Registration Dossier

Administrative data

Endpoint:
acute toxicity: oral
Type of information:
experimental study
Adequacy of study:
key study
Study period:
Start of study: August 28 - End of study: September 11, 1997
Reliability:
1 (reliable without restriction)
Rationale for reliability incl. deficiencies:
other: 1a: GLP guideline study

Data source

Reference
Reference Type:
study report
Title:
Unnamed
Year:
1997
Report date:
1997

Materials and methods

Test guidelineopen allclose all
Qualifier:
according to guideline
Guideline:
OECD Guideline 401 (Acute Oral Toxicity)
Qualifier:
according to guideline
Guideline:
EU Method B.1 (Acute Toxicity (Oral))
GLP compliance:
yes
Remarks:
Principles of Good Laboratory Practice, annex of paragraph 19a, section 1 of the chemical law of July 25, 1994
Test type:
standard acute method

Test material

Constituent 1
Chemical structure
Reference substance name:
α,α-Dimethyl-ethyl ester benzeneacetic acid
EC Number:
608-307-7
Cas Number:
2901-13-5
Molecular formula:
C12 H16 O2
IUPAC Name:
α,α-Dimethyl-ethyl ester benzeneacetic acid
Test material form:
solid - liquid: suspension
Details on test material:
Name: Dimethylphenylessigsäureethylester
Synonyms: EDMPA
Chemical name: Benzeneacetic acid, α,α-dimethyl-, ethyl ester
Certificate of analysis: March 18, 1997
Purity: 99.8%
Appearance: clear, colorless liquid
Solubility: 0.3 g/L in water, miscible with alcohol, acetone and toluene
Batch number: B 0006
Date of production: March 12, 1997
Date of expiry: March 2000
Storage conditions: darkness at approximately 5°C in a refrigerator
Stability and homogeneity in the vehicle: is guaranteed for 4 hours

Test animals

Species:
rat
Strain:
Wistar
Sex:
male/female
Details on test animals or test system and environmental conditions:
TEST ANIMALS
- Source: HMR, Kastengrund, SPF breeding colony
- Age at study initiation: approx. 7 weeks for males, approx. 8 weeks for females
- Weight at study initiation: 175 g ± 2g for males, 173 g ± 5g for females
- Fasting period before study: from about 16 hours before to 3 - 4 hours after treatment
- Housing: in fully air-conditioned rooms in macrolon cages (type 4) on soft wood granulate in groups of 5 animals
- Diet (e.g. ad libitum): ssniff® R/M-H (V 1534)
- Water (e.g. ad libitum): tap water in plastic bottles
- Acclimation period: at least one day

ENVIRONMENTAL CONDITIONS
- Temperature (°C): 22 ± 3 °C
- Humidity (%): 50 ± 20 %
- Photoperiod (hrs dark / hrs light): 12h/12h

Administration / exposure

Route of administration:
oral: gavage
Vehicle:
other: sesame oil (Oleum sesami DAB 10)
Details on oral exposure:
Concentration in vehicle: 20 % solution in sesame oil
Maximum dose volume applied: 10 ml/kg body weight
Doses:
2000 mg/kg bw
No. of animals per sex per dose:
5/sexe/dose
Control animals:
not specified
Details on study design:
- Duration of observation period following administration: 14 days
- Frequency of observations and weighing: twice every day
- Necropsy of survivors performed: yes
- Surviving animals: killed by carbon dioxide asphyxiation, dissected and also examined for macroscopically visible changes.

Results and discussion

Effect levels
Sex:
male/female
Dose descriptor:
LD50
Effect level:
> 2 000 mg/kg bw
Based on:
test mat.
Mortality:
One female animal was found dead at day 2 of the study.
Clinical signs:
Stupor, decreased spontaneous activity, squatting posture, prone position, sunken flanks, bristled coat, irregular respiration, panting, forward crawling, stilted, uncoordinated and ataxie gait, straddled hind limbs, reduced or no placing reaction, narrowed palpebral fissures, blood-encrusted lid margins as well as diarrhea. Additionally, one male animal showed reduced pawreflex to pinching. At day 4 of the study all clinical signs were reversible.
Body weight:
No treatment-related effects
Gross pathology:
Necropsy of the decedent female animal revealed the following findings:
- lobular demarcation of the liver
- small intestine full of yellowish mucus
- caecum full of hardened feed-mash
- lungs discolored red
The animals killed at the end of the observation period showed no macroscopically visible changes.

Applicant's summary and conclusion

Interpretation of results:
not classified
Remarks:
Migrated information Criteria used for interpretation of results: EU
Conclusions:
Based on the results obtained in this study, the LD50 of the substance for the male and female Wistar rat is greater than 2000 mg/kg body weight.