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Toxicological information

Genetic toxicity: in vivo

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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:
Monkeys on a normal diet were given 0, 1.5, 6, or 15 mg lead acetate in drinking water six days per week. Monkeys on a low-calcium diet were given 6 mg lead acetate in the same manner. Chromosome analysis was conducted on cultured lymphocytes from each monkey after 3, 10, and 16 months of treatment.
GLP compliance:
not specified
Type of assay:
other: Mammalian chromosome aberration assay

Test material

Reference
Name:
Unnamed
Type:
Constituent

Test animals

Species:
monkey
Strain:
other: Macaca irus
Sex:
male
Details on test animals and environmental conditions:
TEST ANIMALS
- Age at study initiation: young (age not specified).
- Weight at study initiation: 2.8 kg
- Diet: ad libitum, normal or low-calcium diet.
- Water: ad libitum during the day; no water supplied at night.
- Acclimation period: 2 months.

ENVIRONMENTAL CONDITIONS
- not reported

Administration / exposure

Route of administration:
oral: drinking water
Details on exposure:
Monkeys received treatment in the morning in the first 20 mL of drinking water. There were two dose groups for the 6 mg/day dose: one group on a normal diet and one group on a low-calcium diet.
Duration of treatment / exposure:
16 months.
Frequency of treatment:
6 days/week.
Doses / concentrations
Remarks:
0, 1.5, 6, 15 mg/day
Basis: nominal conc.
No. of animals per sex per dose:
2 males per dose group.
Control animals:
yes, concurrent vehicle
Positive control(s):
None.

Examinations

Tissues and cell types examined:
Blood was collected from the femoral vein after 3, 10, and 16 months and lymphocytes were cultured.
Details of tissue and slide preparation:
Blood samples were collected from the femoral vein after 3, 10, and 16 months of exposure and lymphocytes were cultured in Ham's F-10 medium and prepared according to Deknudt et al. (1973).
Evaluation criteria:
From each culture, 100 metaphases (200 total from each monkey) were analyzed for numerical and structural chromosomal aberrations.
Statistics:
Chi-square test.

Results and discussion

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

Any other information on results incl. tables

One monkey in each of the 1.5 and 15 mg groups and both monkeys in the 6 mg group died between 10 and 16 months. Lead treatment at all doses increased the incidence of slight aberrations (i.e., gaps and fragments) regardless of diet and the frequency increased with time. Severe aberrations (exchanges, translocations, rings, and dicentrics) were increased only in the low-calcium diet group compared to controls as well as to animals receiving the same dose of lead on a normal diet, but no influence of treatment length was observed.

Applicant's summary and conclusion

Conclusions:
Interpretation of results (migrated information): positive
The authors concluded that lead increased the frequency of chromosomal aberrations over time, with the most severe effects occurring in animals on a low-calcium diet.
Executive summary:

Monkeys on a normal diet were given 0, 1.5, 6, or 15 mg lead acetate in drinking water six days per week. Monkeys on a low-calcium diet were given 6 mg lead acetate in the same manner. Chromosome analysis was conducted on cultured lymphocytes from each monkey after 3, 10, and 16 months of treatment. One monkey in each of the 1.5 and 15 mg groups and both monkeys in the 6 mg group died between 10 and 16 months. Lead treatment at all doses increased the incidence of slight aberrations (i.e., gaps and fragments) regardless of diet and the frequency increased with time. Severe aberrations (exchanges, translocations, rings, and dicentrics) were increased only in the low-calcium diet group compared to controls as well as to animals receiving the same dose of lead on a normal diet, but no influence of treatment length was observed.