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Administrative data

Endpoint:
acute toxicity: oral
Type of information:
experimental study
Adequacy of study:
key study
Study period:
From 17 March 1994 to 16 September 1994
Reliability:
2 (reliable with restrictions)
Rationale for reliability incl. deficiencies:
other: A well documented not GLP study according to OECD guideline

Data source

Reference
Reference Type:
study report
Title:
Unnamed
Year:
1995
Report date:
1995

Materials and methods

Test guideline
Qualifier:
according to guideline
Guideline:
OECD Guideline 401 (Acute Oral Toxicity)
GLP compliance:
no
Test type:
standard acute method

Test material

Constituent 1
Chemical structure
Reference substance name:
Thiophene-2-ethylamine
EC Number:
250-196-9
EC Name:
Thiophene-2-ethylamine
Cas Number:
30433-91-1
Molecular formula:
C6H9NS
IUPAC Name:
2-(2-thienyl)ethanamine
Constituent 2
Reference substance name:
2-Thiopheneethanamine
IUPAC Name:
2-Thiopheneethanamine
Test material form:
other: liquid
Details on test material:
- Name of test material (as cited in study report): SR 26825
- Lot/batch No.: 4SNL001

Test animals

Species:
rat
Strain:
other: OFA-SD (IOPS Caw)
Sex:
male/female
Details on test animals or test system and environmental conditions:
TEST ANIMALS
- Source: Iffa Credo
- Age at the beginning of the treatment: approximately 5 weeks
- Weight at the beginning of the treatment: male: 115 to 184 g - female: 122 to 152 g
- Fasting period before treatment: food was withdrawn 18 hours before treatment and redistributed approximately 4 hours after treatment
- Housing: rats were housed 2 or 3 of a same group to stainless steel cages (891cm² x 18 cm).
- Diet: UAR AO4C diet
- Water: tap water
- Acclimation period: at least 5 days

ENVIRONMENTAL CONDITIONS
- Temperature: 22°C (+/- 2°C)
- Humidity: between 40 and 70%
- Air changes: 10 to 11 times per hour without recycling
- Photoperiod: 12/24-hour light cycle

Administration / exposure

Route of administration:
oral: gavage
Vehicle:
other: in a 0.6% methylcellulose aqueous solution
Details on oral exposure:
VEHICLE
- Concentration in vehicle: 0.6% in methylcellulose aqueous solution
- Administration volume: 10 mL/kg

Dose levels were selected in view of available information on the test compound.
Doses:
Dose levels: 0, 125, 200, 250, 500 and 2000 mg/kg
No. of animals per sex per dose:
5 animals per sex per dose
Control animals:
yes
Details on study design:
- Duration of observation period following administration: 15 days
- Frequency of observations and weighing:
Clinical signs: daily observations
Body weight: day 1 (on the day of treatment) and on day 3, day 8 and day 15.
- Post-mortem macroscopic examination was performed in the animals found dead during the study.
- Surviving animals were sacrificed by an intraperitoneal injection of pentobarbital sodium followed by exsanguination and subjected to a macroscopic examination at the end of observation period.

Results and discussion

Effect levelsopen allclose all
Sex:
male/female
Dose descriptor:
LD0
Effect level:
200 other: mg/kg
Based on:
test mat.
Sex:
male/female
Dose descriptor:
LD50
Effect level:
> 200 - <= 250 other: mg/kg
Based on:
test mat.
Sex:
male/female
Dose descriptor:
LD100
Effect level:
500 other: mg/kg
Based on:
test mat.
Mortality:
No mortality occurred for the dose levels: 0, 125 and 200 mg/kg
At 250 mg/kg: 3 males (of 5) and 3 females (of 5) died 3h30 following treatment
At 500 mg/kg: 3 males died in the first hour and 2 other males died, 3h30 following treatment. As for the females, 4 died in the first hour and 1 died, 3h30 following treatment.
At 2000 mg/kg: 2 males died 30 minutes following treatment and the other 3 males died 45 minutes following treatment. As for the females, the 5 animals died 30 minutes following treatment.
Mortality occurred very soon after treatment.
Clinical signs:
other: >= 125 mg/kg: Ptyalism (day 1) >= 200 mg/kg: Prostration (day 1) in surviving animals a few hours after treatment >= 250 mg/kg: Decubitus, tremors, clonic convulsions (day 1) 2000 mg/kg: Piloerection (on day 1 in 3 males only)
Gross pathology:
Observations after necropsy:
- Animals found dead:
>= 250 mg/kg: Intestine and stomach: hemorrhagic contents in all animals; Lungs: non collapsed mostly at 250 mg/kg; Dried blood on the muzzle (3/6 at 250 mg/kg, 8/10 at 500 mg/kg)
>= 500 mg/kg: Liver: slightly pale in all animals
2000 mg/kg: Stomach (glandular area): red spots in all animals
- Animals sacrificed on day 15: No treatment-related changes

Applicant's summary and conclusion

Conclusions:
The maximal non lethal dose is 200 mg/kg in male and female rats. LD50 is between 200 and 250 mg/kg. No intersex differences were noted.

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