Ethyltriphenylfosfonium bromide

Acute Toxicity: inhalation

Administrative data

Endpoint:

acute toxicity: inhalation

Type of information:

experimental study

Adequacy of study:

key study

Reliability:

2 (reliable with restrictions)

Rationale for reliability incl. deficiencies:

guideline study without detailed documentation

Justification for type of information:

Data is from experimental study report.

Data source

Reference

Reference Type:

study report

Title:

Unnamed

Year:

2013

Report date:

2013

Materials and methods

Test guideline

Qualifier:

according to guideline

Guideline:

OECD Guideline 403 (Acute Inhalation Toxicity)

Principles of method if other than guideline:

The aim of this study was to assess the toxicity potential of given test chemical after inhalation exposure in rats and an observation period of 14 days.

GLP compliance:

no

Test type:

other: Acute Inhalation Toxicity

Limit test:

yes

Test material

Test material information

Constituent 1

Reference substance name:

Ethyltriphenylfosfonium bromide

EC Number:

216-223-3

EC Name:

Ethyltriphenylfosfonium bromide

Cas Number:

1530-32-1

Molecular formula:

C20H20P.Br

IUPAC Name:

bromo(ethyl)triphenylphosphorane

Test material form:

solid: particulate/powder

Details on test material:

- Name of test material (as cited in study report):ethyltriphenylfosfonium bromide
- Molecular formula :C20H20BrP
- Molecular weight :371.25656
- Substance type:Organic
- Physical state:powder

Specific details on test material used for the study:

- Name of test material (as cited in study report):ethyltriphenylfosfonium bromide
- Molecular formula :C20H20BrP
- Molecular weight :371.25656
- Substance type:Organic
- Physical state:powder

Test animals

Species:

rat

Strain:

Wistar

Sex:

male/female

Details on test animals or test system and environmental conditions:

TEST ANIMALS
- Age at study initiation:7 to 9 weeks
- Weight at study initiation:200 ±20g
- Identification-By cage tag and corresponding colour body marking
- Housing:Groups of five animals of similar sex in polypropylene cages with stainless steel grill top, facilities for food and water bottle, and bedding of clean paddy husk.
- Diet (e.g. ad libitum):Pelleted feed, ad libitum
- Water (e.g. ad libitum): Community tap water passed through ‘Aqua Guard on line water filter’, was kept in glass bottles, ad-libitum
- Nutritional conditions:For feeding conventional Laboratory diets may be used with an unlimited supply of drinking water.
- Acclimation period:Twenty healthy albino rats were selected and acclimatized for standard laboratory condition for period of one week in experimental room under veterinary examination.
- Randomization:After acclimatization and veterinary examination all the selected rats randomly divided into two groups of five females and five males.

ENVIRONMENTAL CONDITIONS
- Temperature (°C):19-25 deg. C
- Humidity (%):30-60%
- Air changes (per hr):Air conditioned rooms with 10-15 air changes per hour
- Photoperiod (hrs dark / hrs light):illumination cycle set to 12 hours artificial fluorescent light and 12 hours dark.

Administration / exposure

Route of administration:

inhalation: aerosol

Type of inhalation exposure:

nose only

Vehicle:

other: Distilled water

Details on inhalation exposure:

GENERATION OF TEST ATMOSPHERE / CHAMBER DESCRIPTION
- Exposure apparatus:cylindrical chamber built from stainless steel and glass.
- Exposure chamber volume: 8 liters
- Method of holding animals in test chamber:For the inhalation purpose the rats were placed in polycarbonate holder tubes positioned radically around exposure chamber, so that only the snouts and nostrils of the animals were exposed to the aerosol.
- Source and rate of air: The chamber had a inner and outer chamber to minimize the fluctuation in concentration and temperature.
- Treatment of exhaust air: The exhaust air was decontaminated by subsequent passage through 1% NaOH solution, silica gel and activated charcoal filters.
- Temperature, humidity, pressure in air chamber: The chamber was maintained at a slightly negative pressure to prevent leakage of the test atmosphere from the system, as well as its dilution with outside air.

Analytical verification of test atmosphere concentrations:

not specified

Duration of exposure:

4 h

Concentrations:

Group I – Limit test (5 mg/L)
Group II – Confirmatory test (5 mg/L)

No. of animals per sex per dose:

10 (5 males and 5 females)

Control animals:

not specified

Details on study design:

- Duration of observation period following administration: 14 days
- Frequency of observations and weighing: Clinical Signs: The treated animals were observed for signs of intoxication, at various intervals for first six hours after dosing and thereafter twice a day for 14 days. Any clinical signs in the treated group, if observed, recorded and mentioned in the report.
Mortality: All the animals were observed for mortality at various intervals for first six hours on the day of dosing and thereafter twice a day for 14 days.
Body weight: The body weight of all the animals was observed weekly on day 0 (Before treatment), 7th and 14th (post treatment).
- Necropsy of survivors performed: yes, necropsy was carried out on all the animals that died during the study or surviving animals were sacrificed at the end of the study to observe any gross pathological changes.

Statistics:

not specified

Results and discussion

Preliminary study:

LIMIT TEST: Ten healthy Wistar albino rats of both sexes (5 male and 5 female) of body weight 200±20 gm were selected for study after acclimatization. The test group of animals was exposed to aerosol at the concentration of 5 mg/L for period of 4 hrs. After exposure all the animals were closely observed for clinical signs of toxicity at various intervals such as 1 hr, 2 hrs, 4 hrs, and 6 hrs on the day of test compound aerosol exposure and later on twice a day throughout the experimentation period of 14 days. The necropsy was performed on all the animals at termination of experiment. All the albino rats exposed to aerosol of the test compound at the concentration of 5 mg/L did not show any clinical signs of intoxication. Furthermore, no mortality was observed throughout the period of observation.Necropsy findings: The necropsy was performed on all the animals at the termination of study did not show any gross pathological changes.

Effect levels

Sex:

male/female

Dose descriptor:

LC50

Effect level:

> 5 mg/L air

Based on:

test mat.

Exp. duration:

4 h

Remarks on result:

other: no mortality was observed

Mortality:

The test compound did not elicit any mortality at the tested dose level of 5.0 mg/L throughout the period of observation after exposure.

Clinical signs:

other: The test compound did not elicit any clinical signs of intoxication at the tested aerosol concentration of 5 mg/L observed for the period of 14 days.

Body weight:

The body weight of all the animals recorded individually on day 0th and thereafter 7th and 14th (post treatment) showed normal increase as compared to day 0th.

Gross pathology:

NECROPSY FINDING
EXTERNAL
i.Skin- Skin and hair coat was observed wet.
ii.All external orifices- Normal
B. INTERNAL
i. Subcutaneous- No changes were observed.
ii. Superficial and deep lymph nodes- No change in mesenteric lymph node.
ABDOMINAL CAVITY
i.Opening and general examination- In the abdominal cavity all the organs were present in normal position.
ii.Spleen- No changes were recorded.
iii.Digestive system- No gross changes were observed in stomach and intestine.
iv.Liver and biliary ducts- No gross pathological changes were observed
v.Excretory system- No gross pathological changes were observed.
vi.Adrenal- Observed normal.
vii.Male/female genital organs – Showed normal colour, consistency and no inflammatory changes.
2. THORACIC CAVITY
i.Opening and general examination- Thoracic cavity was found to be normal without any fluid, mucous or blood etc.
ii.Lungs- No changes were recorded.
iii.Heart- No changes were observed in color and consistency. Heart found normal.
iv.Thyroid- Normal in shape, size and surface.
3. CRANIAL CAVITY
Brain- Normal in shape and size.

Other findings:

not specified

Any other information on results incl. tables

TABLE – 3

CLINICAL SIGNS AND MORTALITY

Group: I                                                                                           Dose: 5.0 mg/L

WISTAR ALBNINO RATS

Parameters	Incidence of Clinical Signs Observed after Dosing on																			Mortality
	Day 0					DAY
	Min	Hour
	30	1	2	4	6	1	2	3	4	5	6	7	8	9	10	11	12	13	14	Total	%
Mortality (total)	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0/10	0
Clinical Signs	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0

 TABLE – 3 Contd…………….

CLINICAL SIGNS AND MORTALITY

Group: II                                                                                          Dose: 5.0 mg/L

                                                                                               

WISTAR ALBINO RATS

Parameters	Incidence of Clinical Signs Observed after Dosing on																			Mortality
	Day 0					DAY
	Min	Hour
	30	1	2	4	6	1	2	3	4	5	6	7	8	9	10	11	12	13	14	Total	%
Mortality (total)	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0/10	0
Clinical Signs	0	0	0	0	6	0	0	0	0	0	0	0	0	0	0	0	0	0	0

 

0         =   No clinical sign (Normal)

+         =   Mild

++        =   Moderate

+++      =   High

++++    =   Severe

 

TABLE – 4

SUMMARY OF NECROPSY FINDING

S. No.	Fate	Wistar albino rats
		Dose (mg/l)
		5.0 (limit test)	5.0 (confirmatory test)
1	Terminal sacrifice	10/10	10/10
2	Found Dead	0/10	0/10
3	Abnormalities detected	0/10	0/10

 TABLE – 5

INDIVIDUAL ANIMAL FATE & NECROPSY FINDINGS

Group: I                                                                                                       5.0 mg/L        

WISTAR ALBINO RATS

Animal ID	Fate	Time	Gross Findings
20173-1	TS	Day 14	NAD
20173-2	TS	Day 14	NAD
20173-3	TS	Day 14	NAD
20173-4	TS	Day 14	NAD
20173-5	TS	Day 14	NAD
20173-6	TS	Day 14	NAD
20173-7	TS	Day 14	NAD
20173-8	TS	Day 14	NAD
20173-9	TS	Day 14	NAD
20173-10	TS	Day 14	NAD

  

Day 0 is the day of exposure

TS=Terminal Sacrifice

NAD=No Abnormality Detected

FD=Found Dead

 

TABLE- 5 Contd………………

INDIVIDUAL ANIMAL FATE & NECROPSY FINDINGS

Group: II                                                                                                      5.0 mg/L       

 

WISTAR ALBINO RATS

Animal ID	Fate	Time	Gross Findings
20173-11	TS	Day 14	NAD
20173-12	TS	Day 14	NAD
20173-13	TS	Day 14	NAD
20173-14	TS	Day 14	NAD
20173-15	TS	Day 14	NAD
20173-16	TS	Day 14	NAD
20173-17	TS	Day 14	NAD
20173-18	TS	Day 14	NAD
20173-19	TS	Day 14	NAD
20173-20	TS	Day 14	NAD

 

Day 0 is the day of exposure

TS=Terminal Sacrifice

NAD=No Abnormality Detected

FD=Found Dead

Applicant's summary and conclusion

Interpretation of results:

other: Not classified

Conclusions:

Based on the results obtained from above investigation, the acute inhalation toxicity dose (LC50) was considered to be >5.0 mg/l. Hence, it can be concluded that the test compound is non toxic to male and female Wistar rats by inhalation route via aerosol.

Executive summary:

The acute inhalation study of the given test chemical was conducted in albino rat according to OECD-Guideline -403 for testing of chemicals. In limit test, ten healthy Wistar albino rats of both sexes (5 male and 5 female) of body weight 200±20 gm were selected for study after acclimatization. The test group of animals was exposed to aerosol at the concentration of 5 mg/L for period of 4 hrs. After exposure all the animals were closely observed for clinical signs of toxicity at various intervals such as 1 hr, 2 hrs, 4 hrs, and 6 hrs on the day of test compound aerosol exposure and later on twice a day throughout the experimentation period of 14 days. The necropsy was performed on all the animals at termination of experiment. All the albino rats exposed to aerosol of the test compound at the concentration of 5 mg/L did not show any clinical signs of intoxication. Furthermore, no mortality was observed throughout the period of observation. The necropsy was performed on all the animals at the termination of study did not show any gross pathological changes. After 72 hrs, the result obtained from limit test was confirmed in another 10 animal of both sex at similar concentration following same guideline. Ten healthy Wistar albino rats of both sexes (body weight 200±20 gm) were selected for study after acclimatization. The animals of test group were exposed to aerosol of the test compound at the concentration of 5 mg/L for period of 4 hrs. After exposure all the animals were closely observed for any clinical signs of toxicity at various intervals such as 1 hr, 2 hrs, 4 hrs, and 6 hrs on the day of test compound aerosol exposure and later on twice a day throughout the experimentation period of 14 days. The necropsy was performed on all the animals at termination of experiment. All the albino rats exposed to aerosol at the concentration of 5 mg/L did not show any clinical signs of intoxication. Again there was no mortality recorded during the entire observation period. The body weight of animals exposed to test compound, observed on day 0th (pre treatment) and day 7th (post treatment) did not differ significantly as compared to day 0th. Whereas, body weight of animals observed on day 14th showed normal increase as compared to day 0th. The necropsy was performed on all the animals at the termination of study did not show any gross pathological changes. Based on the results obtained from above investigation, the acute inhalation toxicity dose (LC50) was considered to be >5.0 mg/l. Hence, it can be concluded that the test compound is non toxic to male and female Wistar rats by inhalation route via aerosol.