Diphenyl methylphosphonate

Acute Toxicity: oral

Administrative data

Endpoint:

acute toxicity: oral

Type of information:

experimental study

Adequacy of study:

key study

Study period:

05 SEP 1979 - 01 JUN 1980

Reliability:

2 (reliable with restrictions)

Rationale for reliability incl. deficiencies:

other: well documented old study, which meets basic scientific principles

Data source

Reference

Reference Type:

study report

Title:

Unnamed

Year:

1980

Report date:

1980

Materials and methods

Test guideline

Qualifier:

equivalent or similar to guideline

Guideline:

OECD Guideline 401 (Acute Oral Toxicity)

GLP compliance:

not specified

Test type:

standard acute method

Limit test:

no

Test material

Test material information

Constituent 1

Reference substance name:

Diphenyl methylphosphonate

EC Number:

231-388-1

EC Name:

Diphenyl methylphosphonate

Cas Number:

7526-26-3

Molecular formula:

C13H13O3P

IUPAC Name:

diphenyl methylphosphonate

Details on test material:

- Name of test material (as cited in study report): methanphosphonsäurediphenylester
- Substance type: organic
- Physical state: liquid

Test animals

Species:

rat

Strain:

Wistar

Sex:

male

Details on test animals or test system and environmental conditions:

TEST ANIMALS
- Source: Winkelmann, Borchen
- Age at study initiation: approximately 9 weeks
- Weight at study initiation: ca. 190 gr
- Fasting period before study:
- Housing: groups of five, conventionally in Makrolon cages on dust-free wood granules
- Diet (e.g. ad libitum): Altromin R1324 (Altromin GmbH, Lage), ad libitum
- Water (e.g. ad libitum): drinking water ad libitum
- Acclimation period:

ENVIRONMENTAL CONDITIONS
- Temperature (°C): 22 +/- 1.5 °C
- Humidity (%): 60 +/- 5 %
- Air changes (per hr):
- Photoperiod (hrs dark / hrs light): 12 h light/ 12 hours dark

OTHER: identification of the animals was secured by marking of the fur with picrinic acid and cage-labels

Administration / exposure

Route of administration:

oral: gavage

Vehicle:

unchanged (no vehicle)

Details on oral exposure:

MAXIMUM DOSE VOLUME APPLIED: 0.4 mL / kg bw

Doses:

0.05, 0.1, 0.2, 0.3, 0.35 and 0.4 mL/kg bw

No. of animals per sex per dose:

10

Control animals:

not specified

Details on study design:

The test item was administered with the aid of a rigid oesophagus-tube to 10 animals.
The animals were inspected repeatedly on the day of administration, thereafter the animals were inspected twice daily (once daily on weekend days and on holidays) for 14 days and the character, onset, duration and intensity of the clinical symptoms was recorded. Whenever dead animals were found they were removed.
Bodyweights were determined individually shortly before adminsitration and after the end of the observation period.

Statistics:

The LD50 value was calculated (p < 0.05) according to the programmed Probit-analysis (Fink and HUnd (Arzneimittelforschung 15, 1965, p. 624).

Results and discussion

Effect levels

Effect levels 1

Sex:

male

Dose descriptor:

LD50

Effect level:

0.19 mL/kg bw

Based on:

test mat.

95% CL:

>= 0.14 - <= 0.25

Effect levels 2

Key result

Sex:

male

Dose descriptor:

LD50

Effect level:

233 mg/kg bw

Based on:

test mat.

Remarks on result:

other: conversion of the above mentioned value, based on density available for the test item

Mortality:

no animal died in the dose group, which received 0.05 mL/kg bw. 3 animals died in the dose group of 0.1 mL/kg bw. 4 and 6 animals died in the dose groups 0.2 and 0.3, respectively. 8 animals died, dosed with 0.35 mL/kg bw and all animals died in the highest dose group (0.4 mL/kg bw).

Clinical signs:

other: The signs of intoxication were ruffled fur, sedation, bloody eyes and nose, these clinical signs were to be noted in all dose groups beside 0.05 mL/kg bw.

Any other information on results incl. tables

The single doses of 0.1 - 0.4ml/ kg bw had the following symptoms of poisoning in all animals: shaggy fur,sedation, bloody eyesand nose.
At starting doses of 0.3 to 0.35mL/ kg bw weight loss was also observed.
The symptoms occurred within 30 minutes after application and were slightly pronounced and lasted until the last day of the observation period. The deaths were reported from day 1to 7.
The calculated LD50 value was 0.19 ml/ kgbw (confidence interval for p<0.05 =0:14 to 0:25mL kgbw).

When increasing the probit regression line(probit-slope-factor) resulted in a value of b=3.36.
The dose of 0.05 mL/ kgbw was tolerated without symptoms.

Applicant's summary and conclusion

Interpretation of results:

Category 3 based on GHS criteria

Remarks:

based on EU GHS

Conclusions:

The study was performed equivalent of similar to the OECD TG401 and therefore considered to be of high quality (reliability Klimisch 2). The test material did induce mortality and treatment-related clinical signs in the dose groups of 0.1 - 0.4 mL/kg bw (100, 80 %, 60 & 40 % and 30 % mortality). The test material was considered to be toxic if swallowed after oral application under the conditions of the test and as the LD50 of the test item is 50 - 300 is has to classified as GHS Category 3.

Executive summary:

The acute oral toxicity of diphenyl methylphosphonate (MPS) was investigated in rats (Löser, 1980). The study was performed equivalent or similar to the OECD Guideline 401 and considered to be of high quality (reliability Klimisch 2). 10 male rats per group received doses of 0.05 mL/kg bw, 0.1 mL/kg bw, 0.2 mL/kg bw, 0.3 mL/kg bw, 0.35 mL/kg bw or 0.4 mL/kg bw via a rigid tube orally. The symptoms of intoxications were ruffled hair coat, sedation, bloody eyes and nose and in addition body weight loss (0.3 and 0.35 mL/kg bw). All animals in the highest dose group died within the observation period. In the 0.35 and the 0.3mL/kg bw dose group 8 and 6 animals died, respectively. In the 0.2 and 0.1 mL/kg bw dose group 4 and 2 animals died, respectively. No animals died in the lowest dose group. No clinical symptoms were noted in the lowest dose group. Therefore the oral toxicity can be characterised by a LD50 value of 233 mg/kg bw.