Chemistry Reference
In-Depth Information
Succimer, DMSA, less toxic than DMPS, has been the
preferred antidote for lead poisoning, particularly
in children, although adverse effects have also been
reported. Calcium EDTA, given intravenously, will
bind lead with the displacement of calcium. However,
it has marked toxic effects and may redistribute lead to
the brain after acute or chronic lead poisoning. Peni-
cillamine, an effective chelating agent for copper, iron,
lead, mercury, and zinc, is, in particular, effective in the
management of Wilson's disease and in which it may
be given indefi nitely to maintain a negative copper bal-
ance. Trien, TETA, is effective in the treatment of Wil-
son's disease, where intolerance to penicillamine has
developed. Desferrioxamine, DFOA, given parenteral-
ly, has an affi nity for iron and is the treatment of choice
in acute iron poisoning, in particular in children. It is
indicated in the treatment of transfusional siderosis as
in thalassemias and has been effective for the removal
of aluminium in dialysis encephalopathy. Deferiprone,
L1, is effective orally for the long-term chelation thera-
py of transfusional siderosis. Lipophilic derivatives of
DTPA have been administered as an aerosol to dimin-
ish the lung concentration of inhaled insoluble pluto-
nium oxide particles. DEDTC has been effective in the
treatment of acute nickel carbonyl poisoning.
A combination of the two chelating agents has
been shown to be effective in some cases of poisoning.
Combined treatment with EDTA and dimercaprol is ef-
fective in acute lead poisoning in children with enceph-
alopathy or blood lead levels greater than 100
lung, hemopoietic system, and possibly the nervous
system; (2) the induction of cancer after an appropri-
ate latent interval; and (3) teratogenic malformations.
Furthermore, an increasing number of metals are
being shown to give rise to genetic damage in test sys-
tems, and the question arises as to whether mutations
may also occur in man, with a consequent increase in
abnormal individuals in later generations. These other
effects, because of their importance and magnitude,
are considered elsewhere.
Adverse effects, which may become manifest by
biochemical or physiological tests or by abnormal clin-
ical signs, may occur in the absence of symptoms or
in the presence of vague, ill-defi ned complaints of ill
health that do not make up a recognizable syndrome.
Common examples are anemia after exposure to lead
compounds and renal tubular dysfunction after long-
term exposure to cadmium.
The clinical effects described previously imply that
an adverse biological change has been produced in
the organism with some impairment of cellular func-
tion resulting from exposure. The model on which
this adverse effect is based assumes that a critical con-
centration of the toxic metal has been attained in the
critical organ to give rise to a critical effect. This criti-
cal effect may or may not be of immediate importance
to the health of the organism as a whole (Nordberg,
1976). It may be argued that such a critical effect cannot
be considered to be synonymous with a clinical effect.
Here it is useful to distinguish between critical and sub-
critical effects. Effects may also occur below the critical
concentration in the critical organ that do not impair
or seem to impair cellular function (Nordberg, 1976;
see also Chapter 12). Although the biological signifi -
cance of such a subcritical effect may be unknown, it
would be reasonable, given the present state of knowl-
edge, to exclude such a subcritical effect from clinical
consideration.
g/L.
Other therapeutic measures in metal poisoning are
a modifi cation of tissue response to the poison or an
alteration of biochemical or metabolic state of the sub-
ject. Thus, the infl ammatory process in chronic beryl-
lium disease may be arrested by corticosteroid therapy.
In chronic manganese poisoning that closely resem-
bles Parkinson's disease, L-dopa has been effective in
reducing symptoms and neurological signs without
evidence of a reduced body burden of manganese.
µ
1.2 Exposure Pattern and Clinical Effect
Various factors act as determinants of a clinical effect
after exposure to a toxic metal. Such factors include dose;
route of absorption; the chemical and physical form
of the metal concerned; genetic variation manifested
through racial, familial, and individual susceptibility;
dietary pattern and nutritional status; immunological
status; presence of intercurrent disease; and interaction
with other chemical compounds in the environment.
Some of these determinants are considered in Chapter
7 and in those chapters dealing with the specifi c metals.
The exposure pattern, in terms of concentration, time,
and route of exposure, is an important determinant of
clinical effects that requires further consideration here.
1 CLINICAL EFFECTS
1.1 General Considerations
Metal poisoning may be acute, resulting in death
or followed by partial or complete recovery. It may
be subacute in onset, or there may be a latent interval
between absorption and its development, which may
then follow the same course as previously mentioned
or give rise to chronic poisoning. However, toxic met-
als produce other important clinical effects not usually
included under this term. These effects are (1) hyper-
sensitivity reactions that may involve the skin, kidney,
