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Toxicological information

Genetic toxicity: in vivo

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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:
No data
Reliability:
1 (reliable without restriction)
Rationale for reliability incl. deficiencies:
other: No guideline followed but the study is similar to the OECD 474 guideline. Only one sex was tested but quinoline shows carcinogenicity in male and females.

Data source

Reference
Reference Type:
publication
Title:
Effects of quinoline and 8-hydroxyquinoline on mouse bone marrow erythrocytes as measured by the micronucleus assay.
Author:
Hamoud MA, Ong T, Petersen M, Nath J
Year:
1989
Bibliographic source:
Teratogenesis, carcinogenesis and mutagenesis 9: 111-118

Materials and methods

Test guideline
Qualifier:
no guideline followed
Principles of method if other than guideline:
No guideline available when the study was performed.
GLP compliance:
not specified
Type of assay:
micronucleus assay

Test material

Reference
Name:
Unnamed
Type:
Constituent
Details on test material:
Supplier Radian Corp (Austin).
No further information

Test animals

Species:
mouse
Strain:
CD-1
Sex:
male
Details on test animals and environmental conditions:
TEST ANIMALS
- Source: Charles River Breeding lab (USA)
- Age at study initiation: 6 to 8 weeks
- Weight at study initiation: no data
- Assigned to test groups randomly: no data
- Fasting period before study: no data
- Housing: 5 per cage, bedding consisted of hardwood chips and excelsior nesting material.
- Diet: Purina laboratory rodent chow, ad libitum
- Water : ad libitum
- Acclimation period: 5-7 days


ENVIRONMENTAL CONDITIONS
no data


IN-LIFE DATES: no data

Administration / exposure

Route of administration:
intraperitoneal
Vehicle:
- Vehicle(s)/solvent(s) used: corn oil
- Justification for choice of solvent/vehicle: no data
- Concentration of test material in vehicle: 2.5; 5 or 10 mg/mL
- Amount of vehicle : 10 mL/kg
- Lot/batch no. (if required): no data
- Purity: no data
Details on exposure:
Single injection by ip
Duration of treatment / exposure:
Single dose
Frequency of treatment:
Single dose
Post exposure period:
24, 48 or 72 h
Doses / concentrations
Remarks:
Doses / Concentrations:
25, 50 and 100 mg/kg
Basis:
nominal conc.
No. of animals per sex per dose:
15 animals per dose, only males
Control animals:
yes, concurrent vehicle
Positive control(s):
triethylenemelamine
- Justification for choice of positive control(s): no data
- Route of administration: ip
- Doses / concentrations: 0.5 mg/kg in phosphate buffered saline

Examinations

Tissues and cell types examined:
Bone marrow
Details of tissue and slide preparation:
CRITERIA FOR DOSE SELECTION:
Based on a SCE study


DETAILS OF SLIDE PREPARATION:
4 replicate slides were prepared for each animal.
Overnight air-dried smears were fixed for 15 min in absolute methanol and stained by using May-Gruenwald-Giemsa staining technique


METHOD OF ANALYSIS:
No data

Evaluation criteria:
2000 polychromatic erythrocytes (PCE) per animal were scored for the presence of micronuclei (MN).
As measurement of the toxic effect to erythropoietic tissue, the PCE normochromatic erythrocytes (NCE) ratios were calculated by scoring the number of NCE encountered during the screening of the first 1000 PCE.
A PCE (or NCE) with micronucleus, regardless of the number, was counted as one MPCE (or MNCE).
Statistics:
two-tailed Student's t-test to compare MPCE values between treated and control animals.
The Cochran-Armitage two-tailed trend test was used to determine the dose-response relationship.

Results and discussion

Test results
Sex:
male
Genotoxicity:
positive
Toxicity:
yes
Vehicle controls validity:
valid
Positive controls validity:
not specified
Additional information on results:
RESULTS OF RANGE-FINDING STUDY
No range finding, dosing based on a SCE study


Any other information on results incl. tables

Sampling time (h)

Dose (mg/kg)

MPCE / 1000 PCE +/- S.D.a

PCE/NCEb

24

0

3.0 +/- 0.3

0.82

25

4.7 +/- 0.5*

0.69

50

9.2 +/- 1.7**

0.61

100

12.5 +/- 1.7**

0.79

48

25

3.9 +/- 0.2

0.82

50

7.0 +/- 0.5**

1.08

100

8.3 +/- 0.5**

1.04

72

25

2.8 +/- 0.4

1.33

50

2.5 +/- 0.4

1.27

100

3.0 +/- 0.6

1.08

24c

0

2.4 +/- 0.3

0.85

25

4.9 +/- 0.4**

0.69

50

6.9 +/- 0.3**

0.72

100d

7.9 +/- 0.6**

0.75e

aTotal MPCE/10 000 PCE (2 000 PCE were scored for each of 5 animals)

bBased on 5 000 PCE

cResult from repeat experiment

dOnly 4 animals were analyzed

eBased on 4 000 PCE

* P< 0.05

** P < 0.01

Applicant's summary and conclusion

Conclusions:
Interpretation of results (migrated information): positive
Quinoline induced micronucleus in bone marrow cells of the mice treated by ip injection.
Executive summary:

An in vivo micronucleus test has been performed on mice, treated with quinoline at 25, 50 and 100 mg/kg by single ip injection. The animals were sacrificed at 24, 48 and 72 h after treatment and the bone marrow was sampled and analysed.

The experiment was repeated with the same concentrations but with a sampling at 24 h only.

In these conditions, quinoline induced micronucleus in the erythrocytes.