2-phenoxyethanol

Genetic toxicity: in vivo

Administrative data

Endpoint:

in vivo mammalian somatic cell study: cytogenicity / erythrocyte micronucleus

Type of information:

experimental study

Adequacy of study:

key study

Study period:

02 Oct 2001 - 12 Feb 2002

Reliability:

1 (reliable without restriction)

Rationale for reliability incl. deficiencies:

guideline study

Data source

Reference

Reference Type:

study report

Title:

Unnamed

Year:

2002

Report date:

2002

Materials and methods

Test guideline

Test guideline 1

Qualifier:

according to guideline

Guideline:

OECD Guideline 474 (Mammalian Erythrocyte Micronucleus Test)

Deviations:

yes

Remarks:

The initial body weights of 4 males were slightly over 45 g (45.8-47.8 g). The historical data used in this study is the summary of the data obtained in the years 1999 and 2000. These deviations, however, do not affect the validity of the study.

Test guideline 2

Qualifier:

according to guideline

Guideline:

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

Test guideline 3

Qualifier:

according to guideline

Guideline:

EPA OPPTS 870.5395 (In Vivo Mammalian Cytogenetics Tests: Erythrocyte Micronucleus Assay)

Test guideline 4

Qualifier:

according to guideline

Guideline:

JAPAN: Guidelines for Screening Mutagenicity Testing Of Chemicals

Version / remarks:

Kanpoan 287 (Japan EPA), Eisei 127 (MHW) and Heisei 09/10/31 Kikyoku No. 2 (MITI)

GLP compliance:

yes (incl. QA statement)

Remarks:

Hessisches Ministerium für Umwelt, Landwirtschaft und Forsten, Wiesbaden

Type of assay:

micronucleus assay

Test material

Test material information

Constituent 1

Reference substance name:

2-phenoxyethanol

EC Number:

204-589-7

EC Name:

2-phenoxyethanol

Cas Number:

122-99-6

Molecular formula:

C8H10O2

IUPAC Name:

2-phenoxyethan-1-ol

Specific details on test material used for the study:

- Name of test material (as cited in study report): Protectol PE
- Physical state: colorless liquid
- Analytical purity: 99.9%
- Lot/batch No.: 664287
- Stability under test conditions: The stability of the test substance in water over a period of 96 hours has been verified analytically by the data owner.
- Storage condition of test material: Room temperature, under nitrogen

Test animals

Species:

mouse

Strain:

NMRI

Sex:

male

Details on test animals or test system and environmental conditions:

TEST ANIMALS
- Source: RCC Ltd., Biotechnology and Animal Breeding Division, Füllinsdorf, Switzerland
- Age at study initiation: 8 to 10 weeks at start of acclimatization
- Weight at study initiation: 40.7 ± 4.1 g at start of treatment. The initial body weights of 4 males were slightly over 45 g (45.8 - 47.8 g)
- Assigned to test groups randomly: yes
- Housing: single
- Diet (e.g. ad libitum): pelleted standard diet, ad libitum
- Water (e.g. ad libitum): tap water, ad libitum
- Acclimation period: minimum 5 days

ENVIRONMENTAL CONDITIONS
- Temperature (°C): 21 ± 4
- Humidity (%): 30 - 60
- Photoperiod (hrs dark / hrs light): 12/12

Administration / exposure

Route of administration:

intraperitoneal

Vehicle:

- Vehicle(s)/solvent(s) used: 0.5% CMC (carboxymethyl cellulose)
- Justification for choice of solvent/vehicle: The vehicle was chosen to its relative non-toxicity for the animals.
- Concentration of test material in vehicle: In accordance with the scheduled dose to be tested.

Duration of treatment / exposure:

not applicable

Frequency of treatment:

once

Post exposure period:

24 and 48 h after treatment

Doses / concentrations

Doses / concentrations 1

Dose / conc.:

125 mg/kg bw/day (nominal)

Remarks:

10 mL/kg body weight total volume applied

Doses / concentrations 2

Dose / conc.:

250 mg/kg bw/day (nominal)

Remarks:

10 mL/kg body weight total volume applied

Doses / concentrations 3

Dose / conc.:

500 mg/kg bw/day (nominal)

Remarks:

10 mL/kg body weight total volume applied

No. of animals per sex per dose:

6 males per dose

Control animals:

yes, concurrent vehicle

Positive control(s):

cyclophosphamide
- Route of administration: intraperitoneally, once
- Doses / concentrations: 40 mg/kg b.w.

Examinations

Tissues and cell types examined:

Tissue: Bone marrow
Cell type: erythrocytes in bone marrow

Evaluation criteria:

A test substance is classified as mutagenic if it induces either a dose-related increase in the number of micronucleated polychromatic erythrocytes, which clearly exceeds the negative control range or a relevant positive response for at least one of the test points.
A test substance producing neither a dose-related increase in the number of micronucleated polychromatic erythrocytes nor a positive response at any of the test points is considered non-mutagenic in this system.

Statistics:

The statistical significance of the findings at p<0.05 was assessed by means of the non-parametric Mann-Whitney test.

Results and discussion

Test results

Sex:

male

Genotoxicity:

negative

Toxicity:

yes

Remarks:

In the main experiment the males treated with the highest dose (500 mg/kg) showed clear signs of toxicity. For details refer to attached background material.

Any other information on results incl. tables

For tables of results refer to attached background material.

Applicant's summary and conclusion

Conclusions:

Interpretation of results: negative