Registration Dossier

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: This study was carried out in accordance with internationally valid GLP principles.

Data source

Reference
Reference Type:
study report
Title:
Unnamed
Year:
2010
Report Date:
2010

Materials and methods

Test guideline
Qualifier:
according to
Guideline:
EU Method B.1 tris (Acute Oral Toxicity - Acute Toxic Class Method)
Deviations:
no
GLP compliance:
yes
Test type:
acute toxic class method
Limit test:
no

Test material

Reference
Name:
Unnamed
Type:
Constituent
Details on test material:
- Name of test material (as cited in study report): 3,4-Ethylenedioxythiophene
- Comercial name. EDOT
- Substance type: pure organic substance
- Physical state: liquid near colourless to pale yellow
- Analytical purity: > 99%
- Lot/batch No.: 091201
- Expiration date of the lot/batch: 21.1.2011
- Storage condition of test material: Keep in dark at room temperature. Stored in amber glass bottles under the argon atmosphere. Minimalize time for handling with substance without protective argon atmosphere as possible. Maximal time without protective atmosphere is 30 min.
- pH: approximately 4 (by contact of application form with universal indicator pH strip moistened with water, strip producer Lach-Ner, s.r.o. (Neratovice)

Test animals

Species:
rat
Strain:
Wistar
Sex:
female
Details on test animals and environmental conditions:
TEST ANIMALS
- Source: breeding farm VELAZ s.r.o., Koleč u Kladna, Czech Republic, RČH CZ 21760152
- Age at study initiation: 8-10 weeks at the time application
- Weight at study initiation: 140.7 g (mean) for dose 2000 mg/kg, 153 g (mean) for dose 300 mg/kg
- Fasting period before study: 20 hrs
- Housing: sterilized shavings of soft wood
- Diet (e.g. ad libitum): ST 1 BERGMAN – standard pelleted diet ad libitum, (producer: Ing.Mrkvička Miroslav - Výroba krmných směsí, Mlýn Kocanda, 252 42 Jesenice u Prahy)
- Water (e.g. ad libitum): drinking tap water ad libitum (quality corresponding to Regulation No. 252/2004 Czech Coll. of Law)
- Acclimation period:at least 5 days


ENVIRONMENTAL CONDITIONS
- Temperature (°C): 22 + 3°C, permanently monitored
- Humidity (%): 30 – 70 %, permanently monitored
- Air changes (per hr): approximately 15 air changes per hour
- Photoperiod (hrs dark / hrs light): 12-hour light/12 hour dark


STUDY TIME SCHEDULE
Animal supply: 27. 01. 2010
Experimental part of study: 01. 02. - 17. 02. 2010

Administration / exposure

Route of administration:
oral: gavage
Vehicle:
water
Details on oral exposure:
VEHICLE
- Aqua pro injectione
- The single volume of administered suspension was 1ml/100 g of animal body weight.
- Lot/batch no. (if required): Batch No.: 0102050309


MAXIMUM DOSE VOLUME APPLIED: 2000 mg/kg


CLASS METHOD (if applicable)
- Rationale for the selection of the starting dose: (according to EU Method B.1tris, Annex 1D), START: 2000 mg/kg – 3 females (Step No.1): 2 females died ► 300 mg/kg – 3 females (Step No. 2): no death ► 300 mg/kg – 3 females (Step No. 3): no death ► END of study
Doses:
2000 mg/kg, 300 mg/kg
No. of animals per sex per dose:
3 animals per dose
Control animals:
no
Details on study design:
- Duration of observation period following administration: 14 days
- Time schedule of observations:
Body weight: before application, the 8th day and before euthanasia of animals
Mortality: daily
Clinical examination: daily
Pathological examination: 15th day
- Necropsy of survivors performed: yes (gross necropsy)

Results and discussion

Effect levels
Sex:
female
Dose descriptor:
LD50
Effect level:
> 300 - <= 2 000 mg/kg bw
Mortality:
The test substance administered at the dose of 2000 mg/kg caused death of two animals and one animal was humanely killed by reason of moribund condition at the 30 minutes after application.
Clinical signs:
The test substance administered at the dose of 300 mg/kg: clinical signs of intoxication were observed in all animals (piloerection, anaemic mucous membranes, apathy, decreased responses to stimuli, red secretion around nostrils or eyes).
Body weight:
Weight increments were adequate to species, sex and age of animals in experiment.
Gross pathology:
The test substance caused macroscopic pathological lesions in all animals from the 2000 mg/kg dose group which were connected with theirs moribund status and death. Moribund status of one female and death of two females were probably due to extensive internal bleeding caused by the well perfused of stomach.

Applicant's summary and conclusion

Interpretation of results:
harmful
Remarks:
Migrated information Criteria used for interpretation of results: EU
Conclusions:
The test substance toxicity was evaluated on the basis of mortality, clinical signs of intoxication, body weight increments during the observation period and necropsy findings at the end of study.

The test substance administered at the dose of 2000 mg/kg caused death of two animals and one animal was humanely killed by reason of moribund condition at the 30 minutes after application. Clinical signs of intoxication (piloerection, anaemic to skin, anaemic mucous membranes, lying on the abdomen, immobility, decreased response to stimuli, brachypnoe, without defecation) were observed in one animal.
Macroscopic lesions were diagnosed in stomach.

The test substance administered at the dose of 300 mg/kg caused no death in two administered groups of females, clinical signs of intoxication were observed in all animals
(piloerection, anaemic mucous membranes, apathy, decreased responses to stimuli, red secretion around nostrils or eyes). No macroscopic changes were diagnosed during pathological examination of exposed females.
Executive summary:

The aim of the study was to investigate acute toxic effects of the test substance, 3,4-Ethylenedioxythiophene, after a single oral administration to Wistar rats.

The testing was performed according to the Method B.1 tris: Acute Oral Toxicity - Acute Toxic Class Method, Council Regulation (EC) No.440/2008, published in O.J. L 142, 2008.

Test substance was administered in a single dose as a suspension in aqua for injectione (vehicle), given orally via gavage to three groups of three female Wistar rats.

The dosing was performed sequentially in three groups of three females: group No. 1 (first step) using the starting dose of 2000 mg/kg body weight, group No. 2 (second step) and group No. 3 (third step) using a dose of 300 mg/kg body weight. The volume of administered solution was 1 ml/100 g body weight of animals.

The test substance administered at the dose of 2000 mg/kg caused death of two animals and one animal was humanely killed by reason of moribund condition at the 30 minutes after application. Clinical signs of intoxication (piloerection, anaemic to skin, anaemic mucous membranes, lying on the abdomen, immobility, decreased response to stimuli, brachypnoe, no defecation) were observed in one animal.   

Macroscopic lesions were diagnosed in stomach.

The test substance administered at the dose of 300 mg/kg caused no death in two administered groups of females, clinical signs of intoxication were observed in all animals (piloerection, anaemic mucous membranes, apathy, decreased responses to stimuli, red secretion around nostrils or eyes). No macroscopic changes were diagnosed during pathological examination of exposed females.

According to the study results the value of LD50 of the test substance, 3,4-Ethylenedioxythiophene, for rats is in the range > 300 mg/kg to ≤ 2000 mg/kg.