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Administrative data

Endpoint:
acute toxicity: oral
Type of information:
experimental study
Adequacy of study:
key study
Study period:
2001
Reliability:
1 (reliable without restriction)
Rationale for reliability incl. deficiencies:
other: This study was conducted in compliance with OECD GLP (1997) regulations.

Data source

Reference
Reference Type:
study report
Title:
Unnamed
Year:
2001
Report date:
2001

Materials and methods

Test guideline
Qualifier:
according to guideline
Guideline:
OECD Guideline 423 (Acute Oral toxicity - Acute Toxic Class Method)
Deviations:
no
GLP compliance:
yes
Test type:
acute toxic class method
Limit test:
no

Test material

Constituent 1
Reference substance name:
MV31 K-Salz
IUPAC Name:
MV31 K-Salz
Test material form:
solid: crystalline
Details on test material:
- Name of test material (as cited in study report): MV31 K-Salz
- Substance type: Mono-constituent
- Physical state: Solid (Grey granules)
- Analytical purity: 88%
- Purity test date: 19 September 2000
- Lot/batch No.: Lot no. 1268147/1-1268154/1
- Expiration date of the lot/batch:31 December 2001
- Stability under test conditions: Guranteed for 4 hours
- Storage condition of test material: Darkness at approximately 20 C in a fume cupboard

Test animals

Species:
rat
Strain:
Sprague-Dawley
Sex:
male/female
Details on test animals or test system and environmental conditions:
TEST ANIMALS
- Source: Harlan Winkelmann, Gartenstr, 27, 33178 Borchen SPF breeding colony
- Age at study initiation: 6-10 weeks
- Weight at study initiation: Male mean: 198 g, Female mean: 177 g
- Fasting period before study: 16 hours
- Housing: Group housed in macrolon cages on soft wood granulate
- Diet (e.g. ad libitum): Ssniff R/m-H diet ad libitum
- Water (e.g. ad libitum): Tap water ad libitum
- Acclimation period: At least seven days

ENVIRONMENTAL CONDITIONS
- Temperature (°C): 19-25 C
- Humidity (%): 30-70%
- Air changes (per hr): No data
- Photoperiod (hrs dark / hrs light): 12/12

IN-LIFE DATES: From: 23 Janurary 2001 To: 08 February 2001

Administration / exposure

Route of administration:
oral: gavage
Vehicle:
water
Details on oral exposure:
VEHICLE
- Concentration in vehicle: 200 mg/kg: 2% w/v. 2000 mg/kg: 20% w/v
- Amount of vehicle (if gavage): 10 mL/kg
- Justification for choice of vehicle: Test substance solubility

MAXIMUM DOSE VOLUME APPLIED: 10 mL/kg
Doses:
200, 2000 mg/kg body weight
No. of animals per sex per dose:
200 mg/kg: 3 animals/sex/dose
2000 mg/kg: 3 females
Control animals:
no
Details on study design:
- Duration of observation period following administration: 14 days
- Frequency of observations and weighing: Animals were observed at six evently spaced intervals up to 4 hours of dosing and daily thereafter. Animals were weighed on days 1, 8 and 15.
- Necropsy of survivors performed: yes
- Other examinations performed: clinical signs, body weight.

Results and discussion

Effect levels
Sex:
male/female
Dose descriptor:
LD50
Effect level:
> 200 - < 2 000 mg/kg bw
Based on:
act. ingr.
Mortality:
All 2000 mg/kg-dosed animals were found dead between 2 and 8 hours post-dose. All animals dosed at 200 mg/kg bw survived throughout the study.
Clinical signs:
2000 mg/kg animals exhibited hypoacitivity, squatting posture, prone position, stilted gait, uncoordinated and ataxic gait, drawn in flanks, irregular respiration, gasping, respiratory sounds, stupor, bristling coat, narrow palpebral fissures, eye discharge, twitching and tonoclinic convlusions prior to death. The following clinical observations were noted in the 200 mg/kg-dosed animals from 10 minutes to 2 days post-dose: stilted gait (3/3 males, 2/3 females), squatting posture (3/3 males, 3/3 females), and irregular respiration (3/3 males, 3/3 females).
Body weight:
There were no abnormal body weight changes observed.
Gross pathology:
No abnormal findings were observed upon gross necropsy.

Applicant's summary and conclusion

Interpretation of results:
Toxicity Category IV
Remarks:
Migrated information Criteria used for interpretation of results: EU
Conclusions:
Based on the results of the study, the oral LD50 is greater than 200 mg/kg but less than 2000 mg/kg.
Executive summary:

The acute oral toxicity of the test article (grey granules, purity approx. 88 Fl.%, CASRN 496805-64-2, Lot: 1268147/1-1268154/1) was evaluated in Sprague Dawley rats. This study was performed in compliance with OECD GLP (1997) and the German Chemical Law (1999). The study method was based on OECD 423 (1996) and Commission Directive 96/54/EC B.1 (1996). The test article was prepared in deionized water (vehicle) just prior to dosing. Rats received 200 (3/sex) or 2000 (3 males) mg/kg test article via oral gavage at a dose volume of 10 mL/kg. The animals were observed at periodic intervals immediately after dosing and daily thereafter for 14 days. Body weights were recorded at pretest, weekly, and at termination. After the observation period, all animals were euthanized and necropsies were performed.  All 2000 mg/kg-treated animals were found dead between 2 and 8 hours post-dose. Prior to death, the following clinical observations were noted: hypoactivity, squatting posture, prone position, stilted gait, uncoordinated and ataxic gait, drawn in flanks, irregular respiration, gasping, respiratory sounds, stupor, bristling coat, narrow palpebral fissures, eye discharge, twitching, and tonoclonic convulsions. Necropsy revealed red or orange discolored lungs. All animals treated at 200 mg/kg survived. The following clinical observations were noted in 200 mg/kg-treated animals from 10 minutes to 2 days post-dose: stilted gait (3 males, 2 females), squatting posture (3 males, 3 females), and irregular respiration (3 males, 3 females). There were no abnormal body weight changes or necropsy findings in the 200 mg/kg dose group. Based on the results of this study, the oral LD50 is greater than 200 mg/kg but less than 2000 mg/kg.