Triisobutyl phosphate

Acute Toxicity: inhalation

Administrative data

Endpoint:

acute toxicity: inhalation

Type of information:

experimental study

Adequacy of study:

key study

Reliability:

1 (reliable without restriction)

Rationale for reliability incl. deficiencies:

guideline study

Data source

Reference

Reference Type:

study report

Title:

Unnamed

Year:

1989

Report date:

1989

Materials and methods

Test guideline

Qualifier:

according to guideline

Guideline:

OECD Guideline 403 (Acute Inhalation Toxicity)

GLP compliance:

yes

Test type:

standard acute method

Limit test:

yes

Test material

Test material information

Constituent 1

Reference substance name:

Triisobutyl phosphate

EC Number:

204-798-3

EC Name:

Triisobutyl phosphate

Cas Number:

126-71-6

Molecular formula:

C12H27O4P

IUPAC Name:

triisobutyl phosphate

Specific details on test material used for the study:

- Name of test material: Triisobutylphosphat
- Physical state: liquid
- Storage condition of test material: at 20°C in the dark

Test animals

Species:

rat

Strain:

Wistar

Sex:

male/female

Details on test animals or test system and environmental conditions:

TEST ANIMALS
- Source: HOECHST AG, Kastengrund, SPF-Zucht
- Age at study initiation: 8-10 weeks
- Weight at study initiation: male; 201-211g. females; 182-193g
- Fasting period before study: no data
- Housing: Makrolon cages (type 4) on Softwood pellets
- Diet (ad libitum): Altromin 1324 (Altromin-GmbH, Lage/Lippe)
- Water (ad libitum): tap water in plastic bottles
- Acclimation period: minimal 5 days

ENVIRONMENTAL CONDITIONS
- Temperature (°C): 22 ± 2 °C
- Humidity (%): 50 ± 20 %
- Air changes (per hr): not specified
- Photoperiod (hrs dark / hrs light): 12 hours

IN-LIFE DATES: not specified

Administration / exposure

Route of administration:

inhalation: aerosol

Type of inhalation exposure:

nose only

Vehicle:

air

Details on inhalation exposure:

GENERATION OF TEST ATMOSPHERE / CHAMBER DESCRIPTION
- Exposure apparatus: not specified
- Exposure chamber volume: 60 Liter
- Method of holding animals in test chamber: not specified
- Source and rate of air: 800 L/hr
- System of generating particulates/aerosols: the test substance was injected by static speed by a continuous infusion apparatus into the nozzle. Through riser the aerosol was injected into the inhalation chamber.
- Method of particle size determination: The cascade impactor was operated with a vacuum throughput of 9.5L/Min, resulting in a flow rate of ca. 1.25 m/sec The calculation of the mean aerodynamic diameter and geometric standard deviation of the particle size distribution was determined by probit analysis
(Probit against logarithms of the cumulative frequency of the aerodynamic diameter)
- Treatment of exhaust air: Bottom of the inhalation chamber was a suction device, with Buehler filters, a wash bottle with Tetrachloroethylene, a wash bottle with deionized water and a Calciumchlorid bottle where air was extracted with 1100 Liters of air per hour.
- Temperature, humidity, pressure in air chamber: a with water 1000 mL bottle flows through with 100 liters of air per hour. The with moisture-enriched air was passed directly into the chamber.

TEST ATMOSPHERE
- Brief description of analytical method used: during inhalation, the test amosphere was continuous tested by Hartmann Brown; CO, CO2, 02, humidity and temperature in the exposure chamber is measured.
- Samples taken from breathing zone: yes

VEHICLE
- Concentration of test material in vehicle: 5.14mg/L
- Justification of choice of vehicle: not specified

TEST ATMOSPHERE
- Particle size distribution:
< 0,6 µm: 3,9 %
0,6 - 0,8 µm: 17,6 %
0,8 - 1,5 µm: 36,3 %
1,5 - 3,0 µm: 39,2 %
3,0 - 4,8 µm: 2,9 %
4,8 - 7,0 µm: 0 %
7,0 - 10,3 µm: 0 %
>10,3 µm: 0 %
cumulative: 99,9%
- MMAD (Mass median aerodynamic diameter) / GSD (Geometric st. dev.): Anderson-Kaskadenimpaktor Mark III, Firma Anderson Samples INC, Atlanta
The analysis of particle size distribution showed a mean mass-based aerodynamic diameter (MMAD) of 1.3 microns with a geometric standard deviation of 1.6.

CLASS METHOD (if applicable)
- Rationale for the selection of the starting concentration:

Analytical verification of test atmosphere concentrations:

yes

Duration of exposure:

4 h

Concentrations:

5.14 mg/liter

No. of animals per sex per dose:

5 males and 5 females

Control animals:

no

Details on study design:

- Duration of observation period following administration: 21 days
- Frequency of observations and weighing: daily
- Necropsy of survivors performed: yes
- Other examinations performed: clinical signs, body weight,organ weights, histopathology

Statistics:

Not specified

Results and discussion

Effect levels

Sex:

male/female

Dose descriptor:

LC50

Effect level:

> 5.14 mg/L air

Based on:

test mat.

Exp. duration:

4 h

Remarks on result:

other: no mortality occurred

Mortality:

No mortality occurred

Clinical signs:

other: The animals showed irregular breathing, jerky breathing, gasping, cooing and crackling sound of breathing, tremors, long-legged, uncoordinated and staggering gait, decreased spontaneous activity, ruffled fur, squatting, retracted flanks, reduced parking a

Body weight:

In the first week some effect in body weight were observed. At the end of the observation period all animals showed normal body weight gain, except for one female.

Gross pathology:

Two male and found females showed effects on lungs. The other animals were free of macroscopic effects.