Platinum - Toxicology of Metals - page 760

The toxicity of orally dosed platinum compounds in
rats decreased in the order:

symptoms has usually varied between 3 months and
3 years but may, in some cases, be only a few weeks or
several years. Patients show a positive reaction to chal-
lenge to platinum compounds in skin prick tests and a
positive bronchial challenge test to platinum hexachlo-
roplatinic acid (Calverley et al ., 1999; IPCS, 1991; Merget
et al ., 1994; Pepys et al ., 1972). Platinum-exposed work-
ers showed an increased prevalence of bronchial reac-
tion to cold air (Baker et al ., 1990; Brooks et al ., 1990),
but bronchial hyperresponsiveness to methacholine was
not consistently related to platinum sensitivity (Merget
et al ., 1991; 1994; 1996; 1999; 2000). In a follow-up study,
it was shown that if the exposure of workers posi-
tive on prick testing continued unabated, 100% of the
workers became symptomatic (Calverley et al ., 1995).
Of patients with a positive prick test, 2 of 23 also showed
a positive reaction in patch test to H 2 [PtCl 6 ] (Cristaudo
et al ., 2005). The eczema described in the early studies
(Roberts, 1951) apparently is not related to exposure to
platinum but is rather caused by irritation by strong
acids and alkalis used in the process. In contrast, urti-
caria may be related to platinum, notably to splashes of
chloroplatinate solutions (Hughes, 1980).
In early studies (Roberts, 1951), the prevalence of
“platinosis” was 60-100% of the exposed, indicating
that platinum is a very potent sensitizer. In a more
recent study (Niezborala and Garnier, 1996), >30% of
the workforce developed platinum sensitivity within
3 years. In the South African registry of occupational
respiratory diseases (Hnizdo et al ., 2001), platinum was
the third most frequent cause of occupational asthma
(after latex and isocyanates) and represented 12% of
all asthma cases. The risk of developing platinum salt
sensitivity increases with increasing exposure (Baker
et al ., 1990; Bolm-Audorff et al ., 1992; Calverley et al .,
1995; 1999; Cristaudo et al ., 2005; Merget et al ., 1988;
1999; 2000), as well as with time of exposure (Cristaudo
et al ., 2005; Linnett and Hughes, 1999), and removal
from exposure or decrease of exposure was linked to
a decrease in the prevalence of respiratory symptoms
(Merget et al ., 1999; 2001).
Platinum dust has generally been considered to be
biologically inert and nonallergenic. No adverse health
effects have been reported from the exposure solely to
platinum dust (Czerchak and Gromiec, 2001; Gómez
et al ., 2002). Surveillance of newly employed workers
in a platinum company indicated that the proportion of
sensitized workers was high among those exposed to
chloroplatinates but nonexistent among those exposed
to tetraamming platinum dichloride (i.e., a platinum
coordination complex, in which there are no chloride
ligands) (Linnett and Hughes, 1999). Among work-
ers sensitized to platinum, the potency of different
platinum complexes to induce positive skin prick tests
decreased very constantly in the order:

PtCl 4 > Pt(SO 4 ) 2 4 H 2 O > PtCl 2 > PtO 2
Thus, water-soluble platinum compounds are more
toxic than the insoluble (Holbrook et al ., 1975).
Platinum coordination complexes with chloride
ligands, administered orally, are more toxic than plati-
num salts (IPCS, 1991). After high doses of hexachloro-
roplatinic acid, the kidney is the target organ, the cause
of death being renal failure (Ward et al ., 1976). Neph-
rotoxicity is the major side effect of cisplatin therapy
(Bokemeyer et al ., 1996; Ferrari et al ., 2005; Markman
2003, Taguchi et al ., 2005). Also, severe neurotoxic-
ity has been observed when cisplatinum is used in
chemotherapy (Sastry and Kellie, 2005).
Platinum coordination complexes, including
(NH 4 ) 2 [PtCl 4 ], Na 2 [PtCl 6 ], but also Na 2 [Pt(OH) 6 ]
[PtNH 3 ] 4 Cl 2 and [Pt(NO 2 ) 2 (NH 3 ) 2 ], are strongly irritant
or corrosive when applied to the eye and irritant or
strong irritants to the skin; platinum(IV) chloride is an
irritant to the skin, whereas platinum(II) chloride and
platinum oxide are nonirritants (IPCS, 1991).

6.2 Sensitization
Hexa- and tetrachloroplatinates and cisplatin, but
not [Pt(NH 3 ) 4 ]Cl 2 , induced increased weight and cellu-
larity in the popliteal lymph node after a single subcuta-
neous injection in C57 mice (Schuppe et al ., 1992; 1997).
An enhanced reaction was observed after preceding
treatment with [PtCl 6 ] 2− , indicating a specifi c sensitiza-
tion reaction. The reaction was considered to require T
cells, because nude mice lacking T cells did not show
the same reaction. Differences in the reaction between
inbred mouse strains indicate genetic susceptibility to
platinum sensitivity. Sodium hexachloroplatinate also
produced a positive response in an auricular lymph
node assay and mouse ear swelling test for contact
hypersensitivity. However, the concentrations needed
for positive reactions were high enough to also cause
an irritant reaction (Schuppe et al ., 1997). In an abstract,
it was reported that PtO 2 and PtCl 2 did not elicit an
immune response in the mouse popliteal lymph node
assay (Schuppe et al ., 1993).
Exposure to platinum causes a disease, which was
originally called platinosis (Roberts, 1951), but which
is now most often known as platinum salt sensitiv-
ity (IPCS, 1991). The symptoms include watering of
the eyes, sneezing, tightness of the chest, wheezing,
breathlessness, coughing, eczematous and urticarial
skin lesions, and signs of mucous membrane infl am-
mation. The respiratory symptoms subside usually
approximately 1 hour after the cessation of exposure.
The latency period from the fi rst exposure to the fi rst