1158 TOXICOLOGY
biotransformed by the lever and transported to the gallblad-
der, which then excretes the chemical into the GI tract for
elimination. There are some cases where a chemical elimi-
nated by this route is then reabsorbed by the intestine into
the body, resulting in a long half-life for this substance. This
process is known as the “enterohepatic cycle.” Ideally chemi-
cals are metabolized into a polar form, making these poorly
reabsorbable. However, microbes in the intestine can trans-
form these compounds into a more lipid-soluble compound,
which favors reabsorption.ExhalationSubstances that exists in a gas phase are mostly eliminated
through the lungs. These chemicals are mostly eliminated
through simple diffusion, with elimination generally related
to the inverse proportion of their rate of absorption. Thus,
chemicals with low blood-solubility are rapidly eliminated,
while others with high solubility are eliminated slowly.Other RoutesSeveral other routes of excretion have been mentioned.
Overall, these other routes are of minor importance in elim-
ination of toxicants. However, they can be used to test the
existence and concentration of various toxicants in the organ-
ism. This is commonly known as “biological monitoring.” For
example, hair can be used to test where a person has suffered
from previous exposure to and possible toxicity of heavy
metals, like arsenic. Thus, these minor excretion routes can
be important for specific areas of toxicology (e.g., forensic).
It should be noted that the major routes can also be used for
biological monitoring, with urine and blood being the most
important, particularly clinically and occupationally.Biological MonitoringBiological monitoring has become a common method for
evaluating absorption of chemicals and drugs. It has been used
for such activities as drug and alcohol testing. Methods have
been established to determine the absorbed dose of a chemi-
cal, which are therefore important in many areas of toxicol-
ogy, including clinical, forensic, and occupational toxicology.
The ACGIH has established BEI values for some chemicals
as one measure of monitoring risk to industrial populations.
This allows evaluation of exposure from all routes, including
occupational and nonoccupational. In many cases, only one
route of exposure is evaluated, airborne levels, while exposure
from other routes (e.g., dermal) contributes to the absorbed
and toxic dose. Biological monitoring can be used for both
major and minor routes of excretion. As noted, hair and nails
can be used to evaluate exposure to heavy metals. An exam-
ple of biological monitoring in the occupational environment
is for methyl ketone (MEK), which has been suggested to be
measured at the end of a work shift using urine as the biologi-
cal fluid. The ACGIH BEI for MEK is 2 mgl.
Biological monitoring is also used as part of medi-
cal evaluations and in environmental toxicology as well.A good example of its use in medical evaluations is for lead-
abatement workers. Blood lead levels (BLL) for workers in
this industry or exposure category have been established by
OSHA. Here workers having a BLL over 40 gdl (deciliter
of whole blood—100 ml of blood) are required to undergo
an annual medical examination. Workers over 50 gdl are
required to be removed from the work area (removal from
exposure) until the BLL (two connective readings) is below
40 gdl. This illustrates the use of biological monitoring
in prevention of occupational disease and its incorporation
in regulatory toxicology.
Environmentally, lead is often monitored in children
since it can cause harm in a number of organ systems and
with effects that are characterized with a developing organ-
ism. The Centers for Disease Control and Prevention (CDC)
suggest that children below the age of 6 not have a BLL
that exceeds 10 gdl. This is the lowest level that has been
suggested to have biological effects for humans. Biological
concentrations of chemicals have also been used to evaluate
exposure and toxic effects in organisms other than man.
Monitoring of biological fluids and tissue in environmen-
tal toxicology is a common practice (Pip and Mesa, 2002).
Both plants (Pip and Mesa, 2002) and animals (Madenjian
and O’Connor, 2004) are used for evaluating the distribu-
tion and uptake of toxicants from polluted environments.
Monitoring can also be extended to abiotic conditions that
influence toxicity to organisms (Mendez et al., 2004).
The use of biological systems for monitoring can include
effects on metabolism and other systems as well (Lange and
Thomulka, 1996). Thus, biological monitoring is commonly
used in both environmental and occupational settings as well
as other areas of toxicology. Monitoring of this nature has
even been extended to ecosystems as a methodology for
evaluating health.BiotransformationXenobiotic substances that are taken up by an organism
must eventually be eliminated. To eliminate many of these
chemicals, they must be transformed into a water-soluble
product. This transformation is called “biotransformation.”
In many vertebrates, this transformation occurs in the liver,
although other tissues and organs (e.g., the kidney) are also
involved. Generally, chemicals are absorbed as lipid com-
pounds and excreted as water-soluble (hydrophilic) com-
pounds. Hydrophilic compounds can be easily passed along
with the urine and feces. In the lungs, volatile compounds
are favored for excretion in the exhaled gas, while those that
are nonvolatile are generally retained. If chemicals were not
biotransformed, their rate of excretion as lipid-soluble com-
pounds would be very long, and this would result in buildup
of xenobiotics. The rate at which a chemical is metabolized
or excreted is called its half-life ( t 1 2 ). Half-lives can be very
short (as in minutes) or long (as in years).
Biotransformation and metabolism are often used as
synonymous terms. In general they can be used interchange-
ably, although here biotransformation is used in describing
the metabolism of xenobiotics that are not part of normalC020_003_r03.indd 1158C020_003_r03.indd 1158 11/18/2005 11:09:29 AM11/18/2005 11:09:29 AM