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EHC 226: Palladium
6
They decreased slightly  in liver and markedly  in lung, adrenal gland
and blood.
Owing to the ability of palladium ions to form complexes, they
bind to amino acids (e.g., L-cysteine, L-cystine, L-methionine), proteins
(e.g.,  casein,  silk  fibroin,  many  enzymes),  DNA   or  other  macro-
molecules (e.g., vitamin B
6
).
The affinity of palladium compounds for nucleic acids was  con-
firmed in many studies. In vitro  experiments  with palladium(II) chloride
and calf thymus DNA  indicated that palladium(II) interacts with both
the phosphate groups and bases of DNA. Several palladium–organic
complexes were observed to form bonds with calf thymus DNA or
Escherichia   c o l i  plasmid   DNA.  M o s t  of  the  complexes   appear  to
interact via non-covalent binding, mainly  via hydrogen bonding; in a
few cases, however, indications for covalent binding were seen.
1.6
Effects on laboratory mammals and in vitro test
systems 
LD
50 
values   for palladium compounds ranged, depending on
compound and route tested, from 3 to >4900 mg/kg body weight, the
most  toxic  compound  being  palladium(II) chloride, the least toxic,
palladium(II) oxide. Oral administration caused the least toxicity. There
were  very  similar intravenous LD
50
  values  for palladium(II) chloride,
potassium  tetrachloropal l a d a t e ( I I )   ( K
2
PdCl
4
)  and  ammonium
tetrachloropalladate(II) ((NH
4
)
2
PdCl
4
). Marked differences among the
different routes  of administration were  demonstrated with palladium(II)
chloride, showing in Charles-River CD1 rats LD
50 
values  of 5 mg/kg
body weight for the intravenous, 6 mg/kg body weight for the intra-
tracheal, 70 mg/kg body weight for the intraperitoneal and 200 mg/kg
body weight for the oral route. A higher oral LD
50
 value has  been
found in Sprague-Dawley rats.
Signs of acute toxicity of several palladium salts in rats or rabbits
included death, decrease in feed and water uptake, emaciation, cases
of ataxia and tiptoe gait, clonic and tonic convulsions, cardiovascular
effects, peritonitis  or biochemical changes (e.g., changes in activity of
hepatic enzymes, proteinuria  or ketonuria). Functional or histological
changes  in the kidney were  found both with palladium compounds and

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Summary
7
with elemental palladium powder. There were also haemorrhages of
lungs and small intestine.
Effects  recorded in rodents and rabbits after short-term exposure
to various palladium compounds refer mainly to changes in biochem-
ical  parameters   (e.g.,  decrease  in activity of hepatic microsomal
enzymes or yield  of microsomal protein). Clinical signs were sluggish-
ness, weight loss, haematoma  or exudations. Changes in absolute and
relative  organ  weights   and  anaemia   also  occu rred.  One  compound
(sodium tetrachloropalladate(II) complexed with egg albumin) caused
deaths  in  mice.  Effective  concentrations were in the milligram per
kilogram  body  weight  range.  Histopathological  effects   have  been
observed in liver, kidney, spleen or gastric  mucosa of rats  28 days after
daily oral administration of 15 or 150 mg tetraammine palladium hydro-
gen carbonate ([Pd(NH
3
)
4
](HCO
3
)
2
)/kg  body weight. Additionally, an
increase in absolute brain and ovary  weights  at the 1.5 and 15 mg/kg
body weight doses has been found.
The contribution of palladium to effects observed after single or
short-term administration of palladium-containing dental alloy material
is not clear.
There  are  also only  scarce data available  on effects  from long-term
exposure to palladium species (forms).
Mice  given  palladium(II)  chloride  (5  mg  palladiu m/litre) in
drinking-water from weaning until natural death showed suppression
of body weight, a longer life span (in males, but not in females), an
increase in amyloidosis of several inner organs and an approximate
doubling of malignant tumours (see below).
Inhalative exposure of rats to chloropalladosamine ((NH
3
)
2
PdCl
2
)
for about half a year caused slight, reversible (at 5.4 mg/m
3
) or sig-
nificant permanent (at 18 mg/m
3
) changes in several blood serum and
urine  parameters,  indicating damage mainly to liver and kidney (in
addition to reduced body weight gain, changes in organ weights and
glomerulonephritis). Adverse effects were also observed with enteral
exposures,  the  no-observed-adverse-effect  level  being  given  as
0.08 mg/kg body weight.

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EHC 226: Palladium
8
Six months after a single intratracheal application of palladium
d u s t  (143  mg/kg   body  weight),  several  histopathological signs of
inflammation were noted in the lungs of rats. Daily oral administration
of palladium dust (50 mg/kg  body weight) over 6 months resulted in
changes in several blood serum and urine parameters of rats.
Skin tests of a series of palladium compounds in rabbits showed
dermal reactions of different severity, resulting in the following ranking
order: (NH
4
)
2
PdCl
6
 > (NH
4
)
2
PdCl
4
 > (C
3
H
5
PdCl)
2
 > K
2
PdCl
6
 > K
2
PdCl
4
 >
PdCl
2
  >  (NH
3
)
2
PdCl
2
  >  PdO. The first three compounds caused
erythema, oedema or eschar in intact and abraded skin, the next three
substances  elicited erythema  in abraded skin  and the last two were not
irritant. Palladium hydrochloride (formula  no t specified) also caused
dermatitis in the skin of rabbits.
Eye irritation was observed with palladium(II) chloride and tetra-
ammine  palladium  hydrogen  carbonate  (but not with palladium(II)
oxide), both deposited on the eye surface of rabbits. Inhalation expo-
sure  to chloropalladosamine (
$
50 mg/m
3
)
 
affected the mucous mem-
branes of the eyes of rats (conjunctivitis, keratoconjunctivitis).
Some  palladium compounds have been found to be potent sensi-
tizers of the skin  (palladium(II) chloride, tetraammine palladium hydro-
gen  carbonate,  palladium  hydrochloride  [formula   not  specified],
palladium–albumin  complexes). Palladium(II) chloride was  a stronger
sensitizer than nickel sulfate (NiSO
4
) in the guinea-pig maximization
test. Guinea-pigs induced with chromate, cobalt or nickel salts did not
react after challenge with palladium(II) chloride. However, if induced
with palladium(II) chloride, they reacted to nickel sulfate. Somewhat
divergent results  have been obtained in tests  studying cross-reactivity
between palladium and nickel by repeated open applications to the skin
of  guinea-pigs.  In  these  experiments, animals were induced with
palladium(II) chloride (n = 27) or nickel sulfate (n = 30) according to the
guinea-pig maximization test method and then treated once daily  for 10
days according to repeated open applications testing by applying the
sensitizing allergen (palladium(II) chloride or nickel sulfate) as well as
the possibly  cross-reactive compound (nickel sulfate or palladium(II)
chloride)  and  the  vehicle   topically  in  guinea-pigs.  In  this   study,  it
remained unclear whether reactivity to palladium(II) chloride in animals
sensitized  with  nickel  sulfate  was   due  to  cross-reactivity  or  to  the
induction of sensitivity by the repeated treatments. On  the other hand,

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