PRINCIPLES OF TOXICOLOGY

Humans often may be exposed to hazardous levels of metals in the environment through the
alteration of natural biogeochemical cycles. For instance, the use of lead as a gasoline additive increased
the amount of lead to which people in urban areas were exposed to levels far above what would normally
be inhaled if unleaded gasoline was used. The discontinuance of lead as an additive has dramatically
decreased the impact of this exposure route, as well as the presence of lead in soils. However, the
continued presence of lead-based paint and lead pipes (or lead plumbing solder) for transporting
drinking water has maintained lead exposure at far above background levels. The presence of lead in
the paint of old buildings, where it may be inhaled as paint dust or ingested by children swallowing
paint chips, continues to be a major public health problem despite active efforts in the public health
field at local, state, and federal levels.
The organomanganese compound, methylcyclopentadienyl manganese tricarbonyl (MMT), was
used as an antiknock additive to replace lead in gasoline, but serious concerns regarding its health
effects have been raised as well. MMT was banned for this use in the United States in 1977. A court
decision in 1995 ordered EPA to lift the ban and allowed the registration of MMT. Testing for health
effects of this manganese compound is ongoing.
People living near waste sites, mining operations, or smelters may be exposed to higher-than-background
levels of metals in air, drinking water, and soil. Several incidents of massive public poisoning
due to accidental or merely ignorant environmental release of metal wastes have underscored the
potential dangers. Perhaps the most famous is the Minamata disease, named after the area of Japan
where many cases of severe neurological impairment and death appeared among the population in the
1950s. It was eventually discovered that mercury wastes discharged into the nearby bay from a
chloralkali plant were being bioaccumulated by the fish and shellfish. Since mercury is easily converted
into the methyl form under common environmental conditions, and because the form persists for long
periods in biological tissues, a magnification of tissue mercury concentration up the aquatic food chain
would be expected. Thus, by the time the seafood was harvested for human consumption, it contained
extremely toxic levels of methyl mercury, which were reflected in severe effects on adults and children
in the area.
Aside from such catastrophic epidemics of metal poisoning among the general public, exposure to
high levels of metals is usually of greatest concern for workers in industries where metals are commonly
used. These include mining, processing and smelting, manufacturing, and waste disposal operations.
Occupational exposure to some metals may be confined to specific industries. For instance, agricultural
workers may have exposure to arsenic and mercury, which are ingredients in some herbicides and
fungicides. Sheetmetal workers may be exposed to copper and aluminum dust particles. Gold, silver,
platinum, and nickel are metals commonly handled by workers involved in manufacturing jewelry, and
may exert effects under some conditions of exposure.
Although workers are often exposed to higher metal concentrations than members of the general
public, this exposure can be maintained at a safe level through proper enforcement of regulations
regarding exposure limits and workplace safety. Because workplace exposure is often confined to a
specific site with a specific population at risk, routine monitoring of exposure can be performed, with
corrective action taken as necessary to maintain safe limits.
Indicators of Exposure (Biomarkers)
14.5 SOURCES OF METAL EXPOSURE 335
In addition to overt signs of toxicity, exposure to metals may be verified and often quantified by specific
biomarkers of exposure. A biomarker of exposure is any measurable biological parameter that indicates
exposure to a toxic substance, whether it is an induced protein, enzyme, metabolite, or even the toxic
substance itself. In assessing suspected metal exposure, the first step is usually to take blood and/or
urine samples for analysis. Since metals cannot be metabolized beyond recognition, and many metals
are not normal constituents of biological samples, their detection in the samples discussed above certain
defined levels is a reliable indicator of recent metal exposure, and perhaps intoxication. Due to the
relatively short half-life of most metals in the blood and urine, sampling is usually required within