4-(2-aminoethyl)phenol

Genetic toxicity: in vivo

Administrative data

Endpoint:

in vivo mammalian somatic cell study: cytogenicity / erythrocyte micronucleus

Type of information:

experimental study

Adequacy of study:

weight of evidence

Reliability:

2 (reliable with restrictions)

Rationale for reliability incl. deficiencies:

study well documented, meets generally accepted scientific principles, acceptable for assessment

Justification for type of information:

Data is from publication

Data source

Reference

Reference Type:

publication

Title:

Acute cytogenetic effects of tyramine and MTCAs on mouse bone marrow cells in vivo by the micronucleus test

Author:

Kimiko Fujie 1, Junko Nishi 1, Mieko Wada 1, Sakan Maeda and Taketoshi Sugiyama

Year:

1990

Bibliographic source:

Mutation Research, 240 (1990) 19-23

Materials and methods

Test guideline

Qualifier:

according to guideline

Guideline:

other: As mention below

Principles of method if other than guideline:

To evaluate the mutagenic potential of Tyramine in ICR (Crj : CD-1) mice bone marrow cells in vivo by the micronucleus test.

GLP compliance:

not specified

Type of assay:

other: In vivo micronucleus test.

Test material

Test material information

Constituent 1

Reference substance name:

4-(2-aminoethyl)phenol

EC Number:

200-115-8

EC Name:

4-(2-aminoethyl)phenol

Cas Number:

51-67-2

Molecular formula:

C8H11NO

IUPAC Name:

4-(2-aminoethyl)phenol

Test material form:

solid: crystalline

Details on test material:

- Name of test material : 4-(2-aminoethyl) phenol
- Common name : Tyramine
- Molecular formula : C8H11NO
- Molecular weight : 137.1809 g/mol
- Smiles notation : NCCc1ccc(O)cc1
- InChl : 1S/C8H11NO/c9-6-5-7-1-3-8(10)4-2-7/h1-4,10H,5-6,9H2
- Substance type: Organic
- Physical state: Solid

Specific details on test material used for the study:

- Name of test material : 4-(2-aminoethyl) phenol
- Common name : Tyramine
- Molecular formula : C8H11NO
- Molecular weight : 137.1809 g/mol
- Smiles notation : NCCc1ccc(O)cc1
- InChl : 1S/C8H11NO/c9-6-5-7-1-3-8(10)4-2-7/h1-4,10H,5-6,9H2
- Substance type: Organic
- Physical state: Solid

Test animals

Species:

mouse

Strain:

other: (Crj : CD-1)

Sex:

male/female

Details on test animals or test system and environmental conditions:

Details on test animals and env conditions
TEST ANIMALS
- Source: Charles River Japan Inc., Kanagawa, Japan)
- Age at study initiation:
- Weight at study initiation: 25-40 g
- Diet (e.g. ad libitum): They were fed commercial
NMF (Oriental Ferment Co., Tokyo) ad libitum
- Water (e.g. ad libitum): water ad libitum

Administration / exposure

Route of administration:

intraperitoneal

Vehicle:

Vehicles
- Vehicle(s)/solvent(s) used: Ethyl alcohol
- Type and concentration of dispersant aid (if powder): 200µl

Details on exposure:

Details on exposure
0.5-2.0 mmole tyramine/kg (69-274 mg/kg,
Nakarai Chemical Ltd., Tokyo) was swelled in 200µl ethyl alcohol and then homogenized in 2 ml of physiological saline.

Duration of treatment / exposure:

36 hour

Frequency of treatment:

6,12 ,24hour

Post exposure period:

Not specified

Doses / concentrations

Remarks:

0.5,1,1.5and 2.0mmole

No. of animals per sex per dose:

Each dose group consisted of 5 mice (male : female = 3 : 2 or 2 : 3).

Control animals:

yes, concurrent vehicle

Positive control(s):

Positive controls
MMC (mitomycin C)
- Doses / concentrations: 1.0 mg/kg

Examinations

Tissues and cell types examined:

mouse bone marrow cells were examined

Details of tissue and slide preparation:

Details of tissue and slide preparation
The animals were killed 24 h after an intraperitoneal
injection, the bone marrows extracted, and smear preparations made and stained. Micronucleus specimens were prepared by the method of Schmid (1975). Slides were coded and analyzed.

Evaluation criteria:

One thousand PCEs per mouse were screened for MNPCEs and at the same time the number of micronucleated normochromatic erythrocytes (MNNCEs) were scored in the same field of vision where 1000 PCEs were screened. The number of MNPCEs and MNNCEs were scored by 2 investigators and were averaged. The ratios of PCEs to total erythrocytes were also calculated from about 2000 erythrocytes.

Statistics:

The standard tables of Kastenbaum and Bowman
(1970) and the test method of Hayashi et al.
(1985) were both used for calculating significant
differences between the experimental and control
groups.

Results and discussion

Test results

Sex:

male/female

Genotoxicity:

ambiguous

Toxicity:

not specified

Vehicle controls validity:

valid

Negative controls validity:

valid

Positive controls validity:

valid

Remarks on result:

other: The result was not sufficient to classify the substance

Additional information on results:

Additional information on results
Compared to the values for the untreated
control, significant differences were noted for
tyramine above 0.5 mmole/kg (68.5 mg/kg) body weight .Time-dependent increases of MNPCEs after
treatment with 1.0 mmole tyramine/kg (137 mg/kg) were noted. 12 h after tyramine treatment.

The percent of PCEs to total erythrocytes decreased
to a minimum level 12 h after treatment with Tyramine and then returned to the normal level after 24 h .

Applicant's summary and conclusion

Conclusions:

Tyramine (51-67-2) was evaluated for its mutagenic potential in ICR (Crj : CD-1) mice bone marrow cells in vivo by the micronucleus test. The test result was considered to be Ambiguous.

Executive summary:

Genetic toxicity study in vivo was assessed for its possible mutagenic potential. For this purpose micronucleus test was performed in ICR (Crj : CD-1) male and female mice bone marrow cells. The test substance was exposed at the concentration of 0.5,1,1.5and 2.0mmole to each dose group consisted of 5 mice (male : female = 3 : 2 or 2 : 3). The animals were killed 24 h after an intraperitoneal injection, the bone marrows extracted, and smear preparations made and stained. Micronucleus specimens were prepared by the method of Schmid (1975). Slides were coded and analyzed. polychromatic erythrocytes and micronucleated normochromatic erythrocytes were observed. Micronuclei were significantly induced but no severe reduction in the ratio of PCEs/NCEs was observed. The test result was considered to be inconclusive as the result isAmbiguous. Hence further testing should be performed as data is insufficient to classify the substance.