Benzyltriphenylphosphonium chloride

Acute Toxicity: oral

Administrative data

Endpoint:

acute toxicity: oral

Type of information:

experimental study

Adequacy of study:

key study

Study period:

No data (during the 1977 year)

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:

according to guideline

Guideline:

other: The Federal Hazardous substances Act (code of Federal Regulations, Title 16, Chapter II, 1976)

Deviations:

not specified

Principles of method if other than guideline:

- Principle of test: Test sample was administered orally by stomach tube to five groups, each composed of five male albino rats.
- Parameters analysed / observed: mortality/ gross necropsies.

GLP compliance:

no

Test type:

standard acute method

Limit test:

no

Test material

Test material information

Constituent 1

Reference substance name:

Benzyltriphenylphosphonium chloride

EC Number:

214-154-3

EC Name:

Benzyltriphenylphosphonium chloride

Cas Number:

1100-88-5

Molecular formula:

C25H22P.Cl

IUPAC Name:

benzyltriphenylphosphonium chloride

Test material form:

solid: particulate/powder

Details on test material:

Argentimetric title: 100%
weight loose: 0.2%

Test animals

Species:

rat

Strain:

not specified

Sex:

male

Details on test animals or test system and environmental conditions:

TEST ANIMALS
- Source: Harlan Industries, Inc.
- Weight at study initiation: 208 to 267 grams
- Fasting period before study: no data
- Housing: The rats were housed in groups in wire mesh cages suspended above the droppings.
- Diet: ad libitum
- Water: ad libitum
- Acclimation period: no data

Administration / exposure

Route of administration:

oral: gavage

Vehicle:

corn oil

Details on oral exposure:

DOSAGE PREPARATION: Each sample was administered as a 1 % weight per volume suspension in corn oil at dosage levels of 0.01, 0.0215, 0.0464, 0.100 and 0.215 and as a 50% w/v suspension in corn oil at dosage levels of 0.464 grams per kilogram of body weight. These dilutions necessitated use of dosage factors of 1.00, 2.15, 4.64, 10.0 and 10.0 and 21.5 ml/kg for the 1 % suspension and 0.93 ml for the 50% suspension whivh were calculated by the following formula to enable administration of the desired dose of the compounds: Dosage Factor = Dose to be given (mg/kg)/ Concentration of sample (mg/ml)

Doses:

0.01, 0.0215, 0.0464, 0.1 and 0.464 g/kg

No. of animals per sex per dose:

5 males per dose

Control animals:

not specified

Details on study design:

- Duration of observation period following administration: 14 days
- Frequency of observations and weighing: at frequent intervals during the day of dosage, and at least once daily thereafter for a total of 14 days.
- Necropsy of survivors performed: yes
- Other examinations performed: clinical signs, body weight,organ weights.

Statistics:

Statistical analysis of the mortality data was by the moving average method.

Results and discussion

Effect levels

Key result

Sex:

male

Dose descriptor:

LD50

Effect level:

43 mg/kg bw

Based on:

test mat.

95% CL:

> 26.5 - < 69.8

Mortality:

At the 10 mg/kg bw level, no rat died.
At the 21.5 mg/kg bw level, one rat died within two hours following dosage.
At the 46.4 mg/kg bw level, two rats died within four hours.
At the 100 mg/kg bw level, five rats died within 24 hours.
At the 464 mg/kg bw level, five rats died within 1 hour.

Clinical signs:

other: At the 10 mg/kg bw level all rats exhibited diarrhea during the day of dosage but exhibited normal appearance and behavior throughout the 14 post-dosage day observation period. At the 21.5 mg/kg bw level, toxic effects included depression, piloerection, d

Gross pathology:

Gross necropsies on the rats which died before termination of the study revealed the following:
- Externally: At the 21.5 and 46.4 mg/kg bw levels, rats exhibited excessive salivation and diarrhea stains. At the 100 mg/kg bw level, two rats exhibited diarrhea stains, and one exhibited salivation stains.
- Internally: At the 21.5 mg/kg bw level, gross pathological alterations included congested adrenals and kidneys, irritated gastrointestinal tract and peritoneal walls, and diffusely pale liver. At the 46.4 mg/kg bw level, internal gross pathological alterations were the same as above with the addition of stomachs filled with a fluid resembling the sample. At the 100 mg/kg bw level, gross pathological alterations were the same as above with observation of congested lungs and three rats exhibiting darkened livers. At the 46.4 mg/kg bw level, gross pathological alterations included congested lungs and kidneys, stomachs diffusely whitened and thickened and filled with a white, gritty substance resembling the sample. Intestinal tracts were slightly irritated and livers were diffusely pale. No other gross pathological alterations were noted.
Gross necropsies performed at termination revealed one diffusely necrotic liver in one rat at the 100 mg/kg bw level. No other significant gross pathological alterations were seen at any other level tested.

Applicant's summary and conclusion

Interpretation of results:

Category 2 based on GHS criteria

Conclusions:

Under the conditions of this test, a LD50 equal to 43 mg/kg bw was observed. Therefore, according to GHS criteria a classification as Acute Tox. 2, H300 is required.

Executive summary:

This study was conducted to evaluate the acute oral toxicity of the benzyltriphenylphosphonium Chloride. Five male rats per dose were administered the test substance at the following dose level: 10, 21.5, 46.4, 100 and 464 mg/kg bw. All animals were observed closely for gross signs of systemic toxicity and mortality at frequent intervals during the day of dosage, and at least once daily thereafter for a total of 14 days. Gross necropsies were performed on the animals that died. At the end of the 14-day observation period the surviving rats were weighed, sacrificed by cerebral concussion, and gross necrospsies were performed. Statistical analysis of the mortality data was by the moving average method. Deaths were as follows: 0/5, 1/5, 2/5, 5/5 and 5/5 (from the lowest to the highest dose). A LD50 of 43 mg/kg bw was observed. The main clinical signs observed were comatose appearance, depression, depressed righting, placement and pain reflexes, labored respiration, pale extremities, hypotermia, piloerection, squinting, and diarrhea stains. Therefore, according to GHS criteria a classification as Acute Tox. 2, H300 is required.