Tetrabutylammonium hydroxide

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:

guideline study

Justification for type of information:

Data is from experimental report

Data source

Reference

Reference Type:

study report

Title:

Unnamed

Year:

2018

Report date:

2018

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 objective of this acute oral toxicity study was to assess the toxicological profile of the test item when administered to rats by a single oral gavage.

GLP compliance:

yes (incl. QA statement)

Test type:

acute toxic class method

Limit test:

no

Test material

Test material information

Constituent 1

Reference substance name:

Tetrabutylammonium hydrogen sulphate

EC Number:

251-068-5

EC Name:

Tetrabutylammonium hydrogen sulphate

Cas Number:

32503-27-8

Molecular formula:

C16H36N.HO4S

IUPAC Name:

N,N,N-tributylbutan-1-aminium hydrogen sulfate

Details on test material:

- Name of test material (as cited in study report): Tetrabutylammonium hydrogen sulphate
- Molecular formula :C16H36N.HO4S
- Molecular weight : 339.53g/mol
- Smiles notation: C([N+](CCCC)(CCCC)CCCC)CCC.S([O-])(=O)(=O)O
- InChl : 1S/C16H36N.H2O4S/c1-5-9-13-17(14-10-6-2,15-11-7-3)16-12-8-4;1-5(2,3)4/h5-16H2,1-4H3;(H2,1,2,3,4)/q+1;/p-1
- Substance type: Organic
- Physical state: Solid
- Purity as per Certificate of Analysis: 100.03%
- Lot No. : L199101607
- Manufactured date : JUL-2016
- Expiry Date : JUN-2021
- pH : 1.73 at 26°C
- Density : 0.448 g/cm3 at 25.9°C
- Storage conditions : Ambient (+15 to +25°C)

Test animals

Species:

rat

Strain:

Wistar

Sex:

female

Details on test animals or test system and environmental conditions:

TEST ANIMALS
- Source: Geniron Biolabs Pvt. Ltd. Bengaluru
- Females (if applicable) nulliparous and non-pregnant: yes
- Age at study initiation: 10 to 12 Weeks
- Weight at study initiation:165.34 g to 210.05 g
- Identification:By rat accession number. Identification of individual rats was by cage card and turmeric colour body markings. The rat accession number was allotted during the course of the study. The temporary body marking during acclimatization period was done with crystal violet.
- Fasting period before study: rats were fasted for approximately 16 to 18 hours
- Housing:Rats were housed individually in standard polysulfone cages (Size: L 425 x B 266 x H 185 mm), with stainless steel top grill
- Diet (e.g. ad libitum): Hypro Rat & Mice pellet feed, ad libitum
- Water (e.g. ad libitum): Deep bore-well water passed through activated charcoal filter and exposed to UV rays in Aquaguard on-line water filter-cum-purifier, Mumbai, ad libitum
- Acclimation period: The animals were acclimatized six days for G1-FTS, eight days for G1-STS and twelve days for G2-FTS before treatment.

ENVIRONMENTAL CONDITIONS
- Temperature (°C): 21 to 24°C
- Humidity (%): 66 to 68%
- Air changes (per hr): air conditioned with adequate fresh air supply (between 13.1 and13.2 air changes/hour)
- Photoperiod (hrs dark / hrs light): 12 hours light and 12 hours dark cycle.

IN-LIFE DATES: From: 24 July 2018 To: 11 September 2018

Administration / exposure

Route of administration:

oral: gavage

Vehicle:

other: Milli-Q water

Details on oral exposure:

VEHICLE
- Concentration in vehicle: 300 & 2000 mg/kg body weight.
- Amount of vehicle (if gavage):dose volume was 10 mL/kg body weight

Doses:

G1 (FTS) - 300 mg/kg
G1 (STS) - 300 mg/kg
G2 (FTS) - 2000 mg/kg

No. of animals per sex per dose:

G1 (FTS) - 300 mg/kg - 3
G1 (STS) - 300 mg/kg - 3
G2 (FTS) - 2000 mg/kg - 3

Control animals:

not specified

Details on study design:

- Duration of observation period following administration: 14 days
- Frequency of observations and weighing: Clinical signs and pre-terminal deaths - At each step, the animals were observed five times on test day 1 (day of administration) i.e. at 30 minutes and four times at hourly intervals and once daily during days 2 to 15 post administration. Observations included changes in skin and fur, eyes and mucous membranes, and also respiratory, circulatory, autonomic and central nervous systems and somatomotor activity and behaviour pattern. Attention was directed to the observations of tremors, convulsions, salivation, diarrhoea, lethargy, sleep and coma and all observed clinical signs were recorded. Body weights - The body weights were recorded on test day 1 (pre-administration), day 8 (7 days post administration) and day 15 (14 days post administration).
- Necropsy of survivors performed: yes, the rats surviving to the end of the observation period were euthanised by using isoflurane anaesthesia and subjected to detailed necropsy.
- Other examinations performed: Gross pathological findings were recorded and reported. Microscopic examination was not carried out as no gross pathological changes were observed.

Statistics:

not specified

Results and discussion

Preliminary study:

not specified

Effect levels

Sex:

female

Dose descriptor:

LD50

Effect level:

1 000 mg/kg bw

Based on:

test mat.

Mortality:

G1 - [300 mg/kg body weight - Treatment (FTS and STS)]: There were no mortality/morbidity in FTS and STS till the termination.
G2 - [2000 mg/kg body weight - Treatment (FTS)]: There were two mortalities observed at 0.5 hours post-dose observation.

Clinical signs:

other: G1 - [300 mg/kg body weight - Treatment (FTS and STS)]: There were no clinical signs in FTS and STS till the termination. G2 - [2000 mg/kg body weight - Treatment (FTS)]: There were no clinical signs observed in any of the rats.

Gross pathology:

There were no gross pathological changes at necropsy.

Other findings:

not specified

Any other information on results incl. tables

TABLE 1.      Body weight, body weight change and pre-terminal deaths

Group and Dose (mg/kg body weight)	Rat No.	Sex	Body weight (g)						Day of Death  (Time of Death)	No. dead/  No. tested	Pre-terminal deaths (%)
			Initial (Day 1)	8^thday	Weight change (day 8 – Initial)	15^thday	Weight change           (day 15 – Initial)	At Death
G2 (FTS) 2000	Rw313	F	177.04	185.29	8.25	191.87	14.83	NA	NA	2/3	66.67
	Rw314	F	193.57	-	-	-	-	193.29	1 (12.24 PM)
	Rw315	F	165.34	-	-	-	-	165.22	1 (12.24 PM)

F: Female        FTS: First Treatment Step                 NA: Not Applicable

APPENDIX 1.      Individual clinical signs, dose administration and necropsy findings

Group and Dose (mg/kg body weight)	Date and time of administration	Rat No.	Sex	Body weight (Day 1) (g)	Total volume administered (mL)	Day of observation
						Day 1
						30 min	1hour	2 hours	3 hours	4 hours
G1 (FTS) 300	03 July 2018 and 11:51 AM to 11:54 AM	Rw307	F	190.06	1.90	N	N	N	N	N
		Rw308	F	194.65	1.95	N	N	N	N	N
		Rw309	F	174.59	1.75	N	N	N	N	N

Group and Dose (mg/kg body weight)

Rat No.

Sex

Day of observation

Necropsy Findings

2

3

4

5

6

7

8

9

10

11

12

13

14

15

G1 (FTS) 300

Rw307

F

N

N

N

N

N

N

N

N

N

N

N

N

N

N

NAD

Rw308

F

N

N

N

N

N

N

N

N

N

N

N

N

N

N

NAD

Rw309

F

N

N

N

N

N

N

N

N

N

N

N

N

N

N

NAD

F: Female            FTS: First treatment step              N: Normal            min: minutes         mg: milligrams           kg: kilograms 

mL: millilitre       NAD: No Abnormality Detected    

 

 

APPENDIX 2 contd. Individual clinical signs, dose administration and necropsy findings                 

 

Group and Dose (mg/kg body weight)	Date and time of administration	Rat No.	Sex	Body weight (Day 1) (g)	Total volume administered (mL)	Day of observation
						Day 1
						30 min	1hour	2 hours	3 hours	4 hours
G1 (STS) 300	05 July 2018 and 12:10 PM to 12:12 PM	Rw310	F	210.05	2.10	N	N	N	N	N
		Rw311	F	198.68	1.99	N	N	N	N	N
		Rw312	F	196.13	1.96	N	N	N	N	N

Group and Dose (mg/kg body weight)

Rat No.

Sex

Day of observation

Necropsy Findings

2

3

4

5

6

7

8

9

10

11

12

13

14

15

G1 (STS) 300

Rw310

F

N

N

N

N

N

N

N

N

N

N

N

N

N

N

NAD

Rw311

F

N

N

N

N

N

N

N

N

N

N

N

N

N

N

NAD

Rw312

F

N

N

N

N

N

N

N

N

N

N

N

N

N

N

NAD

F: Female         STS: Second treatment step             N: Normal              min: minutes       mg: milligrams                       kg: kilograms            mL: millilitre     NAD: No Abnormality Detected  

 

APPENDIX 2 contd. Individual clinical signs, dose administration and necropsy findings                 

 

Group and Dose (mg/kg body weight)	Date and time of administration	Rat No.	Sex	Body weight (Day 1) (g)	Total volume administered (mL)	Day of observation
						Day 1
						30 min	1hour	2 hours	3 hours	4 hours
G2 (FTS) 2000	10 July 2018 and 11:52 AM to 11:54 AM	Rw313	F	177.04	1.77	N	N	N	N	N
		Rw314	F	193.57	1.94	016	-	-	-	-
		Rw315	F	165.34	1.65	016	-	-	-	-

Group and Dose (mg/kg body weight)	Rat No.	Sex	Day of observation														Necropsy Findings
			2	3	4	5	6	7	8	9	10	11	12	13	14	15
G2 (FTS) 2000	Rw313	F	N	N	N	N	N	N	N	N	N	N	N	N	N	N	NAD
	Rw314	F	-	-	-	-	-	-	-	-	-	-	-	-	-	-	NAD
	Rw315	F	-	-	-	-	-	-	-	-	-	-	-	-	-	-	NAD

F: Female           FTS: First treatment step        N: Normal   016: Dead       min: minutes   kg: kilograms        mL: millilitre NAD: No Abnormality Detected      

Applicant's summary and conclusion

Interpretation of results:

Category 4 based on GHS criteria

Conclusions:

Based on the results of the present study, the LD50 value of the test chemical was considered to be 1000 mg/kg body weight. Thus, the test chemical was classified in “Category 4 (300 – ≤ 2000)” criteria of CLP.

Executive summary:

The acute oral toxicity study was conducted to assess the toxicological profile of the test chemical as per OECD Guideline 423 (Acute Oral toxicity - Acute Toxic Class Method) in Wistar rats. The dose formulation was prepared by using Milli-Q water and administered as a single oral gavage to overnight fasted (16 to 18 hours) three female rats (G1-FTS) at the dose of 300 mg/kg body weight. There were no clinical signs of toxicity and pre-terminal deaths observed. As all the rats survived at this step, the test was confirmed with three additional female animals with the same dose of 300 mg/kg body weight (G1-STS). There were no clinical signs of toxicity and pre-terminal deaths observed at this step. Based on the scheme - Annex 2c of the guideline OECD 423, the test was continued at the dose of 2000 mg/kg body weight (G2-FTS). The two rats (Rw314 and Rw315) were found dead at 0.5 hours post dose observations, hence as per the scheme - Annex 2c of the guideline OECD 423, the further dosing was stopped. The rats were observed for mortality and clinical signs for 14 days post treatment. Body weights were recorded prior to dosing on day 1 and again on days 8 and 15. Gross necropsy was performed for all the rats at termination. The body weight growth of all survived rats was unaffected by the test chemical. There were no gross pathological changes at necropsy, hence histopathology was not performed. Based on the results of the present study, the LD50 value of the test chemical was considered to be 1000 mg/kg body weight. Thus, the test chemical was classified in “Category 4 (300 – ≤ 2000)” criteria of CLP.