Trilead dioxide phosphonate

Genetic toxicity: in vivo

Administrative data

Endpoint:

in vivo mammalian germ cell study: cytogenicity / chromosome aberration

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:

1977

Materials and methods

Test guideline

Qualifier:

no guideline followed

Principles of method if other than guideline:

Female mice (10 per group) were fed diets containing 0, 0.25, 0.5, or 1% lead acetate for one month, and another group of 5 mice received 0.25% lead acetate for three months. Bone marrow was collected and examined for chromosome or chromatid aberrations. Additional female mice (n=10) received two intraperitoneal injections of 25 mg/kg lead at 24-hour intervals and were sacrificed 30 hours after the second injection for the micronucleus test. The micronucleus test was also performed on mice that received 0.25% lead in the diet for one month.

GLP compliance:

not specified

Type of assay:

other: chromosome aberration assay; micronucleus assay

Test material

Reference

Name:

Unnamed

Type:

Constituent

Test animals

Species:

mouse

Strain:

C57BL

Sex:

female

Details on test animals and environmental conditions:

TEST ANIMALS
- Age at study initiation: 8 weeks.
- No other details reported.

Administration / exposure

Route of administration:

oral: feed

Vehicle:

Not reported.

Details on exposure:

Lead acetate was provided in the diet at 0, 0.25, 0.5, or 1%.
The micronucleus test used two intraperitoneal injections of 25 mg/kg lead in 0.1 mL water.

Duration of treatment / exposure:

Diet: one month (an additional group received 0.25% lead in the diet for three months).
Micronucleus test: two injections at 24-hour intervals.

Frequency of treatment:

Diet: animals ate lead-containing food ad libitum.

Post exposure period:

30 hours for the injection studies.

Doses / concentrations

Remarks:

0, 0.25, 0.5, or 1% lead acetate
Basis: nominal in diet

No. of animals per sex per dose:

10 females per group.

Control animals:

yes, concurrent no treatment

Positive control(s):

Micronucleus test: Myleran, 50 mg/kg in 0.01 mL dimethyl sulfoxide, or Mitomycine C, 5 mg/kg in 0.1 mL water.

Examinations

Tissues and cell types examined:

Bone marrow

Details of tissue and slide preparation:

Diet: bone marrow was exposed to hypotonic treatment (sodium citrate), fixed in methanol:acetic acid (3:1), spread on defatted slides, and stained with toluidine blue.
Micronucleus test: bone marrow was centrifuged with fetal calf serum and sedimented cells were spread on a slide. Slides were air-dried and stained by the May-Grunwald-Giemsa method.

Evaluation criteria:

Diet: 100 metaphases per mouse were examined for chromatid or chromosome aberrations.
Micronucleus test: 1,000 polychromatic erythrocytes per mouse were examined for the presence of micronuclei.

Statistics:

Chi-square test.

Results and discussion

Test results

Sex:

female

Genotoxicity:

ambiguous

Toxicity:

not examined

Vehicle controls validity:

not examined

Negative controls validity:

valid

Positive controls validity:

valid

Any other information on results incl. tables

The number of chromatid or chromosome aberrations did not increase with lead treatment except for chromatid gaps at 0.5 or 1% lead acetate. No change in the frequency of micronuclei was observed in mice treated with lead in the diet or by intraperitoneal injection.

Applicant's summary and conclusion

Conclusions:

Interpretation of results (migrated information): ambiguous
The authors suggest that lead appears to have no genetic action, except for the increase in chromatid gaps, which, in their opinion, does not have any genetic consequence.

Executive summary:

Female mice (10 per group) were fed diets containing 0, 0.25, 0.5, or 1% lead acetate for one month, and another group of 5 mice received 0.25% lead acetate for three months. Bone marrow was collected and examined for chromosome or chromatid aberrations. Additional female mice (n=10) received two intraperitoneal injections of 25 mg/kg lead at 24-hour intervals and were sacrificed 30 hours after the second injection for the micronucleus test. The micronucleus test was also performed on mice that received 0.25% lead in the diet for one month. The number of chromatid or chromosome aberrations did not increase with lead treatment except for chromatid gaps at 0.5 or 1% lead acetate. No change in the frequency of micronuclei was observed in mice treated with lead in the diet or by intraperitoneal injection. The authors suggest that lead appears to have no genetic action, except for the increase in chromatid gaps, which, in their opinion, does not have any genetic consequence.