Registration Dossier

Administrative data

Endpoint:
sub-chronic toxicity: oral
Type of information:
experimental study
Adequacy of study:
key study
Study period:
13 weeks
Reliability:
1 (reliable without restriction)
Rationale for reliability incl. deficiencies:
other: Test procedure according to national standards: Guidelines for Designation for Food Additives and for Revision of Standards for Use of Food Additives of Japan (1996)

Data source

Reference
Reference Type:
publication
Title:
Unnamed
Year:
2005

Materials and methods

Test guidelineopen allclose all
Qualifier:
equivalent or similar to
Guideline:
OECD Guideline 408 (Repeated Dose 90-Day Oral Toxicity in Rodents)
Qualifier:
according to
Guideline:
other: Guidelines for Designation for Food Additives and for Revision of Standards for Use of Food Additives of Japan (1996)
GLP compliance:
not specified
Limit test:
no

Test material

Reference
Name:
Unnamed
Type:
Constituent
Type:
Constituent
Type:
Constituent
Test material form:
solid: particulate/powder
Remarks:
migrated information: powder
Details on test material:
>95% (w/w), which was extracted from branch, trunk and root parts of Broussonetia xanthoxylum MARTIUS

Test animals

Species:
rat
Strain:
Fischer 344/DuCrj
Sex:
male/female

Administration / exposure

Route of administration:
oral: feed
Vehicle:
unchanged (no vehicle)
Analytical verification of doses or concentrations:
not specified
Duration of treatment / exposure:
13 weeks
Frequency of treatment:
daily
Doses / concentrationsopen allclose all
Remarks:
Doses / Concentrations:
0 %
Basis:
nominal in diet
Remarks:
Doses / Concentrations:
0.625 %
Basis:
nominal in diet
Remarks:
Doses / Concentrations:
1.25 %
Basis:
nominal in diet
Remarks:
Doses / Concentrations:
2.5 %
Basis:
nominal in diet
Remarks:
Doses / Concentrations:
5 %
Basis:
nominal in diet
No. of animals per sex per dose:
10
Control animals:
yes

Results and discussion

Results of examinations

Clinical signs:
no effects observed
Mortality:
no mortality observed
Body weight and weight changes:
effects observed, treatment-related
Food consumption and compound intake (if feeding study):
effects observed, treatment-related

Effect levels

open allclose all
Dose descriptor:
NOEL
Effect level:
299 mg/kg bw/day (nominal)
Based on:
test mat.
Sex:
male/female
Dose descriptor:
NOAEL
Effect level:
356 mg/kg bw/day (nominal)
Based on:
test mat.
Sex:
male/female

Target system / organ toxicity

Critical effects observed:
not specified

Applicant's summary and conclusion

Conclusions:
NOEL = 299 mg/kg bw/day; NOAEL = 356 mg/kg bw/day.
Executive summary:

Groups of 10 male and 10 female Fischer 344/DuCrj rats received 0 %, 0.625 %, 1.25 % , 2.5 % or 5.0 % (w/w) morin with dietary for 13 weeks. Especially in the higher dose groups food consumption was higher than expected, resulting in a higher than expected intake of Morin (males: 0, 299, 613, 1350, 3485 mg/kg/day; females: 0, 356, 712, 1701, 3802 mg/kg/day). No mortality in any of the tested groups was observed. Even in the highest dose group no deterioration of the general conditions could be monitored. For the male rats significant increases in ALT (over 2.5%), ALP (1.25% and 5.0%) and relative liver weights (1.25% and 2.5%) were observed. For the female rats significant increases in c-GT (over 2.5 %), AST (over 2.5 %), ALT (over 2.5 %), relative liver weights (over 2.5 %), ALP (5 %), BUN (over 1.25 %) and Cre (5.0%) were observed. The dose group0.625 % did not show any changes compared to the control group for both sexes. That concludes in the estimation of the NOEL and NOAEL at 299 and 356 mg/kg/day, respectively.