4-methoxyphenylacetone

Endpoint summary

Description of key information

Acute Oral Toxicity: 

In Acute oral toxicity ,LD50 value was based on experimental data for target substance 4-Methoxyphenylacetone (122-84-9) was considered to be 3330 mg/kg bw and 3200 mg/kg bw based on the QSAR prediction done using the Danish (Q)SAR Database,and for differentstudies available on the structurally similar read across substance 4-(4-methoxyphenyl)butan-2-one (104-20-1) was considered to be >5000 mg/kg bw; (1E)-1-(4-methoxyphenyl)pent-1-en-3-one (104-27-8) was considered to be >2000 mg/kg bw; p-Anisyl acetate (104-21-2) was considered to be 5000 mg/kg bw and 2250 mg/kg bw and Cue-lure (3572-06-3) was considered to be 3038 mg/kg bw. All these studies concluded that the LD50 value is greater than 2000 mg/kg bw. Thus, comparing this value with the criteria of CLP regulation, 4-Methoxyphenylacetone (122-84-9) cannot be classified for acute oral toxicity.

Acute Inhalation Toxicity: 

4-methoxyphenylacetone has very low vapor pressure (0.01027584 mm Hg), so the potential for the generation of inhalable vapours is very low. Also the normal conditions of use of this substance will not result in aerosols, particles or droplets of an inhalable size, so exposure to humans via the inhalatory route will be highly unlikely and therefore this end point for acute inhalation toxicity was considered for waiver.

Acute Dermal Toxicity:

In Acute dermal toxicity, LD50 value was based on experimental data for target substance 4-Methoxyphenylacetone (122-84-9) was considered to be >5000 mg/kg bw,and for differentstudies available on structurally similar read across substance 4-(4-methoxyphenyl)butan-2-one (104-20-1) was considered to be >5000 mg/kg bw; (1E)-1-(4-methoxyphenyl)pent-1-en-3-one (104-27-8) was considered to be >5000 mg/kg bw; p-Anisyl acetate (104-21-2) was considered to be >5000 mg/kg bw and Cue-lure (3572-06-3) was considered to be >2025 mg/kg bw. All these studies concluded that the LD50 value is greater than 2000 mg/kg bw. Thus, comparing this value with the criteria of CLP regulation, 4-Methoxyphenylacetone (122-84-9) 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:

weight of evidence

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 peer-reviewed journal

Qualifier:

according to guideline

Guideline:

other: As mentioned below

Principles of method if other than guideline:

Acute Oral toxicity test was carried out to study the effects of 4-Methoxyphenylacetone (122-84-9) on rats.

GLP compliance:

not specified

Test type:

other: No data available

Limit test:

no

Specific details on test material used for the study:

- Name of test material (as cited in study report):p-Methoxyphenylacetone
- Molecular formula :C10H12O2
- Molecular weight :164.203 g/mol
- Substance type:Organic

Species:

rat

Strain:

not specified

Sex:

not specified

Details on test animals or test system and environmental conditions:

No data available

Route of administration:

oral: unspecified

Vehicle:

not specified

Details on oral exposure:

No data available

Doses:

3330 mg/kg bw

No. of animals per sex per dose:

No data available

Control animals:

not specified

Details on study design:

Details on study design:
- Duration of observation period following administration: No data available
- Frequency of observations and weighing: No data available
- Necropsy of survivors performed: No data available
- Other examinations performed: Clinical signs

Statistics:

No data available

Preliminary study:

No data available

Sex:

not specified

Dose descriptor:

LD50

Effect level:

3 330 mg/kg bw

Based on:

test mat.

Remarks on result:

other: 50% Mortality was observed in treated rats at 3330 mg/kg bw

Mortality:

50% Mortality was observed in treated rats at 3330 mg/kg bw

Clinical signs:

other: Clinical signs like tremor,changes in motor activity (Specific assay) and altered sleep time (including change in righting reflex) were observed.

Gross pathology:

No data available

Other findings:

No data available

Interpretation of results:

Category 5 based on GHS criteria

Conclusions:

The lethal concentration (LD50) value for acute oral toxicity test was considered to be 3330 mg/kg bw,when rats were treated with 4-Methoxyphenylacetone (122-84-9) orally.

Executive summary:

Acute oral toxicity study was done in rats using test material 4-Methoxyphenylacetone (122-84-9).50% Mortality was observed at dose 3330 mg/kg bw.Clinical signs like tremor, changes in motor activity(Specific assay) and altered sleep time (including change in righting reflex) were observed.Hence,LD50 value was considered to be 3330 mg/kg bw,when rats were treated with 4-Methoxyphenylacetone (122-84-9) orally.

Endpoint conclusion

Endpoint conclusion:

no adverse effect observed

Dose descriptor:

LD50

Value:

3 330 mg/kg bw

Quality of whole database:

Data is Klimisch 2 and from experimental data

Acute toxicity: via inhalation route

Link to relevant study records

Reference

Endpoint:

acute toxicity: inhalation

Data waiving:

other justification

Justification for data waiving:

other:

Endpoint conclusion

Quality of whole database:

Waiver

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:

2 (reliable with restrictions)

Rationale for reliability incl. deficiencies:

data from handbook or collection of data

Justification for type of information:

Data is from peer-reviewed journal

Qualifier:

according to guideline

Guideline:

other: As mentioned below

Principles of method if other than guideline:

Acute dermal toxicity test was carried out to study the effects of 4-Methoxyphenylacetone (122-84-9) on rabbits.

GLP compliance:

no

Test type:

other: No data available

Limit test:

no

Specific details on test material used for the study:

- Name of test material (as cited in study report):p-Methoxyphenylacetone
- Molecular formula :C10H12O2
- Molecular weight :164.203 g/mol
- Substance type:Organic

Species:

rabbit

Strain:

not specified

Sex:

not specified

Details on test animals or test system and environmental conditions:

No data available

Type of coverage:

other: Dermal

Vehicle:

not specified

Details on dermal exposure:

No data available

Duration of exposure:

No data available

Doses:

5000 mg/kg bw

No. of animals per sex per dose:

No data available

Control animals:

not specified

Details on study design:

No data available

Statistics:

No data available

Preliminary study:

No data available

Sex:

not specified

Dose descriptor:

LD50

Effect level:

> 5 000 mg/kg bw

Based on:

test mat.

Remarks on result:

other: No mortality was observed in treated rabbits at 5000 mg/kg bw

Mortality:

No mortality was observed in treated rabbits at 5000 mg/kg bw.

Clinical signs:

other: No data available

Gross pathology:

No data available

Other findings:

No data available

Interpretation of results:

Category 5 based on GHS criteria

Conclusions:

The LD50 value was considered to be >5000 mg/kg bw,when rabbits were treated with 4-Methoxyphenylacetone (122-84-9) by dermal application.

Executive summary:

In acute dermal toxicity study,rabbits were treated with 4-Methoxyphenylacetone (122-84-9) in the concentration of 5000 mg/kg bw by dermal application.No mortality was observed in treated rabbits at dose 5000 mg/kg bw.Therefore, LD50 value was considered to be >5000 mg/kg bw,when rabbits were treated with 4-Methoxyphenylacetone (122-84-9) by dermal application.

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 experimental data

Additional information

Acute Oral Toxicity: 

In different studies, 4-Methoxyphenylacetone (122-84-9) has been investigated for acute oral toxicity to a greater or lesser extent. Often the studies are based on in vivo experimental data in rodents, i.e. most commonly in rats for 4-Methoxyphenylacetone (122-84-9) along with the study available on the structurally similar read across substance 4-(4-methoxyphenyl)butan-2-one (104-20-1); (1E)-1-(4-methoxyphenyl)pent-1-en-3-one (104-27-8); p-Anisyl acetate (104-21-2) and Cue-lure (3572-06-3).The studies are summarized as below –

 

In experimental study conducted by D. L. J. Opdyke (Food and Cosmetics Toxicology,Volume 17, Supplement, Pages 695-923 (December 1979) ); U.S. National Library of Medicine (Chemidplus Database,U.S. National Library of Medicine,2017); T.B. Adams et. al. (Food and Chemical Toxicology 45 (2007) 171–201); Richard J. Lewis (Sax's Dangerous Properties of Industrial Materials, 12th Edition, 5 Volume Set,2012);RTECS (RTECS (registry of toxic effect of chemical substance data base ), 2017);World Health Organization (SAFETY EVALUATION OF CERTAIN FOOD ADDITIVES AND CONTAMINANT S AROMATIC SUBSTITUTED SECONDARY ALCOHOLS, KETONES, AND RELATED ESTERS, World Health Organization ,WHO FOOD ADDITIVES SERIES: 48,1978) and U.S. Environmental Protection Agency. Chemistry Dashboard(Chemistry Dashboard, U.S. Environmental Protection Agency,2018) for the target substance4-Methoxyphenylacetone (122-84-9). Acute oral toxicity study was done in rats using test material 4-Methoxyphenylacetone (122-84-9).50% Mortality was observed at dose 3330 mg/kg bw.Clinical signs like tremor, changes in motor activity(Specific assay) and altered sleep time (including change in righting reflex) were observed.Hence,LD50 value was considered to be 3330 mg/kg bw,when rats were treated with 4-Methoxyphenylacetone (122-84-9) orally.

Based on the QSAR prediction done using the Danish (Q)SAR Database, the LD50 was estimated to be 3200 mg/kg bw on rat for 1-(4-methoxyphenyl)propan-2-one(122-84-9) having Reliability Index: 0.95 (high prediction quality.)

This study is further supported by D. L. J. Opdyke (Food and Cosmetics Toxicology. 12, 929, 1974); T.B. Adams et. al. (Food and Chemical Toxicology 45 (2007) 171–201) and U.S. National Library of Medicine (Chemidplus Database,U.S. National Library of Medicine,2017) for the structurally similar read across substance 4-(4-methoxyphenyl)butan-2-one (104-20-1). Acute oral toxicity study was done in rats using test material 4-(p-methoxyphenyl)butan-2-one (104-20-1) .No mortality was observed at dose 5000 mg/kg bw. Hence,LD50 value was considered to be >5000 mg/kg bw,when rats were treated with 4-(p-methoxyphenyl)butan-2-one (104-20-1)orally.

The above study was further supported by D. L. J. Opdyke (Food and Cosmetics Toxicology,Volume 17, Supplement, December 1979, Page 863) and U.S. National Library of Medicine (Chemidplus Database,U.S. National Library of Medicine,2017) for the structurally similar read across substance (1E)-1-(4-methoxyphenyl)pent-1-en-3-one (104-27-8). Acute oral toxicity study was done in rats using test material (1E)-1-(4-methoxyphenyl)pent-1-en-3-one (104-27-8).No mortality was observed at dose 5000 mg/kg bw. Hence,LD50 value was considered to be >5000 mg/kg bw,when rats were treated with (1E)-1-(4-methoxyphenyl)pent-1-en-3-one (104-27-8)orally.

Also these results are further supported by the experimental study conducted by J. Scognamiglio et. al.(Food and chemical toxicology, Volume 50, Supplement 2, September 2012, Pages S134–S139) for the structurally similar read across substance p-Anisyl acetate (104-21-2). Preliminary toxicity study was conducted to evaluate the toxic nature of the test compound p-Anisyl acetate via the oral exposure route. The test compound was dosed to two Sprague Dawley rats by the oral intubation route. Potential toxic signs and mortality were recorded at 1 and 4 hr and then once daily for 14 days. One animal died. The acute oral median lethal dose LD50 for the test compound p-Anisyl acetate is considered to be 5000 mg/Kg bw.

The above study was further supported by D. McGinty et. al.(Food and Chemical Toxicology 50 (2012) S502–S506) for the structurally similar read across substance p-Anisyl acetate (104-21-2). p-Anisyl acetate (50%) in corn oil was administered by oral gavage at doses of 1470, 2150, 3160 and 4640 mg/kg to Sprague–Dawley rats (5/dose) followed by a 14 day observation period.Clinical signs of toxicity included depression, hypopnea and ataxia. Necropsy revealed dark red areas of the lungs of rats in all dose groups except the 2150 mg/kg group.The LD50 was calculated to be 2250 mg/kg. This value indicates that the substance shall not be classified for Acute Oral toxicity as per the CLP criteria.

The above studies are further supported by Morton Beroza et. al.( Toxicology and Applied Pharmacology 31,421-429,1975) for the structurally similar read across substance Cue-lure (3572-06-3). Acute oral toxicity study was conducted to evaluate the toxic nature of the test compound Cue-lure. Food was with held from the rats for 16 hr before dosing. The undiluted liquid test material was administered at four, five, or six dose levels (1360-6834 mg/Kg) to two male and two female rats at each level directly into the stomachs with a hypodermic syringe that had a ball-tipped intubation needle. The rats were then placed individually in suspended wire-mesh cages and observed for 14 days. Necropsy was conducted on any animal that died during the study and on all animals that survived the 14-day observation period.The acute oral median lethal dose of Cue-lure is found to be 3038 (±1266) mg/Kg in albino rats.

Thus, based on the above studies on 4-Methoxyphenylacetone(122-84-9) and it’s structurally similar read across substance 4-(4-methoxyphenyl)butan-2-one (104-20-1); (1E)-1-(4-methoxyphenyl)pent-1-en-3-one (104-27-8); p-Anisyl acetate (104-21-2) and Cue-lure (3572-06-3), it can be concluded that LD50 value is greater than 2000 mg/kg bw. Thus, comparing this value with the criteria of CLP regulation, 4-Methoxyphenylacetone(122-84-9) cannot be classified for acute oral toxicity.

Acute Inhalation toxicity: 

4-methoxyphenylacetone has very low vapor pressure (0.01027584 mm Hg), so the potential for the generation of inhalable vapours is very low. Also the normal conditions of use of this substance will not result in aerosols, particles or droplets of an inhalable size, so exposure to humans via the inhalatory route will be highly unlikely and therefore this end point for acute inhalation toxicity was considered for waiver.

Acute Dermal Toxicity:

In different studies, 4-Methoxyphenylacetone(122-84-9) has been investigated for acute dermal toxicity to a greater or lesser extent. Often the studies are based on in vivo experimental data in rodents, i.e. most commonly in rabbits for 4-Methoxyphenylacetone(122-84-9) along with the study available on structurally similar read across substance 4-(4-methoxyphenyl)butan-2-one (104-20-1); (1E)-1-(4-methoxyphenyl)pent-1-en-3-one (104-27-8); p-Anisyl acetate (104-21-2) and Cue-lure (3572-06-3). The studies are summarized as below –

In experimental study conducted by D. L. J. Opdyke (Food and Cosmetics Toxicology,Volume 17, Supplement, Pages 695-923 (December 1979) ); U.S. National Library of Medicine (Chemidplus Database,U.S. National Library of Medicine,2017) andRTECS (RTECS (registry of toxic effect of chemical substance data base ), 2017) for the target substance4-Methoxyphenylacetone (122-84-9). In acute dermal toxicity study,rabbits were treated with 4-Methoxyphenylacetone (122-84-9) in the concentration of 5000 mg/kg bw by dermal application.No mortality was observed in treated rabbits at dose 5000 mg/kg bw.Therefore, LD50 value was considered to be >5000 mg/kg bw,when rabbits were treated with 4-Methoxyphenylacetone (122-84-9) by dermal application.

This study is further supported by D. L. J. Opdyke (Food and Cosmetics Toxicology. 12, 929, 1974); and U.S. National Library of Medicine (Chemidplus Database,U.S. National Library of Medicine,2017) for the structurally similar read across substance 4-(4-methoxyphenyl)butan-2-one (104-20-1).In acute dermal toxicity study,rabbits were treated with4-(4-methoxyphenyl)butan-2-one(104-20-1) in the concentration of 5000 mg/kg bw by dermal application.No mortality was observed in treated rabbits at dose 5000 mg/kg bw.Therefore, LD50 value was considered to be >5000 mg/kg bw,when rabbits were treated with 4-(4-methoxyphenyl)butan-2-one (104-20-1) by dermal application. 

The above study was further supported by D. L. J. Opdyke (Food and Cosmetics Toxicology,Volume 17, Supplement, December 1979, Page 863) and U.S. National Library of Medicine (Chemidplus Database,U.S. National Library of Medicine,2017) for the structurally similar read across substance (1E)-1-(4-methoxyphenyl)pent-1-en-3-one (104-27-8). In acute dermal toxicity study, rabbits were treated with (1E)-1-(4-methoxyphenyl)pent-1-en-3-one (104-27-8)in the concentration of 5000 mg/kg bw by dermal application.No mortality was observed in treated rabbits at dose 5000 mg/kg bw.Therefore, LD50 value was considered to be >5000 mg/kg bw,when rats were treated with (1E)-1-(4-methoxyphenyl)pent-1-en-3-one (104-27-8)by dermal application.  

Also these results are further supported by the experimental study conducted by J. Scognamiglio et. al.(Food and chemical toxicology, Volume 50, Supplement 2, September 2012, Pages S134–S139) for the structurally similar read across substance p-Anisyl acetate (104-21-2). In acute dermal toxicity study, rabbits were treated with p-anisyl acetate (104-21-2) in the concentration of 5000 mg/kg bw by dermal application.No mortality was observed in treated rabbits at dose 5000 mg/kg bw. Therefore, LD50 value was considered to be >5000 mg/kg bw,when rabbits were treated with p-anisyl acetate (104-21-2) by dermal application.  

The above study was further supported by D. McGinty et. al.(Food and Chemical Toxicology 50 (2012) S502–S506) for the structurally similar read across substance p-Anisyl acetate (104-21-2). p-Anisyl acetate was applied topically for 24 h at a dose of 5000mg/ kg to 6 New Zealand albino rabbits followed by a 14 day observation period. Well-defined to moderate erythema was seen in all rabbits and edema ranged from slight to severe in five rabbits. There was no morality or clinical signs of toxicity in any of the animals. Necropsy showed one animal with dark red specks on the lungs.The acute dermal LD50 of p-anisyl acetate is considered to be >5000mg/Kg. This value indicates that the substance shall not be classified for Acute Dermal toxicity as per the CLP criteria.

The above studies are further supported by Morton Beroza et. al.( Toxicology and Applied Pharmacology 31,421-429,1975) for the structurally similar read across substance Cue-lure (3572-06-3). Acute dermal toxicity study was conducted to evaluate the toxic nature of the test compound Cue-lure.The backs of the rabbits were shaved with electric clippers; the shaved area on each animal was about 30% of the total body surface. After a 24-hr waiting period to allow the stratum corneum to recover from any disturbance accompanying the close-clipping procedure and to permit healing of any microscopic abrasions, the undiluted liquid test material was applied, using two male and two female rabbits at each dose level.The site of application was covered by wrapping the trunk of the animal with plastic sheeting that was taped securely in place, and oral contact with the test material was prevented by fitting each animal with a light-weight flexible plastic collar that was worn throughout the observation period. When the test material had been in contact with the skin for 24 hr, the plastic sheeting was removed and all residues of test material were washed off, the test sites were examined for local skin reactions, and the animals were returned to their separate cages. Observations were continued for 14 days following the skin applications. Necropsies were conducted on all animals that died during the study and on all animals that survived the observation period.No mortality noted at the highest tested dose.Ataxia, muscular weakness, and hypothermia were noted in the animals treated with looplure inhibitor.No untoward behavioral reactions were seen in any of the other animals.The test chemical caused local skin reactions characterized at the end of the 24-hr contact period by erythema and edema. With looplure inhibitor, focal second degree burns were noted at 24 hr. At the 7- and 14-day observations, no skin reactions were observed on animals treated with cue-lure.The acute dermal median lethal dose (LD50) for Cue-lure is considered to be>2025 mg/Kg in male and female albino rabbits.

Thus, based on the above studies on 4-Methoxyphenylacetone(122-84-9) and it’s structurally similar read across substances 4-(4-methoxyphenyl)butan-2-one (104-20-1); (1E)-1-(4-methoxyphenyl)pent-1-en-3-one (104-27-8); p-Anisyl acetate (104-21-2) and Cue-lure (3572-06-3), it can be concluded that LD50 value is greater than 2000 mg/kg bw. Thus, comparing this value with the criteria of CLP regulation, 4-Methoxyphenylacetone (122-84-9) cannot be classified for acute dermal toxicity.

Justification for classification or non-classification

Based on the above experimental studies and prediction on 4-Methoxyphenylacetone(122-84-9) and it’s structurally similar read across substances 4-(4-methoxyphenyl)butan-2-one (104-20-1); (1E)-1-(4-methoxyphenyl)pent-1-en-3-one (104-27-8); p-Anisyl acetate (104-21-2) and Cue-lure (3572-06-3),it can be concluded that LD50 value is greater than 2000 mg/kg bw. Thus, comparing this value with the criteria of CLP regulation, 4-Methoxyphenylacetone(122-84-9) cannot be classified for acute oral and dermal toxicity. For Acute inhalation toxicity wavier was added so, not possible to classify.