Tetrabutylphosphonium chloride

Acute Toxicity: inhalation

Administrative data

Endpoint:

acute toxicity: inhalation

Type of information:

experimental study

Adequacy of study:

key study

Study period:

2012-12-04 - 2013-01-28

Reliability:

1 (reliable without restriction)

Rationale for reliability incl. deficiencies:

guideline study

Data source

Reference

Reference Type:

study report

Title:

Unnamed

Year:

2013

Report date:

2013

Materials and methods

Test guideline

Qualifier:

according to guideline

Guideline:

EPA OPPTS 870.1300 (Acute inhalation toxicity)

GLP compliance:

yes

Test type:

fixed concentration procedure

Limit test:

no

Test material

Test material information

Constituent 1

Reference substance name:

Tributyltetradecylphosphonium chloride

EC Number:

279-808-2

EC Name:

Tributyltetradecylphosphonium chloride

Cas Number:

81741-28-8

Molecular formula:

C26H56P.Cl

IUPAC Name:

tributyl(tetradecyl)phosphonium chloride

Specific details on test material used for the study:

Cyphos 3453W Phosphonium salt
Liquid
Purity: 50% in water
Lot: WEC042091
Expiration date: 30 May 2013

Test animals

Species:

rat

Strain:

Sprague-Dawley

Sex:

male/female

Details on test animals or test system and environmental conditions:

TEST ANIMALS
- Source: Harlan Laboratorins Inc
- Females nulliparous and non-pregnant
- Age at study initiation: 11-12 weeks
- Weight at study initiation: 310-355g for males and 204-245g for females
- Housing: singly housed in suspended stainless steel caging with mesh floors, size recommendations of the Guide for the Care and Use of laboratory animals, litter paper beneath the cage and changed three times per week
- Diet: Harlan Teklad Global 16% Protein Rodent Diet ad libitum except during the exposure
- Water: Filtered tap water ad libitum by an automatic water dispenser except during exposure
- Acclimation period: 22 days

ENVIRONMENTAL CONDITIONS
- Temperature (°C): 19-23 °C
- Humidity (%): 42-50 %
- Air changes/hour: 12
- Photoperiod (hrs dark / hrs light): 12-hour light/dark cycle

Administration / exposure

Route of administration:

inhalation: aerosol

Type of inhalation exposure:

nose only

Vehicle:

air

Mass median aerodynamic diameter (MMAD):

1.93 µm

Details on inhalation exposure:

GENERATION OF TEST ATMOSPHERE / CHAMBER DESCRIPTION
- Exposure apparatus: Nose Only inhalation chamber, ADG Developments LTD
- Exposure chamber volume: 28 liters
- Method of holding animals in test chamber: Animals were individually housed in polycarbonate holding tubes wich seal to the chamber with an "O" ring during exposure. The base unit terminiates the chamber with 0.5-inch diameter tube for discarged air.
- Source and rate of air: 20.0 liters per minute of filtered air was supplied by an air compressor to the spray atomization nozzle. An additional 10.0 liters per minute of compressed mixing air was supplied using air from the same compressor which was introduced into the chamber to help uniformly distribute the test atmosphere by creating a vortex at the chamber inlet. Chamber airflow was monitored throughout the exposure period and recorded periodically. Total airflow was 30.3 liters per minute. Based on the volume fo the inhalation chamber, this airflow provided approximately 64 air changes per hour during the study.
- System of generating particulates/aerosols: The test atmosphere was generated using a 1/4 inch JCO atomizer, FC3 fluid cap and 70SS air cap. Compressed/mixing air was supplied at 30 psi. The test substance was metered to the atomization nozzle through BPT-Size 13 tubing, using a peristaltic pump.
- Method of particle size determination: An eight-stage ACFM Andersen Ambient Particle Sizing Sampler was used to assess the particle size distribution of the test atmospohere. A sample was withdrawn from the breathing zone of the animals at one interval. The filter paper collection stages were weighed before and after sampling to determine the mass collected upon each stage. The aerodynamic mass median diameter and geometric standard deviation were determined graphically using two-cycle logarithmic probit axes.
- Temperature, humidity, pressure in air chamber: The exposure tube temperature and relative humidity ranges during exposure were 20 °C and 21-26%, respectively. The room temperature and relative humidity ranges during exposure were 21 °C and 22-28%, respectively.

TEST ATMOSPHERE
- Brief description of analytical method used: Gravimetric samples were withdrawn at 2 intervals from the breathing zone of the animals. Samples were collected using 37 mm glass fiber filters in a filter holder attached by 1/4 inch Tygon tubing to a vacuum pump. Filer papers were weighed before and after collection to determine the mass collected. This value was divided by the total volume of air sampled to determine the chamber concentration. The collections were carried out for 5 minutes at airflows of 1 liter per minute. Sample airflows were measured unsing a Mass Flowmeter.
- Samples taken from breathing zone: yes

TEST ATMOSPHERE
- MMAD (Mass median aerodynamic diameter): 1.93 µm

Analytical verification of test atmosphere concentrations:

yes

Duration of exposure:

1 h

Remarks on duration:

1h and 5min: The exposure period was extended beyond 1 hour to allow the chamber to reach equilibrium.

Concentrations:

Gravimetric: 0.04 mg/L

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 and weighing: Individual body weights were recorded prior to the exposure and again on days 1, 3, 7 and 14. All animals were observed for mortality during the exposure period. They were examined for signs of gross toxicity and behavioral changes upon removal and at least once daily thereafter up to 14 days.
- Necropsy of survivors performed: yes
- Other examinations performed: gross evaluation of skin and fur, eyes and mucous membranes, respiratory, circulatory, autonomic and central nervous systems, somatomotor activity and behavior pattern. Particular attention was directed to observation of tremors, convulsions, salivation, diarrhea and coma.

Results and discussion

Effect levels

Key result

Sex:

male/female

Dose descriptor:

LC50

Effect level:

> 0.04 mg/L air (analytical)

Exp. duration:

1 h

Mortality:

All animals survived exposure to the test atmosphere.

Clinical signs:

other: Following exposure, all rats exhibited abnormal respiration, hypoactivity and/or ano-genital staining. However, all aniamls recovered from the above symptoms by Day 3 and appeared active and healthy for the remainder of the observation period.

Body weight:

Although all animals lost body weight on Day 1, they showed continued weights gain thereafter and gained weight through Day 14.

Gross pathology:

No gross abnormalities were noted for any of the animals when necropsied at the conclusion of the 14-day observation period.

Applicant's summary and conclusion

Interpretation of results:

study cannot be used for classification

Conclusions:

Under the conditions of this study, the single 1h exposure acute inhalation LC50 of Cyphos 3453W Phosphonium salt is more than 0.04 mg/L in male and female rats.

Executive summary:

The acute inhalation toxicity of Tributyltetradecylphosphonium chloride in the rat was investigated according to the US EPA OPPTS 870.1300 guideline and under GLP.

The substance was administered as an aerosol by inhalation for 1 hour to one group of five male and five female rats at 0.04 mg/L (Gravimetric concentration). Animals were subjected to daily observations and determination of body weights on Days 1, 3, 7, 14 and at death. Macroscopic examination was performed. 

The gravimetric chamber concentration was 0.04 mg/L. Based on graphic analysis of the particle size distribution as measured with an ACFM Andersen Ambient Particle Sizing Sampler, the mass median aerodynamic diameter was estimated to be 1.93 µm (GSD 1.95).

All animals survived the exposure.

Based on the above observations, the inhalatory LC50 1h value of Tributyltetradecylphosphonium chloride in rats was established to be > 0.04 mg/L..