Benzyl(3-hydroxyphenacyl)methylammonium chloride

Genetic toxicity: in vivo

Administrative data

Endpoint:

in vivo mammalian somatic cell study: cytogenicity / erythrocyte micronucleus

Remarks:

Type of genotoxicity: chromosome aberration

Type of information:

experimental study

Adequacy of study:

key study

Study period:

2001

Reliability:

1 (reliable without restriction)

Data source

Reference

Reference Type:

study report

Title:

Unnamed

Year:

2001

Report date:

2001

Materials and methods

Test guideline

Test guideline 1

Qualifier:

according to guideline

Guideline:

OECD Guideline 474 (Mammalian Erythrocyte Micronucleus Test)

Test guideline 2

Qualifier:

according to guideline

Guideline:

EU Method B.12 (Mutagenicity - In Vivo Mammalian Erythrocyte Micronucleus Test)

GLP compliance:

yes

Type of assay:

micronucleus assay

Test material

Test material information

Constituent 1

Reference substance name:

Benzyl(3-hydroxyphenacyl)methylammonium chloride

EC Number:

276-017-4

EC Name:

Benzyl(3-hydroxyphenacyl)methylammonium chloride

Cas Number:

71786-67-9

Molecular formula:

C16H17NO2.ClH

IUPAC Name:

benzyl(3-hydroxyphenacyl)methylammonium chloride

Test material form:

solid: particulate/powder

Remarks:

migrated information: powder

Details on test material:

- Name of test material (as cited in study report): Benzyladrianon HCl
- Physical state: solid
- Analytical purity: 99.07 %
- Stability under test conditions: stable
- Storage condition of test material: At room temperature in the dark

Test animals

Species:

mouse

Strain:

NMRI

Sex:

male

Details on test animals or test system and environmental conditions:

TEST ANIMALS
- Source:Charles River, Sulzfeld, Germany
- Age at study initiation: 6-8 weeks
- Weight at study initiation: 28.9 - 34.5 g
- Assigned to test groups randomly: yes, under following basis: as they came to hand from delivery boxes
- Housing: Group Housing of 5 animals per sex per cage in labeled polycarbonate cages containing purified sawdust bedding material.
- Diet (e.g. ad libitum): Free access to standart pelleted laboratory animal diet ( Altromin )
- Water (e.g. ad libitum):Free access to tap water
- Acclimation period: 5 d

ENVIRONMENTAL CONDITIONS
- Temperature (°C): 18 - 24
- Humidity (%): 30 - 70
- Air changes (per hr): ca. 15
- Photoperiod (hrs dark / hrs light): 12:12

Administration / exposure

Route of administration:

intraperitoneal

Vehicle:

- Vehicle(s)/solvent(s) used: CMC (carboxymethyl cellulose)
- Concentration of test material in vehicle: 150 mg/kg BW
- Type and concentration of dispersant aid (if powder): 1:1 (w:v)

Details on exposure:

dosing volume : 10 mL/kg body weight

Frequency of treatment:

single dosing

Post exposure period:

24 h or 48 h

Doses / concentrations

Remarks:

Doses / Concentrations:
150 mg/kg BW
Basis:
nominal conc.

No. of animals per sex per dose:

2 male animals for the range finding test
10 male animals per dose ( 5 male animals per sampling time )

Control animals:

yes

Positive control(s):

cyclophosphamide dissolved in saline
- Route of administration: intraperitoneal injection
- Doses / concentrations: 50 mg sat/kg BW

Examinations

Tissues and cell types examined:

bone marrow
erythrocytes

Evaluation criteria:

A test substance is considered positive in the micronucleus test if it induced a biologically as well as statistically significant ( Wilcoxon Rank Sum
Test; two-sided test at P < 0.05 ) increase in the ferquency of micronucleated polychromatic erythrocytes.
The preceding criteria were not absolute and other modifying factors might enter into the final evaluation decision.

Results and discussion

Test results

Sex:

male

Genotoxicity:

negative

Toxicity:

yes

Remarks:

see: Any other Information

Vehicle controls validity:

valid

Negative controls validity:

valid

Positive controls validity:

valid

Any other information on results incl. tables

Within one hour after dosing all animals showed ataxia and were agressive, two animals also showed tremor and one animal also showed tremor and convulsion. Within 20 hours and 44 hours after dosing all animals showed no abnormalities.

Applicant's summary and conclusion

Conclusions:

Interpretation of results (migrated information): negative
It is concludet that this test is valid and that Benzyladrianon HCl is not mutagenic in the micronucleus test under the experimental conditions described in this report.

Executive summary:

Benzyldarianon HCl was tested in the Micronucleus test in mice to evalute its genotoxic effect on erythrocytes in bone marrow.

Two groups each comprising 5 males received an interperitoneal injection of 150 mg/kg body weight. After dosing the animals of the

treatment group showed following toxic signs: ataxia, convulsation, tremor and agression.

A vehicle treated group ( 1 % ( w/v) carboxymethylcellulose ) served as negative control, a group trated with a single intraperitoneal injection of cyclophosphamide at 50 mg/kg body weight served as positive control.

Bone marrow of the groups treated with Benzyladrianon HCl was sampled 24 and 48 hours after dosing. Bone marrow from the negative control group was harvested 24 hours after dosing and bone marrow from the positive control group was harvestedat 48 hours after dosing only.

Cyclophosphamide, the positive control substance, induced a statistically significant increase in the number of micronucleated polychromatic erythrocytes.

No biologically significant increase in the frequency of micro nucleated polychromatic erythrocytes was observed in the polychromatic erytrocytes of the bone marrow of animals treated with Benzyladrianon HCl.

The groups that wer treated with Benzyladrianon HCl showed no decrease in the ratio of polycrhomatic to normochromatic erythrocytes compared to the vehicle controls, which reflects a lack of toxic effects of this compound on the erythropoiesis. The groups that were treated with cyclophosphamide showed a decrease in the ratio of polycrhomatic to normochromatic erythrocytes compared to the vehicle controls.

It is concludet that this test is valid and that Benzyladrianon HCl is not mutagenic in the micronucleus test under the experimental conditions described in this report.