Encyclopedia of Environmental Science and Engineering, Volume I and II

TOXICOLOGY 1157

they concentrate (e.g., lead in bone). It is often important to

know where a chemical is concentrated or its organ of toxic-

ity. Some generalities, although not complete, can be made

for different classes of compounds (Table 4). However, when

evaluating toxicity it is necessary to obtain specific informa-

tion on the compound because there are many exceptions to

general rules of site of toxic action. It is not uncommon that

one chemical will have multiple organs or locations of toxic-

ity. A good example of this is the metal arsenic. Arsenic can be

both an environmental and occupational poison. Ingestion of

arsenic in drinking water, at elevated concentrations, has been

shown to result in skin cancer (which has been referred to as

Blackfoot disease) as well as other forms of cancer (e.g., lung;

Bhamra and Costa, 1992) and noncancer diseases (e.g., der-

matological; Lange, 2004a). Environmental problems associ-

ated with arsenic exposure (via water) can be most acute and

are well illustrated in a well-water problem for Bangladesh

(Murshed et al., 2004). Here water wells were established to

provide safe drinking-water sources (free of microbial con-

taminates). However, at the time these wells were placed it

was not known that the soil contained high levels of arsenic.

This resulted in drinking-water sources being contaminated

with this metal. Subsequently, there has been a high rate of

arsenic-related diseases (e.g., bladder, liver, and lung cancer;

Chen and Ahsan, 2004) as a direct result of using these water

sources. Arsenic does not only result in cancer, it also causes

many environmentally related noncancer diseases (Milton

et al., 2003). As mentioned, there are also occupational

diseases from this metal (Bhamra and Costa, 1992; Lange,

2004a). For example, workers in smelting plants that use

arsenic have been shown to exhibit elevated levels of lung

cancer, and from these types of studies arsenic has been

identified as a lung carcinogen. Although arsenic has been

reported to cause detrimental effects, it should be noted that

it is also an essential trace element. Deficiency in arsenic has

been reported to result in various health problems as well as

increased mortality (Bhamra and Costa, 1992). Thus, many

chemicals can have a dual role in causing and preventing

disease. It has even been suggested that some chemicals and

substances can have a protective effect in the occupational

environmental (Lange, 2000; Lange et al., 2003).

Chemicals can also be identified individually with a site

or organ system being affected. Examples of chemicals and

their general site of action are shown in Table 5. Certainly

this list is not comprehensive, but provides the range of

organ systems a single chemical can influence in the disease

process. Effects can be both acute and chronic along with

many having both carcinogenic and noncarcinogenic proper-

ties (e.g., benzene).

Excretion

Toxicants that are taken up by an organism must be eliminated

in some way. There are three major routes of excretion (urine,

feces, and air [exhalation]) and several minor routes (hair, nails,

saliva, skin, milk, and sweat). Many compounds are biotrans-

formed before being excreted. This biotransformation results

in xenobiotics being more water-soluble. As will be mentioned

later, biotransformation involves a two-step process known as

Phase I and Phase II biotransformation. Generally, substances

with the greatest toxicity are those that do not completely

undergo the biotransformation process.

Urinary excretion involves elimination through the

kidney and is commonly considered the most important

route of excretion. The kidney receives about 25% of the

cardiac output. Toxic agents are generally excreted by being

filtered out through the glomeruli or tubules in the kidney.

Fecal excretion can involve both the GI tract and liver


gallbladder. Some toxicants pass through the alimentary

system (GI tract) unabsorbed or modified by bacteria or other

processes in this system. Biliary excretion involves removal

of toxicants from the blood by the liver and their subse-

quent elimination through a fecal route. Here a xenobiotic is

TABLE 4

Locations or organs of toxic action by classes of chemical compound

Class of Chemical/Substance Location or Organ (Example)

Metals Kidney, bone, immune

Solvents Liver

Pesticides Nervous

Radiation Blood

TABLE 5

Specific chemicals and some of their general organs or sites of action

Chemical Location or Organ (Example)

Aluminum Endrocrine, kidney, lung

Arsenic Bladder, skin, heart, liver, lung,

nervous

Benzene Blood, liver

Cadmium Kidney, reproductive

Carbon monoxide Blood

Coke oven gases Lung

Cotton dust Lung

Ethanol Liver

Formaldehyde Lung (respiratory)

Fungus (Fusarium moniliforme) Liver

Lead Bone, blood, heart, kidney, nervous

Mercury Kidney, nervous, heart

Methyl ethyl ketone Heart

Paraquat G1, heart, lung

Phenol Liver, skin

Polyaromatic hydrocarbons Immune, liver, reproductive

Polychlorinated biphenys Immune

Rotenone Endrocrine, eye, lung, skin

Tetrachloroethylene Kidney

Thallium Eye

“Heart” includes the vascular system as a general group.

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