Reaction products of phosphoryl trichloride and 2-methyloxirane

Acute Toxicity: inhalation

Administrative data

Endpoint:

acute toxicity: inhalation

Type of information:

experimental study

Adequacy of study:

key study

Study period:

1990

Reliability:

1 (reliable without restriction)

Rationale for reliability incl. deficiencies:

other: Guideline study performed to GLP

Data source

Reference

Reference Type:

study report

Title:

Unnamed

Year:

1990

Materials and methods

Test guideline

Test guideline 1

Qualifier:

according to guideline

Guideline:

OECD Guideline 403 (Acute Inhalation Toxicity)

Test guideline 2

Qualifier:

according to guideline

Guideline:

OECD Guideline 433 draft (Acute Inhalation Toxicity: Fixed Concentration Procedure) (not officially approved)

GLP compliance:

yes

Test type:

fixed concentration procedure

Limit test:

yes

Test material

Test material information

Constituent 1

Reference substance name:

1-chloropropan-2-yl bis(2-chloropropyl) phosphate; bis(1-chloropropan-2-yl) 2-chloropropyl phosphate; tris(1-chloropropan-2-yl) phosphate; tris(2-chloropropyl) phosphate

EC Number:

807-935-0

Cas Number:

1244733-77-4

Molecular formula:

C9H18Cl3O4P

IUPAC Name:

1-chloropropan-2-yl bis(2-chloropropyl) phosphate; bis(1-chloropropan-2-yl) 2-chloropropyl phosphate; tris(1-chloropropan-2-yl) phosphate; tris(2-chloropropyl) phosphate

Specific details on test material used for the study:

Colourless liquid
received 20 November 1989
stored in dark at ambient temperature
Acid value 0.01 mg KOH/g
water contnet = 0.04%
colour H.U.= 10
Det. Index at 25C: 1.463

Test animals

Species:

rat

Strain:

Sprague-Dawley

Sex:

male/female

Details on test animals or test system and environmental conditions:

TEST ANIMALS
- Source: Charles RiverUk Ltd, Margate
- Age at study initiation: not given
- Weight at study initiation: 111-139g
- Fasting period before study: none
- Housing:1-2 rats per cage, polypropylene with steel mesh lids and bottoms
- Diet (e.g. ad libitum): Rat and Mouse (modified) No1 Diet SQC expanded ad libitum
- Water (e.g. ad libitum): tap water ad libitum
- Acclimation period:at least 12 days


ENVIRONMENTAL CONDITIONS
- Temperature (°C): 16-23C
- Humidity (%): 36-68%
- Air changes (per hr): not given
- Photoperiod (hrs dark / hrs light): 12hr light dark cycle


IN-LIFE DATES: From:20 Feb 1990 To:10 MArch 1990

Administration / exposure

Route of administration:

inhalation: aerosol

Type of inhalation exposure:

nose only

Vehicle:

other: unchanged (no vehicle)

Mass median aerodynamic diameter (MMAD):

4.6 µm

Geometric standard deviation (GSD):

3.3

Details on inhalation exposure:

GENERATION OF TEST ATMOSPHERE / CHAMBER DESCRIPTION
- Exposure apparatus:cylindrical aluminium exposure chamber
- Exposure chamber volume: 41.5 litres
- Method of holding animals in test chamber: polycarbonte restraint tubes
- Source and rate of air: hydrovane compressors 8 litres/min
- Method of conditioning air:
- System of generating particulates/aerosols:sage syringe pump continuous metering of substance through a glass concentric jet atomiser.
- Method of particle size determination: Marple cascade impactor in breathing zone of animals 2l/min sampling rate
- Treatment of exhaust air:high efficiency filter to a metered vaccum system
- Temperature, humidity, pressure in air chamber: 18-19C, RH for three groups 38-72%, 38-80%, 71-90%


TEST ATMOSPHERE
- Brief description of analytical method used: gravimetric method sorbent(silica) gel sampling tubes
- Samples taken from breathing zone: yes


VEHICLE
- Composition of vehicle (if applicable):
- Concentration of test material in vehicle (if applicable):
- Justification of choice of vehicle:
- Lot/batch no. (if required):
- Purity:


TEST ATMOSPHERE (if not tabulated)
- Particle size distribution: 42% <3.5µm
- MMAD (Mass median aerodynamic diameter) / GSD (Geometric st. dev.): MMAD 4.6µm/ GSD 3.3µm


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

Analytical verification of test atmosphere concentrations:

yes

Remarks:

measured gravimetric concentration

Duration of exposure:

4 h

Concentrations:

3.8 mg/L dose rangefinding
7.19 mg/L main study

No. of animals per sex per dose:

2 groups of 2 male and 2 female Sprague-Dawley rats were exposed to a measured gravimetric concentration of TCPP of up to 3.80 mg/L by snout only inhalation, in a dose range finding study, for a period of 4 hours. A further group of 5 female and 5 male Sprague-Dawley rats were exposed to a concentration of TCPP of 7.19 mg/L, also for 4 hours. This was based on the results obtained with the concentration used in the range-finding study.

Control animals:

not specified

Details on study design:

All animals were observed continuously for clinical signs throughout the exposure period, for the first 1-2 hours post-dosing and thereafter once daily during the subsequent 3 day (dose range finding study) or 14 day (main study) observation period. All rats were weighed immediately before dosing and on days 1 and 3 post exposure for the dose ranging finding study and on days 2, 3, 4, 7, 10 and 14 post exposure for the main study. At the end of the study, all animals were subjected to a macroscopic post mortem exam.

Results and discussion

Effect levels

Sex:

male/female

Dose descriptor:

LC50

Effect level:

> 7 mg/L air

Exp. duration:

4 h

Mortality:

There were no deaths during the study.

Clinical signs:

other: No unusual clinical observations were recorded during the exposure period. All animals appeared slightly unkempt and had red staining around the snout and eyes immediately after dosing. No abnormalities were observed during the subsequent 14-day observati

Body weight:

There was no effect on body weight.

Gross pathology:

No abnormalities were observed at post mortem.

Other findings:

lung/bodyweight ratios observed were considered to be within normal limits.

Any other information on results incl. tables

The acute inhalation LC50 is taken to be greater than 7 mg/L from this study.

Applicant's summary and conclusion

Interpretation of results:

GHS criteria not met

Conclusions:

The acute inhalation LC50 is taken to be greater than 7 mg/L from this study.

Executive summary:

2 groups of 2 male and 2 female Sprague-Dawley rats were exposed to a measured gravimetric concentration of TCPP of up to 3.80 mg/L by snout only inhalation, in a dose range finding study, for a period of 4 hours. A further group of 5 female and 5 male Sprague-Dawley rats were exposed to a concentration of TCPP of 7.19 mg/L, also for 4 hours. This was based on the results obtained with the concentration used in the range-finding study. The acute inhalation LC50 is taken to be greater than 7 mg/L from this study.