Dimethyl methylphosphonate

Acute Toxicity: inhalation

Administrative data

Endpoint:

acute toxicity: inhalation

Type of information:

experimental study

Adequacy of study:

key study

Reliability:

2 (reliable with restrictions)

Rationale for reliability incl. deficiencies:

other: scientifically acceptable study (similar to guideline)

Data source

Reference

Reference Type:

study report

Title:

Unnamed

Year:

1977

Report date:

1977

Materials and methods

Test guideline

Qualifier:

equivalent or similar to guideline

Guideline:

OECD Guideline 403 (Acute Inhalation Toxicity)

Principles of method if other than guideline:

Evaluation of acute toxicity after 4-hour exposure to test substance aerosol

GLP compliance:

no

Remarks:

well documented study

Test type:

standard acute method

Limit test:

yes

Test material

Test material information

Constituent 1

Reference substance name:

Dimethyl methylphosphonate

EC Number:

212-052-3

EC Name:

Dimethyl methylphosphonate

Cas Number:

756-79-6

Molecular formula:

C3H9O3P

IUPAC Name:

dimethyl methylphosphonate

Details on test material:

- Name of test material (as cited in study report): Fat 80021/B
No additional data

Test animals

Species:

rat

Strain:

other: Tif: RAIf (SPF)

Sex:

male/female

Details on test animals or test system and environmental conditions:

TEST ANIMALS
- Source: raised on the premises of the testing facility were used for the experiments
- Age at study initiation: no data
- Weight at study initiation: 170 to 205 grams
- Fasting period: animals were fasted overnight before treatment
- Housing: males and females were segregated and kept in Macrolon cages, type 4, (10 animals to a cage)
- Diet (e.g. ad libitum): standard diet of pellets - No. 890, Nafag Gossau SG
- Water (e.g. ad libitum): drinking water
- Acclimation period: a minimum of 4 days

ENVIRONMENTAL CONDITIONS
- Temperature (°C): 22±1°C
- Humidity (%): 55±5%
- Photoperiod (hrs dark / hrs light): 10 hours light cycle day

Administration / exposure

Route of administration:

inhalation: aerosol

Type of inhalation exposure:

head only

Vehicle:

other: unchanged (no vehicle)

Details on inhalation exposure:

GENERATION OF TEST ATMOSPHERE / CHAMBER DESCRIPTION

- Method of holding animals in test chamber: for inhalation the rats were kept on separate PVC tubes positioned radially around the exposure chamber such that snout and nostrils of the animals only were exposed to the aerosol
- Source and rate of air: an air stream was discharged into the exposure chamber through a spray nozzle under a pressure of 2 atm. at a rate of 10 l/min.
- System of generating particulates/aerosols: the aerosol was generated by injecting the test material at a rate of 30 and 60 ml/hour into an air stream
- Method of particle size determination: The size distribution of the aerosol particles was measured with a Cascade Impactor with selectron filters of 25 mm diameter and with a pore size of 0.2 µm (Schleicher and Schuell) at an air flow rate of 17.5 l/min. Fig. 1 contains data on the particle size of the test material.

TEST ATMOSPHERE
The concentration and the particle size distribution of the aerosol in the vicinity of the animals were monitored at 1 hour intervals throughout the aerosol exposure. The concentration was determined gravimetrically by sampling the test atmosphere through a selectron filter of 50 mm diameter and with a pore size of 0.2 µm (Schleicher and Schuell, Feldbach, Switzerland) at an air flow rate of 10 l/min.

TEST ATMOSPHERE (if not tabulated)
- Particle size distribution: for the 1355 mg/m3 test group, 45% of generated particles were approximately greater than 7 µm, 19.5% ranged between 3 and 7 µm, 30% ranged between 1 and 3 µm and 7% were less than 1 µm in diameter. For the 2589 mg/m3 test group, 51% of generated particles were approximately greater than 7 µm, 28% ranged between 3 and 7 µm, 4% ranged between 1 and 3 µm and 18% were less than 1 µm in diameter.

No additional data

Analytical verification of test atmosphere concentrations:

yes

Remarks:

average aerosol concentratio were determined gravimetrically

Duration of exposure:

4 h

Remarks on duration:

The exposure was started 15 minutes after onset of the aerosol production, when the aerosol had reached an even dispersal throughout the chamber. After a 4 hour inhalation the rats were returned to their cages.

Concentrations:

1355 ± 107 and 2589 ± 176 mg/m3 (no higher concentrations were possible)

No. of animals per sex per dose:

10

Control animals:

no

Details on study design:

- Duration of observation period following administration: 14 days
Physical condition and incidence of death were monitored throughout an observation period. The animals were submitted at random to a necropsy at the end of the observation period.

Statistics:

none necessary

Results and discussion

Effect levels

Sex:

male/female

Dose descriptor:

LC50

Effect level:

> 2 589 mg/m³ air

Exp. duration:

4 h

Remarks on result:

other: no deaths observed up to this dose level

Mortality:

No deaths were observed in both test groups until the end of observation period.

Clinical signs:

other: After the 4-hour exposure period the rats in both concentrations showed convulsions, exophthalmus, lateral or ventral position and ruffled fur. These symptoms became more accentuated as the concentration was increased. The animals recovered within 6 to 7

Body weight:

No data

Gross pathology:

Hemorrhages in the lungs and congested organs were observed.

Other findings:

None reported