: 5 G/KG)

Day

0

1

2

3

4

5

6

7

8

9

10

11

12

13

Males Alive

5

3

2

1

1

1

1

1

1

1

1

1

1

1

Males Dead

0

2

3

4

4

4

4

4

4

4

4

4

4

4

Percent Dead

0

0

60

80

80

80

80

80

80

80

80

80

80

80

Females Alive

5

3

1

0

0

0

0

0

0

0

0

0

0

0

Females Dead

0

2

4

5

5

5

5

5

5

5

5

5

5

5

Percent Dead

0

40

80

100

100

100

100

100

100

100

100

100

100

100

 

MORTALITY DATA SUMMARY (DOSE 2 G/KG) 

Day

0

1

2

3

4

5

6

7

8

9

10

11

12

13

Males Alive

5

5

5

5

5

5

5

5

5

5

5

5

5

5

Males Dead

0

0

0

0

0

0

0

0

0

0

0

0

0

0

Percent Dead

0

0

0

0

0

0

0

0

0

0

0

0

0

0

Females Alive

5

5

4

4

4

4

4

4

4

4

4

4

4

4

Females Dead

0

0

1

1

1

1

1

1

1

1

1

1

1

1

Percent Dead

0

0

20

20

20

20

20

20

20

20

20

20

20

20

 

MORTALITY DATA SUMMARY (VEHICLE CONTROL) 

Day

0

1

2

3

4

5

6

7

8

9

10

11

12

13

Males Alive

5

5

5

5

5

5

5

5

5

5

5

5

5

5

Males Dead

0

0

0

0

0

0

0

0

0

0

0

0

0

0

Percent Dead

0

0

0

0

0

0

0

0

0

0

0

0

0

0

Females Alive

5

5

5

5

5

5

5

5

5

5

5

5

5

5

Females Dead

0

0

0

0

0

0

0

0

0

0

0

0

0

0

Percent Dead

0

0

0

0

0

0

0

0

0

0

0

0

0

0

 

Interpretation of results:
not classified
Conclusions:
LD50 was considered to be > 2000 mg/kg bw and < 5000 mg/kg bw when rats were treated with 4-methoxyphenylacetic acid orally by gavage in corn oil.
Executive summary:

In a acute oral toxicity study, Sprague Dawley male and female rats were treated with 4-methoxyphenylacetic acid in the concentration of 0, 2000 and 5000 mg/kg orally by gavage in corn oil and observed for 14 days. 90% mortality was observed at 5000 mg/kg bw and 10% mortality at 2000 mg/kg bw in treated male and female rats as compared to control. Oral discharge, nasal discharge, tremors, ataxia abnormal stool, lethargy, Stained coat, alopecia, hunched posture, necrosis, unthriftinees and anal discharge were observed at 5000 mg/kg in treated male and female rats as compared to control. Decrease in weight was observed in surviving one animal at end of the study at 5000 mg/kg bw, weight gain were observed at 2000 mg/jkg bw and all of the control animals also gained weight through the study period. Liver lesions were observed in all the treated rats at 5000 mg/kg dose group. Increased incidences of liver lesions relative to control were observed in 2000 mg/kg bw treated male and female rats considered to be treatment related. Therefore, LD50 was considered to be > 2000 mg/kg bw and < 5000 mg/kg bw when rats were treated with 4-methoxyphenylacetic acid orally by gavage in corn oil.

Endpoint conclusion
Endpoint conclusion:
no adverse effect observed
Dose descriptor:
LD50
Value:
2 000 mg/kg bw
Quality of whole database:
The data is K4 level as the data has been obtained from the study report.

Acute toxicity: via inhalation route

Endpoint conclusion
Endpoint conclusion:
no study available

Acute toxicity: via dermal route

Link to relevant study records
Reference
Endpoint:
acute toxicity: dermal
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
Principles of method if other than guideline:
Acute dermal toxicity studies of (4-methoxyphenyl) acetic acid were carried out on ten new Zealand rabbits(Male and female) under occlusive wrapping to determine the LD50.
GLP compliance:
not specified
Test type:
other: Acute dermal
Limit test:
yes
Specific details on test material used for the study:
- Name of test material (as cited in study report):(4-methoxyphenyl) acetic acid
- Molecular formula: C9H10O3
- Molecular weight: 166.175 g/mole
- Substance type: Organic
Species:
rabbit
Strain:
New Zealand White
Sex:
male/female
Details on test animals or test system and environmental conditions:
No details available
Type of coverage:
occlusive
Vehicle:
not specified
Details on dermal exposure:
TEST SITE
- Area of exposure:no data
- % coverage:no data
- Type of wrap if used:occlusive wrapping with absorbent pad
Duration of exposure:
24 hrs
Doses:
2000 mg/kg
No. of animals per sex per dose:
5 male, 5 female
Control animals:
not specified
Details on study design:
- Duration of observation period following administration: hourly for first four hours and then twice daily.
- Necropsy of survivors performed: yes
- Frequency of observations and weighing: Twice daily
- Other examinations performed :Mortality, clinical signs, skin Condition and gross pathology were examined.
Statistics:
no data
Preliminary study:
No data available
Sex:
male/female
Dose descriptor:
LD50
Effect level:
> 2 000 mg/kg bw
Based on:
test mat.
Remarks on result:
other: No effect on survival observed
Mortality:
No mortality were observed in treated rabbits at 2000 mg/kg bw
Clinical signs:
Systemic clinical signs were minimal and consisted of abnormal stools in three animals during the first or second day of study
Body weight:
Weight gained during study were observed in all the treated rabbits at 2000 mg/kg bw
Gross pathology:
No macroscopic adverse effects were observed on necropcies.
Other findings:
Skin reaction: Erythema and edema were observed in 3 animals which are free of dermal irritation 5 days of treatment.
Interpretation of results:
not classified
Conclusions:
LD50 was considered to be > 2000 mg/kg bw when New Zealand White male and female rabbits were treated with (4-methoxyphenyl) acetic acid under an occlusive wrapping for 24 hours.
Executive summary:

In a acute dermal toxicity study, New Zealand White 5 male and 5 female rabbits were treated with 4-methoxyphenylacetic acid in the concentration of 2000 mg/kg under an occlusive wrapping for 24 hours. No mortality were observed in treated rabbits at 2000 mg/kg bw. Systemic clinical signs were minimal and consisted of abnormal stools in three animals during the first or second day of study and Weight gain during study were observed in all the treated rabbits at 2000 mg/kg bw. Erythema and edema were observed in 3 animals which are free of dermal irritation 5 days of treatment and no macroscopic adverse effects were observed in necropsies. Therefore, LD50 was considered to be > 2000 mg/kg bw when New Zealand White male and female rabbits were treated with 4-methoxyphenylacetic acid under an occlusive wrapping for 24 hours.

Endpoint conclusion
Endpoint conclusion:
no adverse effect observed
Dose descriptor:
LD50
Value:
2 000 mg/kg bw
Quality of whole database:
The data is K4 level as the data has been obtained from the study report.

Additional information

Acute toxicity: oral

To evaluated the acute oral toxicity of target (4-methoxyphenyl) acetic acid (CAS no 140-39-6) and it’s structurally similar read across tridecan-1-ol (CAS no 112-70-9) studies are summarized below:

Study 1 is for target chemical and 2 and 3 is for read across. All the studies are experimental studies in rats.

In a study conducted by Hoechst Celanese Corporation (1991), acute oral toxicity was evaluated in Sprague Dawley male and female rats by using 4-methoxyphenylacetic acid in the concentration of 0, 2000 and 5000 mg/kg orally by gavage in corn oil and observed for 14 days. 90% mortality was observed at 5000 mg/kg bw and 10% mortality at 2000 mg/kg bw in treated male and female rats as compared to control. Oral discharge, nasal discharge, tremors, ataxia abnormal stool, lethargy, Stained coat, alopecia, hunched posture, necrosis, unthriftinees and anal discharge were observed at 5000 mg/kg in treated male and female rats as compared to control. Decrease in weight was observed in surviving one animal at end of the study at 5000 mg/kg bw, weight gain were observed at 2000 mg/jkg bw and all of the control animals also gained weight through the study period. Liver lesions were observed in all the treated rats at 5000 mg/kg dose group. Increased incidences of liver lesions relative to control were observed in 2000 mg/kg bw treated male and female rats considered to be treatment related. Therefore, LD50 was considered to be > 2000 mg/kg bw and < 5000 mg/kg bw when rats were treated with (4-methoxyphenyl) acetic acid orally by gavage in corn oil.

In another supporting study conducted by Scala et al(1973) for read across, acute oral toxicity was evaluated in Sprague-Dawley male rats by using tridecan-1-ol orally by gavage. 50 % mortality was observed in treated male rats at 4750 mg/kg bw. The principal signs of effect were central nervous system depression and labored respiration. The depression included inactivity, ataxia, limb sprawling, depressed righting and placement reflexes, prostration, and coma. In addition, some evidence of gastrointestinal irritation. Therefore, LD50 was considered to be 4750 mg/kg bw when Sprague-Dawley male rats were treated with tridecan-1-ol orally by gavage.

In a another supporting study given by Henry et al(1962) and OECD SIDS (2006) for read across, acute oral toxicity was evaluated in Carworth –Wistar male rats by using tridecan-1-ol in the concentration of 17200 mg/kg bw orally by gavage. 50 % mortality was observed at 17200 mg/kg bw in treated male rats. Therefore, LD50 was considered to be 17200 mg/kg bw (12300 - 23900) when Carworth –Wistar male rats were treated with tridecan-1-ol orally by gavage.

So, based on the above mentioned studies for target substance 4-methoxyphenylacetic acid (CAS No.104-01-8) and to its read across substance, the median lethal dose (LD50) value was found to be in the range of >2000.0 mg/kg b.wt. to 17200 mg/kg b.wt. Thus, on the basis of these LD50 value and

according to CLP criteria for acute toxicity rating for the chemicals, it infers that 4-methoxyphenylacetic acid (CAS No.104-01-8) does not classify as an acute oral toxicant.

Acute toxicity: inhalation

According to column 2 of REACH Annex VIII, the acute toxicity inhalation study need not be conducted because exposure of humans via inhalation route is not likely taking into account the low vapour pressure of the substance 4-methoxyphenylacetic acid, which is reported as 0.000535 mm Hg. Also considering the particle size distribution of the substance, the majority of the particles were found to be in the size of 150 micrometer which is much larger size range compared to the inhalable particulate matter. Thus, exposure to inhalable dust, mist and vapour of the chemical 4-methoxyphenylacetic acid is highly unlikely. Therefore this study is considered for waiver.

Acute toxicity: dermal

To evaluated the acute dermal toxicity study of target 4-methoxyphenylacetic acid (CAS no 140-39-6) and it’s structurally similar read across (4-methoxyphenyl) methanol (CAS no 105-13-5) studies are summarized below:

Study 1 is for target chemical and 2 and 3 is for read across. All the studies are experimental studies in rabbits and mice.

In a study conducted by NTIS (1991), acute dermal toxicity was evaluated in New Zealand White 5 male and 5 female rabbits by using 4-Methoxyphenylacetic acid in the concentration of 2000 mg/kg under an occlusive wrapping for 24 hours. No mortality were observed in treated rabbits at 2000 mg/kg bw. Systemic clinical signs were minimal and consisted of abnormal stools in three animals during the first or second day of study and Weight gain during study were observed in all the treated rabbits at 2000 mg/kg bw. Erythema and edema were observed in 3 animals which are free of dermal irritation 5 days of treatment and no macroscopic adverse effects were observed in necropsies. Therefore, LD50 was considered to be > 2000 mg/kg bw when New Zealand White male and female rabbits were treated with 4-Methoxyphenyl-Acetic Acid under an occlusive wrapping for 24 hours.

In a study conducted by Moreno et al(1974) for read across, acute dermal toxicity was evaluated in rabbits by using (4-methoxyphenyl) methanol in the concentration of 3000 mg/kg bw by dermal application. 50 % mortality was observed in treated rabbits at 3000 mg/kg bw. Therefore, LD50 was considered to be 3000 mg/kg bw (1940 - 1060) when rabbits were treated with (4-methoxyphenyl) methanol alcohol dermally.

In a study conducted by Draize et al(1947) for read across, acute dermal toxicity was evaluated in mice by using (4-methoxyphenyl) methanol in the concentration of 10000 mg/kg bw by dermal application. No mortality was observed in treated mice at 10000 mg/kg bw. Therefore, LD50 was considered to be >10000 mg/kg bw when mice were treated with (4-methoxyphenyl) methanol alcohol dermally.

So, based on the above mentioned studies for target substance 4-methoxyphenylacetic acid (CAS No. 104-01-8) and to its read across substance, the median lethal dose (LD50) value was found to be in the range of >10000.0 mg/kg b.wt. to 3000.0 mg/kg b.wt. Thus, on the basis of these LD50 value and

according to CLP criteria for acute toxicity rating for the chemicals, it infers that 4-methoxyphenylacetic acid (CAS No.104-01-8) does not classify as an acute dermal toxicant.

Justification for classification or non-classification

Based on the above mentioned studies for target substance 4-methoxyphenylacetic acid (CAS No. 104-01-8) and to its read across substance, it can be found that LD50 oral and dermal value is greater than 2000 mg/kg b.wt. Thus, according to CLP criteria for acute toxicity rating for the chemicals, it infers that the test substance 4-methoxyphenylacetic acid (CAS No.104-01-8) does not classify as an acute toxicant by the oral and dermal route.