Phenylacetic acid

Endpoint summary

Description of key information

Acute oral toxicity: 

The acute oral toxicity dose (LD50) was considered based on different studies conducted on rats, mice and guinea pigs for the given test chemical. The LD50 value is >5000 mg/kg bw. The study concluded that the LD50 value is >2000 mg/kg bw, for acute oral toxicity. Thus, comparing this value with the criteria of CLP regulation, the given test chemical cannot be classified for acute oral toxicity.

Acute Inhalation Toxicity:

The acute inhalation toxicity dose (LC50) was considered based on different studies conducted on rats for the given test chemical. The studies concluded that the LC50 value is >5 mg/L (>5000 mg/m3), for acute inhalation toxicity. Thus, comparing this value with the criteria of CLP regulation, the given test chemical cannot be classified for acute inhalation toxicity.

Acute Dermal toxicity:

The acute dermal toxicity dose (LD50) was considered based on different studies conducted on rats for the test chemical. The LD50 value is >5000 mg/kg bw. The study concluded that LD50 value is >2000 mg/kg bw, for acute dermal toxicity. Thus, comparing this value with the criteria of CLP regulation, the given test chemical cannot be classified for acute dermal toxicity.

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:

key study

Reliability:

2 (reliable with restrictions)

Rationale for reliability incl. deficiencies:

data from handbook or collection of data

Justification for type of information:

Data is from publication.

Qualifier:

according to guideline

Guideline:

other: As mentioned below

Principles of method if other than guideline:

Acute oral toxicity study was conducted by using the given test chemical in rats.

GLP compliance:

not specified

Test type:

other: not specified

Limit test:

no

Species:

rat

Strain:

not specified

Sex:

not specified

Details on test animals or test system and environmental conditions:

not specified

Route of administration:

oral: unspecified

Vehicle:

not specified

Details on oral exposure:

not specified

Doses:

5000 mg/kg bw

No. of animals per sex per dose:

not specified

Control animals:

not specified

Details on study design:

not specified

Statistics:

not specified

Preliminary study:

not specified

Sex:

not specified

Dose descriptor:

LD50

Effect level:

> 5 000 mg/kg bw

Based on:

test mat.

Mortality:

No mortality was observed at 5000 mg/kg bw.

Clinical signs:

other: not specified

Gross pathology:

not specified

Other findings:

not specified

Interpretation of results:

other: Not classified

Conclusions:

The acute oral LD50 value was considered to be >5000 mg/kg bw, when rats were treated with the given test chemical via oral route.

Executive summary:

The acute oral toxicity study was conducted by using the given test chemical in rats at the dose concentration of 5000 mg/kg bw. The animals were observed for mortality.

No mortality was observed at 5000 mg/kg bw. Hence, the LD50 value was considered to be >5000 mg/kg bw, when rats were treated with the given test chemical via oral route.

Endpoint conclusion

Endpoint conclusion:

no adverse effect observed

Dose descriptor:

LD50

Value:

5 000 mg/kg bw

Quality of whole database:

Data is Klimisch 2 and from publication.

Acute toxicity: via inhalation route

Link to relevant study records

Reference

Endpoint:

acute toxicity: inhalation

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 secondary database.

Qualifier:

according to guideline

Guideline:

OECD Guideline 403 (Acute Inhalation Toxicity)

Principles of method if other than guideline:

Acute inhalation toxicity study was conducted by using the given test chemical

GLP compliance:

not specified

Test type:

other: not specified

Limit test:

no

Species:

rat

Strain:

Wistar

Sex:

male/female

Details on test animals or test system and environmental conditions:

TEST ANIMALS
- Age at study initiation: 7-9 weeks
- Weight at study initiation: mean 200g weight

Route of administration:

inhalation: aerosol

Type of inhalation exposure:

not specified

Vehicle:

not specified

Details on inhalation exposure:

not specified

Analytical verification of test atmosphere concentrations:

not specified

Duration of exposure:

4 h

Concentrations:

5 mg/L

No. of animals per sex per dose:

5 M and 5 W / dose

Control animals:

not specified

Details on study design:

- Duration of observation period following administration: 14 days
- Other examinations performed: Animals were observed for mortality, clinical signs, and body weight changes.

Statistics:

not specified

Preliminary study:

not specified

Sex:

male/female

Dose descriptor:

LC50

Effect level:

> 5 mg/L air

Based on:

test mat.

Exp. duration:

4 h

Mortality:

No mortality was observed at 5 mg/L.

Clinical signs:

other: No clinical signs of intoxication within 14 d of follow-up.

Body weight:

No effect on body weight on the 7th and 14th day after exposure.

Gross pathology:

not specified

Other findings:

not specified

Interpretation of results:

other: Not classified

Conclusions:

The acute inhalation toxicity dose (LC50) value was considered to be >5 mg/L (>5000 mg/m3), when male and female wistar rats were treated with the given test chemical via inhalation route by aerosoles for 4-h exposure.

Executive summary:

The acute inhalation toxicity study was conducted by using the given test chemical as per OECD Guideline 403 (Acute Inhalation Toxicity) in 10 male and female Wistar rats via inhalation route by aerosoles for 4-h exposure at the dose concentration of 5 mg/L.

Animals were observed for mortality, clinical signs, and body weight changes for 14 days. No mortality was observed at 5 mg/L. No clinical signs of intoxication within 14 d of follow-up. No effect on body weight on the 7th and 14th day after exposure.

Hence, the  acute inhalation toxicity dose (LC50) value was considered to be >5 mg/L (>5000 mg/m3), when male and female wistar rats were treated with the given test chemical via inhalation route by aerosoles for 4-h exposure.

Endpoint conclusion

Endpoint conclusion:

no adverse effect observed

Dose descriptor:

LC50

Value:

5 000 mg/m³ air

Quality of whole database:

Data is from secondary database.

Acute toxicity: via dermal route

Link to relevant study records

Reference

Endpoint:

acute toxicity: dermal

Type of information:

experimental study

Adequacy of study:

key study

Reliability:

2 (reliable with restrictions)

Rationale for reliability incl. deficiencies:

data from handbook or collection of data

Justification for type of information:

Data is from publication.

Qualifier:

according to guideline

Guideline:

other: As mentioned below

Principles of method if other than guideline:

Acute dermal toxicity study was conducted by using the given test chemcial.

GLP compliance:

not specified

Test type:

other: not specified

Limit test:

no

Species:

rabbit

Strain:

not specified

Sex:

not specified

Details on test animals or test system and environmental conditions:

not specified

Type of coverage:

other: Dermal

Vehicle:

not specified

Details on dermal exposure:

not specified

Duration of exposure:

not specified

Doses:

5000 mg/kg bw

No. of animals per sex per dose:

not specified

Control animals:

not specified

Details on study design:

not specified

Statistics:

not specified

Preliminary study:

not specified

Sex:

not specified

Dose descriptor:

LD50

Effect level:

> 5 000 mg/kg bw

Based on:

test mat.

Mortality:

No mortality was observed at 5000 mg/kg bw.

Clinical signs:

other: not specified

Gross pathology:

not specified

Other findings:

not specified

Interpretation of results:

other: Not classified

Conclusions:

The acute dermal median lethal dose (LD50) was considered to be >5000 mg/kg of body weight, when rabbits were treated with the given test chemical by dermal route.

Executive summary:

The acute dermal toxicity study was conducted by using the given test chemical in rabbits at the dose concentration of 5000 mg/kg bw. Animals were observed for mortality. No mortality was observed at 5000 mg/kg bw. Hence, the acute dermal median lethal dose (LD50) was considered to be >5000 mg/kg of body weight, when rabbits were treated with the given test chemical by dermal route.

Endpoint conclusion

Endpoint conclusion:

no adverse effect observed

Dose descriptor:

LD50

Value:

5 000 mg/kg bw

Quality of whole database:

Data is Klimisch 2 and from publication.

Additional information

Acute oral toxicity:

In different studies, the given test chemical has been investigated for acute oral toxicity to a greater or lesser extent. Often are the studies based on in-vivo experiments in rodents, i.e. most commonly in rats, mice and guinea pigs for test chemical. The studies are summarized as below –

 

The reported study was mentioned in different publications and conducted to assess the toxicological profile of the given test chemical in rats at the dose concentration of 5000 mg/kg bw. The animals were observed for mortality. No mortality was observed at 5000 mg/kg bw. Hence, the LD50 value was considered to be >5000 mg/kg bw, when rats were treated with the given test chemical via oral route.

 

The above study report is supported with another study mentioned in different publications, handbook and authoritative databases for the given test chemical. The acute oral toxicity study was conducted in male and female rats at the dose concentration of 2250 mg/kg. Animals were observed for mortality. 50% mortality was observed at 2250 mg/kg bw. Hence, the acute oral median lethal dose (LD50) was considered to be 2250 mg/kg of body weight, when male and female rats were treated with the given test chemical via oral gavage route.

 

This study is supported with the data available in publications, handbook and authoritative databases for the given test chemical. The acute oral toxicity study was conducted in mice at the dose concentration of 2250 mg/kg bw. Animals were observed for mortality. 50% mortality was observed at 2250 mg/kg bw. Hence, the acute oral median lethal dose (LD50) was considered to be 2250 mg/kg of body weight, when male and female mice were treated with the given test chemical via oral gavage route.

These studies are supported with the data available in publications, handbook and authoritative databases for the given test chemical. The acute oral toxicity study was conducted in guinea pigs at the dose concentration of 2250 mg/kg of body weight. Animals were observed for mortality. 50% mortality was observed at 2250 mg/kg bw. Hence, the acute oral median lethal dose (LD50) was considered to be 2250 mg/kg of body weight, when guinea pigs were treated with the given test chemical via oral gavage route.

 

All the above studies are further supported with the data available in study report and the study was conducted as per OECD No. 423 by using the given test chemical in Rats. Six female Wistar rats were selected for acute oral toxicity study. The animals were fasted for minimum 16-18 hours prior to dosing and for 4 hours post dosing, food was withheld but drinking water provided ad libitum. The time intervals between dosing were determined by the onset, duration and severity of toxic signs. Three rats of first group were dosed with starting dose of 2000 mg/kg body weight and the animals did not show any mortality so another three animals of the same group were dosed with 2000 mg/kg body weight and no mortality was observed. Hence, further dosing was stopped. Body weights were recorded on day 0 (prior to dosing) 7 and 14. Mean body weight of all the animals treated with 2000 mg/kg body weight was observed with gain on day 7 and 14, as compared to day 0. At 2000 mg/kg, all the animals were normal throughout the experimental period. No external and internal gross pathological changes were seen in all the six animals treated with 2000 mg/kg body weight during terminal sacrifice. Under the condition of the study, the acute oral toxicity dose (LD50) value was considered to be >2000 mg/kg bw, when female Wistar rats were treated with the given test chemical via oral route.

 

Thus, based on the above summarised studies on test chemical, it can be concluded that LD50 value is >2000 mg/kg bw, for acute oral toxicity. Thus, comparing this value with the criteria of CLP regulation, the given test chemical cannot be classified for acute oral toxicity.

 

Acute inhalation toxicity:

In different studies, the given test chemical has been investigated for acute inhalation toxicity to a greater or lesser extent. Often are the studies based on in-vivo experiments in rodents, i.e. most commonly in rats for the given test chemical. The studies are summarized as below –

 

The acute inhalation toxicity study was conducted by using the given test chemical as per OECD Guideline 403 (Acute Inhalation Toxicity) in 10 male and female Wistar rats via inhalation route by aerosols for 4-h exposure at the dose concentration of 5 mg/L. Animals were observed for mortality, clinical signs, and body weight changes for 14 days. No mortality was observed at 5 mg/L. No clinical signs of intoxication within 14 d of follow-up. No effect on body weight on the 7th and 14th day after exposure.

Hence, the acute inhalation toxicity dose (LC50) value was considered to be >5 mg/L (>5000 mg/m3), when male and female wistar rats were treated with the given test chemical via inhalation route by aerosols for 4-h exposure.

 

The above study is supported with the data available in study report and conducted according to OECD-Guideline -403 for testing of chemicals in albino rat. LIMIT TEST: Ten healthy Wistar albino rats of both sexes (5 male and 5 female) of body weight 200±20 gm were selected for study after acclimatization. The test group of animals was exposed to aerosol at the concentration of 5 mg/L for period of 4 hrs. After exposure all the animals were closely observed for clinical signs of toxicity at various internals such as 1 hr, 2 hrs, 4 hrs, and 6 hrs on the day of test compound aerosol exposure and later on twice a day throughout the experimentation period of 14 days. The necropsy was performed on all the animals which were died during the exposure or were sacrificed at termination of experiment. All the albino rats exposed to aerosol at the concentration of 5 mg/L did not show any clinical signs of intoxication. Furthermore, no mortality was observed throughout the period of observation. The necropsy was performed on all the animals at the termination of study did not show any gross pathological changes.

After 72 hrs, the result obtained from limit test was confirmed in another 10 animal of both sex at similar concentration following same guideline. Ten healthy Wistar albino rats of both sex body weight 200±20 gm were selected for study after acclimatization. The test groups of animals were exposed to aerosol at the concentration of 5 mg/L for period of 4 hrs. After exposure all the animals were closely observed for any clinical signs of toxicity at various intervals such as 1 hr, 2 hrs, 4 hrs, and 6 hrs on the day of test compound aerosol exposure and later on twice a day throughout the experimentation period of 14 days.The necropsy was performed on all the animals at termination of experiment. All the albino rats exposed to aerosol at the concentration of 5mg/L did not show any clinical signs of intoxication. Furthermore, no mortality was observed throughout the period of observation. The body weight of animals exposed to test compound, observed on day 0th (pre treatment) and day 7th (post treatment) did not differ significantly as compared to day 0th. Whereas, body weight of animals observed on day 14th showed normal increase as compared to day 0th. The necropsy was performed on all the animals at the termination of study did not show any gross pathological changes. The acute inhalation toxicity dose (LC50) was considered to be >5 mg/L (>5000 mg/m3), when male and female Wistar rats were exposed with the given test chemical via inhalation route by nose only exposure for 4 hours.

From the results obtained from present investigation, it can be concluded that test compound is non toxic at the aerosol concentration of 5.0 mg/L under the test condition.

 

Both the above studies are further supported with the data mentioned in database and the study was conducted by using given test chemical in rat at the concentration of 38600 mg/m3. 50% mortality was observed at 38600 mg/m3. Rats showed the symptoms like: difficulty in breathing, ataxia, exhaustion, sedation and narcosis. No substance-related macroscopic changes to organs were observed. Therefore, LC50 was considered to be 38600 mg/m3, when rat was treated with given test chemical by inhalation. 

 

Thus, based on the above summarised studies on test chemical, it can be concluded that LC50 value is >5 mg/L (>5000 mg/m3), for acute inhalation toxicity. Thus, comparing this value with the criteria of CLP regulation, the given test chemical cannot be classified for acute inhalation toxicity.

 

Acute Dermal Toxicity:

In different studies, the given test chemical has been investigated for acute dermal toxicity to a greater or lesser extent. Often are the studies based on in-vivo experiments in rodents, i.e. most commonly in rats for test chemical. The studies are summarized as below -

 

The reported study was mentioned in peer-reviewed journal and different authoritative databases to determine the acute dermal toxicity dose by using the given test chemical in rabbits at the dose concentration of 5000 mg/kg bw. Animals were observed for mortality. No mortality was observed at 5000 mg/kg bw. Hence, the acute dermal median lethal dose (LD50) was considered to be >5000 mg/kg of body weight, when rabbits were treated with the given test chemical by dermal route.

 

Another study mentioned in study report was carried out to determine the acute dermal toxicity dose by using the given test chemical as per OECD No.402 in 10 male and female healthy young adult Wistar rats which were randomly selected and used for conducting acute dermal toxicity study at the concentration of 2000 mg/kg bw. Rats free from injury and irritation of skin were selected for the study. 24 hours prior to dermal application of test item, approximately 10% of body surface area of each rat was clipped. A limit dose of 2000 mg/ kg body weight of test item was applied by single dermal application and observed for 14 days after treatment. On test day 0,as such amount of test item, calculated based on density (1.0016) and body weight was applied directly on the intact skin of clipped area of rats; the surgical gauze patch was put on to the intact skin of clipped area. This porous gauze dressing was covered with a non-irritating adhesive tape. The porous gauze dressing was wrapped around the abdomen and anchored with non-irritating adhesive tape. After the 24-hour application period, the dressings were removed and the skin was gently wiped with distilled water. The skin reactions were assessed. The animals were observed daily for mortality and clinical signs, during the acclimatization period. All animals were observed for clinical signs at approximately 1, 2, 3 and 4 hours after treatment on day 0 and once daily during test days 1‑14. Mortality was recorded after application on test day 0 and twice daily during days 1-14 (at least once on the day of sacrifice). Local signs / Skin reactions were observed daily from test days 1-14 (in common with clinical signs). Body weights were re­corded on day 0 (prior to application) and on day 7 and 14. All animals were necropsied and examined macroscopically. No mortality was observed in any animal till the end of the experimental period. No clinical signs and any skin reaction were observed throughout the experimental period in all treated animals. The male and female animals were observed with body weight gain throughout the experiment, except on day 7 male animals were observed with decline in mean body weight gain as compared to day 0. The external and internal gross pathological observation of all terminally sacrificed animals did not show any pathological abnormality. Hence the LD50 was considered to be >2000mg/kg bw, when rats were treated with test chemical by dermal application.

 

Both the above studies are further supported with the data mentioned in study report and the acute dermal toxicity study was conducted as per OECD No. 402 by using the given test chemical in Wistar Rats. Five male and five female healthy young adult rats were randomly selected and used for conducting acute dermal toxicity study. Rats free from injury and irritation of skin were selected for the study. Approximately, twenty four hours prior to dermal application of test item, greater than 10% of body surface area of each rat was clipped. A limit dose of 2000 mg/ kg body weight based on the test item density (1.07513) and latest body weight was applied by single dermal application and observed for 14 days after treatment. On test day 0, calculated volume of test item was applied directly on the intact skin of clipped area of rats; the porous gauze dressing was put on to the intact skin of clipped area. This porous gauze dressing was covered with a non-irritating tape. After the 24-hour application period, the dressings were removed and the skin was gently wiped with distilled water. The skin reactions were assessed. The animals were observed daily for mortality and clinical signs, during the acclimatization period and post dosing till the termination. All animals were observed for clinical signs at approximately 1, 2, 3 and 4 hours after treatment on day 0 and once daily during test days 1 14. Mortality was recorded after application on test day 0 and twice daily during days 1-14 (at least once on the day of sacrifice). Local signs / Skin reactions were observed daily from test days 1-14 (in common with clinical signs). Body weights were re¬corded on day 0 (prior to application) and on day 7 and 14. All animals were necropsied and examined macroscopically. No mortality was observed in any animal till the end of the experimental period. At 2000 mg/kg, all the animals were observed normal throughout the experimental period. Mean body weight was observed with gain on day 7 and 14 of male and female animals, as compared to day 0. The external and internal gross pathological observation of all terminally sacrificed animals did not show any pathological abnormality. Under the conditions of the study, the acute dermal toxicity dose (LD50) was considered to be >2000 mg/kg bw, when rats were treated with the given test chemical by dermal application.

 

Thus, based on the above summarised studies for test chemical, it can be concluded that LD50 value is >2000 mg/kg bw, for acute dermal toxicity. Thus, comparing this value with the criteria of CLP regulation, the given test chemical cannot be classified for acute dermal toxicity.

Justification for classification or non-classification

Based on the above studies for the test chemical, it can be concluded that LD50 value is >2000 mg/kg bw, for acute oral toxicity and acute dermal toxicity; LC50 value is >5 mg/L (>5000 mg/m3), for acute inhalation toxicity. Thus, comparing these values with the criteria of CLP regulation, the given test chemical cannot be classified for acute oral, acute inhalation and acute dermal toxicity.