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Administrative data

Endpoint:
acute toxicity: oral
Type of information:
experimental study
Adequacy of study:
key study
Reliability:
2 (reliable with restrictions)
Rationale for reliability incl. deficiencies:
guideline study without detailed documentation

Data source

Reference
Reference Type:
other company data
Title:
Unnamed
Year:
2013

Materials and methods

Test guideline
Qualifier:
according to guideline
Guideline:
EU Method B.1 bis (Acute Oral Toxicity - Fixed Dose Procedure)
GLP compliance:
yes
Test type:
fixed dose procedure
Limit test:
yes

Test material

Constituent 1
Chemical structure
Reference substance name:
(R)-1,2,3,4-tetrahydro-6,7-dimethoxy-1-veratrylisoquinoline hydrochloride
EC Number:
415-110-8
EC Name:
(R)-1,2,3,4-tetrahydro-6,7-dimethoxy-1-veratrylisoquinoline hydrochloride
Cas Number:
54417-53-7
Molecular formula:
C20H25NO4.HCl
IUPAC Name:
(1R)-1-[(3,4-dimethoxyphenyl)methyl]-6,7-dimethoxy-1,2,3,4-tetrahydroisoquinoline hydrochloride
Test material form:
solid: crystalline

Test animals

Species:
rat
Strain:
Sprague-Dawley

Administration / exposure

Route of administration:
oral: unspecified
Vehicle:
water
Remarks:
distilled water
No. of animals per sex per dose:
Preliminary sighting study: 2 (female)
Main study: 10 (male)
Main study: 10 (female)
Details on study design:
Preliminary sighting study:
A preliminary study was carried out by dosing one female rat at 50 and one female rat at 500 mg/kg bodyweight respectively.
Main study:
Groups of ten rats (five males and five females) were treated at 50 mg/kg and 500 mg/kg bodyweight to determine the acute toxicity of the test substance more precisely.

Results and discussion

Preliminary study:
Species/strain: Rat (Sprague-Dawley)
2000 mg/kg bw: not administered
500 mg/kg bw: Evident toxicity: Y; Mortality: Y
50 mg/kg bw: Evident toxicity: N; Mortality: N
5 mg/kg bw: not administered
<5 mg/kg bw: not administered
mg/kg bw: Evident toxicity: ; Mortality:
Observations:
The animal died 3 hours after dosing at 500 mg/kg
Effect levelsopen allclose all
Sex:
male/female
Dose descriptor:
discriminating dose
Effect level:
50 mg/kg bw
Remarks on result:
other: fixed dose initial
Remarks:
No mortality. Evident toxicity
Sex:
male/female
Dose descriptor:
discriminating dose
Effect level:
500 mg/kg bw
Remarks on result:
other: fixed dose initial
Remarks:
Mortality and evident toxicity.
Mortality:
5/5 males and 4/5 females died following treatment at 500 mg/kg bodyweight. All deaths occurred within two hours of dosing. There were no deaths at 50 mg/kg bodyweight.
Clinical signs:
Piloerection was observed in all rats within five minutes of
dosing. This sign persisted and was accompanied from Day 1
by hunched posture in two males and one female at 50 mg/kg,
and two females at 500 mg/kg. Abnormal gait, lethargy,
decreased respiratory rates, partially closed eyelids and
pallor of the extremities were also noted in two females at
500 mg/kg, and increased salivation and body tremors was
noted in one female at 500 mg/kg.
Among surviving rats, satisfactory bodyweight gains were
achieved throughout the study. No macroscopic abnormalities
were seen for these rats killed on Day 15.
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36
Recovery of surviving rats, as judged by external appearance
and behaviour, was complete by Day 2 (50 mg/kg) or by Day 6
(500 mg/kg)
Gross pathology:
Effects on organs:
Macroscopic examination of rats that died revealed fluid
contents in the stomach. No other abnormalities were seen.

Applicant's summary and conclusion

Interpretation of results:
Category 4 based on GHS criteria