Tetrabutylammonium bromide

Acute Toxicity: dermal

Administrative data

Endpoint:

acute toxicity: dermal

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

Materials and methods

Test guideline

Qualifier:

according to guideline

Guideline:

OECD Guideline 402 (Acute Dermal Toxicity)

Principles of method if other than guideline:

The objective of the study was to assess the dermal toxicity of the test chemical after single dose application by dermal route in rats.

GLP compliance:

yes

Test type:

standard acute method

Limit test:

yes

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)
- Lot/batch No.:Lot 1/02
- Analytical purity:99.9%
- Storage condition of test material:Store in cool, dry place. Keep container closed 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:

male/female

Details on test animals or test system and environmental conditions:

TEST ANIMALS
- Source:In-House Bred at Sa-Ford, Animal Facility.
- Age at study initiation:Healthy young adult animals were used for the study.
- Females (if applicable) nulliparous and non-pregnant: yes
- Weight (Prior to Treatment):Male:Minimum: 217 g and Maximum: 251 g, Female:Minimum: 227 g and Maximum: 242 g
- 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:All animals were acclimatized to the test conditions for 5 days prior to administration of the test item.
- Randomization : Animals were selected manually. No computer generated randomization program was used.

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 21, 2014

Administration / exposure

Type of coverage:

occlusive

Vehicle:

other: distilled water

Details on dermal exposure:

TEST SITE
- Area of exposure:The test item was applied uniformly over clipped dorsal area of rat skin.
- % coverage:Approximately 10% body surface area of rat.
- Type of wrap if used:The porous gauze dressing and non-irritating tape.

REMOVAL OF TEST SUBSTANCE
- Washing (if done):The residual test item was removed by using distilled water.
- Time after start of exposure:24-hour.

TEST MATERIAL
- Amount(s) applied (volume or weight with unit):A limit dose of 2000 mg/ kg body weight of test item was applied.
- Constant volume or concentration used: yes
- For solids, paste formed: yes

VEHICLE
- Amount(s) applied (volume or weight with unit):0.2 ml distilled water

Duration of exposure:

24 hrs

Doses:

2000 mg/kg body weight.

No. of animals per sex per dose:

10 (Five per sex)

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 surviving rats were euthanised by overdose of CO2 and subjected to gross pathology examination, for external and internal observations.
- Other examinations performed:
- Clinical signs : After test item administration, individual animals were frequently observed at 1, 2, 3 and 4 hours post dosing on day 0 (day of dosing). Subsequently, all animals were observed once a day during the 14 day observation period.
- Body weight: All rats were weighed on days 0 (prior to dosing), 7 and 14.
other:
- Local Signs/Skin Reactions
All animals were observed once daily during days 1-14 (in common with clinical signs).
- Mortality
Animals were observed twice daily for any mortality during the experimental period.

Statistics:

No statistical analysis was performed since the study was terminated with limit test.

Results and discussion

Preliminary study:

not specified

Effect levels

Key result

Sex:

male/female

Dose descriptor:

LD50

Effect level:

> 2 000 mg/kg bw

Based on:

test mat.

Remarks on result:

other: no other details available

Mortality:

No mortality was observed at limit dose of 2000 mg/kg body weight of test item during the 14 day observation period.

Clinical signs:

other: In males, animal nos. 1 and 2 were observed with vocalization at 1 hour, normal at 2, 3, 4 hours and on day 7 to 14, moderate to mild erythema on day 1 to 2 and mild scaling on day 3 to 6. Animal no. 3 was observed with vocalization at 1 hour, normal at 2

Gross pathology:

The external and internal gross pathological observation of all terminally sacrificed animals did not show any pathological abnormality, except animal nos. 6 to 9 were observed externally with scab formation.

Other findings:

not specified

Any other information on results incl. tables

Table 1: Individual Animal Body Weight (g) andBody Weight Changes(%)

 

Dose:2000 mg/ kg bodyweight                                                                                                         

Animal No.	Sex	Body Weight (gram)			Body Weight Change (%)
		Day 0	Day 7	Day 14	Day 0-7	Day 0-14
1	Male	217	213	215	-1.84	-0.92
2		238	221	238	-7.14	0.00
3		235	223	252	-5.11	7.23
4		248	255	296	2.82	19.35
5		251	237	271	-5.58	7.97
6	Female	238	248	255	4.20	7.14
7		242	238	241	-1.65	-0.41
8		236	232	226	-1.69	-4.24
9		227	237	228	4.41	0.44
10		232	210	196	-9.48	-15.52

Keys:* = Based on day 0 body weight taken prior to dose application.

Table 2: Individual Animal Clinical Signs and Symptoms

 

Dose:2000 mg/kg body weight

Animal No.	Sex	Hour(s) - Day 0				Day
		1	2	3	4	1	2	3	4	5	6	7
1	Male	172	1	1	1	65^++	65^+	147^+	147^+	147^+	147^+	1
2		172	1	1	1	65^++	65^+	147^+	147^+	147^+	147^+	1
3		172	1	1	1	65^++	65^+	65^+ 147^+	147^++	147^++	147^+	1
4		172	1	1	1	65^++	65^+	65^+ 147^+	65^+ 147^+	147^+	147^+	1
5		172	1	1	1	65^+	1	1	1	1	1	1
6	Female	172	1	1	1	65^++	65^++	65^++	65^++	65^++	65^++	65^++
7		172	1	1	1	65^+++	65^+++	65^+++	65^+++	65^+++	65^++	146
8		172	1	1	1	65^+++	65^+++	65^+++	65^+++	65^+++	65^++	65^++ 146
9		172	1	1	1	65^+++	65^+++	65^+++	65^+++	65^+++	65^++	146
10		172	1	1	1	65^+	65^+	147^+	147^+	147^+	147^+	1

 

Animal No.	Sex	Day
		8	9	10	11	12	13	14
1	Male	1	1	1	1	1	1	1
2		1	1	1	1	1	1	1
3		1	1	1	1	1	1	1
4		1	1	1	1	1	1	1
5		1	1	1	1	1	1	1
6	Female	146	146	146	146	146	146	146
7		146	146	146	146	146	146	146
8		65^+ 146	146	146	146	146	146	146
9		146	146	146	146	146	146	146
10		1	1	1	1	1	1	1

Keys: 1 = Normal, 65 = Erythema, 146 = Scab, 147 = Scale, 172 = Vocalization, + =Mild (slight),                  ++ = Moderate, +++ = Severe

Table 3: Individual Animal Mortality Record

 

Dose:2000 mg/kg body weight

Animal No.	Sex	Days of Observation (0 to 14)
		Morning Observations	Evening Observations
1	Male	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	Female	No mortality and morbidity	No mortality and morbidity
7		No mortality and morbidity	No mortality and morbidity
8		No mortality and morbidity	No mortality and morbidity
9		No mortality and morbidity	No mortality and morbidity
10		No mortality and morbidity	No mortality and morbidity

Applicant's summary and conclusion

Interpretation of results:

other: Not classified

Conclusions:

The acute dermal median lethal dose of the test chemical was considered to be >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 does not exhibit acute dermal toxicity i.e it is acutely non toxic to animals.

Executive summary:

Acute dermal toxicity study of given test chemical was performed as per OECD No.402 in rats. Five male and five female healthy young adult rats were randomly selected and used for conducting acute dermal toxicity study. Rats free from injury and irritation of skin were selected for the study. Twenty four hours prior to dermal application of test item, approximately 10% of body surface area of each rat was clipped. A limit dose of 2000 mg/ kg body weight of test item moistened with 0.2 ml distilled water was applied by single dermal application and observed for 14 days after treatment. On test day 0, an amount of test item moistened with 0.2 ml distilled water was applied directly on the intact skin of clipped area of rats; the porous gauze dressing was put on to the intact skin of clipped area. This porous gauze dressing was covered with a non-irritating tape. The dressing was wrapped around the abdomen and anchored with non-irritating adhesive tape.After the 24-hour application period, the dressings were removed and theskin was gently wiped with distilled water. The skin reactions were assessed. The animals were observed daily for mortality and clinical signs, during the acclimatization period. All animals were observed for clinical signs at approximately 1, 2, 3 and 4 hours after treatment on day 0 and once daily during test days 1‑14. Mortality was recorded after application on test day 0 and twice daily during days 1-14 (at least once on the day of sacrifice). Local signs / Skin reactions were observed daily from test days 1-14 (in common with clinical signs). Body weights were re­corded on day 0 (prior to application) and on day 7 and 14. All animals were necropsied and examined macroscopically. No mortality was observed in any animal till the end of the experimental period. In males, animal nos. 1 and 2 were observed with vocalization at 1 hour, normal at 2, 3, 4 hours and on day 7 to 14, moderate to mild erythema on day 1 to 2 and mild scaling on day 3 to 6. Animal no. 3 was observed with vocalization at 1 hour, normal at 2, 3, 4 hours and on day 7 to 14, moderate to mild erythema on day 1 to 3 and mild to moderate scaling on day 3 to 6. Animal no. 4 was observed with vocalization at 1 hour, normal at 2, 3, 4 hours and on day 7 to 14, moderate to mild erythema on day 1 to 3 and mild scaling on day 3 to 6.Animal no. 5 was observed with vocalization at 1 hour, normal at 2, 3, 4 hours and on day 2 to 14 and mild erythema on day 1.  In females, animal no. 6 was observed with vocalization at 1 hour, normal at 2, 3 and 4 hours, severe to moderate erythema on day 1 to 7 and scab from day 8 to 14. Animal nos. 7 and 9 were observed with vocalization at 1 hour, normal at 2, 3 and 4 hours, severe to moderate erythema on day 1 to 6 and scab from day 7 to 14. Animal no. 8 was observed with vocalization at 1 hour, normal at 2, 3 and 4 hours, severe to moderate erythema on day 1 to 8 and scab from day 8 to 14. Animal no. 10 was observed with vocalization at 1 hour, normal at 2, 3, 4 hours and on day 7 to 14, mild erythema on day 1 to 2 and mild scaling from day 3 to 6. In males, mean body weight gain was observed with on day 14, whereas decline in mean body weight gain was observed on day 7 as compared to day 0. In females, declined mean body weight gain was observed with on day 7 and 14 as compared to day 0. The external and internal gross pathological observation of all terminally sacrificed animals did not show any pathological abnormality, except animal nos. 6 to 9 were observed externally with scab formation. Under the conditions of this, the acute dermal median lethal dose of test chemical was considered to be >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 does not exhibit acute dermal toxicity i.e it is acutely non toxic to animals.