Ethyltriphenylphosphonium acetate

Acute Toxicity: oral

Administrative data

Endpoint:

acute toxicity: oral

Type of information:

experimental study

Adequacy of study:

key study

Study period:

April 1977

Reliability:

2 (reliable with restrictions)

Rationale for reliability incl. deficiencies:

comparable to guideline study with acceptable restrictions

Data source

Reference

Reference Type:

study report

Title:

Unnamed

Year:

1977

Report date:

1977

Materials and methods

Test guideline

Qualifier:

equivalent or similar to guideline

Guideline:

OECD Guideline 401 (Acute Oral Toxicity)

GLP compliance:

no

Remarks:

study conducted before imlementation of GLP

Test type:

standard acute method

Limit test:

no

Test material

Test material information

Constituent 1

Reference substance name:

Ethyltriphenylphosphonium acetate

EC Number:

252-743-7

EC Name:

Ethyltriphenylphosphonium acetate

Cas Number:

35835-94-0

Molecular formula:

C20H20P.C2H3O2

IUPAC Name:

ethyltriphenylphosphanium acetate

Test material form:

solid

Specific details on test material used for the study:

Chemical name as given in report: Ethyltriphenylphosphonium acid acetate

Test animals

Species:

rat

Strain:

Sprague-Dawley

Sex:

male

Details on test animals or test system and environmental conditions:

TEST ANIMALS
- Source: Harlan Industries
- Weight at study initiation: 200 - 266 g
- Fasting period before study: 18 h
- Housing: in groupsin wire mesh cages

Administration / exposure

Route of administration:

oral: gavage

Vehicle:

water

Details on oral exposure:

VEHICLE
- Concentration in vehicle: 1% (50 % for highest dose group)

Doses:

21.5, 46.4, 100, 215, 464 mg/kg bw

No. of animals per sex per dose:

5

Control animals:

no

Details on study design:

- Duration of observation period following administration: 14 days
- Frequency of observations: frequent intervals during the day of dosage, once daily thereafter
- Necropsy of survivors performed: no
- Other examinations performed: clinical signs

Statistics:

moving average method (Horn, H. J., 1956, Biometrics 12 (3): 311-322)

Results and discussion

Effect levels

Key result

Sex:

male

Dose descriptor:

LD50

Effect level:

126 mg/kg bw

Based on:

test mat.

95% CL:

>= 92.6 - <= 171

Mortality:

yes

Clinical signs:

other: 21.5 mg/kg: all rats exhibiting mucoid diarrhea stains and one rat exhibiting bloody stains around the nose late in the dosage day. 46.4 mg/kg: one rat exhibiting slight diarrhea at the initial observation of the day of dosage. Four rats exhibited mucoid

Gross pathology:

Gross necropsy findings of the rats that died at the 0.100 gm/kg, 0.215 gm/kg, and the 0.464 gm/kg levels included externally evidence of excessive salivation stains in seven rats, diarrhea stains in six rats, and bloody stains around the nose and eyes of one rat.
Internally, all rats exhibited congested kidneys, ten rats exhibited congested adrenals, and six rats exhibited congested lungs. A clear to yellowish fluid resembling sample was found in the stomach or gastrointestinal tracts of all eleven rats, five of which exhibited a thickened pyloric region of the stomach, and three of which exhibited distended stomachs. Eight rats also exhibited irritated gastrointestinal tracts, including five which exhibited diffuse irritated areas in the small intestine. Six rats exhibited irritated peritoneal walls of which four of the peritoneal walls were wrinkled. One rat exhibited a pale liver where in contact with the stomach. Advanced autolysis was noted in four rats. No other gross pathological alterations were noted.

Gross necropsies performed at termination revealed three rats exhibiting slightly congested adrenals. No other significant gross pathological alterations were noted.

Any other information on results incl. tables

Dose	Conc.	Time of death
mg (kg bw	%	Hours				Days
		0.5 – 1	2	3-4	24	2	3	4	5	6	7-14
21.5	1	0/5	0/5	0/5	0/5	0/5	0/5	0/5	0/5	0/5	0/5
46.4	1	0/5	0/5	0/5	0/5	0/5	0/5	0/5	0/5	0/5	0/5
100	1	0/5	0/5	0/5	1/5	1/5	1/5	1/5	1/5	1/5	1/5
215	1	0/5	0/5	2/5	5/5
464	50	5/5

Applicant's summary and conclusion

Interpretation of results:

Category 3 based on GHS criteria

Conclusions:

The acute oral LD50 of Ethyltriphenylphosphonium acid acetate in male rats was 126 mg/kg bw.

Executive summary:

In an acute oral toxicity study comparable to OECD guideline 401, 5 male fasted rats were given a single oral dose of Ethyltriphenylphosphonium acid acetate in distilled water by gavage at doses of 21.5, 46.4, 100, 215 or 464 mg/kg bw and observed for 14 days.

5/5 animals in the highest dose died within the first hour. In the 215 mg/kg dose group, 2/5 rats died within 4 hours and 5/5 animals died within 24 hours. In the 100 mg/kg dose group, 1/5 animals died within 24 hours. Clinical signs shown by the animals found dead and surviving animals included mucoid diarrhea, comatose appearance, depression, depressed righting, placement, and pain reflexes, labored respiration, excessive salivation, and intermittent tremors.

 Gross necropsy findings of the rats that died at the 0.100 gm/kg, 0.215 gm/kg, and the 0.464 gm/kg levels included externally evidence of excessive salivation stains, diarrhea stains. All rats exhibited congested kidneys, ten rats exhibited congested adrenals, and six rats exhibited congested lungs. A clear to yellowish fluid resembling sample was found in the stomach or gastrointestinal tracts of all eleven rats, five of which exhibited a thickened pyloric region of the stomach, and three of which exhibited distended stomachs. Eight rats also exhibited irritated gastrointestinal tracts, including five which exhibited diffuse irritated areas in the small intestine. Six rats exhibited irritated peritoneal walls of which four of the peritoneal walls were wrinkled. One rat exhibited a pale liver where in contact with the stomach. Advanced autolysis was noted in four rats. No other gross pathological alterations were noted.

Gross necropsies performed at termination revealed three rats exhibiting slightly congested adrenals. No other significant gross pathological alterations were noted.

 The surviving animals had recovered from the symptoms between days 4 and 5. The average body weight gain of survivors was within the normal limits for the rats of the age, sex, and strain used in this study.

 

Oral LD50 (rat, males) 126 mg/kg bw