Naphthalene-1,5-diol

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:

other information

Reliability:

2 (reliable with restrictions)

Rationale for reliability incl. deficiencies:

other: only as secondary citation available: guideline study and GLP

Data source

Reference

Reference Type:

publication

Title:

Unnamed

Year:

2010

Materials and methods

Test guideline

Qualifier:

according to guideline

Guideline:

OECD Guideline 474 (Mammalian Erythrocyte Micronucleus Test)

GLP compliance:

yes

Type of assay:

micronucleus assay

Test material

Test material information

Constituent 1

Reference substance name:

Naphthalene-1,5-diol

EC Number:

201-487-4

EC Name:

Naphthalene-1,5-diol

Cas Number:

83-56-7

Molecular formula:

C10H8O2

IUPAC Name:

naphthalene-1,5-diol

Test material form:

other: solid

Details on test material:

content: 99.9 %

Test animals

Species:

mouse

Strain:

NMRI

Sex:

male/female

Details on test animals or test system and environmental conditions:

no data

Administration / exposure

Route of administration:

intraperitoneal

Vehicle:

aqueous DMSO (30 %)

Details on exposure:

Test concentrations
were based on the acute toxicity in a pre-test, measuredat various intervals around 1 to 48 h after treatment.
In the main experiment
mice were exposed to single i.p. doses of 0, 12.5, 25 and 50 mg/kg bw. 24 h or 48 h (highest dose
only) after dosing bone marrow cells were collected. The animals of the highest dose group
were examined for acute toxic symptoms 1, 2-4, 6 and 24 h after start of treatment.
Toxicity and thus exposure of the target cells was determined by measuring the ratio
between polychromatic and total erythrocytes (PCE/TE).
Satellite groups of
3 male mice per
sampling time (20 min, 40 min, 1 h and 4 h after start of treatment) treated with 50 mg/kg
bw were included for determination of blood concentrations of 1,5-naphthalenediol.
Bone marrow preparations were stained with May-Grünwald and examined microscopically
for the PCE/TE ratio and micronuclei. 5 mice/sex/group were analysed; the remaining 6th
animals of each group were only evaluated in case a mouse died spontaneously.

Duration of treatment / exposure:

single

Frequency of treatment:

once

Post exposure period:

as required by the guideline

Doses / concentrations

Remarks:

Doses / Concentrations:
0, 12.5, 25.0, 50.0 mg/kg bw
Basis:

No. of animals per sex per dose:

5/sex/group

Control animals:

other: negative controls were in accordance with the OECD guideline

Positive control(s):

positive controls were in accordance with the OECD guideline

Examinations

Tissues and cell types examined:

bone marrow cells

Details of tissue and slide preparation:

Bone marrow preparations were stained with May-Grünwald and examined microscopically
for the PCE/TE ratio and micronuclei. 5 mice/sex/group were analysed;
the remaining 6th animals of each group were only evaluated in case a mouse died spontaneously.

Evaluation criteria:

positive result: biological relevant increase in the number of micronucleated PCEs compared to concurrent vehicle controls

Statistics:

no data

Results and discussion

Test results

Sex:

male/female

Genotoxicity:

negative

Toxicity:

yes

Vehicle controls validity:

valid

Negative controls validity:

valid

Positive controls validity:

not applicable

Additional information on results:

Treatment with 1,5-naphthalenediol did not result in substantially decreased PCE/TE ratios
compared to the untreated controls indicating that 1,5-naphthalenediol did not have
cytotoxic properties in the bone marrow.
In contrast, clinical signs like reduction in spontaneous activity, abdominal position and ruffled fur
indicating systemic toxicity were observed at all doses in most treated animals up to 24 h after start of the
treatment. 1,5-naphthalenediol could be quantified in the blood of the treated males 20 minutes after start of the
treatment but not at later time points confirming the bioavailability of 1,5-naphthalenediol.

Biological relevant increases in the number of micronucleated PCEs compared to the
concurrent vehicle controls were not found following treatment with 1,5-naphthalenediol at
any time point or dose level tested.
Conclusion
Under the experimental conditions used 1,5-naphthalenediol did not induce an increase in
bone marrow cells with micronuclei in treated mice and, consequently, is 1,5-
naphthalenediol not genotoxic (clastogenic and/or aneugenic) in bone marrow cells of mice.

Applicant's summary and conclusion

Conclusions:

Interpretation of results (migrated information): negative
Under the experimental conditions used 1,5-naphthalenediol did not induce an increase in
bone marrow cells with micronuclei in treated mice and, consequently, is 1,5-
naphthalenediol not genotoxic (clastogenic and/or aneugenic) in bone marrow cells of mice.

Executive summary:

According to OECD TG 474 1,5 -Naphthalenediol has been investigated for the induction of micronuclei in bone marrow cells of mice. Test concentrations were based on the acute toxicity in a pre-test, measured at various intervals around 1 to 48 h after treatment. In the main experiment mice were exposed to single i.p. doses of 0, 12.5, 25 and 50 mg/kg bw. Clinical signs like reduction in spontaneous activity, abdominal position and ruffled fur indicating systemic toxicity were observed at all doses in most treated animals up to 24 h after start of the treatment. Biological relevant increases in the number of micronucleated PCEs compared to the concurrent vehicle controls were not found following treatment with 1,5-naphthalenediol at any time point or dose level tested. therefore, under the experimental conditions used, 1,5-naphthalenediol did not induce an increase in bone marrow cells with micronuclei in treated mice and, consequently, is 1,5- naphthalenediol not genotoxic (clastogenic and/or aneugenic) in bone marrow cells of mice.