Phosphorothioic triamide, N-propyl-

Acute Toxicity: oral

Administrative data

Endpoint:

acute toxicity: oral

Type of information:

experimental study

Adequacy of study:

key study

Study period:

April - July 2008

Reliability:

1 (reliable without restriction)

Rationale for reliability incl. deficiencies:

guideline study

Data source

Reference

Reference Type:

study report

Title:

Unnamed

Year:

2008

Report date:

2008

Materials and methods

Test guideline

Qualifier:

according to guideline

Guideline:

OECD Guideline 423 (Acute Oral toxicity - Acute Toxic Class Method)

Version / remarks:

December 17, 2001

Deviations:

no

GLP compliance:

yes (incl. QA statement)

Remarks:

(from the competent authority) Baden-Württemberg Umweltministerium

Test type:

acute toxic class method

Limit test:

yes

Test material

Test material information

Constituent 1

Reference substance name:

Reaction mass of N-butylphosphorothioic triamide and N-propylphosphorothioic triamide

EC Number:

700-457-2

Molecular formula:

Unspecified

IUPAC Name:

Reaction mass of N-butylphosphorothioic triamide and N-propylphosphorothioic triamide

Specific details on test material used for the study:

SOURCE OF TEST MATERIAL
- Batch No.of test material: 8712 / 056
- Purity: > 95 %
- Physical state / color: solid / white

STABILITY AND STORAGE CONDITIONS OF TEST MATERIAL
- Storage condition of test material: < - 18 °C
- Solubility and stability of the test substance in the vehicle: Good homogeneity in olive oil Ph. Eur / DAB. The stability of the test substance in the vehicle was determined indirectly by the concentration control analysis by the sponsor. For this purpose, the samples taken were stored at room temperature over the maximum duration of the administration period and were subsequently deep-frozen and sent to the sponsor for analysis.

TREATMENT OF TEST MATERIAL PRIOR TO TESTING
- Treatment of test material prior to testing: For better handling the test substance was ground with a mortar and a pistel. The test substance preparation was produced for each administration group shortly before administration by stirring with a high speed homogenizer (Ultra-Turrax) and a magnetic stirrer. The homogeneity of the test substance preparation during application was provided by stirring with a magnetic stirrer.

FORM OF ADMINISTRATION
Emulsion

Test animals

Species:

rat

Strain:

Wistar

Remarks:

Crl:WI (Han)

Sex:

female

Details on test animals or test system and environmental conditions:

TEST ANIMALS
- Source: Charles River Wiga GmbH, Sandhofer Weg 7, 97633 Sulzfeld, Germany
- Females nulliparous and non-pregnant: yes
- Age at study initiation: 10 - 11 weeks
- Weight at study initiation: 178 g (group 1) and 187 g (group 2) ± 20 %, respectively
- Fasting period before study: feed was withdrawn from the animals at least 16 hours before administration, but water was available ad libitum
- Housing: The animals were housed in fully air-conditioned rooms.
- Diet (e.g. ad libitum): VRF1 (P), SDS Special Diets Services, 67122 Altrip, Germany
- Water (e.g. ad libitum): Tap water, ad libitum
- Acclimation period: at least 5 days

ENVIRONMENTAL CONDITIONS
- Temperature (°C): 20 - 24 °C
- Humidity (%): 20 - 80 %
- Air changes (per hr): fully air-conditioned rooms
- Photoperiod (hrs dark / hrs light): 12 h / 12 h

Administration / exposure

Route of administration:

oral: gavage

Vehicle:

olive oil

Details on oral exposure:

VEHICLE
- Concentration in vehicle: 20 g/100 mL
- Amount of vehicle (if gavage): 10 mL/kg bw
- Justification for choice of vehicle: good homogeneity in olive oil Ph. Eur / DAB

CLASS METHOD
- Rationale for the selection of the starting dose: By the request of the sponsor a starting dose of 2000 mg/kg body weight has been chosen in the first step with 3 female animals. As none of these animals died, 2000 mg/kg body weight was administered to an additional group of 3 female animals in a second step. Because no mortality occured the study was terminated.

Doses:

2000 mg/kg bw

No. of animals per sex per dose:

6 female animals

Control animals:

not specified

Details on study design:

- Duration of observation period following administration: 14 days
- Frequency of observations and weighing:
- individual body weights shortly before administration (day 0), weekly thereafter and on the last day of observation
- recording of signs and symptoms several times on the day of administration, at least once each work day for the individual animals
- a check for any dead or moribund animal was made twice each workday and once on Saturdays, Sundays and on public holidays
- necropsy with gross-pathology examination on the last day of the observation period after killing by CO2-inhalation in a chamber with increasing concentrations over time
- no histological examinations were performed
- Necropsy of survivors performed: yes
- Other examinations performed: clinical signs, body weight,mortality, necropsy, gross-pathology examination

Results and discussion

Effect levels

Sex:

female

Dose descriptor:

LD50

Effect level:

> 2 000 mg/kg bw

Based on:

test mat.

Remarks on result:

other: no mortality observed

Mortality:

No mortality occured.

Clinical signs:

other: Clinical observation revealed impaired general state, dyspnea, reduced feces, staggering, salivation, exsiccosis and piloerection. Findings were observed from hour 0 through up to study day 8 after administration.

Gross pathology:

No macroscopic abnormalities were noted in the animals examined on the last day of observation.

Applicant's summary and conclusion

Interpretation of results:

GHS criteria not met

Remarks:

no mortality observed

Conclusions:

Under the conditions of this study the median lethal dose of the test substance after oral administration was found to be greater than 2000 mg/kg body weight in rats.

Executive summary:

The study was performed to assess the acute toxicity following oral administration of the test substance in Wistar rats.

Single doses of 2000 mg/kg body weight of the test material preparations in olive oil Ph. Eur. / DAB were given to 2 test groups of three fasted female animals each, (2000 mg/kg in 6 females) by gavage in a sequential manner.

No mortality occured.

Clinical observation revealed impaired general state, dyspnea, reduced feces, staggering, salivation, exsiccosis and piloerection. Findings were observed from hour 0 through up to study day 8 after administration.

The mean body weights of the administration groups increased normally throughout the study period.

No macroscopic pathologic abnormalities were noted in the animals on the last day of observation.

Under the conditions of this study the median lethal dose of the test substance after oral administration was found to be greater than 2000 mg/kg body weight in rats.