Benzeneacetic acid, .alpha.-hydroxy-, (.alpha.R)-(1R,2S)-compd. with 2-(3,4-difluorophenyl)cyclopropanamine (1:1)

Specific investigations: other studies

Administrative data

Endpoint:

specific investigations: other studies

Type of information:

experimental study

Adequacy of study:

other information

Reliability:

1 (reliable without restriction)

Data source

Reference

Reference Type:

study report

Title:

Unnamed

Year:

2006

Report date:

2009

Materials and methods

Test guideline

Qualifier:

according to guideline

Guideline:

other: OECD 474

Deviations:

no

Principles of method if other than guideline:

Test procedure:
C3RO was given at doses of 5, 25, and 50 mg/kg to groups of
7 male Wistar Han rats, approximately 9 to 10 weeks old at
dosing; two groups of 7 control rats were given the vehicle
alone. Male rats only were used because there was no data to
indicate a sex difference in response to the toxicity of
C3RO. A group of 3 rats was given the positive control
cyclophosphamide, at 20 mg/kg.




Vehicle: 1% Carboxymethylcellulose / 0.1% Tween 80 in
purified water




Strain: Wistar Hanover, substrain AlpkHsdBrlHan:WIST




Positive control: Cyclophosphamide 2 mg/l in purified water

GLP compliance:

yes

Test material

Test material information

Constituent 1

Reference substance name:

-

EC Number:

454-140-6

EC Name:

-

Cas Number:

376608-71-8

Molecular formula:

C9H9F2N*C8H8O3

IUPAC Name:

(1R)-2-(3,4-difluorophenyl)cyclopropan-1-aminium (2R)-2-hydroxy-2-phenylacetate

Test animals

Species:

rat

Strain:

Wistar

Sex:

male

Administration / exposure

Route of administration:

oral: gavage

Vehicle:

other: 1% CMC (carboxymethyl cellulose)0.1 % Tween 80 in purified water

Analytical verification of doses or concentrations:

yes

Results and discussion

Details on results:

C3RO induced a statistically and biologically significant
increase in micronucleated immature erythrocytes (MIE) in
the bone marrow of male Wistar Han rats after a single oral
dose of 25 mg/kg, no increase in MIE was seen with 5 mg/kg.

There was no evidence of bone marrow toxicity as the

immature erythrocytes:mature erythrocytes (IE:E) ratio was
similar in the treated and vehicle control groups at both
sampling times.


It was concluded that, 25 mg/kg of C3RO induced a

statistically significant level of micronucleated immature
erythrocytes in the bone marrow of male Wistar Han rats.

Applicant's summary and conclusion

Conclusions:

It was concluded that, 25 mg/kg of C3RO induced a
statistically significant level of micronucleated immature
erythrocytes in the bone marrow of male Wistar Han rats.