(R)-1,2,3,4-tetrahydro-6,7-dimethoxy-1-veratrylisoquinoline hydrochloride

Acute Toxicity: oral

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

Test material information

Constituent 1

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 levels

Effect levels 1

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

Effect levels 2

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