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Toxicological information

Acute Toxicity: oral

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Administrative data

Endpoint:
acute toxicity: oral
Type of information:
experimental study
Adequacy of study:
weight of evidence
Study period:
03/03/2014 to 18-03-2014
Reliability:
1 (reliable without restriction)
Rationale for reliability incl. deficiencies:
guideline study
Justification for type of information:
Data is from 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:
OECD Guideline 423 (Acute Oral toxicity - Acute Toxic Class Method)
Principles of method if other than guideline:
Acute Oral Toxicity Study (Acute Toxic Class Method) of “Tetrabutylammonium bromide (CAS No.- 1643-19-2)” in Rats
GLP compliance:
yes
Test type:
acute toxic class method
Limit test:
no

Test material

Reference
Name:
Unnamed
Type:
Constituent
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.
Disposal:The remaining unused test item formulations were disposed as per internal SOPs of sa-FORD.
Specific details on test material used for the study:
Identification : Tetrabutylammonium bromide
Appearance : White Solid (Crystals)
Molecular Formula: C16H36N.Br
Molecular Weight: 322.371 g/mole
Purity: 99.9%

Test animals

Species:
rat
Strain:
Wistar
Sex:
female
Details on test animals 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

Administration / exposure

Route of administration:
oral: gavage
Vehicle:
water
Remarks:
distilled
Details on oral exposure:
VEHICLE
- Amount of vehicle (if gavage):10 ml
- Justification for choice of vehicle:N/A
- Lot/batch no. (if required):N/A
- Purity:N/A

MAXIMUM DOSE VOLUME APPLIED:No data available

Doses:
G1 = 300 mg/kg bw
G2 = 2000 mg/kg bw
No. of animals per sex per dose:
Total: 9
300 mg/kg bw: 6 emale rats
2000 mg/kg bw: 3 emale 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.

Results and discussion

Preliminary study:
No data available
Effect levels
Sex:
female
Dose descriptor:
LD50
Effect level:
500 mg/kg bw
Based on:
test mat.
Remarks on result:
other: 50 % mortality based on cut-off value
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:
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.
Body weight:
Body weight gain was observed in the animals treated with 300 mg/kg body weight, during the 14 day observation period, as compared to day 0.
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:
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

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:
Toxicity Category IV
Conclusions:
The acute oral LD50 (cut-off value) of Tetrabutylammonium bromide was 500 mg/kg body weight.Thus by considering the CLP criteria for acute toxicity rating for the chemicals, it infers that Tetrabutylammonium bromide (CAS No.- 1643-19-2) exhibits acute oral toxicity in “Category 4” LD50 >300 to ≤ 2000 mg/kg body weight.
Executive summary:

Acute Oral Toxicity Study of Tetrabutylammonium bromide (CAS No. - 1643-19-2) in Rats, sponsored by Sustainability Support Services (Europe) AB was conducted at sa-FORD (Sanctuary for Research and Development), Maharashtra, India.This study was performed as per OECD No. 423.

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 intestineUnder the conditions of this; acute oral toxicity study of Tetrabutylammonium bromide (CAS No.- 1643-19-2) in female rats is as given below:

The acute oralLD50(cut-off value) of Tetrabutylammonium bromide was 500 mg/kg body weight.Thus by considering the CLP criteria for acute toxicity rating for the chemicals, it infers that Tetrabutylammonium bromide (CAS No.- 1643-19-2) exhibits acute oral toxicity in “Category 4” LD50 >300 to 2000 mg/kg body weight.