Registration Dossier

Administrative data

Description of key information

ACUTE TOXICITY ORAL:
The LD50 of 1-phenylethyl acetate was determined to be >5000 mg/kg according to a study performed in line with Federal Hazardous Substances Labelling Act: Hazardous Substances; US Department of Health, Education and Welfare, Food and Drug Administration.
ACUTE TOXICITY: INHALATION
In line with point 8.5.2, Column 2, Annex VIII of Regulation 1907/2006, an acute inhalation study does not need to be performed as the 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 unlikely to occur. The acute toxicity endpoint has been addressed by assessing the toxicity via the oral and dermal routes which are more appropriate when considering the properties of this substance.
ACUTE TOXICITY: DERMAL
The LD50 of 1-phenylethyl acetate was determined to be >8 mL according to a study performed in line with Association of Food and Drug Officials of the United States, Appraisal of the Safety of Chemicals in Foods, Drugs and Cosmetics, 1959, pp 54-56.

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:
Not reported
Reliability:
2 (reliable with restrictions)
Rationale for reliability incl. deficiencies:
other: see 'Remark'
Remarks:
Study conducted in accordance with generally accepted scientific principles, but incomplete reporting on methods and results, which do not affect the quality of the relevant results. Study also not performed to GLP and the method used is a non-standardised guideline.
Qualifier:
according to guideline
Guideline:
other: Federal Hazardous Substances Labelling Act: Hazardous Substances; US Department of Health, Education and Welfare, Food and Drug Administration
Deviations:
not specified
GLP compliance:
no
Test type:
acute toxic class method
Limit test:
yes
Specific details on test material used for the study:
- Name of test material: 1-phenylethyl acetate
- Name of test material (as cited in study report): USA2850 Methyl Phenyl Carbinyl Acetate
Species:
rat
Strain:
Wistar
Sex:
not specified
Details on test animals or test system and environmental conditions:
TEST ANIMALS- Weight at study initiation: 180-200 g- Fasting period before study: 18 hours with water ad libitum- Water (e.g. ad libitum): ad libitum
Route of administration:
oral: unspecified
Vehicle:
unchanged (no vehicle)
Remarks:
reported as undiluted
Doses:
5 gm/kg (5000 mg/kg bw)
No. of animals per sex per dose:
Ten animals per dose
Control animals:
no
Details on study design:
- Duration of observation period following administration: 1, 3, 6 and 24 hours and then every day up to 14 days after treatment- Frequency of observations and weighing: at each time interval- Other examinations performed: pharmacological activity and toxic effects
Sex:
not specified
Dose descriptor:
other: mortality
Effect level:
20 other: %
Based on:
test mat.
Mortality:
Two deaths occurred at 24 hours (autopsy revealed respiratory failure).
Clinical signs:
Severe depression, loss of righting reflex, gasping, ataxia, loss of coordination and motor reflex were noted in all animals up to 3 hours. At 6 hours, animals remained depressed with continued loss of righting reflex and ataxia.
Other findings:
All surviving animals returned to normalcy at 24 hours.
Interpretation of results:
GHS criteria not met
Conclusions:
Under the conditions of the test, 20% mortality was seen when the test substance was administered orally at 5000 mg/kg bw.
Executive summary:

In a pre-GLP acute oral toxicity study conducted in line with Regulations under the Federal Hazardous Substances Labeling Act: Hazardous Substances, the acute oral toxicity of the test substance was determined to be 20% mortality at 5000 mg/kg bw. The LD50 of the test substance under the conditions of the study can therefore be concluded to be greater than 5000 mg/kg bw.

Endpoint conclusion
Endpoint conclusion:
no adverse effect observed
Quality of whole database:
The acute oral toxicity test by Posner (1971) was performed on rats in compliance with the Federal Hazardous Substances Labelling Act: Haz-ardous Substances; US Department of Health, Education and Welfare, Food and Drug Administration. A robust LD50 value was generated and will be used for risk assessment purposes.

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:
key study
Study period:
Not stated
Reliability:
2 (reliable with restrictions)
Rationale for reliability incl. deficiencies:
other: see 'Remark'
Remarks:
Study conducted in accordance with generally accepted scientific principles, but incomplete reporting on results and discussion, which do not affect the quality of the relevant results. Study also not performed to GLP and the method used is a non-standardised guideline.
Qualifier:
according to guideline
Guideline:
other: Association of Food and Drug Officials of the United States, Appraisal of the Safety of Chemicals in Foods, Drugs, and Cosmetics, 1959, pp 54-56
Deviations:
not specified
GLP compliance:
no
Limit test:
no
Specific details on test material used for the study:
- Name of test material: 1-phenylethyl acetate
- Name of test material (as cited in study report): USA2850 Methyl Phenyl Carbinyl Acetate (Styrallyl Acetate)
Species:
rabbit
Strain:
New Zealand White
Sex:
not specified
Details on test animals or test system and environmental conditions:
TEST ANIMALS- Weight at study initiation: 2-2.5 kg
Type of coverage:
occlusive
Vehicle:
unchanged (no vehicle)
Details on dermal exposure:
Rabbits were prepared by clipping the trunk free of hair. Six rabbits were abraded over the entire shaved area with the exception of an area left unabraded. This area served as the control. The remaining rabbits were not abraded. Test substance was applied to each rabbit's back and then each was wrapped in a sleeve to allow the material to remain moist on the treated areas. After twenty-four hours, the rabbits were unwrapped and wiped free of any excess material.
Duration of exposure:
24 hours
Doses:
Approximately 8 mL of test substance
No. of animals per sex per dose:
12 animals (sex not specified)
Control animals:
no
Details on study design:
- Duration of observation period following administration: 14 days- Frequency of observations and weighing: At 24, 48 and 72 h and then daily throughout the 14 days.Evaluation of the skin reaction for erythema and edema was scored in line with the method followed.
Sex:
not specified
Dose descriptor:
LD50
Effect level:
> 8 other: mL
Based on:
test mat.
Mortality:
No mortality occurred during the study.
Clinical signs:
Very slight erythema in two rabbits at 24 hours, which was fully reversible. No behavioural abnormalities or signs of toxicity were observed.
Other findings:
Blood chemistries and urinalysis were within normal ranges.

There was very slight erythema evident in rabbits #4 and #6 at 24 hours. However, during the remainder of the test period, all animals showed no signs of irritation or abnormality. No behavioural changes nor evidence of toxicity were seen within the 14 day test period. Blood chemistries and urinanalysis are within normal ranges and the test substance was considered to be slightly to non-irritating.

Table 1: Readings

   Rabbit no.  Hours        Days                              
     24  48  72  4  5  6  7  8  9  10  11  12  13  14
 Erythema  1  0  0  0  0  0  0  0  0  0  0  0  0  0  0
 Edema    0  0  0  0  0  0  0  0  0  0  0  0  0  0
 Erythema  2  0  0  0  0  0  0  0  0  0  0  0  0  0  0
 Edema    0  0  0  0  0  0  0  0  0  0  0  0  0  0
Erythema  3  0  0  0  0  0  0  0  0  0  0  0  0  0  0
 Edema    0  0  0  0  0  0  0  0  0  0  0  0  0  0
 Erythema  4  0  0  0  0  0  0  0  0  0  0  0  0  0  0
 Edema    0  0  0  0  0  0  0  0  0  0  0  0  0  0
 Erythema  5  0  0  0  0  0  0  0  0  0  0  0  0  0  0
 Edema    0  0  0  0  0  0  0  0  0  0  0  0  0  0
 Erythema  6  0  0  0  0  0  0  0  0  0  0  0  0  0  0
 Edema    0  0  0  0  0  0  0  0  0  0  0  0  0  0
 Erythema  7  0  0  0  0  0  0  0  0  0  0  0  0  0  0
 Edema    0  0  0  0  0  0  0  0  0  0  0  0  0  0
 Erythema  8  0  0  0  0  0  0  0  0  0  0  0  0  0  0
 Edema    0  0  0  0  0  0  0  0  0  0  0  0  0  0
 Erythema  9  0  0  0  0  0  0  0  0  0  0  0  0  0  0
 Edema    0  0  0  0  0  0  0  0  0  0  0  0  0  0
 Erythema  10  0  0  0  0  0  0  0  0  0  0  0  0  0  0
 Edema    0  0  0  0  0  0  0  0  0  0  0  0  0  0
 Erythema  11  0  0  0  0  0  0  0  0  0  0  0  0  0  0
 Edema    0  0  0  0  0  0  0  0  0  0  0  0  0  0
 Erythema  12  0  0  0  0  0  0  0  0  0  0  0  0  0  0
 Edema    0  0  0  0  0  0  0  0  0  0  0  0  0  0
Interpretation of results:
GHS criteria not met
Conclusions:
Under the conditions of the test, the dermal LD50 of the test substance was determined to be > 8 mL. The LD50 of the test substance was greater than 4 mL/kg bw (approximate).
Executive summary:

In a pre-GLP acute dermal toxicity study conducted in line with the Association of Food and Drug Officials of the United States, Appraisal of the Safety of Chemicals in Foods, Drugs and Cosmetics, 1959, pp 54-56, the acute dermal toxicity LD50 of the test substance was determined to be >8 ml (approximately 3.2-4 mL/kg bw) equivalent to 3200 to 4000 mg/kg bw.

Endpoint conclusion
Endpoint conclusion:
no adverse effect observed
Quality of whole database:
The key study (McGee, 1971) is a non-GLP study and was performed in compliance with the Association of Food and Drug Officials of the United States, Appraisal of the Safety of Chemicals in Foods, Drugs, and Cosmetics (1959) pp 54-56 with a sufficient level of detail to assess the quality of the presented data. The study was performed to a good standard in line with sound scientific principles and was assigned a reliability score of 2 in accordance with Klimisch (1997). The study was allocated this score as it was non-GLP performed to a non-standardised guideline.

Additional information

Justification for selection of acute toxicity – oral endpoint
Weight of evidence approach used - no key study available.

Justification for selection of acute toxicity – dermal endpoint
Only one study available.

Justification for classification or non-classification

Acute toxicity: oral

The acute oral toxicity studies indicate that the test substance has no effect in acute oral toxicity which requires the substance to be classified. Therefore the substance does not require classification in line with Directive 67/548/EEC and Regulation 1272/2008.

Acute toxicity: dermal

The key study for acute dermal toxicity indicates that the test substance has no effect on acute dermal toxicity which requires the substance to be classified. Therefore the substance does not require classification in line with Directive 67/548/EEC and Regulation 1272/2008.