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Repeated dose toxicity: oral

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Administrative data

repeated dose toxicity: oral
Type of information:
experimental study
Adequacy of study:
key study
1 (reliable without restriction)
Justification for type of information:
May, 2017. Because of in the NDA 01-04-1385-00 carried out by Germany was not requested to indicate the endpoint study record, considering the data inserted in the course of the assessment to be correct and exhaustive the proper “Adequacy of study” has been selected.

Data source

Reference Type:
other: Body responsible for the test
Report date:

Materials and methods

Test guideline
according to guideline
other: 96/54/EG, B.7 (1996); OECD 407 (1995)
GLP compliance:
Limit test:

Test material

Constituent 1
Chemical structure
Reference substance name:
EC Number:
EC Name:
Cas Number:
Molecular formula:
Hill formula: C7H7BO3 CAS formula: C7H7BO3
(4-formylphenyl)boronic acid
Test material form:

Test animals

other: rat, Sprague-Dawley

Administration / exposure

Route of administration:
oral: unspecified
other: 0,5 % CMC
Details on oral exposure:
Method of administration:
Duration of treatment / exposure:
Test duration: 28 days
Frequency of treatment:
Dosing regime: 7 days/week
No. of animals per sex per dose:
Male: 5 animals at 0 mg/kg bw/day
Male: 5 animals at 50 mg/kg bw/day
Male: 5 animals at 250 mg/kg bw/day
Male: 5 animals at 1000 mg/kg bw/day
Female: 5 animals at 0 mg/kg bw/day
Female: 5 animals at 50 mg/kg bw/day
Female: 5 animals at 250 mg/kg bw/day
Female: 5 animals at 1000 mg/kg bw/day

Results and discussion

Results of examinations

Details on results:
Clinical observations:
There were no treatment-related deaths or other differences
from control for other parameters measured, including
clinical appearance, body weight, food and water consumption
that were considered to be related to treatment.

The functional observations (behavioral assessments,
functional performance tests, and sensory reactivity
assessments) showed no signs or symptoms indicating evidence
for systemic toxic and neurotoxic potential in both sexes at
doses of 1000 mg/kg bw/d and below.

Laboratory findings:
Hematology revealed statistically significant decreases in
hemoglobin and hematocrit, and significant increases in
white blood cells (primarily in neutrophils, monocytes,
eosinophiles, and large unclassified cells) for the 1000
mg/kg bw/d females, and a marginal increase primarily in
neutrophils and large unclassified cells for the 1000 mg/kg
bw/d males.

At 1000 mg/kg bw/d clinical biochemistry revealed
statistically significant increase in alanine
aminotransferase activities in animals of both sexes; a
decrease in potassium values, an increase in chloride and
sodium values in males; and an significant increase in
phosphorous in females.

Effects in organs:
There were increases in liver, spleen, lung and ovary
weights in 1000 mg/kg bw/d females.

Enlarged mandibular lymph node was observed in males at 250
and 1000 mg/kg bw/d (3/5 animals of each group).
Histopatholgy revealed in one 1000 mg/kg bw/d female rat
eosinophilic foci, cytomegaly, moderately increased numbers
of mitotic figures and mildly increased apoptosis of the

The mandibular lymph node was affected in three males given
1000 mg/kg bw/d. Lymphoid hyperplasia was noted in two males
and cell infiltration in a third animal. However,
histopathology was not performed on animals treated at 50
and 250 mg/kg bw/d.

Effect levels

open allclose all
Dose descriptor:
Effect level:
250 mg/kg bw/day (nominal)
Basis for effect level:
other: original NCD unit is mg/kg/day.
Dose descriptor:
Effect level:
50 mg/kg bw/day (nominal)
Basis for effect level:
other: original NCD unit is mg/kg/day.

Target system / organ toxicity

Critical effects observed:
not specified

Applicant's summary and conclusion

Classified as: Not classified