Phosphinic acid, P-[3-(acetyloxy)-3-cyanopropyl]-P-methyl-, butyl ester

Acute Toxicity: oral

Administrative data

Endpoint:

acute toxicity: oral

Type of information:

experimental study

Adequacy of study:

key study

Study period:

1995

Reliability:

1 (reliable without restriction)

Rationale for reliability incl. deficiencies:

other: guideline study

Data source

Reference

Reference Type:

study report

Title:

Unnamed

Year:

1995

Report date:

1995

Materials and methods

Test guideline

Qualifier:

according to guideline

Guideline:

OECD Guideline 401 (Acute Oral Toxicity)

Version / remarks:

24 February 1987

GLP compliance:

yes (incl. QA statement)

Test type:

fixed dose procedure

Test material

Test material information

Constituent 1

Reference substance name:

Phosphinic acid, P-[3-(acetyloxy)-3-cyanopropyl]-P-methyl-, butyl ester

EC Number:

605-460-1

Cas Number:

167004-78-6

Molecular formula:

C11 H20 N O4 P

IUPAC Name:

Phosphinic acid, P-[3-(acetyloxy)-3-cyanopropyl]-P-methyl-, butyl ester

Details on test material:

Molecular weight: 261 g/mol
Molecular formular: C11H2ONO4P

Specific details on test material used for the study:

SOURCE OF TEST MATERIAL
- Source (i.e. manufacturer or supplier) and lot/batch number of test material: supplied by the sponsor; batch number CR 21422/01/940801
- Purity, including information on contaminants, isomers, etc.: 90 % (w/w)

STABILITY AND STORAGE CONDITIONS OF TEST MATERIAL
- Storage condition of test material: -10°C (+-5°C) in the dark
- Solubility and stability of the test material in the solvent/vehicle and the exposure medium: The stability of the test material in the vehickle was confirmed over the dosing period
- Reactivity of the test material with the incubation material used (e.g. plastic ware): not determined

Test animals

Species:

rat

Strain:

Sprague-Dawley

Sex:

male/female

Details on test animals or test system and environmental conditions:

TEST ANIMALS
- Source: Charles River UK Ltd., Manston Road, Margate, Kent, UK
- Age at study initiation: 6 weeks
- Weight at study initiation: males: approx. 155 g (141-178 g); females: approx. 170 g (154-184 g)
- Fasting period before study: overnight prior to dosing.
- Housing: polycarbonate cages with mesh floors.
- Diet (e.g. ad libitum): ad libitum
- Water (e.g. ad libitum): Domestic quality tap water was supplied ad libitum.
- Acclimation period: 1 or 2 days

ENVIRONMENTAL CONDITIONS
- Temperature (°C): between 19 and 23°C
- Humidity (%): between 45 and 65%.
- Photoperiod (hrs light): 12 hours per day

Administration / exposure

Route of administration:

oral: gavage

Vehicle:

other: sesame oil

Details on oral exposure:

The test material was administered by gavage as a suspension in sesame oil at a constant volume of 10 ml/kg body weight. Dose levels were based on the results of a preliminary rangefinding and on the findings resulting from dosing males at 450 and 900 mg/kg body weight.

Doses:

females: 0, 112.5, 225 or 450 mg/kg body weight
males: 0, 112.5, 225, 450 and 900 mg/kg body weight

No. of animals per sex per dose:

males: 5; females: 5

Control animals:

yes

Details on study design:

- Duration of observation period following administration: 14 days
- Frequency of observations and weighing: Body weights were recorded immediately prior to treatment (except for control females) and 7 and 14 days after dosing.
- Necropsy of survivors performed: yes
- Other examinations performed: clinical signs, body weight

Results and discussion

Preliminary study:

All males treated with 450 and 900 mg test material/kg and 1 male treated at 225 mg test material/kg died immediately after dosing. Three females treated with 450 mg/kg and 2 females treated with 225 and 112.5 mg/kg also died on the day of dosing within 10-20 minutes.

Effect levels

Effect levels 1

Sex:

male

Dose descriptor:

LD50

Effect level:

277 mg/kg bw

95% CL:

210 - 366

Effect levels 2

Sex:

female

Dose descriptor:

LD50

Effect level:

253 mg/kg bw

95% CL:

100 - 639

Mortality:

All males treated with 450 and 900 mg test material/kg and 1 male treated at 225 mg test material/kg died immediately after dosing. Three females treated with 450 mg/kg and 2 females treated with 225 and 112.5 mg/kg also died on the day of dosing within 10-20 minutes.

Clinical signs:

other: Clinical signs were noted in all males treated at 112.5 and 225 mg/kg and in all treated females. In each animal the onset of the first clinical sign was rapid {c. 5-12 minutes). The principal clinical signs which were non-specific and seen in the majorit

Gross pathology:

Dark livers with pale areas were noted in 5/5 males treated at 450 mg/kg and 2/5 males treated at 900 mg/kg.
No macroscopic abnormalities were detected.

Applicant's summary and conclusion

Interpretation of results:

Category 3 based on GHS criteria

Conclusions:

Under the evaluated conditions the LD50 was determined at 253 (females) and 277 mg/kg bw, warranting a classification as acute oral tox Cat. 3 (H301) according to CLP (EG) No. 1272/2008.

Executive summary:

The acute oral LD50 value (with 95% confidence limits) of test substance in the rat were :

Males : 277 (210-366) mg/kg body weight

Females : 253 (100-639) mg/kg body weight