Phosphorodithioic acid, O,O-bis(2-methylpropyl) ester, compd. with N,N-dimethylmethanamine (1:1)

Acute Toxicity: oral

Administrative data

Endpoint:

acute toxicity: oral

Type of information:

experimental study

Adequacy of study:

key study

Study period:

30 June - 16 August 2011

Reliability:

1 (reliable without restriction)

Rationale for reliability incl. deficiencies:

guideline study

Remarks:

Also in accordance with GLP principles.

Data source

Reference

Reference Type:

study report

Title:

Unnamed

Year:

2012

Report date:

2012

Materials and methods

Test guideline

Test guideline 1

Qualifier:

according to guideline

Guideline:

OECD Guideline 420 (Acute Oral Toxicity - Fixed Dose Method)

Deviations:

no

Test guideline 2

Qualifier:

according to guideline

Guideline:

EU Method B.1 bis (Acute Oral Toxicity - Fixed Dose Procedure)

Deviations:

no

GLP compliance:

yes (incl. QA statement)

Test type:

fixed dose procedure

Limit test:

no

Test material

Test material information

Constituent 1

Reference substance name:

O,O-bis(2-methylpropyl) sulfanidylphosphonothioate; trimethylazanium

EC Number:

700-910-4

Cas Number:

1354201-99-2

Molecular formula:

C11H28NO2PS2

IUPAC Name:

O,O-bis(2-methylpropyl) sulfanidylphosphonothioate; trimethylazanium

Test material form:

solid

Remarks:

pale yellow glassy solid

Specific details on test material used for the study:

- Name of test material (as cited in study report): S-10713
- Physical state: solid
- Colour: brown
- Storage condition of test material: at room temperature in the dark
- Lot/batch No.: S20227-179

Test animals

Species:

rat

Strain:

Wistar

Sex:

female

Details on test animals or test system and environmental conditions:

TEST ANIMALS
- Source: Harlan Laboratories UK Ltd., Oxon, UK
- Females nulliparous and non-pregnant: yes
- Age at study initiation: 8-12 weeks
- Weight at study initiation: 161-175 g
- Fasting period before study: yes
- Housing: groups of up to four in solid-floor polypropylene cages furnished with woodflakes
- Diet: free access to 2014C Teklad Global Rodent diet (Harlan Laboratories UK Ltd., Oxon, UK)
- Water: free access to mains drinking water
- Acclimation period: at least 5 days

ENVIRONMENTAL CONDITIONS
- Temperature (°C): 19-25
- Humidity (%): 30-70
- Air changes (per hr): at least 15
- Photoperiod (hrs dark / hrs light): 12/12

IN-LIFE DATES: 30 June - 16 August 2011

Administration / exposure

Route of administration:

oral: gavage

Vehicle:

water

Details on oral exposure:

VEHICLE
- Concentration in vehicle: 200 mg/ml (at 2000 mg/kg bw) and 30 mg/ml (at 300 mg/kg bw)

MAXIMUM DOSE VOLUME APPLIED: 10 ml/kg

DOSAGE PREPARATION: the substance was prepared as a suspension in distilled water within 2 hours of administration

- Rationale for the selection of the starting dose: based on available information of toxicity of the test substance

Doses:

2000 and 300 mg/kg bw (stepwise procedure)

No. of animals per sex per dose:

5 females

Control animals:

no

Details on study design:

- Duration of observation period following administration: 14 days
- Frequency of observations and weighing:
Clinical observations: 0.5, 1, 2 and 4 hours after dosing and daily thereafter
Morbidity and mortality: twice daily
Body weight: day of dosing and on day 7 and 14
- Necropsy of all animals performed: yes

Statistics:

Not applicable

Results and discussion

Preliminary study:

One female per dose was treated. No mortality or evident toxicity was observed.

Effect levels

Sex:

female

Dose descriptor:

LD50

Effect level:

> 300 - < 2 000 mg/kg bw

Based on:

test mat.

Mortality:

Two animals were found dead four hours after dosing at 2000 mg/kg bw. No deaths occurred at 300 mg/kg bw.

Clinical signs:

other: At 2000 mg/kg bw hunched posture, lethargy, ataxia, pilo-erection, ptosis, tiptoe gait, prostration and increased respiratory rate of noisy respiration were observed. Surviving animals appeared normal throughout the study or one day after dosing. At 300 m

Gross pathology:

2000 mg/kg bw: patchy pallor of the liver was noted at necropsy of animals that died during the study; no abnormalities in surviving animals
300 m/kg bw: no abnormalities observed

Applicant's summary and conclusion

Interpretation of results:

Category 4 based on GHS criteria

Conclusions:

The LD50 of the test substance in female Wistar rats was found to be between 300 and 2000 mg/kg bw. According to EC Regulation 1272/2008 the substance requires classification in category 4.

Executive summary:

An acute oral toxicity study in rats was performed according to OECD 420 and EC 440/2008, B1bis, following GLP principles. Clinical observations at 2000 mg/kg bw included hunched posture, lethargy, ataxia, pilo-erection, ptosis, tiptoe gait, prostration and increased respiratory rate of noisy respiration. Patchy pallor of the liver was noted in the animals that died. The LD50 of the test substance in female Wistar rats was found to be between 300 and 2000 mg/kg bw.

According to EC Regulation 1272/2008 the substance requires classification in category 4.