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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
Reliability:
2 (reliable with restrictions)

Data source

Reference
Reference Type:
publication
Title:
Unnamed
Year:
2005

Materials and methods

Test guideline
Qualifier:
no guideline followed
Principles of method if other than guideline:
Female Wistar rats were treated by gavage once per week for 10 weeks with cumulative doses of 140, 250, and 500 mg/kg lead acetate and genotoxicity was evaluated in erythrocytes from whole blood via the micronucleus test.
GLP compliance:
not specified
Type of assay:
other: micronucleus assay

Test material

Reference
Name:
Unnamed
Type:
Constituent
Specific details on test material used for the study:
Lead acetate trihydrate (CAS No. 301-04-2) was obtained from Riedel de Haen (Seelze, Germany).

Test animals

Species:
rat
Strain:
Wistar
Sex:
female
Details on test animals and environmental conditions:
TEST ANIMALS
- Source: Experimental Animal Center, University of Gaziantep, Turkey
- Age at study initiation: 6-8 weeks
- Weight at study initiation: 180-200 g
- Assigned to test groups randomly: yes
- Housing: polycarbonate boxes with steel wire tops and rice husk bedding, four rats per box
- Diet: ad libitum, pelleted feed
- Water: ad libitum, tap water
- Acclimation period: 14 days

ENVIRONMENTAL CONDITIONS
- Temperature (°C): 20-24
- Humidity (%): 50-70
- Photoperiod: 12 hours light/12 hours dark

Administration / exposure

Route of administration:
oral: gavage
Vehicle:
Saline
Details on exposure:
Rats were treated by oral gavage with 140, 250, or 500 mg/kg lead acetate dissolved in saline.
Duration of treatment / exposure:
70 days
Frequency of treatment:
Once per week
Doses / concentrations
Remarks:
140, 250, and 500 mg/kg
Basis: nominal conc.
No. of animals per sex per dose:
4 per dose
Control animals:
yes, concurrent vehicle
Positive control(s):
A single dose of mitomycin C (2 mg/kg) was administered intraperitoneally at the 10th week dosing time.

Examinations

Tissues and cell types examined:
Whole blood smears were collected on the day following the last lead acetate administration or one day after mitomycin C treatment.
Details of tissue and slide preparation:
Whole blood smears were prepared on clean microscope slides, air dried, fixed in methanol and stained with acridine orange (125 mg/ml in pH 6.8 phosphate buffer) for one minute just before the evaluation with a fluoresence microscope.
Evaluation criteria:
The frequency of polychromatic erythrocytes (PCEs) per total erythrocytes was determined using a sample size of 2000 erythrocytes per animal. The number of micronucleated PCEs was determined using 2000 PCEs per animal.
Statistics:
Data were compared by one-way variance analysis. Mulltiple comparisons were performed by least significant difference test. P < 0.05 was
considered to be the level of significance.

Results and discussion

Test results
Sex:
female
Genotoxicity:
positive
Toxicity:
yes
Vehicle controls validity:
valid
Negative controls validity:
not examined
Positive controls validity:
valid

Any other information on results incl. tables

Lead acetate induced a dose-related increase in micronuclei frequency, with all doses producing statistically significant increases in the frequency of micronucleated PNEs. Lead acetate also reduced the number of PCEs per total erythrocytes in the blood of treated animals. However, the doses of lead applied were of sufficient duration and intensity to induce anaemia in the test animals. Anaemia, whether induced by chemical or other (blood loss) means has been demonstrated to result in similar increases in micronuclei. It is not possible to determine if the positive finding is an effect of lead or an indirect nonspecific effect related to anaemia induction.

Applicant's summary and conclusion

Conclusions:
Interpretation of results (migrated information): positive
The authors concluded that lead acetate increased the frequency of micronucleated polychromatic erythrocytes and decreased the percentage of polychromatic erythrocytes in the blood of rats.
Executive summary:

Female Wistar rats were treated by gavage once per week for 10 weeks with cumulative doses of 140, 250, and 500 mg/kg lead acetate and genotoxicity was evaluated in erythrocytes from whole blood via the micronucleus test. Lead acetate induced a dose-related increase in micronuclei frequency, with all doses producing statistically significant increases in the frequency of micronucleated PNEs. Lead acetate also reduced the number of PCEs per total erythrocytes in the blood of treated animals.