2-aminopyridin-3-ol

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:

30.08. - 07.12.2004

Reliability:

1 (reliable without restriction)

Data source

Reference

Reference Type:

study report

Title:

Unnamed

Year:

2004

Report date:

2005

Materials and methods

Test guideline

Qualifier:

according to guideline

Guideline:

OECD Guideline 474 (Mammalian Erythrocyte Micronucleus Test)

GLP compliance:

yes (incl. QA statement)

Type of assay:

mammalian germ cell cytogenetic assay

Test material

Test material information

1

Reference substance name:

2-aminopyridin-3-ol

EC Number:

240-886-8

EC Name:

2-aminopyridin-3-ol

Cas Number:

16867-03-1

Molecular formula:

C5H6N2O

IUPAC Name:

2-aminopyridin-3-ol

Test animals

Species:

mouse

Strain:

NMRI

Sex:

male/female

Details on test animals or test system and environmental conditions:

Number of animals: 81 (45 males/36 females)
Initial age at start of acclimatization: Males: 5 - 8 weeks, females: 7 - 10 weeks
Acclimatisation: minimum 5 days
Initial Body Weight at Start of Treatment: males mean value 35.4 g (SD ± 2.4 g), females mean value 31.7 g (SD ± 2.8 g)
Housing: single
Bedding: Granulated soft wood bedding
Feed: Pelleted standard diet, ad libitum
Water: Tap water, ad libitum
Environment: Temperature 22 ± 3 °C, relative humidity 30 - 83 %, artificial light 6.00 a.m. - 6.00 p.m.

Administration / exposure

Route of administration:

intraperitoneal

Vehicle:

CMC

Details on exposure:

The test item was formulated in 2.5% CMC. The vehicle was chosen to its relative non-toxicity for the animals. All animals received a single standard volume of 10 mL/kg body weight intraperitoneally.

Duration of treatment / exposure:

single administration

Frequency of treatment:

single administration

Post exposure period:

24 and 48 hours

Doses / concentrations

Doses / concentrations 1

Dose / conc.:

12.5 mg/kg bw/day (nominal)

Remarks:

24 h preparation interval

Doses / concentrations 2

Dose / conc.:

25 mg/kg bw/day (nominal)

Remarks:

24 h preparation interval

Doses / concentrations 3

Dose / conc.:

50 mg/kg bw/day (nominal)

Remarks:

24 h preparation interval

Doses / concentrations 4

Dose / conc.:

50 mg/kg bw/day (nominal)

Remarks:

48 h preparation interval

No. of animals per sex per dose:

5

Control animals:

yes, concurrent vehicle

Positive control(s):

Substance: Cyclophosphamide (CPA)
Dissolved in: deionised water
Dosing: 40 mg/kg bw
Route and frequency of administration: i.p., once
Volume adminstered: 10 ml/ kg bw

Solution prepared on day of administration.

Examinations

Tissues and cell types examined:

Blood cells - erythrocytes

Results and discussion

Test results

Key result

Sex:

male/female

Genotoxicity:

negative

Toxicity:

yes

Vehicle controls validity:

valid

Negative controls validity:

other: vehicle served as negative control

Positive controls validity:

valid

Applicant's summary and conclusion

Conclusions:

In conclusion, it can be stated that under the experimental conditions reported, the test item did not induce micronuclei as determined by the micronucleus test with bone marrow cells of the mouse.

Therefore, A 132 is considered to be non-mutagenic in this micronucleus assay.

Executive summary:

This study was performed to investigate the potential of A 132 to induce micronuclei in polychromatic erythrocytes (PCE) in the bone marrow of the mouse.

The test item was formulated in 2.5% CMC, which was also used as vehicle control. The volume administered intraperitoneally (i.p.) was 10 mL/kg b.w.. 24 h and 48 h after a single administration of the test item the bone marrow cells

were collected for micronuclei analysis.  

Ten animals (5 males, 5 females) per test group were evaluated for the occurrence of micronuclei. At least 2000 polychromatic erythrocytes (PCEs) per animal were scored for micronuclei.

To describe a cytotoxic effect due to the treatment with the test item the ratio between polychromatic and total erythrocytes

was determined in the same sample and reported as the number of PCEs per 2000 erythrocytes.

The following dose levels of the test item were investigated:

24 h preparation interval: 12.5, 25 and 50 mg/kg b.w..

48 h preparation interval: 50 mg/kg b.w..

As estimated by pre-experiments 50 mg A 132 per kg b.w. was the highest applicable dose without significant effects on the survival rates, but with clear signs of toxicity. At a higher dose (75 mg/kg) all 4 treated animals died.

After treatment with the test item the number of PCEs was not substantially decreased as compared to the mean value of PCEs of the vehicle control thus indicating that A 132 did not exert any cytotoxic effects in the bone marrow. The bioavailability of the test item was, however, confirmed by chemical analysis of the blood of the treated animals.

In comparison to the corresponding vehicle controls there was no biologically relevant or statistically significant enhancement in the frequency of the detected micronuclei at any preparation interval after administration of the test item and with any dose level used.

40 mg/kg b.w. cyclophosphamide administered i.p. was used as positive control which showed a substantial increase of induced micronucleus frequency.