Methyltriphenylphosphonium chloride

Acute Toxicity: oral

Administrative data

Endpoint:

acute toxicity: oral

Type of information:

experimental study

Adequacy of study:

key study

Study period:

Jan 21 - March 28, 1994

Reliability:

2 (reliable with restrictions)

Rationale for reliability incl. deficiencies:

guideline study with acceptable restrictions

Data source

Reference

Reference Type:

study report

Title:

Unnamed

Year:

1994

Report date:

1994

Materials and methods

Test guideline

Qualifier:

according to guideline

Guideline:

OECD Guideline 401 (Acute Oral Toxicity)

Version / remarks:

Feb 24, 1987

Deviations:

no

GLP compliance:

yes

Test type:

standard acute method

Test material

Test material information

Constituent 1

Reference substance name:

Methyltriphenylphosphonium chloride

EC Number:

418-400-2

EC Name:

Methyltriphenylphosphonium chloride

Cas Number:

1031-15-8

Molecular formula:

C19H18ClP

IUPAC Name:

methyltriphenylphosphanium chloride

Test animals

Species:

rat

Strain:

Wistar

Sex:

male/female

Details on test animals or test system and environmental conditions:

Housing:
collective housing up to a maximum of 5 animals
per cage (Makrolon@ type III)
llumination:
artificial lighting (120 lux) from 7.00 a.m. -7.00 p.m
Temperature:
22 +/- 3°C
Relative humidity:
30-70 %
Measurement:
twice dail

Administration / exposure

Route of administration:

oral: gavage

Vehicle:

water

Details on oral exposure:

A single oral administration of the test article was performed by gavage using a stomach tube. The test article was administered as a 2 % (group I) or a 5 % (group II) dilution in aqua ad iniectabilia in a volume of 10 ml/kg.

Doses:

500 and 200 mg/kg bw
Preliminary range finding tests with doses of 2000, 1000, 500 and 200 mg/kg body weight were conducted using two female rats per dose.

No. of animals per sex per dose:

200 mg//kg bw: 5 males, 5 females
500 mg/kg bw: 5 males, 5 females

Control animals:

no

Details on study design:

Clinical observations:
In each animal a number of clinical-toxicological signs were evaluated according to a modified Irwin-Screening procedure (Screening Methods in Pharmacology, R. A. Turner, 1965, p. 26). Any change from the normal condition was noted (increase or decrease) and the degree of severity of any clinical symptoms was assessed. The animals were examined at the fonowing post-treatment intervals: 10 min, 1 h, 2 h, 6 h, 24 h, and thereafter once daily up to day 14.
Body weights:
The body weights of an animals were recorded immediately before treatment (day 0) and surviving animals were reweighed on days 7 and 14 p.a. (termination).
Necropsy
Animals found dead were immediately necropsied. The surviving animals were sacrificed by CO2 asphyxiation after 14 days and gross pathological examinations were subsequently performed.
LD50 values were calculated by linear interpolation.

Results and discussion

Effect levels

Effect levels 1

Key result

Sex:

female

Dose descriptor:

LD50

Effect level:

ca. 275 mg/kg bw

Based on:

test mat.

Effect levels 2

Key result

Sex:

male

Dose descriptor:

LD50

Effect level:

ca. 250 mg/kg bw

Based on:

test mat.

Mortality:

at 200 mg/kg bw: 2 of 5 males, 2 of 5 females (after 14 days)
at 500 mg/kg bw: 5 of 5 males, 4 of 5 females (after 14 days)

Clinical signs:

other: Severe dose-dependent clinical signs were observed mainly 1 and 2 h p.a. The most frequent findings were reduced activity, abnormal gait, abdominal, lateral or squatting position, abnormal body posture, decreased body tone, decreased ear, plantary and cor

Gross pathology:

Gross pathological examinations on animals found dead and at 14 days p. a. (terminal necropsy) revealed no test article-related findings.
The liquid filling of the gastro-intestinal tract found in animals which died within a short time after the administration was most probably caused by the administered test substance preparation. Other macroscopic changes observed were attributable to the sacrificing procedure or to minor variations which can occur spontaneously in rats of this strain and age.

Applicant's summary and conclusion

Interpretation of results:

Category 3 based on GHS criteria

Conclusions:

Under the conditions of the present study, after single oral application of the test item to rats the follwing LD50 values were determined:LD50 (rat, male): ca. 250 mg/ kg bw
LD50 (rat, female): ca. 275 mg/ kg bw
LD50 (rat, male): ca. 250 mg/kg bw