Nickel - Toxicology of Metals - page 731

in mice did not protect these animals against nickel-
induced tumors (Waalkes et al ., 2004).

cant associations between Ni levels in whole blood
and plasma before and after work were found. Com-
pared with other welding methods such as manual
metal arc (MMA) welding (Stridsklev et al ., 1993)
and tungsten inert gas welding (TIG) (Stridsklev
et al ., 1994), the levels of nickel in biological fl uids
were the same or slightly higher for the FCW weld-
ers than for the MMA welders and were lower for
the FCW welders than TIG welders. When measur-
ing blood, plasma, and serum levels of nickel, inves-
tigators must consider the use of nonstainless steel
needles because of the potential for unintended Ni
contamination of the samples.
The lungs have been found to contain the high-
est concentration of retained nickel in humans with
no known occupational exposure. Reported levels of
nickel in the lungs of autopsied U. S. subjects ranged
from 1.8-2.1

5.5 Biological Half-Time
In animals, the biological half-time for nickel clear-
ance is on the order of 2-3 days (Onkelinx et al ., 1973).
In human studies that examined the absorption and
retention of nickel added to drinking water, peak nickel
concentrations in serum were found 1 hour after intake
of nickel in drinking water, and median urinary nickel
excretion half-times varied between 19.9 and 26.7 hours
(Nielsen et al ., 1999). This correlates well with previous
reports of the biological half-time of nickel in human
plasma and urine of approximately 20-34 hours and
17-39 hours, respectively (Tossavainen et al ., 1980).
Compared with the relatively effi cient systemic clear-
ance of soluble nickel salts, lung clearance of insoluble
nickel particles such as nickel oxide can take several
months.

g/cm 2 of lung surface area (Edelman
and Roggli, 1989). The pulmonary burden of nickel
has been shown to increase with age (Kollmeier et al .,
1987). Nickel measurements in smokers' blood ranges
from 0.01-0.42

µ

g Ni/L, not much higher than in the
nonsmokers' blood (0.01-0.26

µ

g Ni/L), whereas nickel
in the urine of smokers (<0.01-8.20

µ

6 BIOLOGICAL MONITORING

g/L, median) is
signifi cantly higher than in nonsmokers (<0.01-4.60

µ

µ g

6.1 Levels in Human Tissues and Fluids
Both serum and urinary nickel measurements can
be useful monitors of environmental or occupational
exposures. Normal levels of nickel in unexposed
adults are reported to be in the range of 0.05-0.1

Ni/L) (Stojanovic et al ., 2004).
In a study of nickel-allergic individuals with hand
eczema compared with healthy controls, both groups
had similar levels of urinary nickel, whereas nickel lev-
els in serum were signifi cantly lower in nickel-allergic
individuals than controls, perhaps related to the lower
dietary intake of nickel-rich foods by the sensitive
individuals (Christensen et al ., 1999).

g
Ni/L serum and 0.5-4.0 mg/g creatinine in urine
(WHO, 1991). In a study of Finnish factory work-
ers (Kiilunen et al ., 1997), after-shift urinary concen-
trations of nickel were 0.1-2

µ

mol/L and were still
elevated after a 2-4 week vacation. However, con-
centrations of nickel in urine in this study showed no
correlation with nickel concentrations in the air. In a
Norwegian study of potential nickel exposure from
nearby Russian refi neries, nickel levels in urine of
residents living near the refi neries were signifi cantly
lower than for urban residents living away from the
refi neries in areas of high vehicular traffi c (Smith-
Sivertsen et al ., 1997). In fl ux-core-wire (FCW) stain-
less steel welders exposed to workplace air levels of
nickel of 50.4

µ

6.2 Biomarkers of Exposure
To date, there are still no good, well-validated
biomarkers for Ni exposure or nickel effects besides
direct measures of nickel in serum or urine, although
attempts have been made to identify informative
biomarkers. In a Finnish nickel worker study, the fre-
quency of micronucleated epithelial cells in the buc-
cal mucosa was not signifi cantly elevated, nor was
any relationship observed between micronucleus
frequencies and levels of nickel in air, urine, or blood
(Kiilunen et al ., 1997). However, in a recent study of
dental workers exposed to airborne dusts of metal
alloys (up to 30% Ni) during the production of dental
appliances such as crowns and bridges, nickel levels
in urine were found to be measurable at 7.65 ± 2.5

g/m 3 ),
whole blood and plasma levels were found to be low
at 0.84

µ g/m 3 (ranging from <2-416.7 µ

µ g Ni/L and 0.57 µ g Ni/L, and urine levels

were also very low at 2.5 g/g creatinine (Stridsk-

lev et al ., 2004). These values were all near the cur-
rent detection limit ranges for Ni in whole blood
(0.48-1.5

µ

g/g
creatinine, with signifi cant correlation between dura-
tion of exposure and micronucleus frequencies in lym-
phocytes ( r = 0.642, P < 0.01), but not in nasal cells of
technicians (Burgaz et al ., 2002).

µ

µ g Ni/L whole blood), plasma (0.3-0.9 µ g

Ni/L), and urine (0.3 g/g creatinine). Although

there were no associations between the Ni levels in
air and in the biological fl uids; statistically signifi -

µ