Silver - Toxicology of Metals - page 793

less than 2 weeks after inhalation, suggesting absorp-
tion of silver compounds deposited in the alveoli,
although clearance and partial absorption of the sil-
ver compounds by the gastrointestinal tract cannot be
excluded. Takenaka et al . (2001) found rapid clearance
of ultrafi ne silver particles from the lungs of rats, with
96% clearance in 7 days. The fate of inhaled silver nano-
particles has not been studied.

5.4 Biological Half-Time
After rabbits had inhaled 4-

m mass median
aerodynamic diameter (MMAD) monodispersed
silver-coated Tefl on particles, Camner et al . (1974)
found that an average of 30% of the particles depos-
ited were cleared from the lung in 1 day and another
30% during the rest of the fi rst week of the exposure.
After exposure by inhalation, dogs cleared 59% of an
administered dose of radioactive silver from the lungs
in 1.7 days (Phalen and Morrow, 1973). The liver had
a somewhat slower clearance. An apparent biological
half-time of approximately 1 day was found by whole-
body scintillation counting in mice, rats, monkeys, and
dogs after oral ingestion. This short half-time is partly
due to fecal elimination of unabsorbed silver (Furch-
ner et al ., 1968). Somewhat longer half-times were
observed for these species after intravenous injection
of silver, with monkeys and dogs having half-times
of 1.8 and 2.4 days, respectively. Silver injected into
rats as radioactive silver nitrate had a half-time of 2.2
days (Habighorst and Buchwald, 1971). Matuk (1983)
reported, for rats given a single intraperitoneal injec-
tion of radioactive silver nitrate, a 50% reduction in
radioactivity of whole blood, plasma, kidney, and
liver after approximately 40 hours. A 50% reduction
in the radioactivity content of spleen occurred after
approximately 70 hours, whereas that of brain took
approximately 84 hours. The biological half-time of
silver in the lungs of a human exposed to silver has
been estimated to be 1 day, whereas that in the liver
was 52 days (Newton and Holmes, 1966). In a carci-
noid patient, Polachek et al . (1960) estimated a half-
time of 48 days in the liver by external counting after
intravenous injection of radioactive silver. On post-
mortem examination, 195 days after injection, the
highest concentration of radioactive silver was found
in the liver and the second highest in the skin, indicat-
ing a relatively long half-time for the skin as well.

µ

5.1.2 Ingestion

The intestinal absorption of silver by mice, rats,
monkeys, and dogs has been recorded at approxi-
mately 10% or less after ingestion of radioactive silver
(Furchner et al ., 1968). A value of 18% was estimated
from studies in one single human subject (East et al .,
1980) given silver acetate.

5.2 Distribution
Dogs exposed to silver by inhalation accumulated most
of the administered dose in the liver, with lower concentra-
tions in the lung, brain, and muscle (Phalen and Morrow,
1973). Studies on rodents have also indicated a high initial
concentration of silver in the liver that decreases greatly
within 10 days, whereas silver concentrations in the
spleen and brain are retained for longer periods (Furch-
ner et al ., 1968; Gammill et al ., 1950). Other studies (Matuk,
1983; Oh et al ., 1981; Tanaka et al ., 1983) have shown that
approximately 60% of the silver in liver and kidneys of
silver-injected rats may be recovered in the cytosol frac-
tion bound to both high-molecular-weight proteins and
the metallothionein fractions. Only approximately 30% of
total tissue silver could be recovered in cytosol fractions of
rat spleen and forebrain (Matuk, 1983). In a human being
exposed to radioactive silver, >50% of the body burden of
silver was found in the liver 16 days and later after expo-
sure (Newton and Holmes, 1966).

5.3 Excretion
Mice, rats, monkeys, and dogs given radioactive
silver salts by oral, intravenous, or intraperitoneal
routes were found to excrete >90% of the absorbed
dose through the feces (Furchner et al ., 1968). The fecal
elimination is mainly explained by biliary excretion
(Scott and Hamilton, 1948). Fecal elimination has also
been found to be the primary excretory pathway after
exposure by inhalation to silver in dogs (Phalen and
Morrow, 1973) and in humans (Newton and Holmes,
1966). Alexander and Aaseth (1981) reported that rats
injected intravenously with radioactive silver nitrate
excreted silver in the bile mainly bound to a low-molec-
ular-weight complex that seemed to be glutathione.

6 LEVELS IN TISSUES AND BIOLOGICAL
FLUIDS—REFERENCE VALUES

The concentrations of silver in the kidneys, liver, and
spleen of “normal, healthy people” have been reported
by emission spectroscopy to be approximately 0.4, 0.7,
and 2.7 mg/kg, respectively, on a dry-weight basis
(Indraprasit et al ., 1974). Lower values (nd 0.05 [kid-
ney], nd 0.032 [liver] and nd 0.06 [lung] mg/kg wet
wt) have been reported by neutron activation analy-
ses by Brune et al . (1980). Normal concentration in
skin was reported as 0.035

0.015 mg/kg dry weight
by Schropl et al . (1968). Hamilton et al . (1972) reported

±