C H A P T E R
49
Palladium
TOMOHIRO UMEMURA, KAZUHIRO SATO, YUKINORI KUSAKA, AND HIROSHI SATOH
ABSTRACT
Palladium is one of the six platinum group met-
als and possesses strong catalytic activity. Demand
for palladium is high owing to its uses in electrical
equipment, dental materials, and automobile cata-
lysts. Environmental levels of palladium in water,
soil, and ambient air are not high, and environmen-
tal exposure and intake from food are not significant;
however, palladium concentrations are increasing in
the general environment because of its increased use
in automobile catalysts. Workers in palladium mines
and refineries may be exposed to palladium, as are
dental personnel during the processing of dental
alloys containing palladium. The general popula-
tion may be exposed to palladium through inhala-
tion of ambient respirable particles from automobile
catalytic converters that incorporate palladium, but
relevant data are rare. The oral toxicity of palladium
is believed to be low, although it does depend on
the water solubility of the palladium compounds.
Therefore, similar intravenous median lethal dose
values have been reported for several palladium
compounds: from 3 to 6.4 mg/kg body weight. From
a 28-day toxicity study of tetraammine palladium
hydrogen carbonate in rats performed through
gavage, the no observed adverse effect level was
1.5 mg/kg body weight/day. Among the general
population, skin exposure may occur through con-
tact with jewelry containing palladium. Many case
reports describe palladium sensitivity and recov-
ery after the removal of dental restorations. Symp-
toms that have been observed include swelling of
the lips and cheeks, stomatitis, oral lichen planus,
Handbook on the Toxicology of Metals 4E
http://dx.doi.org/10.1016/B978-0-444-59453-2.00049-4
itching, dizziness, asthma, and chronic urticaria.
Recently, 103Pd has been used for radioactive sources
implanted directly into malignant tumors; no pal-
ladium-related complications have been reported.
Although respiratory sensitization effects, such as
bronchial asthma, can occur among workers exposed
to palladium and its compounds, its incidence is
extremely low. On the other hand, its contact sensi-
tivity rate has recently increased. No data are avail-
able on its carcinogenicity, reproductive toxicity, or
other effects in humans.
1  PHYSICAL AND CHEMICAL PROPERTIES
Palladium (Pd); atomic number: 46; Chemical
Abstracts Service (CAS) No. 7440-05-3; relative atomic
mass 106.42 [abundances of major natural isotopes are
104Pd (11.14%), 105Pd (22.33%), 106Pd (27.33%), 108Pd
(26.46%), and 110Pd (11.72%)]; density at 20°C, 12.02 g/
cm3; melting point, 1554°C; boiling point, 2963°C; sil-
ver-white metal, oxidation states, +2, +4.
Palladium was discovered by William Wollaston in
1803 and named after the asteroid Pallas, which had
been discovered about the same time (Hammond,
1990). Palladium belongs to group 10 of the periodic
table of the elements and is one of the six platinum
group metals (the others being Pt, Rh, Ru, Ir, and Os).
These metals commonly occur together in nature. Pal-
ladium, as well as Pt and sometimes Ir, is considered to
be a precious and noble metal. Palladium is stable and
does not tarnish in air at room temperature. The crystal
structure is face-centered cubic. It has a strong catalytic
activity for hydrogenation and oxidation reactions.
1113 Copyright © 2015 Elsevier B.V. All rights reserved.
1114 Tomohiro Umemura, Kazuhiro Sato, Yukinori Kusaka and Hiroshi Satoh
Under an oxygen atmosphere, palladium powder may
be a fire hazard.
2  METHODS AND PROBLEMS
OF ANALYSIS
Current measurement techniques do not allow the
separate chemical species of palladium to be differen-
tiated when more than one form is present. Almost all
measurements of palladium determine the total palla-
dium content.
A solution of palladium(II) nitrate at high concen-
tration (mg/L range) is frequently used as a chemical
modifier in graphite furnace atomic absorption spec-
trometry (GFAAS) (Schlemmer and Welz, 1986; Taylor
et al., 1998). Therefore, to avoid contamination, care
must be taken in analytical laboratories that use pal-
ladium as a chemical modifier.
For biological materials such as blood and urine,
atomic absorption spectrometry (AAS) and induc-
tively coupled plasma mass spectrometry (ICP-MS)
are often applied. Using quadrupole ICP-MS, Sch-
ramel et al. (1997) reported a detection limit for pal-
ladium of 0.03 μg/L of urine after acidification with
nitric acid. When using flameless AAS, decomposi-
tion with nitric acid gives much lower detection lim-
its: 0.003 μg/L urine and 0.01 μg/g blood (Jones, 1976).
More recently, Begerow et al. (1997a,b) reported a limit
of 0.2 ng/L for whole blood and urine upon cleaning
of all materials [ultraviolet (UV) photolysis], result-
ing in a drastic reduction of blanks, when using sec-
tor field ICP-MS. When applying high performance
liquid chromatography, a detection limit of 10 ng/L
for urine was reported after UV photolysis (Philippeit
and Angerer, 2001).
For particulate matter in ambient air, X-ray fluo-
rescence analysis has been performed, with detection
limits of 1 ng/m3 (Lu et al., 1994) or 0.5 ng/m3 (Gertler,
1994). For the analysis of water, AAS and ICP-MS are
often applied, with their limits of detection differing
depending on the pretreatment procedure.
Palladium is rarely found in significant concen-
trations in environmental and biological materials.
Materials being investigated for very low levels
of palladium must therefore be sampled in large
amounts, and homogenization, digestion, storage,
and matrix effects consequently become major prob-
lems. For biological materials, destructive methods
are often required during the analytical procedures.
For example, samples may be ashed to destroy
organic materials and then treated with strong acids,
causing information about the palladium species to
be lost.
3  PRODUCTION AND USES
3.1 Production
Russia, the Republic of South Africa, , the USA,
Zimbabwe, and Canada are the five primary produc-
ers of palladium. Production in Zimbabwe has been
increased around since 2006 (USGS, 2008). The mine
productions were 84.7, 82.2, 11.6, 7, and 6.7 tons,
respectively, for the countries listed above, and the
total mine production including other countries was
202 tons in 2010 (USGS, 2012). Because the production
of palladium is relatively limited to a few production
sites and the demand is increasing, supply shortages
or surpluses can cause substantial fluctuations in the
market price. In 2000 and early 2001, the price rose and
peaked at about five times the market price of 1995.
After that, the price showed a downward tendency.
However, the price bottomed out and has started to
rise again in recent years (USGS, 2000, 2008, 2012).
As demand for palladium has increased, the recy-
cling of palladium has risen. Recycled palladium
in 2011 was 68.3 tons, an increase of 19% from 2010
(­Johnson Matthey, 2011).
3.2 Uses
Demand for palladium is high for its use in electrical
equipment, dental materials, and automobile catalysts.
Palladium metal and silver-palladium powder
pastes are important in the production of many elec-
tronic components. The pastes are used in active com-
ponents such as diodes, transistors, integrated circuits,
hybrid circuits, and semiconductor memories. They are
also used for passive electronic components, such as
small multilayer ceramic capacitors, and for thick film
resistors and conductors. Palladium alloys are used in
electrical contacts, electrical relays, and switching sys-
tems in telecommunications devices. The gold in the
coatings of electronics, electrical connectors, and lead
frames of semiconductors can sometimes be replaced
with palladium (Kroschwitz, 1996).
Palladium is a component in some dental amalgams.
Palladium alloys (gold-silver-copper-palladium) can
be matched to any dental application such as inlays,
full-cast crowns, long-span bridges, ceramic metal sys-
tems, and removable partial dentures (Stümke, 1992).
Catalysts are used to reduce the levels of nitrogen
oxides, carbon monoxide, and hydrocarbons in auto-
mobile exhausts. Recently developed catalysts employ
combinations of precious metals, such as platinum, pal-
ladium, and rhodium (Abthoff et al., 1994; Degussa, 1995;
Kroschwitz, 1996). Concentrations of the precious metals
in the catalysts vary depending upon the specifications
 49 Palladium
of the manufacturer (IPCS, 1991). Worldwide demand
for palladium in automobile catalysts rose from 23.5
tons in 1993 to 139 tons in 1998. Around 60% of Euro-
pean gasoline-powered cars sold in 1997 were equipped
with palladium-based catalysts; many Japanese cars are
also equipped with palladium systems, but platinum-
rich technology remains dominant elsewhere in Asia
(Cowley, 1997). North American carmakers continue to
use platinum-rich catalysts, but there has been increas-
ing use of palladium catalysts to meet the hydrocarbon
limits imposed by low-emission-vehicle legislation.
Palladium is used in jewelry and coinage. In the
fabrication of jewelry in Japan, palladium is a subsid-
iary alloying component of the platinum alloys used
(Coombes, 1990). From recent case reports (Bircher
and Stern, 2001; Suhonen and Kanerva, 2001) the so-
called “titanium” spectacle frames that actually consist
of palladium can cause contact allergies. Alloys are
also used for bearings, springs, and balance wheels in
watches and for mirrors in astronomical instruments.
Because palladium has a strong catalytic activity
for hydrogenation, dehydrogenation, oxidation, and
hydrogenolysis reactions, palladium compounds are
used as catalysts for chemical processes in many indus-
tries. Palladium also catalyzes cross-coupling reactions
(Heck and Nolley, 1972; King et al., 1977; MIyaura et al.,
1979); this discovery was considered a great achieve-
ment, and these authors were awarded the Nobel Prize
in Chemistry in 2010 for their work on palladium catal-
ysis of cross-coupling in organic synthesis.
The following list summarized the uses of some
important palladium compounds (IPCS, 2002a):
  
1. Ammine complexes of palladium: industrial
separation of palladium, electroless plating,
and bright palladium plating. Ammonium
hexachloropalladate(IV) is important in separa-
tion technology.
2. Palladium(II) acetate: preparative chemistry.
3. Palladium(II) chloride: plating baths, photog-
raphy, toning solutions, electroplating parts of
clocks and watches, detecting carbon monoxide
leaks in buried gas pipes, manufacture of indelible
ink, the preparation of catalysts, and medical use.
4. Palladium(II) nitrate: a catalyst in organic syn-
theses, and for the separation of chlorine and
iodine.
5. Palladium(II) oxide: a hydrogenation catalyst in
the synthesis of organic compounds.
6. Hydrogen tetrachloropalladate(II): palladium
preparation.
7. Tetraammine palladium hydrogen carbonate:
an intermediate in the production of automo-
bile catalysts.
1115
3.3  Anticancer Drug
Cisplatin [Pt(NH3)2(Cl)2] is a platinum complex and
a major anticancer drug, but it has a few problems such
as nephrotoxicity and drug resistance. As palladium is
a congener of platinum, its character is similar to that of
platinum. Thus, palladium complexes are expected to
provide alternatives to cisplatin. Various types of pal-
ladium complexes have been synthesized and studied
in terms of their synthesis, antitumor effect, side effect,
drug tolerance, and so on. For example, Yano et al. (2012)
synthesized palladium(II) complexes with sugar-conju-
gated bipyridine-type triazole ligands and indicated
that those complexes had in vitro cytotoxicity against
human cervix tumor cells (HeLa), although weaker than
that of cisplatin. Tanaka et al. (2013) also synthesized a
glycoconjugated palladium(II) complex, which showed
significant antitumor effects in cisplatin-resistant gas-
tric cancer both in vitro and in vivo compared to cispla-
tin and other platinum complex. Matesanz et al. (2011)
reported that bis(thiosemicarbazone) palladium(II)
complexes had antiproliferative activity in vitro against
epithelial ovarian cancer cell lines and very low toxicity
in kidney cells.
4  ENVIRONMENTAL LEVELS
AND EXPOSURES
4.1  Water, Soil, and Ambient Air
Water samples collected from streams and ponds
in and around the mining and ore-processing facili-
ties located in Sudbury, Ontario (Canada), were below
the detection limit of 15 ng Pd/L (Johnson et al., 1976).
Although detection limits vary, concentrations of pal-
ladium in the ng/L range in natural waters have been
reported; 0.4 ± 0.1 ng Pd/L in Idaho, USA (Shah and
Wai, 1985); 1.0  ± 0.1 
ng/L (Schwarzbach river) and
0.4 ± 0.1 ng/L (River Rhine) in Germany (Eller et al.,
1989); and 1-2 ng/L in the lakes of Canada (Hall and
Pelchat, 1993).
For spring water samples, the values are somewhat
or considerably higher: 3 ng/L in water samples from
springs in Nevada, USA (Stetzenbach et al., 1994);
22 ng/L in Osaka, Japan (Chikuma et al., 1991); and
0.1 μg/L in the People’s Republic of China (Zhou and
Liu, 1997).
Palladium concentrations in rain collected in Stutt-
gart, Germany, were at levels below the detection limit
of 5 ng/L (Helmers et al., 1998).
In seawater, palladium concentrations of 22 pg/L
(depth < 10 m) and 60 pg/L (depth 3000 m) were found
in filtered samples of Pacific Ocean water (Goldberg,
1987). The palladium concentration in the water
1116 Tomohiro Umemura, Kazuhiro Sato, Yukinori Kusaka and Hiroshi Satoh
column of the northeast Pacific Ocean increased from
19 pg/kg at the surface to 70 pg/kg in deep waters
(Lee, 1983).
It has been reported that the palladium concentra-
tion in the soil of an area with high traffic density in
California, USA, was below the detection limit (0.7 μg/
kg) of the AAS used (Johnson et al., 1976). There have
been two reports concerning the increased palladium
concentrations along the autobahn near Frankfurt,
Germany. Samples taken in 1990 and 1991 gave a mean
value of 2 μg Pd/kg (Zereini et al., 1993) and samples
taken in 1994 gave a mean value of 6 μg Pd/kg (Zereini
et al., 1997). It was suggested that the elevated level
was due to the increased use of catalytic converters in
automobiles.
However, it is suggested that the level has been ele-
vated due to the increased use of catalytic converters in
automobiles. For instance, the tendency is particularly
rapid and noticeable in Beijing, China. The number
of vehicles has increased dramatically, from 1 million
(1997) to 4 million (2009) in Beijing. Accordingly, the
average concentration of palladium in the roadside
dust of Beijing has increased, from 36.5 μg/kg (2002) to
112.6 μg/kg (2010) (Gao et al., 2012). On the other hand,
the palladium concentration of tunnel dust in Munich,
Germany, has also increased considerably within the
last 13 years, from 18 μg/kg (in 1994) to 389 μg/kg (in
2007) (Leopold et al., 2008).
Actually, demand for palladium as an automobile
catalyst has been steadily increasing: 56 tons in 1995,
120 tons in 2005, 174 tons in 2010, and 206 tons in 2012
(Johnson Matthey, 2002, 2010, 2012, 2013). Moreover,
global exhaust emission regulations have become
stricter in recent years. EURO 6, a considerably strict
regulation concerning exhaust emission in Europe,
was introduced in 2014. Considering these circum-
stances, the demand is bound to increase more than
ever before.
Data on palladium concentrations in the surface soil
near a palladium production site are extremely scarce.
The palladium concentration in an area around a plati-
num group metal mine (Sudbury, Ontario, Canada)
was determined to be 2.0-4.5 μg/kg (Johnson et al.,
1976).
Although data on palladium concentrations in the
atmosphere are limited, the values are quite variable.
Before the introduction of automobile catalytic con-
verters, palladium concentrations in an area in Cali-
fornia (USA) were reported to be below the detection
limit (0.06 pg Pd/m3) in spite of the high traffic den-
sity (Johnson et al., 1976). In the 1990s, palladium con-
centrations in aerosols were determined in different
places. In Imperial County, California, the level of par-
ticulate matter having an aerodynamic diameter below
10 μm (PM10) was 52.2 μg/m3, with an average palla-
dium concentration of below 1 pg/m3 (Lu et al., 1994).
At Caesarea, Israel, Gertler (1994) observed an average
PM2.5 concentration of 25.5 μg/m3, with an average
palladium concentration of 3.3 pg/m3. In contrast, in
the city of Chernivtsi, Ukraine, the levels of particulate
matter and palladium were 144 μg/m3 and 56.6 ng/m3,
respectively (Scheff et al., 1997).
The levels of platinum group metals have been
determined in ancient and recent samples of ice and
snow in Greenland. The concentrations of these metals
in snow from the mid-1990s are 40-120 times higher
than those in ice from 7000 years ago (Barbante et al.,
2001). This finding is considered to be due to air pollu-
tion caused by automobile catalysts.
4.2  Food and Daily Intake
In 1994, the United Kingdom’s Ministry of Agricul-
ture, Fisheries, and Food conducted a total diet study
(MAFF, 1997; 1998; Ysart et al., 1999) in which they used
ICP-MS to determine the levels of 30 elements (includ-
ing palladium) in foods. Milk and poultry contained
palladium concentrations below the limit of detection
(0.3 μg/kg). Fish, offal, and bread contained 2 μg/kg,
and nuts contained 3 μg/kg. Other groups—including
miscellaneous cereals, carcass meat, meat products,
oils and fats, eggs, sugars and preserves, green veg-
etables, potatoes, other vegetables, canned vegetables,
fresh fruit, fruit products, beverages, and dairy pro-
duce—had mean values of 0.4-0.9 μg Pd/kg. Applying
the dietary intake estimates based on the United King-
dom National Food Survey to the mean concentration
for each food group provides an estimate of the daily
palladium intake: a mean of 1 μg Pd/day with a 97.7th
percentile of 2 μg/day. Other data on the palladium
contents of food and drinking water are scarce.
4.3  Working Environment
Workers involved in mining, processing, recycling,
refining, and catalyst manufacture are thought to be
exposed to palladium and/or its compounds. Dental
personnel are also exposed to palladium during the
processing of dental alloys containing palladium.
Air samples collected in and around the mining
and ore-processing facilities in Sudbury, Ontario, did
not display measurable levels of palladium (detec-
tion limit 0.003 μg Pd/m3), except in the precious met-
als area, where the value was as high as 0.29 μg Pd/
m3 (Johnson et al., 1976). In a platinum and palladium
refinery in New Jersey, USA, air samples were reported
to contain palladium at concentrations between 0.001
and 0.36 μg/m3 (Johnson et al., 1976).
 49 Palladium
Average palladium concentrations of 3.5-5.5 μg/m3
were reported in the breathing zone of dental techni-
cians (Purt, 1991). Palladium contributed to approxi-
mately one-third of the dust concentrations.
The urinary excretion of platinum, palladium, and
gold was analyzed in 27 dental technicians and 17 road
construction workers, with 17 adolescents as controls
(Begerow et al., 1999). The average urinary palladium
concentration in dental technicians (135.4 ± 183.5 ng/L)
was significantly higher than that in the control group
(31.0 ± 
10.8 ng/L); and road construction workers
exhibited a level of 52.2 ± 35.3 ng/L. Although these
results indicate that the processing of palladium-con-
taining alloys leads to occupational exposure, it is note-
worthy that the dental technicians were exposed to a
significantly larger number (246) of materials contain-
ing metals compared to the other study groups (18 for
construction workers; 14 for controls). More recently,
however, no appreciable increases in palladium and
other metals, such as titanium, mercury, platinum,
and rhodium, were found in dental health-care work-
ers (Iavicoli et al. 2004). There was a tendency toward
higher palladium levels in road construction workers
than in the reference group. Although it was not sig-
nificant, higher concentration of palladium in roadside
areas may cause this difference.
4.4  Iatrogenic Exposure
A large number of palladium-containing dental
alloys have been used. Many researchers have claimed
that palladium is released from materials containing
palladium alloy. The release rate of an alloy (Au52,
Ni28, Ga13, Pd4, In4; atomic percentages) was calcu-
lated to be 3 ng Pd/cm2/day (Wataha et al., 1991, 1995),
reaching a concentration of c. 30 μg/L after a few days
in a cell culture medium. This release rate is, however,
much lower than those of either gallium (0.97 μg Ga/
cm2/day) or nickel (1.46 μg Ni/cm2/day).
Palladium-based dental alloys containing copper or
copper and tin released more palladium in the artificial
saliva (0.2-6 and 6-22.5 μg Pd/cm2/day, respectively)
(Pfeiffer and Schwickerath, 1995).
The palladium content in saliva was higher in the
group of persons with amalgam (mercury and silver)
fillings (2.8 ± 2.7 μg/L) and significantly higher in the
group of persons with amalgam fillings and metallic
dental appliances (10.6 ± 7.4 μg/L) than in a control
group of persons with intact teeth (1.5 ± 1.5 μg/L) (Wirz
et al., 1993).
A palladium concentration of 1.4 mg/g was found
in inflamed gingival tissue of a patient suffering from
allergic reactions (mainly to nickel, chromium, and
jewelry) (Wirz et al., 1993).
1117
Mechanical stimulation, such as continuous gum
chewing, dramatically increased the palladium
release rate from dental alloys in two patients, from
0.4 and 1.8 μg/L saliva to 204 and 472 μg/L saliva,
respectively (Daunderer, 1993). Because palladium-
containing dental alloys exhibit complex release
kinetics, it is difficult to predict the release of palla-
dium from their nominal composition. The results
of limited clinical studies, however, suggest that a
daily mean intake of 1.5-15 μg Pd/adult/day is to
be expected, assuming a median value of 1-1.5 L of
ingested saliva (IPCS, 2002b).
5 METABOLISM
5.1 Absorption
Generally, absorption of a metal appears to depend
on its chemical form and its route of administration; its
solubility in aqueous media is an important factor. It is
noteworthy that palladium dust, which is nearly insol-
uble in distilled water, was found to dissolve apprecia-
bly in biological media, such as gastric juice and blood
serum (Roshchin et al., 1984), or in aqueous solutions
of biogenic compounds, such as peptides and amino
acids, under an oxygen atmosphere (Freiesleben et al.,
1993).
Quantitative data are scarce for the absorption of
palladium. Palladium ions are absorbed to a lesser
extent from the digestive tract in fasted adult rats
(0.5% of the initial dose after 3 days) than in nonfasted
suckling rats (approximately 5% at 4 days after dosing)
(Moore et al., 1974, 1975). It has also been reported that
endotracheal administration and inhalation of aque-
ous aerosols resulted in a higher absorption than did
oral administration (Moore et al., 1974, 1975). Data on
the absorption of palladium or palladium compounds
in humans are not available.
5.2 Distribution
Limited data exist on the distribution of palladium
in the tissues of rats, rabbits, and dogs after single
oral, intravenous, or endotracheal doses of palladium
compounds. After endotracheal exposure, the high-
est concentrations were found in the kidney, liver,
lymph nodes, spleen, and lungs. Dietary administra-
tion to rats of high doses (approximately 700 mg/kg
body weight/day) of palladium salts [palladium(II)
chloride and palladium(II) sulfate] resulted in the fol-
lowing palladium tissue concentrations (in mg/kg wet
weight): kidney (35 and 22, respectively) > liver (2 and
3) > spleen (0.7 and 0.9) > testis (0.24 and 0.26) > blood
(< 0.04 and 0.16) > brain (< 0.01 and < 0.01).
1118 Tomohiro Umemura, Kazuhiro Sato, Yukinori Kusaka and Hiroshi Satoh
Placental transfer at a considerably low concentra-
tion was found in fetuses of rats given single intra-
venous doses of 103PdCl2 (Moore et al., 1975). The
content in fetal liver (as a radioactive count) was
1429 counts/g tissue, while that in maternal liver was
319,153 counts/g tissue. A small amount of 103Pd was
detected in the tissue of young rats whose dams had
received single intravenous doses of 103PdCl2 (25 μCi/
rat) within 24 h postpartum (Moore et al., 1974). There-
fore, it is believed that transfer via the placenta or milk
occurs only to a small degree.
5.3 Excretion
After rats had been given an oral dose of PdCl2,
most of it (> 95%) was eliminated via the feces as a con-
sequence of nonabsorption (Moore et al., 1974, 1975).
Intravenous administration, however, resulted in simi-
lar (Moore et al., 1974, 1975) or greater (Durbin et al.,
1957) contents in the urine than in the feces of rats. It
is interesting to note that urinary excretion was much
lower in tumor-bearing animals (Ando and Ando,
1994).
Taubler (1977) found increased palladium concen-
trations in the urine of guinea pigs and rabbits follow-
ing their subcutaneous injections with palladium(II)
sulfate, and also in the urine of guinea pigs following
their exposure to a palladium-albumin complex. After
dermal treatment with “chloropalladium,” palladium
was found in their urine (Roshchin et al., 1984).
Palladium was also found in human urine sampled
from Germans who had not been subjected to occupa-
tional exposure. The values were less than 0.22 μg/L,
with a minimum of 6 ng/L (Begerow et al., 1997b,c,
1998, 1999). A recent study (Violante et al., 2005) com-
paring the relationship between the concentration of
palladium in ambient air and in biological materials,
such as hair, blood, and urine, revealed that a strong
correlation existed with levels in the hair and urine;
it was concluded that the palladium content in urine
could be considered as a satisfactory exposure bio-
marker for occupational monitoring.
6  LEVELS IN TISSUES AND BIOLOGICAL
FLUIDS
In earlier studies, the palladium concentrations
in blood, hair, feces, and urine were reported to be
below the detection limit (Johnson et al., 1975). More
recent studies in Germany gave levels of 0.03-0.2 μg/L
(mean 0.1) for 24-h urine samples from 14 nonsmok-
ers ­(Schramel et al., 1997), 0.02-0.08  μg/L (mean
0.04) for 24-h urine samples (Begerow et al., 1997c),
0.03-0.08 μg/L (mean 0.05) for whole blood (Begerow
et al., 1997a), 0.03-0.22 μg/L (mean 0.14) for 24-h urine
samples (Begerow et al., 1997b), and slightly lower
values of 0.013-0.048 μg/L (mean 0.031) for morning
urine. A comparison of morning urine levels among
groups living in areas with different automobile traf-
fic densities did not show a definite difference: the
overall range was 0.006-0.091 μg/L (mean 0.033), with
mean values of 0.033, 0.035, and 0.032 μg/L in the low-,
medium-, and high-traffic zones, respectively.
7  EFFECTS AND DOSE-RESPONSE
RELATIONSHIPS
7.1 Animals
7.1.1  Single Exposure
Median lethal dose (LD50) values ranged from
3 mg/kg body weight [palladium(II) chloride; rat;
intravenous] (Moore et al., 1975) to > 4.9 g/kg body
weight [palladium(II) oxide; rat; oral] (Holbrook et al.,
1975), depending on the choice of animal, compound,
and route of exposure. Compounds with lower absorp-
tion rates displayed lower toxicities after oral admin-
istration. In contrast, very similar values of LD50 were
reported (Charles-River CD-1 rats) (Moore et al., 1975)
for intravenous exposure to palladium(II) chloride,
potassium tetrachloropalladate(II), and ammonium
tetrachloropalladate(II) (3, 6.4, and 5.6 mg/kg body
weight, respectively). Clinical signs of toxicity after
such exposure included death, tonic-clonic convul-
sions, decreased food and water uptake, and emacia-
tion, as well as some instances of ataxia and tiptoe gait
(Moore et al., 1975).
Six months after a single endotracheal application
of 50 mg palladium dust, there were several signs
of inflammatory responses in the lungs of rats, but
no indications of interstitial fibrosis or carcinogenic
changes (Augthun et al., 1991).
A lowest effective dose of 0.4 mg Pd2+/kg body
weight (intravenous) was reported for cardiovascu-
lar effects in rats (ventricular arrhythmia; ventricular
fibrillation and death at higher doses) (Wiester, 1975).
7.1.2  Repeated Exposure
A 28-day toxicity study (Johnson Matthey, 1997a)
on tetraammine palladium hydrogen carbonate in rats
through gavage at dose levels of 1.5, 15, and 150 mg/
kg body weight established the no observed adverse
effect level (NOAEL) to be 1.5 mg/kg body weight/
day. The observed effects were reduced body weight
gain, anemia, and increases in absolute and relative
 49 Palladium
kidney weight (150 mg/kg body weight/day); and
histopathological changes in the liver and kidney
(150 mg/kg body weight/day) and spleen and stom-
ach (15 and 150 mg/kg body weight/day).
7.1.3  Chronic Exposure
Male mice given palladium(II) chloride (5 mg Pd/L)
in drinking water from weaning until natural death
displayed suppression of body weight gain and lon-
ger life spans. The mean age of the palladium-fed male
mice was 555 days (vs. 444 days in controls). Increased
amyloidosis of several organs and malignant tumors
[27.7% (n = 18/65) vs. 13.8% in controls (n = 11/80)] was
observed (Schroeder and Mitchener, 1971).
The chronic effects of palladium dust have also been
investigated. Daily oral administration of 50 mg pal-
ladium powder/kg body weight to rats for 6 months
resulted in suppressed body weight gain, shortening
of the prothrombin clotting time, decreases in the urea
and lipoprotein contents, and an increase in serum
(Roshchin et al., 1984).
7.1.4  Irritation and Sensitization
As expected from other metal compounds, palla-
dium and its compounds have the potential to cause
irritation and sensitization. Campbell et al. (1975)
reported an evaluation of skin irritation by eight pal-
ladium compounds, following the procedures and
evaluation criteria of U.S. National Institute of Occu-
pational Safety and Health. Three compounds—
(NH4)2PdCl6, (NH4)2PdCl4, and (C3H5PdCl)2—caused
erythema, edema, or eschar and were considered to be
unsafe for skin contact; K2PdCl6, K2PdCl4, and PdCl2
were nonirritant to intact skin, but caused erythema in
abraded skin; and (NH3)2PdCl2 and PdO did not pro-
duce any adverse effects. The degree of irritation may
correspond to the solubility of these compounds.
In guinea pig maximization tests, palladium(II) chlo-
ride (Wahlberg and Boman, 1990) and tetraammine pal-
ladium hydrogen carbonate (Johnson Matthey, 1997b)
proved to be strong sensitizers. Significant primary
immune responses were reported to palladium(II)
chloride, sodium tetrachloropalladate(II), potas-
sium tetrachloropalladate(II), and ammonium
hexachloropalladate(IV) in the popliteal lymph node
assay in BALB/c mice (Kulig et al., 1995; Schuppe
et al., 1998). In one study, signs of respiratory sensi-
tization were reported in cats after the intravenous
administration of several palladium salts (Tomilets
and Zakharova, 1979).
Palladium(II) chloride is considered to be a stron-
ger sensitizer than nickel sulfate, a well-known potent
sensitizer. Animals sensitized with palladium(II)
1119
chloride showed cross-reactivity to nickel sulfate
(Wahlberg and Boman, 1992), but the reverse effect
was not seen.
7.1.5  DNA Interactions and Mutagenicity
Various palladium compounds have been found to
interact with isolated DNA in vitro (Pillai and Nandi,
1977) and the interaction can induce conformational
changes in DNA structures (Shishniashvili et al., 1971;
Pillai and Nandi, 1977). Mutagenicity tests, such as
the Ames test with Salmonella typhimurium (Suraikina
et al., 1979; Uno and Morita, 1993; Bünger et al., 1996;
Bünger, 1997), the SOS chromotest with Escherichia coli
(Gebel et al., 1997; Lantzsch and Gebel, 1997), and the
micronucleus test with human lymphocytes (Gebel
et al., 1997), gave negative results; the exception was
tetraammine palladium hydrogen carbonate, which
induced a clastogenic response in human lymphocytes
in vitro (Johnson Matthey, 1997c).
7.1.6 Carcinogenicity
Only limited information is available on the carcino-
genicity of palladium.
As mentioned above, Schroeder and Mitchener
(1971) performed a long-term experiment in mice
given 5 mg Pd/L in drinking water from weaning until
their natural death. An increased rate of malignant
tumors was observed [27.7% (n = 18/65) versus 13.8%
in the controls (n = 11/80)]. It was suggested, how-
ever, that the significantly enhanced longevity of the
exposed group, relative to that of the controls, might
have caused their higher rate of malignant tumors.
Subcutaneous implantation of a silver-palladium-
gold alloy resulted in the formation of fibrosarco-
mas, myosarcomas, fibromas, and fibroadenomas at
the implantation site in 7 out of 14 rats after 504 days
(Fujita, 1971). The author suggested that the observed
carcinogenicity was due to the chronic physical stimu-
lus of the imbedded alloy.
As of 2012, palladium is not listed as a carcinogen by
the International Agency for Research on Cancer.
7.2 Humans
7.2.1  General Population Exposure
It is possible that humans can be exposed to pal-
ladium through the inhalation of ambient respirable
particles from automobile catalytic converters that
incorporate palladium, but no data are available.
Among the general population, skin exposure
may occur through contact with jewelry that contains
palladium. The major role of palladium in jewelry
1120 Tomohiro Umemura, Kazuhiro Sato, Yukinori Kusaka and Hiroshi Satoh

fabrication in Japan is as a subsidiary alloying compo- Finger et al., 1999). No palladium-related complica-
nent of the platinum alloys used (Coombes, 1990). tions have been reported to date that might suggest
Body piercing is considered a risk factor for the devel- the need to prohibit the use of 103Pd needles in cancer
opment of sensitivity to palladium and other metals. It radiotherapy.
has been reported that individuals with more piercings
have more positive reactions in patch tests involving 7.2.3  Occupational Exposure
palladium chloride, nickel sulfate, gold sodium thiosul-
Although details were not given, Roshchin et al.
fate, and cobalt chloride (Ehrlich et al., 2001). Human
(1984) reported (in a review article on the frequent
exposure to palladium comes mainly from jewelry
occurrence of allergic diseases of the respiratory pas-
and dental materials. It is noted that the prevalence of
sages) that dermatosis and other effects on the eyes
palladium sensitization is much higher in the female
occurred among Russian workers producing platinum
population (Muris et al., 2012; Larese et al., 2003). Most
group metals. In contrast, only one or two workers out
Pd-positive patients also had a positive cross-reaction
of 300 had positive skin-prick test reactions to solu-
to Ni SO4 (Muris et al., 2012; Kielhorn et al., 2002). Palla-
tions of palladium halide salts in a survey of South
dium sensitivity was associated with oral diseases (e.g.
African platinum refinery workers, who are known to
burning mouth syndrome) (Durosaro and el-Azhary,
be exposed to palladium (Murdoch et al., 1986; Mur-
2009; Larese et al., 2003). Epidemiological studies dem-
doch and Pepys, 1987; Peschel et al., 1999).
onstrated that Pd ions are among the most frequent
An isolated case study showed sensitization to palla-
reacting sensitizers within metals (ranked second after
dium in a worker with rhinoconjunctivitis and asthma:
nickel) (Kielhorn et al., 2002). The palladium sensitiv-
examination by skin-prick tests gave positive results
ity rate has recently increased (Larese et al., 2003; Cris-
for Pd(NH3)4Cl2, but not for Pd(NH4)2Cl4;. and effects
taudo et al., 2009).
of the corresponding platinum compounds were nega-
tive (Daenen et al., 1999).
7.2.2  Iatrogenic Exposure Dental technicians appear to be exposed to respi-
rable dust particles of palladium (Begerow et al., 1999)
Another source of exposure is dental restorations
(see Section 5.3), but the contribution of palladium
containing palladium. Many reports describe recovery
(within a series of other substances generated dur-
from palladium sensitivity after the removal of dental
ing dental-working processes) as a health hazard was
restorations. The symptoms observed included swell-
unclear.
ing of the lips and cheeks, stomatitis, oral lichen pla-
Because palladium is contained in automobile cat-
nus, itching, dizziness, asthma, and chronic urticaria
alysts, workers in the automobile industry may be
(Akiya et al., 1996; Adachi et al., 1997; Castelain and
exposed to it. Four out of 130 workers displayed posi-
Castelain, 1987; Downey, 1989; Fernandez-Redondo
tive reactions to palladium(II) chloride after prick tests
et al., 1998; Hackel et al., 1991; Hay and Ormerod, 1998;
performed in 1990-1991 in workers in a German plant
Koch and Baum, 1996; Kütting and Brehler, 1994; Mizo-
manufacturing automobile catalysts (Merget, 1991).
guchi et al., 1998; Richter, 1996; Stejskal et al., 1994;
They also reacted to hexachloroplatinic acid (H2PtCl6).
van Joost and Roesyanto-Mahadi, 1990; van Ketel and
Pd-sensitized occupational contact dermatitis was
Niebber, 1981; Yoshida et al., 1999).
reported in some occupations (Bordel-Gomez et al.,
It is believed that the potential harmful effects of
2010).
palladium in dental alloys may vary depending on the
composition and preceding preparation of the alloy
7.2.4  Carcinogenicity and Other Effects
because of their different corrosive properties and
interactions with the other components. Drasch et al. No data are available on the carcinogenicity, repro-
(2000) reported palladium concentrations in saliva ductive toxicity, or other effects in humans.
and other biological samples; there was an elevated
concentration in the saliva of individuals with dental
7.3  Dose-Response Relationships
crowns and inlays, and the concentration increased
during chewing. The increasing amount of palladium There are wide variations in the LD50 val-
in the feces in relation to the number of dental crowns ues for oral administration in experimental ani-
and inlays in the mouth suggests a low absorption rate mals. The intravenous injection of palladium
in the gastrointestinal tract. compounds such as palladium(II) chloride, potas-
Recently, 103Pd has been used for brachytherapy, a sium tetrachloropalladate(II), and ammonium
process in which radioactive sources are implanted tetrachloropalladate(II) provided LD50 values of
directly into a malignant tumor (Sharkey et al., 1998; 3-6.4 mg/kg body weight. The lowest effective dose—of
 49 Palladium
0.4 mg Pd2+/kg body weight (intravenously)—was
reported for cardiovascular effects (see Section 7.1).
From a 28-day toxicity study (Johnson Matthey,
1997a), the NOAEL for oral administration in rats
was determined to be 1.5 mg/kg body weight/day.
Chronic exposure of males over the course of a life-
time to palladium(II) chloride (5 mg Pd/L) in drinking
water led to the suppression of body weight gain and a
longer life span, with increased amyloidosis of several
organs. The ingested amount of palladium was esti-
mated to be 600 μg/day/mouse, assuming a drinking
volume of 3 mL/day and a body weight of 25 g.
Although sensitization is a major concern, it is dif-
ficult to establish dose-response relationships from the
available data, including NOAEL, for sensitization in
humans.
8  DIAGNOSIS, TREATMENT, PROGNOSIS,
AND PREVENTION
Palladium and its compounds, if ingested, display
very low to moderate acute toxicity: toxicity depends
mainly on solubility. The intake of palladium from food
or drinking water is low in the general population.
From a survey conducted in the United Kingdom, the
maximum daily intake of drinking water has been cal-
culated to be 0.03 μg Pd/person/day (assuming a max-
imum palladium concentration of 15 ng/L × 2 L/day),
with a total daily dietary intake of up to 2 μg/person/
day. If dental alloys are present, then additional expo-
sure to palladium occurs. It has been reported that the
palladium concentration in saliva may reach as high as
10 μg/L; thus, it contributes considerably (up t015 μg/
person/day) to the total palladium intake in subjects
with dental alloys. Although data is scarce, palladium
concentrations in ambient air are usually found to be
in the magnitude of pg/m3. Therefore, exposure to
palladium is not considered to cause serious health
problems in the general population. Skin or mucosal
contact with palladium-containing jewelry and dental
alloys appears, however, to be an important route of
exposure. Some subgroups, such as individuals with
pierced ears or other body parts, may be at special risk
of developing sensitivity to palladium. Because palla-
dium-containing dental alloys have been identified as
a possible source of sensitization, the public should be
protected from possible adverse effects by minimizing
the use of palladium-containing alloys or the release of
palladium from alloys.
It is evident that several palladium salts cause
severe primary skin and eye irritations. Individu-
als known to suffer from a palladium allergy should
not work with palladium compounds. Workers with
1121
known nickel allergies should be advised that work-
ing with palladium salts may cause allergic reactions.
It is advisable that a questionnaire for skin disease spe-
cifically resulting from allergy to metals (nickel, cobalt,
and palladium) be given during preemployment
screening, although patch tests should be performed
only to determine the cause of occupational dermati-
tis. Health checks—through questionnaires and exam-
inations—for skin and respiratory disorders should be
performed regularly throughout the period of employ-
ment. Improvement in the working environment and
the provision of protective equipment, if necessary,
should be used to lower exposure to palladium and its
compounds. It is noteworthy that a protective cream
containing diethylentriaminepentaacetic acid did not
protect against a contact allergic reaction to palladium
chloride, even though it was effective against nickel
sulfate, cobalt chloride, and copper sulfate (Wohrl
et al. 2001).
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