Lead 2,4,6-trinitro-m-phenylene dioxide

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:

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:

micronucleus assay

Test material

Test material information

Constituent 1

Reference substance name:

Lead acetate trihydrate

IUPAC Name:

Lead acetate trihydrate

Details on test material:

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 or test system 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:

Doses / Concentrations:
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.