Tetrabutylammonium bromide

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 study report.

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 after single oral administration in rats.

GLP compliance:

yes

Test type:

acute toxic class method

Limit test:

no

Test material

Test material information

Constituent 1

Reference substance name:

Tetrabutylammonium bromide

EC Number:

216-699-2

EC Name:

Tetrabutylammonium bromide

Cas Number:

1643-19-2

Molecular formula:

C16H36N.Br

IUPAC Name:

tetrabutylazanium bromide

Test material form:

solid

Details on test material:

- Name of test material (as cited in study report):Tetrabutylammonium bromide
- Molecular formula : C16H36N.Br
- Molecular weight :322.37 g/mol
- Substance type:Organic
- Physical state:White Solid (Crystals)
- Analytical purity:99.9%
- Lot/batch No.:Lot 1/02
- Storage condition of test material:Stored in cool, dry place. Kept in closed container when not in use.
- Other: Handling and Disposal
Safety precautions: Avoided eye and skin contact. Avoided inhalation and spilling. Aprons, caps, mask, gloves and goggles were used to ensure the health and safety of the personnel.

Specific details on test material used for the study:

- Substance type:Organic
- Physical state:White Solid (Crystals)
- Analytical purity:99.9%
- Lot/batch No.:Lot 1/02
- Storage condition of test material:Stored in cool, dry place. Kept in closed container when not in use.
- Other: Handling and Disposal
Safety precautions: Avoided eye and skin contact. Avoided inhalation and spilling. Aprons, caps, mask, gloves and goggles were used to ensure the health and safety of the personnel.

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: 197 g and Maximum: 218 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 3-4 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 (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

IN-LIFE DATES: From: February 05, 2014 To: February 26, 2014

Administration / exposure

Route of administration:

oral: unspecified

Vehicle:

other: distilled water

Details on oral exposure:

VEHICLE
- Concentration in vehicle: 300 mg/kg and 2000 mg/kg
- Amount of vehicle (if gavage):10 ml

Doses:

G1 = 300 mg/kg bw
G2 = 2000 mg/kg bw

No. of animals per sex per dose:

9 female rats

Control animals:

not specified

Details on study design:

- Duration of observation period following administration: 14 days
- Frequency of observations and weighing: 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.
- 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.

Statistics:

not specified

Results and discussion

Preliminary study:

not specified

Effect levels

Key result

Sex:

female

Dose descriptor:

LD50

Effect level:

> 300 - < 2 000 mg/kg bw

Based on:

test mat.

Remarks on result:

other: no other details available

Mortality:

No mortality was observed in the animals treated with 300 mg/kg dose throught out the 14 days observation period, whereas all three animals treated with 2000 mg/kg dose level were found dead on day 0 post dosing.

Clinical signs:

other: At 300 mg/kg, all the six animals were observed normal throughout the experiment period. At 2000 mg/kg, animal no. 7 was observed with mild tremors at 30 minutes, mild to moderate abdominal breathing at 30 minutes and 1 hour and sternal recumbency at 1 h

Gross pathology:

No external gross pathological changes were seen in all the six animals treated with 300 mg/kg body weight during terminal sacrifice. At 2000 mg/kg, animal no. 7 was observed with no abnormalities, whereas animal nos. 8 and 9 were observed with wet around mouth. No internal gross pathological changes were seen in all the six animals treated with 300 mg/kg body weight during terminal sacrifice. At 2000 mg/kg, all three animals were observed with severe red discoloration of all lobes lungs and test item was observed in stomach and intestine.

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	Found Dead Animal	Day 0-7	Day 0-14
1	G1/ 300	197	219	227	-	11.17	15.23
2		206	238	258	-	15.53	25.24
3		207	230	246	-	11.11	18.84
4		200	205	210	-	2.50	5.00
5		197	218	212	-	10.66	7.61
6		198	220	223	-	11.11	12.63
7	G2/ 2000	218	-	-	214	-	-
8		215	-	-	217	-	-
9		212	-	-	211	-	-

Key:- = Not Applicable

 

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/ 300	Mean	200.83	221.67	229.33	10.35	14.09
	SD	4.54	11.29	19.08	4.25	7.42
	n	6	6	6	6	6
G2/ 2000	Mean	215.00	-	-	-	-
	SD	3.00	-	-	-	-
	n	3	-	-	-	-

Keys:- = Not Applicable, 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/ 300	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
7	G2/ 2000	166^+ 4^+	155 4^++ 2	-	-	-
8		166^+ 4^++ 155 145^++ 2	-	-	-	-
9		166^+ 4^++ 155 145^++ 2	-	-	-	-

 

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/ 300		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
7		G2/ 2000		-		-		-		-		-		-		-		-		-		-		-		-		-		-
8			-		-		-		-		-		-		-		-		-		-		-		-		-		-
9			-		-		-		-		-		-		-		-		-		-		-		-		-		-

Keys:- = Not applicable, 1 = Normal, 2 = Found dead, 4 = Abdominal breathing, 145 = Salivation,      155 = Sternal recumbency, 166 = Tremors, + = Mild, ++ = Moderate

Applicant's summary and conclusion

Interpretation of results:

Category 4 based on GHS criteria

Conclusions:

The acute oral LD50 value of test chemical was considered in between 300-2000 mg/kg body weight. Thus by considering the CLP criteria for acute toxicity rating for the chemicals, it infers that the given test chemical exhibits acute oral toxicity in “Category 4” LD50 >300 to ≤ 2000 mg/kg body weight.

Executive summary:

Acute oral toxicity study of test chemical was conducted as per OECD No. 423 in rats. Nine female Wistar rats were selected for acute oral toxicity study. 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 providedad 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 300 mg/kg body weight and the animals did not show any mortality so another three animals of the same group were dosed with 300 mg/kg body weight and no mortality was observed. Hence three rats of second group were dosed with 2000 mg/kg weight. All the rats at 2000mg/kg were found dead on day 0 post dosing. 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 surviving animals treated with 300 mg/kg body weight, during the 14 day observation period, as compared to day 0. At 300 mg/kg, all the six animals were observed normal throughout the experiment period. At 2000 mg/kg, animal no. 7 was observed with mild tremors at 30 minutes, mild to moderate abdominal breathing at 30 minutes and 1 hour and sternal recumbency at 1 hour followed by found dead. Animal nos. 8 and 9 were observed with mild tremors, moderate abdominal breathing, sternal recumbency and moderate salivation at 30 minutes followed by found dead. No external gross pathological changes were seen in all the six animals treated with 300 mg/kg body weight during terminal sacrifice. At 2000 mg/kg, animal no. 7 was observed with no abnormalities, whereas animal nos. 8 and 9 were observed with wet around mouth. No internal gross pathological changes were seen in all the six animals treated with 300 mg/kg body weight during terminal sacrifice. At 2000 mg/kg, all three animals were observed with severe red discoloration of all lobes lungs and test item was observed in stomach and intestine. Under the conditions of this, acute oral toxicity dose LD50 value of test chemical was considered in between 300-2000 mg/kg body weight. Thus by considering the CLP criteria for acute toxicity rating for the chemicals, it infers that the given test chemical exhibits acute oral toxicity in “Category 4” LD50 >300 to ≤ 2000 mg/kg body weight.