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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:
key study
Reliability:
1 (reliable without restriction)
Rationale for reliability incl. deficiencies:
guideline study

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:
The aim of this study was to assess the toxicity potential of Tetrabutylammonium bromide after single oral administration in rats.
GLP compliance:
yes
Test type:
acute toxic class method
Limit test:
no

Test material

Reference
Name:
Unnamed
Type:
Constituent
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.

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: 197 g - 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.
- Diet: All animals were provided conventional laboratory rodent diet (Nutrivet Life Sciences, Pune), ad libitum.
- Water: Aqua guard filtered tap water was provided ad libitum via drinking bottles.
- Acclimation period: at least five days.

ENVIRONMENTAL CONDITIONS
- Temperature (°C): 20.4 - 23.1.
- Humidity (%):Minimum: 38.4 - 58.7.
- 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:
other: distilled water
Details on oral exposure:
VEHICLE
- Amount of vehicle (if gavage):up to 10 ml
- Justification for choice of vehicle:N/A
- Lot/batch no. (if required):N/A
- Purity:N/A

MAXIMUM DOSE VOLUME APPLIED:10 ml/kg body weight.

Doses:
300 mg/kg bw, 2000 mg/kg bw
No. of animals per sex per dose:
9
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 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

Effect levels
Key result
Sex:
female
Dose descriptor:
LD50
Effect level:
500 mg/kg bw
Based on:
test mat.
Mortality:
No mortality was observed in the animals treated with 300 mg/kg dose throughout the 14 days observation period, whereas all three animals treated with 2000 mg/kg dose level were found dead on day 0 post dosing (two rats found dead after 1 hour, one rat found dead after 2 hours).
Clinical signs:
At 300 mg/kg, all six animals were observed normal throughout the experiment period. At 2000 mg/kg bw, one animal 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 death. The other two animals dosed at 2000 mg/kg bw were observed with mild tremors, moderate abdominal breathing, sternal recumbency and moderate salivation at 30 minutes followed by death.
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 or 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, one rat was observed with no abnormalities, whereas the other two animals were observed with wet around mouth.
The rats dosed at 2000 mg/kg bw showed severe red discoloration of all lung lobes and test item was observed in stomach and intestine.

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:
Based on the results of an acute oral toxicity study, the acute oral LD50 (cut-off value) of tetrabutylammonium bromide was found to exceed 500 mg/kg body weight. This result is read across to SAM-3, as described in the read across rationale attached in section 13.
Executive summary:

An acute oral toxicity study was performed with tetrabutylammonium bromide in ratsaccording to OECD guideline 423.

Three female rats were dosed at 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. Three other rats were dosed with 2000 mg/kg weight. All the rats at 2000 mg/kg were found dead on day 0 post dosing. Hence, further dosing was stopped. 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 six animals were observed normal throughout the experiment period. No external gross pathological changes were seen in all six animals treated with 300 mg/kg body weight at terminal sacrifice. At 2000 mg/kg, one animal was observed with no abnormalities, whereas two animals 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.

Based on these data, it was concluded that the acute oral LD50 of tetrabutylammonium bromide exceeded 500 mg/kg body weight. This result is read across to SAM-3, as described in the read across rationale attached in section 13.