large that it exceeds the ability of an organism to excrete the substance, then the chemical
accumulates within the tissues of that organism, leading to the phenomenon of bioaccu-
mulation. If the organism that is bioaccumulating contaminants is an integral part of the
food chain, then the concentration of the contaminant may be magnified thousands of
times as it passes up the food chain—this is the process of biomagnification. Recently,
concern has been expressed concerning the possibility of biomagnification of toxins
within farmed fish such as salmon.
A wide variety of specific chemicals have been implicated as toxins in occupational
and environmental toxicology. Gaseous toxins include sulphur dioxide, nitrogen oxides,
carbon monoxide, and ozone. These arise from a diverse range of industrial, recre-
ational, and automotive sources. Halogenated aliphatic hydrocarbons (carbon tetra-
chloride, chloroform, trichloroethylene, tetrachloroethylene) are extensively used as
industrial solvents, cleaning agents, and degreasing agents. The environment also con-
tains many insecticides, including chlorinated hydrocarbons (chlorophenothanes, ben-
zene hexachlorides, cyclodienes, toxaphenes), carbamates (aminocarb, carbofuran,
isolan, pyramat), organophosphorus compounds (diazinon, malathion, parathion), and
botanical insecticides (rotenone, pyrethrum). In addition to insecticides, various herbi-
cides with “agrotech” applications also pollute our environment, including chlorophe-
noxy herbicides (2,4-dichlorophenoxyacetic acid) and bipyridyl herbicides (paraquat).
The treatment of acute exposure to these various toxins is typically nonspecific and
involves removing the victim from the contaminated environment, coupled with general
supportive measures. The toxic effects of low-level, long-term exposure to these agents
have yet to be fully determined.
Toxicity from inorganic pollutants and heavy-metal intoxication is also a significant
public health concern. Lead poisoning is probably the oldest environmental disease in
the world; it is credited with the downfall of the Roman Empire. Although lead has been
removed from gasoline and paint, it still lurks as an environmental contaminant. Lead
can cause damage to the brain, peripheral nervous system, and kidneys. Lead serves
absolutely no useful purpose in the human body; no safe limit for exposure to lead
exists. Arsenic is also a toxic element. In recent years, arsenic has received widespread
commercial application in the manufacture of electronic semiconductors, cotton desic-
cants, and wood preservatives. In addition, arsenic leached from natural mineral
deposits can contaminate groundwater; arsenic in the drinking water in the Ganges delta
region of India has emerged as one of the world’s largest environmental health prob-
lems. Like lead, mercury can also cause diffuse brain injury. In the 1950s, an epidemic
of neurologic disease occurred in the Japanese fishing village of Minamata. The result-
ing Minamata disease was due to mercury poisoning. A number of other heavy metals
can also contribute to human disease.
Specific treatments do exist for heavy metal toxicity. Chelating agentsserve as antidotes
for inorganic metal poisonings. Chelates(from Greek: chele =claw [of crayfish]) are com-
plexes between the chelating agent and the metal ion. The chelating agent possesses several
binding sites (ligands) that act to complex and “inactivate” the heavy metal ion.
The rational design of chelating agents as antidotes requires a careful consideration
of acid–base chemistry. Metal ions are Lewis acids, while the chelating agents or
ligands are Lewis bases. The concepts of hardness and softness may be used to describe
systematically the interaction between them. A hard metal cation is one that retains its
594 MEDICINAL CHEMISTRY