Air Quality Criteria for Lead Volume II of II - (NEPIS)(EPA) - US ...

AX5-82
Table AX5-6.4 (cont’d). Genotoxic/Carcinogenic Effects of Lead—Genotoxicity Laboratory Animal Studies.
Compound Dose and Duration Species Co-exposure Effects Reference
Pb nitrate 100–200 mg/kg given i.v.
on 9th day of gestation
onwards for 9 days.
Mothers and fetuses
analyzed on G18.
Group size not given.
Resorptions, fetal viability
and chromosome damage,
SCE and NOR in the
mother and fetus were
examined. Mother–bone
marrow; fetus liver or lung
3 mothers and fetuses per
dose were analyzed.
Pb nitrate 10, 20, or 40 mg/kg given
i.p. 24 h
6 animals per group.
Chromosome damage and
Mitotic Index in bone
marrow
Pb nitrate 5, 10, or 20 mg/kg given
i.p. 24 h
6 animals per group.
Chromosome damage in
bone marrow.
50 metaphases per animal
for a total of 300 (X6).
ICR Swiss Webster Mice,
6–8 wk old
Swiss Albino Mice,
8 wks old
Swiss Albino Mice,
8 wks old
None Pb levels were found in both mother and fetus indicating no
problems crossing the placenta.
All doses indicated increased resorption and decreased
placental weights. No effects on fetal weight.
Significant increase in SCE in mothers at 150 and 200 mg/kg.
No increase in SCE in fetuses.
Significant decrease in NOR in both mother and fetuses.
No gaps or breaks in mothers or fetuses.
Some weak aneuploidy at lowest dose.
Some karyotypic chromosome damage was seen.
No explanation of how many cells analyzed per animal
(3 animals per dose were analyzed) as only 20– 40 cells were
analyzed.
There was no dose response and no statistical analyses for
chromosome damage. No details on how many animals
analyzed for metaphase damage or how many cells per
animal.
Data interpretation is also complicated as too few metaphases
were analyzed 10–25 for SCE. Not given for CA.
No detail on potential maternal toxicity.
Phyllanthus fruit extract
(685 mg/kg) or ascorbic
acid (16.66 mg/kg)
given by gavage for
7 days
Ferric chloride
(18 mg/kg) given i.p.
for 24 h administered
1 h before, 1 h after, or
together with Pb nitrate
Pb nitrate increased the amount of chromosome damage at
each dose. But there was no dose response and a similar
level of damage was seen for each dose.
Phyllanthus fruit extract reduced the amount of damage at
each dose. Ascorbic acid reduced the damage at the lowest
dose but increased it at the higher doses.
Higher concentrations of Pb nitrate reduced the mitotic index.
This effect was reversed by ascorbate and Phyllanthus only at
the moderate dose.
Pb nitrate increased the amount of chromosome damage in a
dose-dependent manner.
Iron exhibited some modifications of Pb induced damage:
If administered 1 h before Pb plus simultaneously it reduced
the damage. If administered with Pb only at same time it
reduced damage in the lower doses. If Pb was started 1 h
before iron there was no effect.
Thus iron may antagonize Pb perhaps by blocking uptake.
Nayak et al. (1989b)
Dhir et al. (1990)
Dhir et al. (1992a)