Benzyl propionate

Acute Toxicity: dermal

Administrative data

Endpoint:

acute toxicity: dermal

Type of information:

experimental study

Adequacy of study:

key study

Reliability:

1 (reliable without restriction)

Rationale for reliability incl. deficiencies:

comparable to 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 402 (Acute Dermal Toxicity)

Principles of method if other than guideline:

The dermal toxicity study of Benzyl propionate was performed in rats by dermal route.

GLP compliance:

yes

Test type:

standard acute method

Limit test:

yes

Test material

Test material information

Constituent 1

Reference substance name:

Benzyl propionate

EC Number:

204-559-3

EC Name:

Benzyl propionate

Cas Number:

122-63-4

Molecular formula:

C10H12O2

IUPAC Name:

benzyl propanoate

Details on test material:

- Name of test material (as cited in study report):Benzyl propionate
- Molecular formula :C10H12O2
- Molecular weight :164.20 g/mol
- Substance type:Organic
- Physical state:Colourless Liquid
- Analytical purity:99.39%
- Lot/batch No.:Lot 1/04
- Storage condition of test material:Tightly closed, in well-ventilated place. Kept away from source of ignition – no smoking.
- Other:
Handling and Disposal
Safety precautions : Precautionary measures against static discharges were taken. Kept away from source of ignition. When using did not eat or drink. Aprons, caps, mask, gloves and goggles were used to ensure the health and safety of the Personnel.
Disposal : The remaining unused test item was disposed as per internal SOPs of sa-FORD.

Specific details on test material used for the study:

- Name of test material (as cited in study report):Benzyl propionate
- Molecular formula :C10H12O2
- Molecular weight :164.20 g/mol
- Substance type:Organic
- Physical state:Colourless Liquid
- Analytical purity:99.39%
- Lot/batch No.:Lot 1/04
- Storage condition of test material:Tightly closed, in well-ventilated place. Kept away from source of ignition – no smoking.
- Other:
Handling and Disposal
Safety precautions : Precautionary measures against static discharges were taken. Kept away from source of ignition. When using did not eat or drink. Aprons, caps, mask, gloves and goggles were used to ensure the health and safety of the Personnel.

Test animals

Species:

rat

Strain:

Wistar

Sex:

male/female

Details on test animals or test system and environmental conditions:

TEST ANIMALS
- Source:In-House Bred at Sa-Ford, Animal Facility.
- Age at study initiation:N/A
- Health Status:Healthy young adult animals were used for the study. Females were nulliparous and non pregnant.
- Weight (Prior to Treatment):Male:Minimum: 247 g and Maximum: 251 g ,Female:Minimum: 247 g and Maximum: 260 g
- Fasting period before study:N/A
- 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 (Nutrivet Life Sciences, Pune) ad libitum.
- Water (e.g. ad libitum):Aqua guard filtered tap water was provided ad libitum via drinking bottles.
- Acclimation period:All animals were acclimatized to the test conditions for 5 days prior to administration of the test item.
- Randomization : Animals were selected manually. No computer generated randomization program was used.

ENVIRONMENTAL CONDITIONS
- Temperature (°C):Minimum: 20.40 °C and Maximum: 23.10 °C
- Humidity (%):Minimum: 38.40% and Maximum: 58.70%
- Air changes (per hr):More than 12 changes per hour
- Photoperiod (hrs dark / hrs light):12:12
- IN-LIFE DATES: From: January 30, 2014 to: March, 2014

Administration / exposure

Type of coverage:

semiocclusive

Vehicle:

unchanged (no vehicle)

Details on dermal exposure:

TEST SITE
- Area of exposure:The test item was applied uniformly over clipped dorsal area of rat skin.
- % coverage:Approximately 10% body surface area of rat.
- Type of wrap if used:The porous gauze dressing and non-irritating tape.

REMOVAL OF TEST SUBSTANCE
- Washing (if done):The residual test item was removed by using distilled water.
- Time after start of exposure:24-hour.

TEST MATERIAL
- Amount(s) applied (volume or weight with unit):A limit dose of 2000 mg/ kg body weight of test item was applied.
- Constant volume or concentration used: yes
- For solids, paste formed: no

VEHICLE
- Amount(s) applied (volume or weight with unit):N/A
- Concentration (if solution):N/A
- Lot/batch no. (if required):N/A
- Purity:N/A

Duration of exposure:

24 hrs

Doses:

2000 mg/kg body weight.

No. of animals per sex per dose:

10 (Five per sex)

Control animals:

no

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 surviving rats were euthanised by overdose of CO2 and subjected to gross pathology examination, for external and internal observations.
- Other examinations performed:
- Clinical signs : After test item administration, individual animals were frequently observed at 1, 2, 3 and 4 hours post dosing on day 0 (day of dosing). Subsequently, all animals were observed once a day during the 14 day observation period.

- Body weight: All rats were weighed on days 0 (prior to dosing), 7 and 14.

other:
- Local Signs/Skin Reactions
All animals were observed once daily during days 1-14 (in common with clinical signs).

- Mortality
Animals were observed twice daily for any mortality during the experimental period.

Statistics:

No statistical analysis was performed since the study was terminated with limit test.

Results and discussion

Preliminary study:

No data available

Effect levels

Sex:

male/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 at limit dose of 2000 mg/kg body weight of test item during the 14 day observation period.

Clinical signs:

other: No systemic or local signs of toxicity were observed at limit dose of 2000 mg/kg body weight of test item during the experimental period.

Gross pathology:

The external and internal gross pathological observation of all terminally sacrificed animals did not show any pathological abnormality.

Other findings:

No data available

Any other information on results incl. tables

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

 

Dose:2000 mg/ kg bodyweight                                                                              Density:1.0016

Animal No.	Sex	Dose (ml) Applied*	Body Weight (gram)			Body Weight Change (%)
			Day 0	Day 7	Day 14	Day 0-7	Day 0-14
1	Male	0.50	250	238	260	-4.80	4.00
2		0.49	247	227	245	-8.10	-0.81
3		0.50	250	243	272	-2.80	8.80
4		0.50	249	244	256	-2.01	2.81
5		0.50	251	256	271	1.99	7.97
6	Female	0.51	253	259	258	2.37	1.98
7		0.50	249	251	255	0.80	2.41
8		0.50	250	248	260	-0.80	4.00
9		0.52	260	267	270	2.69	3.85
10		0.49	247	254	255	2.83	3.24

Key:* = Based on density of test item and day 0 body weight taken prior to dose application.

Table 2: Individual Animal Clinical Signs and Symptoms

 

Dose:2000 mg/kg body weight

Animal No.	Sex	Hour(s) - Day 0				Day
		1	2	3	4	1	2	3	4	5	6	7	8	9	10	11	12	13	14
1	Male	1	1	1	1	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	1	1	1	1
3		1	1	1	1	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	1	1	1	1
5		1	1	1	1	1	1	1	1	1	1	1	1	1	1	1	1	1	1
6	Female	1	1	1	1	1	1	1	1	1	1	1	1	1	1	1	1	1	1
7		1	1	1	1	1	1	1	1	1	1	1	1	1	1	1	1	1	1
8		1	1	1	1	1	1	1	1	1	1	1	1	1	1	1	1	1	1
9		1	1	1	1	1	1	1	1	1	1	1	1	1	1	1	1	1	1
10		1	1	1	1	1	1	1	1	1	1	1	1	1	1	1	1	1	1

Key: 1 = Normal

Table 3: Individual Animal Mortality Record

 

Dose:2000 mg/kg body weight

Animal No.	Sex	Days of Observation (0 to 14)
		Morning Observations	Evening Observations
1	Male	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	Female	No mortality and morbidity	No mortality and morbidity
7		No mortality and morbidity	No mortality and morbidity
8		No mortality and morbidity	No mortality and morbidity
9		No mortality and morbidity	No mortality and morbidity
10		No mortality and morbidity	No mortality and morbidity

Applicant's summary and conclusion

Interpretation of results:

other: not classified

Conclusions:

The LD50 was considered to be >2000mg/kg bw, when rats were treated with Benzyl propionate (CAS No. - 122-63-4) by dermal application.

Executive summary:

Acute Dermal Toxicity Study was conducted using Benzyl propionate (CAS No. - 122-63-4) 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  Benzyl propionate (CAS No. - 122-63-4) by dermal application.