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

Acute Toxicity: oral

Administrative data

Endpoint:

acute toxicity: oral

Type of information:

experimental study

Adequacy of study:

key study

Reliability:

1 (reliable without restriction)

Rationale for reliability incl. deficiencies:

other: According to GLP and OECD-guideline 423, Commission Regulation (EC) No 440/2008, US EPA OPPTS 870.1100 and Japan MAFF 8147.

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)

GLP compliance:

yes

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

Details on test material:

- Name of test material (as cited in study report): LIMUS-Sambaydestillation
- Test-substance No.: 07/0684-1
- Physical state: solid/yellowish
- Analytical purity: 87%
- Lot/batch No.: 8712 / 062
- Storage condition of test material: < -18°C
- Stability: stable over 5 days

Test animals

Species:

rat

Strain:

other: Wistar / 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
- Age at study initiation: Young adult animals (female animals approx. 10 – 11 weeks)
- Weight at study initiation: 173 - 184 g
- Fasting period before study: 16 h before administration
- Housing: single housing in Makrolon cages, type III
- Diet (e.g. ad libitum): VRF1(P); SDS Special Diets Services, 67122 Altrip, Germany.
- Water (e.g. ad libitum): tap water
- Acclimation period: 5 days

ENVIRONMENTAL CONDITIONS
- Temperature (°C): 20 - 24
- Humidity (%): 20 - 80
- Photoperiod (hrs dark / hrs light): 12/12

Administration / exposure

Route of administration:

oral: gavage

Vehicle:

olive oil

Remarks:

Ph.Eur./DAB

Details on oral exposure:

VEHICLE
- Concentration in vehicle: 20 g/100 mL (2000 mg/kg b.w.) and 3 g/100 mL (300 mg/kg b.w.)
- Amount of vehicle (if gavage): 10 mL/kg b.w.
- Justification for choice of vehicle: Good homogeneity in olive oil Ph.Eur./DAB

Doses:

300 and 2000 mg/kg b.w.

No. of animals per sex per dose:

6 (Administration 1: 3 animals; Administration 2: 3 animals)

Control animals:

no

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 obs ervation. Recording of signs and symptoms several times on the day of administration, at least once each workday for the individual animals.
- Necropsy of survivors performed: yes
- Other examinations performed: clinical signs, body weight, gross pathology

Results and discussion

Effect levels

Sex:

female

Dose descriptor:

LD50

Effect level:

ca. 2 000 mg/kg bw

Remarks on result:

other: Clinical observation in the 2000 mg/kg test groups: impaired and poor general state, dyspnoea, piloerection, exsiccosis, staggering, salivation, ataxia and reduced feces.

Mortality:

One animal of the first 2000 mg/kg test group was found dead hour 3 after administration. Two animals of the second 2000 mg/kg test groups were found dead hour 2 and hour 3 after administration. No mortality occurred in the 300 mg/kg test groups.

Clinical signs:

other: Clinical observation in the 2000 mg/kg test groups revealed impaired and poor general state, dyspnoea, piloerection, exsiccosis, staggering, salivation, ataxia and reduced feces. Findings were observed from hour 0 through to study day 10 after administrat

Gross pathology:

No macroscopic pathologic abnormalities were noted in the animals examined on the last day of observation (2000 mg/kg: 3 females; 300 mg/kg: 6 females).

At necropsy the animals that died showed bilateral hydrothorax (ca. 2 mL), edema in all lobes of lung, dark spotted discoloration of all lobes of lung and congestion in heart, kidneys, stomach and intestine (2000 mg/kg: 3 females). At necropsy the animals that died showed bilateral hydrothorax (ca. 2 mL), edema in all lobes of lung, dark spotted discoloration of all lobes of lung and congestion in heart, kidneys, stomach and intestine (2000 mg/k: 3 females).

Applicant's summary and conclusion

Conclusions:

Under the conditions of this study the median lethal dose of LIMUS-Sambaydestillation after oral administration was found to be ca. 2000 mg/kg bodyweight in rats. According to the results of this study, the substance was classified R22 (according to Directive 67/548/EEC) and Acute toxicity oral Cat 4 (according to GHS (UN)).