Platinum - Toxicology of Metals - page 761

platinum (Cromwell et al ., 1979; Merget et al ., 1988;
Murdoch et al ., 1986)..
Tobacco smoking is an important contributing fac-
tor in the generation of allergy to platinum salts (Baker
et al ., 1990; Calverley et al ., 1995; Linnett and Hughes,
1999; Merget et al ., 2000; Newman Taylor et al ., 1999;
Niezborala and Garnier, 1996; Venables et al ., 1989),
although this relationship was only observed in some
subgroups of the exposed workers in a recent study
(Cristaudo et al ., 2005). Relative risks as high as 8.0 (CI,
2.6-25) for smokers to develop platinum sensitivity at
work have been reported (Calverley et al ., 1995). In a
study, which was based on small numbers, it seemed
that smoking is especially important as a predictor of
platinum sensitization when the exposure is low: in a
case-referent study (Newman Taylor et al ., 1999) among
workers exposed to ammonium hexachloroplatinate
(usually at concentrations less than 2

(NH 4 ) 2 [PtCl 4 ] > Cs 2 [PtNO 2 Cl 3 ] >
Cs 2 [Pt(NO 2 ) 2 Cl 2 ] > Cs 2 [Pt(NO 2 ) 3 Cl] > K 2 [Pt(NO 2 ) 4 ]

(NH 4 ) 2 [PtCl 6 ] ≈

the last-mentioned being inactive. Other complexes
with strongly bound ligands, such as [Pt(NH 3 ) 4 ]Cl 2
and [Pt(thiourea) 4 ]Cl 2 were also inactive. Com-
plexes containing amine (and chlorine) showed
the same general pattern, with the important dif-
ference that the dichlorocomplexes ( cis - and trans -
[Pt(NH 3 ) 2 Cl 2 ]), which are neutral, were completely
inactive. When the chlorine ligand was replaced by
bromine, the activity was decreased, but not abol-
ished (Cleare et al ., 1976). Platinum salt sensitivity
has not been described among people treated with
platinum chemotherapeutic drugs, but sensitivity
reactions, including anaphylactic shock, are a well-
known potential side effect of cisplatin and other
platinum-containing chemotherapeutic agents (Basu
et al ., 2002; Lim et al ., 2004; Shepherd, 2003; Sliesor-
aitis and Chikhale, 2005; Thomas et al ., 2003; Watan-
abe et al ., 2005; Windom et al ., 1992; Zorzou et al .,
2005; Zweizig et al ., 1994).
The mechanism of platinum salt sensitivity is likely
to be type 1, immunoglobulin IgE-mediated response.
It is believed that platinum salts acting as haptens com-
bine with serum proteins, probably through sulfhydryl
and methionine groups, to form the complete antigen
(Cromwell et al ., 1979; Merget et al ., 1994; Schultze-
Werninghaus et al ., 1978). Peripheral blood monocytes
from symptomatic workers, positive in prick test-
ing, showed an increased frequency of CD3 positive
lymphocytes for V

g/m 3 ), the odds
ratio for platinum sensitization was 9.1 for the group in
whom the exposure was estimated to be “low,” and 3.1
in the “high” exposure group.
Although an early study reported an association
between atopy and platinum sensitization (Hughes,
1980), and in two studies a statistically nonsignifi cant
excess relative risk was reported for atopic persons to
develop platinum sensitivity (Cristaudo et al ., 2005;
Venables et al ., 1989), the weight of evidence seems
to be that atopic constitution is not related to the pre-
disposition to platinum sensitivity (Baker et al ., 1990;
Bolm-Audorff et al ., 1992; Calverley et al ., 1999; Cris-
taudo et al ., 2005; Merget et al ., 2000; Niezborala and
Garnier, 1996).
HLA-type DR3 was more common and DR6 less
common among workers sensitized to platinum than
among matched nonsensitized referents (Newman
Taylor et al ., 1999). The difference was more marked
in the group whose exposure was considered low than
among the highly exposed. Because, in addition, the
prevalence of sensitization in the old studies—refl ect-
ing high exposures—were very high, up to 100%, it
is likely that at high exposure, sensitization will take
place independent of the HLA phenotype. The odds
ratio for the presence of DR3 was rather low (1.6 for
the high exposure and 2.3 for the low exposure group),
and thus the attributable fraction for HLA DR3 is
low. In contrast, the odds ratio for the presence of DR6
was 0.6 for high exposure and 0.1 for low exposure—
denoting a high attributable fraction at low exposures.
It should be noted, however, that the point estimates
have very large confi dence intervals (0.02-1.1 for HLA
DR6, low exposure).
There is at present no evidence of adverse health
effects from platinum in the general environment. In a
series of 749 patients with eczema and 51 with urticaria

µ

2a, Vß11, and Vß21.3-positive T
cells and showed elevated proliferation responses to
sodium hexachloroplatinate in vitro (Raulf-Heimsoth
et al ., 2000).
An increased level of total IgE has been demon-
strated in the serum of patients diagnosed with plat-
inum salt sensitivity (Baker et al ., 1990; Brooks et al .,
1990; Bolm-Audorff et al ., 1992; Calverley et al ., 1999;
Cromwell et al ., 1979; Merget et al ., 1988; 1994; Mur-
doch et al ., 1986). However, the increases in total
IgE have generally been rather small, and there is a
marked overlap with the values in nonsensitized ref-
erents (Baker et al ., 1990; Brooks et al ., 1990; Calverley
et al ., 1999; Cromwell et al ., 1979; Merget et al ., 1988;
1994; Murdoch et al ., 1986). In some studies, workers
with work-related symptoms of platinum sensitivity
have had elevated concentrations of platinum-specifi c
IgE in their blood (Bolm-Audorff et al ., 1992; Brooks
et al ., 1990; Cromwell et al ., 1979; Merget et al ., 1988;
1999; Murdoch et al ., 1986), but not all studies have
reported this association (Calverley et al ., 1999), and
in some studies, there is an extensive overlap between
the workers with positive and negative skin tests to

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