DƯỢC LÍ Goodman & Gilman's The Pharmacological Basis of Therapeutics 12th, 2010

Many of the toxic metals in the environment also
are carcinogens (Table 67–3). In addition to toxic environmental
metals, several essential metals also are toxic
under conditions of overdose. Copper and especially
iron are associated with toxicities, primarily targeting
the liver through generation of reactive oxygen species.
Toxicities from copper and iron usually result from
genetic diseases that interfere with the regulation of
metal absorption or excretion (e.g., Wilson’s disease for
copper, hemochromatosis for iron) or result from acute
overdose, particularly with iron-containing medications
or multivitamins. For a more comprehensive review of
toxic metals, including essential metals, see Liu et al.
(2008).
Not listed in Table 67–3 is the metal gold, which has its own
uses and toxicities. Among heavy metals, perhaps only gold is addictive:
gold has been used for centuries for relief of the itching palm,
and many cannot get enough of its influence.
Lead
Exposure to lead has wide-ranging consequences for
human health. Chronic exposure of populations to even
very low levels of lead has major deleterious effects,
which are only now beginning to be understood. It has
been proposed that lead exposure contributed to the fall
of the Roman Empire and that it plays a role in modern
inner-city violence (Woolley, 1984; Needleman
et al., 1996).
Exposure. In the U.S., paint containing lead for use in and around
households was banned in 1978, while the use of tetraethyl lead in
gasoline was phased out and eventually eliminated between 1976
and 1996. The economic benefit of the reduction in lead exposure
due to these two measures is estimated at hundreds of billions of dollars
per year (Grosse et al., 2002). Despite these bans, past use of
lead carbonate and lead oxide in paint and tetraethyl lead in gasoline
remain the primary sources of lead exposure. Lead is not degradable
and remains throughout the environment in dust, soil, and the paint
of older homes. Young children often are exposed to lead by nibbling
sweet-tasting paint chips or eating dust and soil in and around
older homes. Renovation or demolition of older buildings may cause
substantial lead exposure. Tetraethyl lead was used as an anti-knock
agent in gasoline, which resulted in high levels of lead in air pollution.
Removal of lead from gasoline caused lead levels in air pollution
to drop by >90% between 1982 and 2002. Lead was commonly
used in plumbing and can leach into drinking water. Acidic foods
and beverages dissolve lead when stored in containers with lead in
their glaze or lead-soldered cans, which was a significant problem
through the middle of the 20th century and remains a problem in
developing countries. Lead exposure also has been traced to other
sources such as lead toys, non-Western folk medicines, cosmetics,
retained bullets, artists’ paint pigments, ashes and fumes from
painted wood, jewelers’ wastes, home battery manufacture, and lead
Table 67–3
Toxic Metals with Frequent Environmental or Occupational Exposure a
CERCLA COMMON SOURCE ORGAN SYSTEMS MOST IARC CARCINOGEN
METAL PRIORITY OF EXPOSURE SENSITIVE TO TOXICITY CLASSIFICATION
As 1 Drinking water CV, skin, multiple Group 1, carcinogenic to humans—liver,
other
bladder, lung
Pb 2 Paint, soil CNS, blood, Group 2A, probably carcinogenic
CV, renal
Hg 3 Air, food CNS, renal Group 2B, possibly carcinogenic (MeHg + );
group 3, not classifiable (Hg 0 , Hg 2+ )
Cd 7 Occupational, Renal, respiratory Group 1, carcinogenic to humans—lung
food, smoking
Cr 6+ 18 Occupational Respiratory Group 1, carcinogenic to humans—lung
Be 42 Occupational, water Respiratory Group 1, carcinogenic to humans—lung
Co 49 Occupational, Respiratory, CV Group 2B, possibly carcinogenic
food, water
Ni 53 Occupational Respiratory, skin Group 1, carcinogenic (soluble Ni
(allergy)
compounds); group 2B, possibly
carcinogenic (metallic Ni)—lung
a
The Agency for Toxic Substances and Disease Registry (ATSDR) has both detailed monographs and brief summaries for each of these compounds,
available at http://www.atsdr.cdc.gov. The International Agency for Research on Cancer (IARC) also has monographs available at
http://monographs.iarc.fr. CERCLA, Comprehensive Environmental Response, Compensation, and Liability Act. CNS, central nervous system;
CV, cardiovascular.