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Administrative data

Endpoint:
acute toxicity: oral
Type of information:
experimental study
Adequacy of study:
key study
Study period:
2009-08-03 to 2009-10-01; day of dosing: 2009-08-05
Reliability:
1 (reliable without restriction)
Rationale for reliability incl. deficiencies:
other: GLP guideline study.

Data source

Reference
Reference Type:
study report
Title:
Unnamed
Year:
2009

Materials and methods

Test guidelineopen allclose all
Qualifier:
according to guideline
Guideline:
OECD Guideline 423 (Acute Oral toxicity - Acute Toxic Class Method)
Version / remarks:
2001-12-17
Deviations:
no
Qualifier:
according to guideline
Guideline:
EU Method B.1 tris (Acute Oral Toxicity - Acute Toxic Class Method)
Version / remarks:
2008-05-30
Deviations:
no
Qualifier:
according to guideline
Guideline:
EPA OPPTS 870.1100 (Acute Oral Toxicity)
Version / remarks:
December 2002
Deviations:
no
Qualifier:
according to guideline
Guideline:
other: Japan MAFF Testing Guideline of 12 Nosan No. 8147 as this in line with OECD 423
Deviations:
no
GLP compliance:
yes (incl. QA statement)
Test type:
acute toxic class method
Limit test:
no

Test material

Constituent 1
Chemical structure
Reference substance name:
Reaction mass of ethyl (2S,3S)-3,4-dibromo-2-methylbutanoate and ethyl (2R,3R)-3,4-dibromo-2-methylbutanoate and ethyl (2S,3R)-3,4-dibromo-2-methylbutanoate and ethyl (2R,3S)-3,4-dibromo-2-methylbutanoate
EC Number:
700-225-0
Cas Number:
1160806-44-9
Molecular formula:
C7 H12 Br2 O2
IUPAC Name:
Reaction mass of ethyl (2S,3S)-3,4-dibromo-2-methylbutanoate and ethyl (2R,3R)-3,4-dibromo-2-methylbutanoate and ethyl (2S,3R)-3,4-dibromo-2-methylbutanoate and ethyl (2R,3S)-3,4-dibromo-2-methylbutanoate
Details on test material:
- Name of test material (as cited in study report): 2-Methyl-3,4-dibrombuttersäureethylester
- Physical state: liquid/ colorless, clear
- Analytical purity: 98.1 wt%
- Lot/batch No.: 35684-12-5
- Stability under test conditions: The stability under storage conditions over the study period was guaranteed by BASF SE
- Storage condition of test material: Refrigerator; under light exclusion
- Other: density: 1.640 g/ml (determined by Bioassay)
No further data.

Test animals

Species:
rat
Strain:
Wistar
Sex:
female
Details on test animals or test system and environmental conditions:
TEST ANIMALS
female Wistar/Crl:WI (Han) rats
Rats were selected since this rodent species is recommended in the respective test guidelines. Wistar rats were selected since there is extensive experience available in the laboratory with this strain of rats. As suggested by the OECD guideline nulliparous and non-pregnant female animals were used for the test, because there is no indication that male animals are likely to be more sensitive to the acute effects of the test substance.
- Source: Charles River Wiga GmbH, Sandhofer Weg 7, 97633 Sulzfeld, Germany
- Age at study initiation: ca. 10 weeks
- Weight at study initiation: group mean body weights were in the range between 177 and 190 g.
- Fasting period before study: yes; feed was withdrawn from the animals at least 16 hours before administration, but water was available ad libitum.
- Housing: single housing in Makrolon cage, type III
- Diet (ad libitum): VRF1(P); SDS Special Diets Services, 67122 Altrip, Germany)
- Water (ad libitum): tap water
- Acclimation period: at least 5 days before administration

ENVIRONMENTAL CONDITIONS
- Temperature (°C): 20 - 24°C
- Humidity (%): 20 - 80%
- Air changes (per hr): no data
- Photoperiod (hrs dark / hrs light): 12/12

IN-LIFE DATES: From: 2009-07-31 To: 2009-09-02

Administration / exposure

Route of administration:
oral: gavage
Vehicle:
other: unchanged (no vehicle) or olive oil
Details on oral exposure:
For the high dose, the liquid test substance was administered unchanged. For the low dose, the test substance was dissolved in olive oil.

1) 2000 mg/kg dose level
VEHICLE : no vehicle
MAXIMUM DOSE VOLUME APPLIED: 1.22 ml/kg

2) 50 mg/kg dose level
VEHICLE: Olive oil Ph.Eur.
- Concentration in vehicle: 4.1 g/100 ml; i.e. 4.1% (w/v)
- Amount of vehicle (if gavage): 1.22 ml/kg bw
- Justification for choice of vehicle: solubility of the test substance
Because no analyses of the test substance preparation were requested by BASF SE, no samples have been taken.
MAXIMUM DOSE VOLUME APPLIED: 1.22 ml/kg bw
DOSAGE PREPARATION (if unusual): The test-item preparation of the 50 mg/kg bw was produced for each test group shortly before administration by stirring with a magnetic stirrer.

CLASS METHOD (if applicable)
- Rationale for the selection of the starting dose:
By the request of BASF SE, a starting dose of 50 mg/kg bw was chosen in the first step with 3 female animals. As no animal died, 2000 mg/kg bw was administered to 3 female rats in the second step. Because no animal died at the second step, 2000 mg/kg bw was administered to another group of 3 female animals in the third step. As no animal died in this step the study was terminated.
Doses:
2000 mg/kg bw, undiluted
50 mg/kg bw, as a 4.1% (w/v) solution in olive oil
No. of animals per sex per dose:
6 females for the 2000 mg/kg dose level (2 subgroups of 3)
3 females for the 50 mg/kg dose level
Control animals:
no
Details on study design:
Duration of observation period following administration: 14 days
- Frequency of observations and weighing:
-- Individual body weights were determined shortly before administration (day 0), weekly thereafter and on the last day of observation.
-- Recording of signs and symptoms was made several times on the day of administration, and at least once daily thereafter each workday for the individual animals.
-- A check for any dead or moribund animal was made at least once each workdays.
- Necropsy of survivors performed: yes
- Other: No histological examinations were performed.
Statistics:
Calculations were performed using Microsoft Excel 2003 and checked with a calculator.

Results and discussion

Effect levelsopen allclose all
Sex:
female
Dose descriptor:
LD50
Effect level:
> 2 000 mg/kg bw
Remarks on result:
other: No deaths occurred. Clinical symptoms were noted at 2000 mg/kg.
Sex:
male/female
Dose descriptor:
LD50
Effect level:
> 2 000 mg/kg bw
Remarks on result:
other: The combined acute oral LD50 was calculated.
Mortality:
No mortality occurred.
Clinical signs:
2000 mg/kg bw groups:
Clinical observation in two animals of the 2000 mg/kg bw test groups revealed impaired general state, dyspnea, piloerection, staggering and reduced feces from hour 3 until study day 2 after the administration.
In one animal dosed with 2000 mg/kg bw impaired general state, dyspnea, staggering, lacrimation, chromodacryorrhea, diarrhea, exsiccosis, piloerection and reduced feces from hour 1 until study day 12 after the administration was observed. In contrast, two animals dosed with 2000 mg/kg bw showed no clinical findings.

50 mg/kg bw group:
No clinical signs and findings were observed.

For details, see attached file.
Body weight:
The mean body weight of the test groups increased throughout the study period within the normal range. For details, see table below.
Gross pathology:
There were no macroscopic pathological findings in the animals sacrificed at the end of the observation period.

Any other information on results incl. tables

Table: individual and group mean body weights

Dose

[mg/kg bw]

2000

2000

50

Animal no.

Animal code

1

R130

2

R131

3

R132

mean ± SD

4

R148

5

R149

6

R150

mean ± SD

7

R108

8

R109

9

R110

mean ± SD

Body weight [g] at study day

 

 

 

 

 

 

 

 

 

 

 

 

0

190

185

195

190.0± 5.00

176

177

178

177.0± 1.00

178

183

179

180.0± 2.65

7

198

190

198

195.3± 4.62

182

167

190

179.7 ± 11.68

194

200

195

196.3± 3.21

14

215

203

209

209.0 ± 6.00

189

180

201

190.0± 10.54

207

208

202

205.7± 3.21

Applicant's summary and conclusion

Interpretation of results:
Category 5 based on GHS criteria
Remarks:
Migrated information
Conclusions:
Under the conditions of this study the median lethal dose of 2-Methyl-3,4-dibrombuttersäureethylester after oral administration was found to be greater than 2000 mg/kg bw in rats.