1154 TOXICOLOGY
data, the endpoint must be identified, especially when look-
ing at nonlethal measurements such as EC 50 ’s.
There are three general routes of exposure: inhalation,
dermal (skin), and ingestion (oral). A fourth route, which is
more related to medical situations, is injection. Depending on
the chemical and the activity employed, one or more of these
will have a great deal of importance in the toxic outcome.
Occupationally, the most important route is inhalation, since
it generally results in the most severe health consequences.
Dermal effects are the most numerous, but in most cases are
of minor importance. Most dermal effects are related to irri-
tation of the skin and related allergic reactions. As a general
rule in occupational toxicology, skin problems are the most
common, although effects such as cancer of various organs
can also be of concern (Lange, 2003). Using cement as an
example, epidemiological studies have reported this agent to
cause cancer in a variety of organs. The organs or systems
of carcinogenic concern include the skin, bladder, stomach,
and lungs (Smailyte et al., 2004), although the most common
problem reported in occupations using this building material
is dermatological (skin) (Winder and Carmondy, 2002; Lange,
2003), which is a noncarcinogenic occupational hazard. This
illustrates that a chemical can have multiple toxic endpoints
for different organs.
Most toxicologists divide the exposure to humans and
organisms into four categories: acute, subacute, subchronic,
and chronic. Acute is commonly defined as a single or repeated
exposure that occurs over a 24-hour period that results in a
measurable effect. Although this definition is not perfect, it
tells us that acute cases are generally of short duration and
high concentration. Subacute, on the other hand, is exposure
that occurs over about a 1-month time period and in this case
is generally lower in concentration, and the effect requires a
longer period of time to occur in comparison to a true acute
exposure. It is not uncommon to report acute effects as case
studies. In the case report by Dote et al. (2003), an industrial
worker accidentally exposed (sprayed) himself with the agent
hydrogen fluoride (HF), or hydrofluoric acid. HF is a highly
corrosive agent that can result in serous chemical burns, and
in this case the burns occurred on the face of the industrial
worker. As a result of this exposure, the worker died within a
half hour as a result of acute respiratory failure. In the case of
HF, this substance would be considered a hazard to both the
respiratory and dermal systems, in this case inhalation being
the main route of exposure that resulted in death. To put HF
exposure in perspective, Hathaway et al. (1991) reported that
the LD 50 for a 5-minute exposure is between 500 and 800
parts per million (ppm).
Chronic toxicology is defined as an effect resulting from
an exposure that occurs over a long period of time, like years.
Certainly the time period of measurement also depends on the
length of an organism’s life history as well. Subchronic, as
compared to chronic, is of shorter duration with a higher con-
centration and can be considered to occur within a time period
of 1 to 3 months for people. Although these terms are dis-
cussed for an occupational setting, the terms are also applied to
environmental toxicology. Historically, acute exposure was a
key factor in exposure prevention. As industrial exposures arebecoming better controlled, there has been a change in focus to
chronic conditions, at least in the developed countries.
Since inhalation is the most important route of exposure
in the occupational (industrial) environment, most reported
limits of acceptable exposure are for this route. However, in
other systems, such as aquatic or terrestrial, dermal contact
or ingestion may be the most important routes of exposure.OCCUPATIONAL EXPOSURE LIMIT VALUESFor occupational exposure, established upper limits have been
published by governmental and private agencies or groups.
These values are: permissible exposure limit (PEL), thresh-
old limit value (TLV), and recommended exposure limit
(REL). PELs are established by the U.S. Occupational Safety
and Health Administration (OSHA) and are the legal stan-
dard for the maximum exposure level. OSHA PELs are pub-
lished in the Code of Federal Regulations (CFR) at 29 CFR
1910.1000. It should be noted that these exposure concentra-
tions are mostly for inhalation, as previously mentioned, and
the levels represented are somewhat out of date, since they
have to go through a regulatory process for updating. TLVs
are established by the American Conference of Governmental
Industrial Hygienists (ACGIH), which is considered a consen-
sus organization. Many consider these values to be the most
up-to-date, although they are, like most decision-making pro-
cesses, subject to industry pressure and other political factors
when being established. Generally, TLVs are lower in concen-
tration than PELs, although there are exceptions to this state-
ment. It can be considered that the PELs, as they change, are
also subject to industry and political considerations as well.
Both the PELs and TLVs are established for an 8-hour time-
weighted average (TWA). This average is an arithmetic mean
of all the exposures collected in that workday. The formula for
making a TWA is shown below.TWA ( C 1 T 1 ) ( C 2 T 2 ) ... ( C n T n )
( T 1 ) ( T 2 ) ... ( T n )C —concentration
T —timeThe maximum and ideal time of sample (exposure) col-
lection is 8 hours, although this is not usually feasible. Most
consider that to obtain a TWA the sample should be collected
for at least 6.5 hours of the 8-hour work shift. The remaining
1.5 hours would be included as a 0 exposure level. The REL
is a 10-hour TWA exposure limit and is set by the National
Institute of Occupational Safety and Health (NIOSH) as a
value to be considered by OSHA in the rule-making process.
For all the values (PEL, TLV, and REL), they are established
for a 40-hour workweek.
When evaluating exposure limits, exceedance can be
considered for a single measurement or summation of mea-
surements (Letters to the Editor, 1998). There has been
considerable discussion of the correct evaluation for expo-
sure. For those chemicals that are considered to be chronic
in nature, disease appears to follow the arithmetic mean ofC020_003_r03.indd 1154C020_003_r03.indd 1154 11/18/2005 11:09:27 AM11/18/2005 11:09:27 AM