Phosphonium, trihexyltetradecyl-, chloride

Acute Toxicity: oral

Administrative data

Endpoint:

acute toxicity: oral

Type of information:

experimental study

Adequacy of study:

key study

Study period:

2015-03-27 - 2015-05-29

Reliability:

1 (reliable without restriction)

Rationale for reliability incl. deficiencies:

guideline study

Data source

Reference

Reference Type:

study report

Title:

Unnamed

Year:

2015

Report date:

2015

Materials and methods

Test guideline

Qualifier:

according to guideline

Guideline:

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

Deviations:

no

GLP compliance:

yes

Test type:

acute toxic class method

Limit test:

no

Test material

Test material information

Constituent 1

Reference substance name:

trihexyl(tetradecyl)phosphanium chloride

Cas Number:

258864-54-9

Molecular formula:

C32H68ClP

IUPAC Name:

trihexyl(tetradecyl)phosphanium chloride

Test material form:

liquid

Remarks:

Homogenous Liquid

Specific details on test material used for the study:

Trade name: CYPHOS IL 101 Phosphonium Salt
Physical state: liquid
Composition of test material, percentage of components: Trihexyl(tetradecyl)phosphonium chloride (258864-54-9), > 95%
Lot/batch No.: WEC031280
Expiration date of the lot/batch: >1 year (March 2016) when stored at room temperature and protected from direct contact with water (hydrophobic)

Test animals

Species:

rat

Strain:

Sprague-Dawley

Sex:

male/female

Details on test animals or test system and environmental conditions:

TEST ANIMALS
- Source: Charles River Stone Ridge NY, USA
- Females nulliparous and non-pregnant: yes
- Age at study initiation: Approx. 9 weeks old
- Weight at study initiation: 201 - 302 g for males and 197 - 220 for females; the weight variation did not exceed 20%
- Fasting period before study: Animals were deprived of food for 16-20 hours prior to dosing.
- Housing: housed in suspended wire cages; 5/sex/cage prior to dosing and 3/sex/cage following dosing; containing absorbent paper as bedding material.
- Diet: Fresh PMI Rat Chow (Diet #5012); ad libitum except just prior to dosing
- Water; ad libitum; tap water
- Acclimation period: At least 5 days

ENVIRONMENTAL CONDITIONS
- Temperature (°C): controlled temperature
- Photoperiod (hrs dark / hrs light): 12/12

Administration / exposure

Route of administration:

oral: gavage

Vehicle:

unchanged (no vehicle)

Details on oral exposure:

The test article was used as received.

MAXIMUM DOSE VOLUME APPLIED: 2000 ml/kg

Doses:

Females: 300 and 2000 mg/kg bw
Males: 300 mg/kg bw

No. of animals per sex per dose:

- 300 mg/kg bw: 3 females and 3 males
- 2000 mg/kg bw: 3 females

Control animals:

no

Details on study design:

- Duration of observation period following administration: 14 days
- Frequency of observations and weighing: Mortality/Viability was observed twice daily. The time of death was recorded as precisely as possible. Body weights were measured on Days 1 (pre-administration), 8, at death and on Day 15 in the survivors. Clinical signs were observed at periodic intervals on the day of dosing (Day 1) and once daily thereafter, until Day 15.
- Necropsy of survivors performed: yes
The animals surviving to the end of the observation period were sacrificed by oxygen/carbon dioxide procedure. All animals assigned to the study were subjected to necropsy and descriptions of all internal macroscopic abnormalities recorded.

Statistics:

No statistical analysis was performed.

Results and discussion

Effect levels

Sex:

female

Dose descriptor:

LD50

Effect level:

> 300 - < 2 000 mg/kg bw

Based on:

test mat.

Mortality:

All animals survived following a single 300 mg/kg bw oral dose.
All three females died on Day 1 or Day 5 following a single 2000 mg/kg bw oral dose.

Clinical signs:

other: 300 mg/kg bw: Abnormal physical signs including chromorhinorrhea, yellow staining, localized hair loss, soiling, and wetness of the anogenital area, few feces, chromodacryorrhea, unkempt appaerence, and piloerection were observed. 2000 mg/kg bw: Prior to

Gross pathology:

300 mg/kg bw (females/males): Hair loss on the anogenital area was found at macroscopic post mortem examination of two females that survived until termination. No abnormalities were found at macroscopic post mortem examination of one female and all three males that survived until termination.
2000 mg/kg bw (females): The gross necropsy revealed localized hair loss, yellow and brown staining, soilin, and wetness of the anogenital area, chromodacryorrhea, chromorhinorrhea, brown staining of the nose/mouth area, and abnormalities of the gastrointestinal tract.

Applicant's summary and conclusion

Interpretation of results:

Category 4 based on GHS criteria

Conclusions:

The oral LD50 value of Trihexyltetradecylphosphonium chloride in Sprague Dawley rats was established to be greater than 300 mg/kg but less than 2000 mg/kg body weight.

Executive summary:

A GLP-compliant acute toxicity study according to OECD Guideline 423 was conducted. A group of 3 female Sprague Dawley rats was given a single oral dose of Trihexyltetradecylphosphonium chloride at 300 mg/kg bw. An additional three healthy males were dosed as a confirmatory group at 300 mg/kg bw. Three additional healthy females were dosed at 2000 mg/kg. The rats were observed for 14 days.

300 mg/kg: All three females and males survived following a single 300 mg/kg oral dose. Abnormal physical signs were observed and all six animals gained body weights by study termination; one animal lost weight from Day 0 to Day 7. The gross necropsy revealed hair loss on the anogenital area.

2000 mg/kg: All three females died, on Day 1 or Day 5, following a single 2000 mg/kg oral dose. Prior to death, abnormal physical signs were observed. Terminal body weight loss was observed among all three animals. The gross necropsy revealed hair loss, yellow and brown staining, soiling, and wetness of the anogenital area, chromodacryorrhea, chromiorhinorrhea, brown stainig of the nose/mouth area, and abnormalities of the gastrointestinal tract.

In conclusion, the oral LD50 value of Trihexyltetradecylphosphonium chloride in Sprague Dawley rats was established to be greater than 300 mg/kg but less than 2000 mg/kg body weight.