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Administrative data

Endpoint:
short-term repeated dose toxicity: oral
Type of information:
experimental study
Adequacy of study:
key study
Reliability:
2 (reliable with restrictions)
Rationale for reliability incl. deficiencies:
data from handbook or collection of data

Data source

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

Materials and methods

Principles of method if other than guideline:
Annex V
GLP compliance:
no
Limit test:
no

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: gavage
Vehicle:
water
Remarks:
distilled water
Duration of treatment / exposure:
28 days
Frequency of treatment:
Dosing regime: 7 days/week
No. of animals per sex per dose:
Male: 5 animals at 15 mg/kg bw/day
Male: 5 animals at 150 mg/kg bw/day
Male: 5 animals at 500 mg/kg bw/day
Female: 5 animals at 15 mg/kg bw/day
Female: 5 animals at 150 mg/kg bw/day
Female: 5 animals at 500 mg/kg bw/day

Results and discussion

Results of examinations

Description (incidence and severity):
Increased salivation was detected up to 10 minutes after dosing for animals of either sex treated with 500mg/kg/d from day 4 onwards. No clinical signs were apparent in the decedents prior to death or in animals of either sex treated with 150 or 15 mg/kg/day throughout the study.
Description (incidence and severity):
No adverse effect on bodyweight development, dietary intake, food efficiency or water consumption was detected.
Description (incidence and severity):
Laboratory findings:
Females treated with 500Mg/kg/day showed a reduction in
haemoglobin, haemocrit and erythrocyte count. No such
effects were detected for males treated with 500mg/kg/d or
for animals of either sex at 150 or 15mg/kg/d
Description (incidence and severity):
No treatment related effects were detected in behavioural
assessment tests, sensory reactivity assessments or
functional performance tests.
Description (incidence and severity):
No treatment related macroscopic abnormalities were detected
at terminal kill. The macroscopic abnormalities detected in
teh 500mg/kg/d decedents were all considered to be normal post mortem findings.
Description (incidence and severity):
Histopathological examination revealed treatent related
changes in the thyroid glands. Higher grades of severity of
follicular cell hypertrophy were observed in relation to
treatment for males treated at 500mg/kg/d or at 150mg/kg/d.
No such changes were detected for animals of either sex
treated at 15mg/kg/d.

Effect levels

open allclose all
Dose descriptor:
NOAEL
Effect level:
150 mg/kg bw/day (nominal)
Basis for effect level:
clinical biochemistry
clinical signs
gross pathology
haematology
mortality
organ weights and organ / body weight ratios
Dose descriptor:
NOEL
Effect level:
15 mg/kg bw/day (nominal)
Basis for effect level:
clinical biochemistry
clinical signs
gross pathology
haematology
mortality
organ weights and organ / body weight ratios

Target system / organ toxicity

Critical effects observed:
no

Applicant's summary and conclusion

Conclusions:
The substance is not classified for the repeted toxicity.