Dimethyl methylphosphonate

Acute Toxicity: other routes

Administrative data

Endpoint:

acute toxicity: other routes

Type of information:

experimental study

Adequacy of study:

supporting study

Reliability:

2 (reliable with restrictions)

Rationale for reliability incl. deficiencies:

other: scientifically acceptable study

Data source

Reference

Reference Type:

study report

Title:

Unnamed

Year:

1977

Report date:

1978

Materials and methods

Test guideline

Qualifier:

no guideline available

Principles of method if other than guideline:

Evaluation of acute toxicity of the test substance after single I.V. application to rat animals

GLP compliance:

no

Remarks:

well documented study

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 80 021/B
No additional data

Test animals

Species:

rat

Strain:

other: Tif RAIf strain

Sex:

male/female

Details on test animals or test system and environmental conditions:

TEST ANIMALS
- Source: random bred rats raised on the premises of the testing facility were used for the experiments
- Age at study initiation: no data
- Weight at study initiation: 74 to 88 grams
- Fasting period: animals were fasted overnight before treatment
- Housing: on the day of the administration, the animals were randomised (HP 9810 Calculator) and distributed in groups of 5 into Macrolon cages (type 3) where they remained during the treatment and observation period
- 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 5 days

ENVIRONMENTAL CONDITIONS
- Temperature (°C): 22±1°C
- Humidity (%): 55±5%
- Photoperiod (hrs dark / hrs light): 14 hours light cycle day

Administration / exposure

Route of administration:

intravenous

Vehicle:

other: distilled water

Details on exposure:

The animals were treated by slow intravenous injection (duration: 10 sec) into the tail vein. The concentration of the test substance in vehicle was 6%, 8%, 10%, 12% and 12% respectively for the 600, 800, 1000, 1200 and 1500 mg/kg bw dose groups.

Doses:

600, 800, 1000, 1200 and 1500 mg/kg bw

No. of animals per sex per dose:

5

Control animals:

no

Details on study design:

- Duration of observation period following administration: 15 days
Physical condition and rate of death were monitored throughout the whole observation period. Autopsies were performed on those that died and on survivors at day 15 of the study.

Statistics:

LD50 values including 95% confidence limits was calculated by the probit analysis method (Goulden A., Methods of Statistical Analysis, John Wiley and Sons, 1960, 3rd printing, pages 404-408.

Results and discussion

Effect levels

Sex:

male/female

Dose descriptor:

LD50

Effect level:

ca. 1 050 mg/kg bw

95% CL:

940 - 1 180

Remarks on result:

other: A total of 0/10, 2/10, 4/10, 6/10 and 10/10 animals died respectively, in the 600, 800, 1000, 1200 and 1500 mg/kg bw dose groups

Mortality:

Death occurred within 5 – 30 min in respiratory failure (see Table 1)

Clinical signs:

- In the 600 mg/kg bw group: after 5 min and lasting >60 min, reduction in spontaneous motility, ataxia, humpbacked, hyperventilation. After 3 hours no symptoms.
- In the 800, 1000, and 1200 mg/kg bw groups: same as for the 600 mg/kg bw group; additionally, laboured respiration, ventricurnbency, muscle twitches, humpbacked, roughening of the coat, restlessness. Tremor and cyanosis were further observed in the 1000 and 1200 mg/kg bw dose groups.

Body weight:

no adverse effect recorded (see Table 1)

Gross pathology:

- In the 600 mg/kg bw group: no gross organ changes were seen.
- In the 800, 1000, 1200 and 1500 mg/kg bw groups: gross examination of the animals that died showed no pathology.

Any other information on results incl. tables

Table 1: Mortality and body weight

Dose level (mg/kg)	Absolute mortality/total treated animal			Mean body weight (g)
	Males	Females	Day of test	Pretest	After 15 days
600	0/5	0/5	-	74	159
800	1/5	1/5	1	82	161
1000	3/5	1/5	1	82	176
1200	4/5	2/5	1	85	174
1500	5/5	5/5	1	88	-