1-methyl-3-phenylpropylamine

Acute Toxicity: oral

Administrative data

Endpoint:

acute toxicity: oral

Type of information:

experimental study

Adequacy of study:

weight of evidence

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 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 test chemical in rats.

GLP compliance:

yes

Test type:

acute toxic class 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 propionate

Test material form:

liquid

Details on test material:

- Name of test material (as cited in study report): Benzyl propionate
- Molecular formula: C10H12O2
- Molecular weight: 164.203 g/mol
- Substance type: organic
- Physical state: Liquid
- Smiles notation: c1(COC(CC)=O)ccccc1
- InChl: 1S/C10H12O2/c1-2-10(11)12-8-9-6-4-3-5-7-9/h3-7H,2,8H2,1H3

Test animals

Species:

rat

Strain:

Wistar

Sex:

female

Details on test animals or test system and environmental conditions:

TEST ANIMALS
- Source:Bharat Serum and Vaccines Limited, India.
- Age at study initiation:8- 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: 181 g and Maximum: 213 g (Individual body weights were within ± 6% prior to treatment after overnight fasting) - Fasting period:Wistar rats were fasted for 16-18 hrs.
- 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:Animal nos. 1-3 were acclimatized for five days and 4-6 for seven days prior to administration of the test item.

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

Administration / exposure

Route of administration:

oral: gavage

Vehicle:

corn oil

Details on oral exposure:

VEHICLE
- Amount of vehicle (if gavage):10 ml
- Lot/batch no. (if required):MKBD4650
MAXIMUM DOSE VOLUME APPLIED:10 ml/kg body weight.

Doses:

2000 mg/kg bw

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.
other: Mortality - All surviving animals were observed twice daily (morning and evening) for morbidity and mortality, throughout the acclimatization and study period.

Statistics:

No data available

Results and discussion

Preliminary study:

No data available

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 post dosing.

Clinical signs:

other: At 2000 mg/kg, animal nos. 1, 2, 3, 5 and 6 were observed normal throughout the experimental period, whereas animal no. 4 was observed normal at 30 minutes, 1, 2, 3 and 4 hours, with mild ataxia from day 1 to 4, with mild tremors on day 1, with mild chrom

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:

No data available

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	213	233	247	9.39	15.96
2		200	227	240	13.50	20.00
3		189	221	252	16.93	33.33
4		194	173	205	-10.82	5.67
5		186	203	209	9.14	12.37
6		181	195	196	7.73	8.29

 

 

 

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

Sex:Female

Group/ Dose (mg/kg)		Rats Body Weight (g)			Body Weight Changes (%)
		Day 0	Day 7	Day 14	0-7	0-14
G1/ 2000	Mean	193.83	208.67	224.83	7.65	15.94
	SD	11.44	22.68	24.23	9.66	9.96
	n	6	6	6	6	6

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

 

Table 3: Individual Animal Clinical Signs and Symptoms

Sex:Female

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		21^+ 166^+		21^+ 32^++		21^+ 32^+ 99^++		21^+ 99^+ 32^+		32^+ 99^++		32^+ 99^++		99^++		99^+		99^+		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, 21 = Ataxia, 32 = Chromodacryorrhea, 99 = Lethargy, 166 = Tremors, + = Mild, ++ = Moderate

 

 

Table 4: Individual Animal Mortality Record

Sex:Female

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

 Sex:Female

 

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

 

Applicant's summary and conclusion

Interpretation of results:

other: not classified

Conclusions:

The LD50 was considered to be >2000 mg/kg bw, when female Wistar rats were treated with test chemical orally.

Executive summary:

Acute Oral Toxicity Study of given test chemical was conducted as per OECD No. 423 on 6 female Wistar rats at the concentration of 2000 mg/kg bw. The animals were fasted for minimum 16-18 hours prior to dosing and for 3-4 hours post dosing, with food 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.Body weight gain was observed in all the animals treated with 2000 mg/kg body weight, during the 14 day observation period, as compared to day 0. At 2000 mg/kg, animal nos. 1, 2, 3, 5 and 6 were observed normal throughout the experimental period, whereas animal no. 4 was observed normal at 30 minutes, 1, 2, 3 and 4 hours, with mild ataxia from day 1 to 4, with mild tremors on day 1, with mild chromodacryorrhea from day 2 to 6 and with moderate to mild lethargy from day 3 to 9 post dosing followed by normal observation till day 14. No external and internal gross pathological changes were seen in all the six animals treated with 2000 mg/kg body weight during terminal sacrifice. No mortality was observed in the animals treated with 2000 mg/kg dose throught out the 14 days observation period post dosing. Hence the LD50 was considered to be >2000mg/kg bw, when female Wistar rats were treated with test chemical orally.