Ethyltriphenylfosfonium bromide

Acute Toxicity: oral

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

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 423 (Acute Oral toxicity - Acute Toxic Class Method)

Principles of method if other than guideline:

According to OECD Guideline 423 (Acute Oral toxicity - Acute Toxic Class Method)

GLP compliance:

yes

Test type:

acute toxic class method

Limit test:

no

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

Details on test material:

- Name of test material: ETHYL TRI-PHENYL PHOSPHONIUM BROMIDE
- Appearance: White to off-white crystalline powder
- Substance type: Organic
- Physical state: solid
- AI Content (purity): 99.7%
- Storage conditions : Room temperature (20 - 30 °C)
- Batch number: ETPB1/B/14016
- Manufactured date: February, 2014
- Expiry Date : January, 2015 (Retest date)
- Other: Handling and Disposal
- Safety precautions:Aprons, masks, caps, gloves and goggles were used to ensure the health and safety of the Personnel.

Specific details on test material used for the study:

- Name of test material: ETHYL TRI-PHENYL PHOSPHONIUM BROMIDE
- Appearance: White to off-white crystalline powder
- Substance type: Organic
- Physical state: solid
- AI Content (purity): 99.7%
- Storage conditions : Room temperature (20 - 30 °C)
- Batch number: ETPB1/B/14016
- Manufactured date: February, 2014
- Expiry Date : January, 2015 (Retest date)
- Other: Handling and Disposal
- Safety precautions:Aprons, masks, caps, gloves and goggles were used to ensure the health and safety of the Personnel.

Test animals

Species:

rat

Strain:

Wistar

Sex:

female

Details on test animals or test system and environmental conditions:

TEST ANIMALS
- Source: In-House Bred
- Females (if applicable) nulliparous and non-pregnant: yes
- Age at study initiation: 8- 11 weeks at the time of dosing. Healthy young adult animals were used for the study.
- Weight at study initiation: Minimum: 136 g Maximum: 155 g (Individual body weights were within ± 4% prior to treatment after overnight fasting)
- Fasting period before study: The animals were fasted for minimum 16-18 hours prior to dosing and for 4 hours post dosing, with food withheld but drinking water provided ad libitum.
- 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, 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 7 days and 4-6 for 9 days, 7-9 for 10 days and 10-12 for 6 days prior to administration of the test item.
- Identification:The animals were marked temporarily on tail, permanently on toe pad micro tattooing and cage cards. Individual cage cards were labelled with study no., study type, test system, group, dose, sex, animal number, experimental start and completion date.

ENVIRONMENTAL CONDITIONS
- Temperature (°C): Minimum: 19.60°C Maximum: 23.30°C
- Humidity (%): Minimum: 51.60 % Maximum: 64.60 %
- Air changes (per hr): More than 12 changes per hour
- Photoperiod (hrs dark / hrs light): 12:12

IN-LIFE DATES: From: April 26, 2014 To: May 26, 2014

Administration / exposure

Route of administration:

oral: unspecified

Vehicle:

corn oil

Details on oral exposure:

VEHICLE
- Concentration in vehicle: 2000 mg/kg, 300 mg/kg and 50 mg/kg
- Amount of vehicle (if gavage):10 ml/kg body weight.
- Justification for choice of vehicle: Corn oil was selected as a vehicle because test item was not soluble in the distilled water during solubility testing.

Doses:

2000 mg/kg bw, 300 mg/kg bw and 50 mg/kg bw

No. of animals per sex per dose:

2000 mg/kg bw-3 female rats
300 mg/kg bw-3 female rats
50 mg/kg bw-6 female 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 surviving rats were euthanised by overdose of CO2. All the animals were subjected 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.
Mortality - All surviving animals were observed twice daily (morning and evening) for morbidity and mortality, throughout the acclimatization and study period.
Body weight - All rats were weighed on days 0 (prior to dosing), 7 and 14. Animals were weighed immediately after found dead.

Statistics:

not specified

Results and discussion

Preliminary study:

not specified

Effect levels

Sex:

female

Dose descriptor:

LD50

Effect level:

> 50 - < 300 mg/kg bw

Based on:

test mat.

Mortality:

At 2000 and 300 mg/ kg, all the animals were found dead on day 0 post dosing. No mortality was observed in the animals treated with 50 mg/kg dose throughtout the 14 days observation period.

Clinical signs:

other: At 2000 mg/kg, animal no. 1 was observed with salivation, mild tremors, mild abdominal breathing, sternal recumbency and found dead at 30 minutes post dosing. Animal no. 2 was observed with salivation, mild tremors, mild abdominal breathing, lateral recum

Gross pathology:

At 2000 mg/kg, all three animals were observed with wet area around mouth during external gross pathological examination.
At 300 mg/kg, animal nos. 4 and 5 were observed with no abnormality and animal no. 6 with red area around nose.
At 50 mg/kg, all the six animals were observed with no abnormality.
At 2000 mg/kg, all the animals were observed with moderate red discolouration of all lobes of the lungs, test item in stomach and mild dark colored liver during internal gross pathological examination.
At 300 mg/kg, Animal no. 4 was observed with mild red discolouration of all lobes of the lungs, test item in stomach and mild congestion of Intestine. Animal no. 5 was observed with mild red discolouration of all lobes of the lungs and test item in stomach. Animal no. 6 was observed severe hemorrhages and congestion of lungs, test item in stomach and mild congestion of Intestine.
At 50 mg/kg, all the six animals were observed with no abnormality.

Other findings:

not specified

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	Day 0-7	Day 0-14
1	G1/ 2000	146	-	-	147	-	-
2		143	-	-	147	-	-
3		142	-	-	143	-	-
4	G2/ 300	155	-	-	153	-	-
5		153	-	-	154	-	-
6		150	-	-	146	-	-
7	G3/ 50	152	189	202	-	24.34	26.46
8		146	185	197	-	26.71	27.57
9		136	153	157	-	12.50	13.73
10		148	182	201	-	22.97	29.12
11		143	181	196	-	26.57	29.28
12		146	179	195	-	22.60	27.37

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/ 2000	Mean	143.67	-	-	-	-
	SD	2.08	-	-	-	-
	N	3	-	-	-	-
G2/ 300	Mean	152.67	-	-	-	-
	SD	2.52	-	-	-	-
	N	3	-	-	-	-
G3/ 50	Mean	145.17	178.17	191.33	22.62	25.59
	SD	5.38	12.81	17.05	5.25	5.91
	N	6	6	6	6	6

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/ 2000	145 166^+ 4^+ 155 2	-	-	-	^-
2		145 166^+ 98 4^+ 2	-	-	-	-
3		145 166^++ 4^+ 98 2	-	-	-	-
4	G2/ 300	99^++	98 4^+ 166^+ 2	-	-	-
5		99^++	166^+ 4^+ 98 2	-	-	-
6		1	99^+ 64	99^+ 64	98 4^+ 64	2
7	G3/ 50	1	1	1	49^+	49^+ 99^+
8		1	1	1	64^+ 49^+	64^+ 49^+
9		1	1	1	49^+	49^+
10		1	1	1	49^+	49^+
11		1	1	1	49^+	49^+
12		1	1	1	1	1

Keys:- = Not applicable, 1 = Normal, 2 = Dead, 4 = Abdominal breathing, 49 = Diarrhoea, 64 = Epistaxis, 98 = Lateral recumbency, 99 = Lethargy, 145 = Salivation, 155 = Sternal recumbency, 166 = Tremors,⁺= Mild, ++ = Moderate.

Table 3: Individual Animal Clinical Signs and Symptoms(Contd...)

 

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/ 2000		-		-		-		-		-		-		-		-		-		-		-		-		-		-
2			-		-		-		-		-		-		-		-		-		-		-		-		-		-
3			-		-		-		-		-		-		-		-		-		-		-		-		-		-
4		G2/ 300		-		-		-		-		-		-		-		-		-		-		-		-		-		-
5			-		-		-		-		-		-		-		-		-		-		-		-		-		-
6			-		-		-		-		-		-		-		-		-		-		-		-		-		-
7		G3/ 50		1		1		1		1		1		1		1		1		1		1		1		1		1		1
8			1		1		1		1		1		1		1		1		1		1		1		1		1		1
9			1		1		1		1		1		1		1		1		1		1		1		1		1		1
10			1		1		1		1		1		1		1		1		1		1		1		1		1		1
11			1		1		1		1		1		1		1		1		1		1		1		1		1		1
12			1		1		1		1		1		1		1		1		1		1		1		1		1		1

Keys:- = Not applicable, 1 = Normal

Table 4: Individual Animal Mortality Record

 

Sex:Female

Animal No.	Group/ Dose (mg/kg)	Day of Observation (Day 0 to 14)
		Morning Observations	Evening Observations
1	G1/ 2000	Found dead on day 0 post dosing	Not applicable
2		Found dead on day 0 post dosing	Not applicable
3		Found dead on day 0 post dosing	Not applicable
4	G2/ 300	Found dead on day 0 post dosing	Not applicable
5		Found dead on day 0 post dosing	Not applicable
6		Found dead on day 0 post dosing	Not applicable
7	G3/ 50	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
11		No mortality and morbidity	No mortality and morbidity
12		No mortality and morbidity	No mortality and morbidity

Table 5: Gross Necropsy Observation

 

Sex:Female                                                                                                                                        

Animal No.	Group/ Dose (mg/kg)	Mode of Death	Gross Observation
			External	Internal
1	G1/ 2000	Found dead	Wet area around mouth	Lungs: Red discolouration, all lobes (moderate) Stomach: Test item observed Liver: Dark colored (mild)
2		Found dead	Wet area around mouth	Lungs: Red discolouration, all lobes (moderate) Stomach: Test item observed Liver: Dark colored (mild)
3		Found dead	Wet area around mouth	Lungs: Red discolouration, all lobes (moderate) Stomach: Test item observed Liver: Dark colored (mild)
4	G2/ 300	Found dead	No abnormality detected	Lungs: Red discolouration, all lobes (mild) Stomach: Test item observed Intestine: Congestion (mild)
5		Found dead	No abnormality detected	Lungs: Red discolouration, all lobes (mild) Stomach: Test item observed
6		Found dead	Red area around nose	Lungs: Hemorrhages and congestion (severe) Stomach: Test item observed Intestine: Congestion (mild)
7	G3/ 50	Terminal Sacrifice	No abnormality detected	No abnormality detected
8		Terminal Sacrifice	No abnormality detected	No abnormality detected
9		Terminal Sacrifice	No abnormality detected	No abnormality detected
10		Terminal Sacrifice	No abnormality detected	No abnormality detected
11		Terminal Sacrifice	No abnormality detected	No abnormality detected
12		Terminal Sacrifice	No abnormality detected	No abnormality detected

Applicant's summary and conclusion

Interpretation of results:

other: Category '3' as per CLP criteria of classification and labeling.

Conclusions:

The acute oral LD50 value of test chemical was considered in between 50-300 mg/kg body weight. Thus by considering the CLP criteria for acute toxicity rating for the chemicals, it infers that the given test chemical exhibits acute oral toxicity in “Category 3” LD50 >50 to ≤300 mg/kg body weight.

Executive summary:

Acute oral toxicity study of the given test chemical was conducted as per OECD No. 423 in rats. Twelve female Wistar rats were selected for acute oral toxicity study. The animals were fasted for minimum 16-18 hours prior to dosing and for 4 hours post dosing, with food withheld but drinking water provided ad libitum. The time intervals between dosing were determined by the onset, duration and severity of toxic signs. Three rats of group G1 were dosed with starting dose of 2000 mg/kg body weight and all the animals died post dosing on day 0. At 2000 mg/kg, animal no. 1 was observed with salivation, mild tremors, mild abdominal breathing, sternal recumbency and found dead at 30 minutes post dosing. Animal no. 2 was observed with salivation, mild tremors, mild abdominal breathing, lateral recumbency and found dead at 30 minutes post dosing. Animal no. 3 was observed with salivation, moderate tremors, mild abdominal breathing, lateral recumbency and found dead at 30 minutes post dosing. So, three rats of group G2 were dosed with 300 mg/kg weight and all animals died on day 0 post dosing. At 300 mg/kg, animal nos. 4 and 5 were observed with moderate lethargy at 30 minutes, mild tremors, mild abdominal breathing, lateral recumbency and found dead at 1 hour post dosing. Animal no. 6 was observed with normal sign at 30 minutes, mild lethargy at 1 and 2 hours, epistaxis at 1, 2 and 3 hours, lateral recumbency and mild abdominal breathing at 3 hours and found dead at 4 hours post dosing. So, three rats of G3 were dosed with 50 mg/kg body weight and no mortality was observed. So, another three animals of the same group G3 were dosed with 50 mg/kg body weight and no mortality was observed. Hence, further dosing was stopped. Body weights of surviving animals were re­corded on day 0 (prior to dosing) 7 and 14. Mean body weight of animals treated with 50 mg/kg body weight was observed with gain on day 7 and 14, as compared to day 0. At 50 mg/kg, animal no. 7 was observed with mild diarrhoea at 3 and 4 hours and mild lethargy at 4 hours, animal no. 8 with mild epistaxis and diarrhoea at 3 and 4 hours, animal nos. 9, 10 and 11 with mild diarrhoea at 3 and 4 hours and normal rest of the observation period. Animal no. 12 was observed normal throughout the experiment period. At 2000 mg/kg, all three animals were observed with wet area around mouth during external gross pathological examination. At 300 mg/kg, animal nos. 4 and 5 were observed with no abnormality and animal no. 6 with red area around nose. At 50 mg/kg, all the six animals were observed with no abnormality. At 2000 mg/kg, all the animals were observed with moderate red discolouration of all lobes of the lungs, test item in stomach and mild dark colored liver during internal gross pathological examination. At 300 mg/kg, Animal no. 4 was observed with mild red discolouration of all lobes of the lungs, test item in stomach and mild congestion of Intestine. Animal no. 5 was observed with mild red discolouration of all lobes of the lungs and test item in stomach. Animal no. 6 was observed severe haemorrhages and congestion of lungs, test item in stomach and mild congestion of Intestine. At 50 mg/kg, all the six animals were observed with no abnormality. Under the conditions of this; the acute oral LD50 value of test chemical was considered in between 50-300 mg/kg body weight. Thus by considering the CLP criteria for acute toxicity rating for the chemicals, it infers that the given test chemical exhibits acute oral toxicity in “Category 3” LD50 >50 to ≤300 mg/kg body weight.