Phenethyl phenylacetate

Acute Toxicity: oral

Administrative data

Endpoint:

acute toxicity: oral

Type of information:

experimental study

Adequacy of study:

key study

Reliability:

1 (reliable without restriction)

Rationale for reliability incl. deficiencies:

guideline study

Justification for type of information:

data is from experimental reports

Data source

Reference

Reference Type:

study report

Title:

Unnamed

Year:

2014

Report date:

2014

Materials and methods

Test guideline

Qualifier:

according to guideline

Guideline:

OECD Guideline 423 (Acute Oral toxicity - Acute Toxic Class Method)

Principles of method if other than guideline:

The aim of this study was to assess the toxicity potential of the given test chemical after single oral administration in rats and an observation period of 14 days.

GLP compliance:

yes

Test type:

acute toxic class method

Limit test:

no

Test material

Test material information

Constituent 1

Reference substance name:

Phenethyl phenylacetate

EC Number:

203-013-1

EC Name:

Phenethyl phenylacetate

Cas Number:

102-20-5

Molecular formula:

C16H16O2

IUPAC Name:

2-phenylethyl phenylacetate

Test material form:

liquid

Details on test material:

- Name of test material (as cited in study report): Phenethyl phenyl acetate
- Molecular formula : C16H16O2
- Molecular weight : 240.30 g/mole
- Substance type:Organic
- Physical state: Colorless Liquid
- Analytical purity: 99.55 %
- Lot/batch No.: 2012052101
- Storage condition of test material: Room temperature (20° - 30 °C)
- Other: Handling and Disposal
Safety precautions: Aprons, masks, caps, gloves and goggles were used to ensure the health and safety of the Personnel
Disposal:The remaining unused test item formulations were disposed as per internal SOPs

Test animals

Species:

rat

Strain:

Wistar

Sex:

female

Details on test animals or test system and environmental conditions:

TEST ANIMALS
- Source: In-house animals, bred at Animal House.
- Age at study initiation: 9-11 weeks at the time of dosing.
- Health Status: Healthy young adult animals were used for the study. Females were nulliparous and non pregnant.
- Weight at study initiation: Minimum: 148 g and Maximum: 165 g (Individual body weights were within ± 4% prior to treatment after overnight fasting)
- Fasting period:The animals were fasted for minimum 16-18 hours prior to dosing and for 4 hours post dosing.
- Housing: The animals were housed individually in polycarbonate cages.
- Bedding: All cages were provided with corn cobs.
- Room Sanitation: The experimental room floor and work tops were swept and mopped with disinfectant solution every day.
- Cages and water bottle: All the cages and water bottles were changed at least twice every week.
- Diet (e.g. ad libitum): All animals were provided conventional laboratory rodent diet, ad libitum.
- Water (e.g. ad libitum): Aqua guard filtered tap water was provided ad libitum via drinking bottles.
- Acclimation period: Animal nos. 1-3 were acclimatized for seven days and 4-6 for nine days prior to administration of the test item.

ENVIRONMENTAL CONDITIONS
- Temperature (°C):Minimum: 19.60°C and Maximum: 21.40°C.
- Humidity (%):Minimum: 47.40 % and Maximum: 58.60 %.
- Air changes (per hr): More than 12 changes per hour.
- Photoperiod (hrs dark / hrs light):12:12

Administration / exposure

Route of administration:

oral: unspecified

Vehicle:

corn oil

Details on oral exposure:

VEHICLE
- Concentration in vehicle: 2000 mg/kg body weight
- Amount of vehicle (if gavage): No data
- Justification for choice of vehicle: based on solubility testing
- Lot/batch no.: MKBG9426V

MAXIMUM DOSE VOLUME APPLIED: 10 ml/kg body weight

DOSAGE PREPARATION: Added slowly vehicle in to the test item and mixed well. Transferred the formulation to the measuring cylinder and made the volume up to desired quantity of 10 ml. The dosing solution was prepared freshly, shortly prior to dose administration

Doses:

G1 = 2000 mg/kg body weight

No. of animals per sex per dose:

6 female rats

Control animals:

not specified

Details on study design:

- Duration of observation period following administration: 14 days
- Frequency of observations and weighing: Daily
- Necropsy of survivors performed: yes, at the end of 14 day observation period, all the survived rats were euthanised by overdose of CO2 for external and internal observations.
- Other examinations performed: Clinical Observation - After test item administration, individual animals were frequently observed at 30 minutes, 1, 2, 3 and 4 hours post dosing on day 0 (day of dosing). Subsequently, all the surviving animals were observed once a day during the 14 day observation period.
Body weight - All surviving rats were weighed on days 0 (prior to dosing), 7 and 14. Animals were weighed immediately after found dead.
Mortality - All surviving animals were observed twice daily (morning and evening) for morbidity and mortality, throughout the acclimatization and study period.

Statistics:

not specified

Results and discussion

Preliminary study:

not specified

Effect levels

Sex:

female

Dose descriptor:

LD50

Effect level:

> 2 000 mg/kg bw

Based on:

test mat.

Remarks on result:

other: No mortality was observed

Mortality:

No mortality was observed in the animals treated with 2000 mg/kg dose throught out the 14 days observation period

Clinical signs:

other: At 2000 mg/kg, all the animals were normal throughout the experimental period.

Gross pathology:

No external and internal gross pathological changes were seen in all the six animals treated with 2000 mg/kg body weight during terminal sacrifice

Other findings:

not specified

Any other information on results incl. tables

Table 1: Individual Animal Body Weight (g) andBody Weight Changes(%)

Sex:Female

Animal No.	Group/ Dose (mg/kg)	Body Weight (gram)			Body Weight Change (%)
		Day 0	Day 7	Day 14	Day 0-7	Day 0-14
1	G1/ 2000	165	198	212	20.00	28.48
2		160	185	196	15.63	22.50
3		148	177	187	19.59	26.35
4		152	178	196	17.11	28.95
5		157	183	196	16.56	24.84
6		157	181	204	15.29	29.94

Table 2: Summary of Animal Body Weight (g) and Body Weight Changes (%)

Group/ Dose (mg/kg)		Rats Body Weight (g)			Body Weight Changes (%)
		Day 0	Day 7	Day 14	0-7	0-14
G1/ 2000	Mean	156.50	183.67	198.50	17.36	26.84
	SD	5.96	7.63	8.53	2.00	2.82
	n	6	6	6	6	6

Keys:SD = Standard Deviation, n = Number of Animals

Table 3: Individual Animal Clinical Signs and Symptoms

Animal No.	Group/ Dose (mg/kg)	Hours (Day 0)
		1/2	1	2	3	4
1	G1/ 2000	1	1	1	1	1
2		1	1	1	1	1
3		1	1	1	1	1
4		1	1	1	1	1
5		1	1	1	1	1
6		1	1	1	1	1

Animal No.	Group/ Dose (mg/kg)	Days post dosing
		1	2	3	4	5	6	7	8	9	10	11	12	13	14
1	G1/ 2000	1	1	1	1	1	1	1	1	1	1	1	1	1	1
2		1	1	1	1	1	1	1	1	1	1	1	1	1	1
3		1	1	1	1	1	1	1	1	1	1	1	1	1	1
4		1	1	1	1	1	1	1	1	1	1	1	1	1	1
5		1	1	1	1	1	1	1	1	1	1	1	1	1	1
6		1	1	1	1	1	1	1	1	1	1	1	1	1	1

Keys: 1 = Normal

Table 4: Individual Animal Mortality Record

Animal No.	Group/ Dose (mg/kg)	Day of Observation (Day 0 to 14)
		Morning Observations	Evening Observations
1	G1/ 2000	No mortality and morbidity	No mortality and morbidity
2		No mortality and morbidity	No mortality and morbidity
3		No mortality and morbidity	No mortality and morbidity
4		No mortality and morbidity	No mortality and morbidity
5		No mortality and morbidity	No mortality and morbidity
6		No mortality and morbidity	No mortality and morbidity

Table 5: Gross Necropsy Observation

Animal No.	Group/ Dose (mg/kg)	Mode of Death	Gross Observation
			External	Internal
1	G1/ 2000	TS	No abnormality detected	No abnormality detected
2		TS	No abnormality detected	No abnormality detected
3		TS	No abnormality detected	No abnormality detected
4		TS	No abnormality detected	No abnormality detected
5		TS	No abnormality detected	No abnormality detected
6		TS	No abnormality detected	No abnormality detected

Keys: TS =Terminal Sacrifice

Applicant's summary and conclusion

Interpretation of results:

other: Not classified

Conclusions:

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 conditions of this acute oral toxicity study, the acute oral LD50 value was greater than 2000 mg/kg. Hence, the test chemical can be classified under the category "Not Classified" as per CLP Regulation.

Executive summary:

Acute Oral Toxicity Study of the test chemical was conducted as per OECD 423 Guidelines 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. 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 theexperimental 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 conditions of this acute oral toxicity study, the acute oral LD₅₀ value was greater than 2000 mg/kg. Hence, the test chemical can be classified under the category "Not Classified" as per CLP Regulation.