N-(4-(methoxybenzyl))-N,N-dimethylanilinium hexafluoroantimonate

Acute Toxicity: oral

Administrative data

Endpoint:

acute toxicity: oral

Type of information:

experimental study

Adequacy of study:

key study

Study period:

From Dec. 12, 2003 to Feb. 26, 2004

Reliability:

1 (reliable without restriction)

Rationale for reliability incl. deficiencies:

guideline study

Data source

Reference

Reference Type:

study report

Title:

Unnamed

Year:

2004

Report date:

2004

Materials and methods

Test guideline

Test guideline 1

Qualifier:

according to guideline

Guideline:

EPA OPPTS 870.1100 (Acute Oral Toxicity)

Version / remarks:

2002

Deviations:

no

Test guideline 2

Qualifier:

according to guideline

Guideline:

OECD Guideline 425 (Acute Oral Toxicity: Up-and-Down Procedure)

Version / remarks:

2001

Deviations:

no

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:

-

EC Number:

457-280-6

EC Name:

-

Cas Number:

126803-19-8

Molecular formula:

C16H20F6NOSb

IUPAC Name:

λ⁵-antimony(5+) N-[(4-methoxyphenyl)methyl]-N,N-dimethylanilinium hexafluoride

Test material form:

solid

Test animals

Species:

rat

Strain:

Wistar

Remarks:

Albino

Sex:

female

Details on test animals or test system and environmental conditions:

TEST ANIMALS
- Rationale for alternative/additional species to rat (if applicable): N/A
- Source: Ace Animals, Boyertown, PA
- Females nulliparous and non-pregnant: yes
- Rationale for use of males (if applicable): N/A
- Age at study initiation: 8-12 weeks at experimental start
- Weight at study initiation: 187 - 244 grams. The weight variation of each animal used did not exceed .±20% of the mean initial weight of all previously dosed animals.
- Fasting period before study: 16-20 hours
- Housing: The animals were housed in suspended wire mesh cages; 1/cage. Bedding was placed beneath the cages and changed at least three times/week. The animal room, reserved exclusively for rats on acute tests, was temperature controlled, and equipped with a 12-hour light/dark cycle. Temperature and humidity were continuously recorded using automatic recording devices.
- Historical data:
- Diet (e.g. ad libitum): fresh PMI Rat Chow (Diet #5012)
- Water (e.g. ad libitum): ad libitum
- Acclimation period: at least five (5) days prior to experimental start.
- Microbiological status when known:
- Method of randomisation in assigning animals to test and control groups: From the available pool of animals, healthy rats of the sex and weight range specified herein will be selected for dosing without conscious bias.

ENVIRONMENTAL CONDITIONS
- Temperature (°C):
- Humidity (%):
- Air changes (per hr):
- Photoperiod (hrs dark / hrs light): 12-hour light/dark cycle

IN-LIFE DATES: From: Dec 17, 2003 To: Feb 12, 2004

Administration / exposure

Route of administration:

oral: gavage

Vehicle:

corn oil

Details on oral exposure:

The dose was based on the dry weight of the test article. Initially, a single female Wistar rat was dosed orally by syringe and dosing needle at a dose level of 2000 mg/kg. Due to the death of the first animal, additional animals were dosed, one at a time, by a single ordered dose progression.

Doses:

175, 550, 2000 mg/kg bw/day

No. of animals per sex per dose:

6 animals 2000 mg/kg bw/day
3 animals 550 mg/kg bw/day
1 animal 175 mg/kg bw/day

Control animals:

no

Remarks:

Not required

Details on study design:

- Duration of observation period following administration: 14 days
- Frequency of observations and weighing: Animals were observed 1/2, 1,2 and 4 hours postdose and once daily for 14 days for toxicity and pharmacological effects. All animals were observed twice daily for mortality. Body weights were recorded immediately pretest, weekly, at death and at termination in the survivors.
- Necropsy of survivors performed: yes. All animals were humanely sacrificed using CO2 following study termination and examined for gross pathology. Abnormal tissues were preserved in 10% buffered formalin for possible future microscopic examination.
- Clinical signs including body weight : yes
- Other examinations performed: clinical signs, body weight, organ weights, histopathology, other:

Statistics:

The LD50 and 95% Confidence Limits were calculated using AOT425 Stat Pgm provided by the EPA.

Results and discussion

Effect levels

Key result

Sex:

female

Dose descriptor:

LD50

Effect level:

>= 2 000 mg/kg bw

Based on:

test mat.

95% CL:

793.2 - 20 000

Mortality:

4/6 animals at 2000 mg/kg bw/day
0/3 animals at 550 mg/kg bw/day
0/1 animal at 175 mg/kg bw/day

Clinical signs:

other:

Body weight:

greater than 10% body weight loss

Remarks:

Body weight changes of survivors were generally normal. One survivor dosed at 550 mg/kg (#9) lost weight during the second week of the observation period.

Gross pathology:

Necropsy results of the dead animals revealed abnormalities of the lungs, thymus, liver, adrenals and gastrointestinal tract, as well as chromorhinorrhea, chromodacryorrhea, red staining of the nose/mouth area, yellow staining of the anogenital area and soiling of the anogenital area.
Necropsy results of the survivors were normal.

Any other information on results incl. tables

 

Mortality responses to the oral dosing:

Animal # (F)	Dose mg/kg	Response (O=alive, X=dead)
1	2000	X
2	175	0
3	550	0
4	2000	0
5	2000	0
6	2000	X
7	550	0
8	2000	X
9	550	0
10	2000	X

 

Table 1: Dose Volume, Dose Level and Body Weights in grams

 

An.#	Sex	Dose mg/kg	Dose Volume in cc	Body Weight (g) Day0	Body Weight (g) Day7	Body Weight (g) Day14
1	F	2000	0.81	203	-
2	F	175	0.072	206	244	246
3	F	550	0.26	240	259	282
4	F	2000	0.89	222	264	270
5	F	2000	0.98	244	285	290
6	F	2000	0.79	197	-	-
7	F	550	0.21	187	228	241
8	F	2000	0.82	206	-	-
9	F	550	0.22	207	275	272
10	F	2000	0.8	200	-	-

 

 

Table 2: Systemic Observations

 

DOSE - mg/kg	2000	175	550	2000	2000	2000	550	2000	550	2000
Animal # / Sex	1/F	2/F	3/F	4/F	5/F	6/F	7/F	8/F	9/F	10/F
Time Periods
1/2 Hour				D
1 Hour				D,T	D,T	D,T		D,T
2 Hour				D,T	D	D,T		D,T
4 Hour	D,T			D,T	D,T	D,T		D,T	D,T
Day 1	X,D,R,B			T		T	X,T	D,T,X,3		R
Day 2	B,X,T,W.J,1,2			T	R,X	T,X	X	D,T,X,R,4,5		R,X,B,2,4.5
Day 3	Z (162g)				X	T,X,8,Q,S.F	X	Z (163g)		Z (177g)
Day 4						Z (171g)
Day 5
Day 6
Day 7
Day 8
Day 9
Day 10
Day 11
Day 12
Day 13
Day 14

No entry indicates animal appeared normal at that observation period. Systemic observation code is on page preceding systemic observation tables.

TOXICITY CODE

B = Lethargy

D = Diarrhea

F = Piloerection

J = Chromodacryorrhea

Q = Sagging eyelids

R = Anogenital area wet

S = Chromorhinorrhea

T = Anogenitaf area soiled

W = Appears emaciated

X = Few feces

Z = Dead

1 = Lacrimation of the eyes

2 = Hunched posture

3 = Nose/mouth area wet

4 = Nose/mouth area stained red

5 = Front paws stained red

 

Table 3: Necropsy Observations

 

DOSE - mg/kg	2000	175	550	2000	2000	2000	550	2000	550	2000
Animal # / Sex	1/F	2/F	3/F	4/F	5/F	6/F	7/F	8/F	9/F	10/F
Observations	D	S	S	S	S	D	S	D	S	D
Normal		X	X	X	X		X		X
Chromodacryorrhea	3					1
Chromorhinorrhea										1
Nose/mouth area: stained red								2
Anogenital area: stained yellow	1
Anogenital area: soiled	1					2		2
Lungs: red areas	3					1
Thymus: dark areas	1
Liver: dark areas										2
Adrenals: darker than normal	1									1
Adrenals: larger than normal	1					1				1
Stomach: red areas	1					1				1
Stomach: distended with gas	1
Stomach: distended with mucus	1							2
Intestines: red areas	1					3		2		2
Intestines: distended with mucus	1					1
Intestines: yellow areas	1							2		2
Cecum: darker than normal								2
Stomach: contains white substance										1

 

CODES:

D= death

S =sacrifice

X = observed

1=slight or scattered

2= moderate or few

3= pronounced or many

 

Applicant's summary and conclusion

Interpretation of results:

Category 4 based on GHS criteria

Conclusions:

The estimated acute oral LD50 and 95% confidence limits are: 2000 (793.2 - >20,000) mg/kg.

Executive summary:

According to the results obtained from an acute oral toxicity study in rats, the estimated acute oral LD50 and 95% confidence limits of N-(4-(methoxybenzyl))-N,N-dimethylanilinium hexafluoroantimonate are: 2000 (793.2 - >20,000) mg/kg. 

The substance meets the GHS criteria for classification as Category 4 for acute oral toxicity.