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Limitations
of the toxicity data
 WARNING!
Limitations of Available Human Toxicity Data
Hazard
Assessment vs. Risk Assessment
Weight-of-the-Evidence
Evaluations
WARNING!
Limitations of Available Human Toxicity Data
Human toxicity data do
not exist for many chemicals, which makes it difficult to draw firm
conclusions about the probable toxicity of a compound. Toxicity
tests on laboratory animals are more readily available, with U.S.
EPA requiring a certain minimum set of studies for different kinds
of toxicity before the chemical is registered (1). In spite of these
precautions, there are a number of reasons that the available toxicity
data may not accurately reflect the hazard potential of the chemical
to humans, including:
- Humans are
not necessarily similar to rats and other laboratory animals used
for testing. Because most test results are extrapolated from rats,
mice, dogs or rabbits to humans, noted effects may be different
than what humans actually experience. To attempt to discover interspecies
differences, U.S. EPA will often require studies on two species
of laboratory animal for some types of toxicity testing. In addition,
U.S. EPA builds in an interspecies uncertainty
factor to set "acceptable" safety thresholds when
human data are not available.
- Different
individuals have different susceptibilities to toxic substances.
U.S. EPA builds in an intraspecies uncertainty
factor to attempt to take this into account; however, the
range of human susceptibility is not actually known. This factor
may not be sufficiently protective.
- Children
and the developing fetus are particularly susceptible to the effects
of toxic substances. An exposure that would normally not cause
observable adverse effects in an adult animal can cause devastating
birth defects or interfere with normal development of a child.
U.S. EPA builds in a child uncertainty factor
to attempt to take this into account; however, because we lack
full knowledge of the mechanism of toxicity in some cases, this
factor may not be sufficiently protective.
- In laboratory
studies, the test animal is exposed to only a single chemical.
In the environment, humans are exposed to multiple toxins simultaneously,
which can lead to additive or synergistic effects.
- Not all
types of toxicity are studied in detail. The incidence of some
diseases linked to chemical exposure have increased substantially
in industrialized countries over the last 30 years or so. Attention
Deficit Disorder (ADD), Attention Deficit Hyperactivity Disorder
(ADHD), asthma, early onset of menstruation, multiple chemical
sensitivity, certain diseases related to immune system dysfunction,
and others. Yet although there is evidence that these diseases
have been linked to chemical exposure, the science of understanding
the mechanisms of these interactions is not far enough along for
regulatory agencies to test a chemical for the potential to cause
these effects. Thus, when there is insufficient information about
the link between exposure and disease, the process of risk assessment
does not fully evaluate these effects. Endocrine disrupting chemicals
are an excellent example of a group of chemicals that we know
have the potential to be problematic. While EPA is presently developing
a test for these chemicals and ramping up a testing program, it
is a fact that presently registered pesticides have not been tested
for their endocrine disrupting abilities. In the risk assessment
process then, this effect is not included as part of the hazard
assessment and is therefore ignored.
- The process
by which chemicals are prioritized for study or included on an
official toxcity list (carcinogens, reproductive toxins, etc.)
can be as much political as it is scientific. Some chemicals have
escaped extensive scrutiny because of interference from the chemical
industry.
- Fewer independent
studies (those conducted by someone other than the pesticide manufacturer)
have been conducted on newly registered chemicals, resulting in
the appearance that they are less hazardous than those that have
been on the market for a longer time and have been more thoroughly
studied. While it is often true that these chemicals are less
hazardous than the older chemicals, there is no way to be sure
this is actually true until 15-20 years have elapsed and the unanticipated
side effects have become apparent.
U.S. EPA attempts
to compensate for some of these limitations in the data by adding
in "Uncertainty Factors" which lower U.S. EPA's "acceptable"
dose of the pesticide that is used to set allowable uses, residue
tolerances, worker protection standards, and limits for drinking
water. Three types of uncertainty factors are used:
Interspecies
comparison uncertainty factor: The acceptable dose is lowered
by a factor of between 2 and 10 for chemicals for which there are
no human data available. For example, if the dose that results in
no observed acute toxicity in a rat study was 0.3 mg/kg and there
were no human studies available on acute toxicity, the "acceptable"
dose for a human is lowered to 0.03 mg/kg. If partial information
is available that indicates that humans and rats respond in a similar
fashion to the chemical, the uncertainty factor might be less than
10.
Intraspecies
comparison uncertainty factor: There are genetic differences
in humans' ability to detoxify and eliminate toxic substances in
their bodies. A good example is the 80-year-old who has smoked two
packs of cigarettes per day for 60 years and does not yet have cancer
compared to the 25 year-old who acquires multiple chemical sensitivity
after a single exposure to a toxic substance. To account for these
differences in susceptibility to toxic substances among humans,
the acceptable dose is lowered by an additional factor of 10.
Child
uncertainty factor: Since 1996, the Food Quality Protection
Act requires the U.S. EPA to add an additional uncertainty factor
of between 2 and 10 to account for the special susceptibility of
infants and children to toxic substances, unless there are data
to the contrary. If additional information is available indicating
that children and rats respond in a similar fashion to the chemical,
the uncertainty factor might be less than 10.
Reference:
- OPPTS
Harmonized Test Guidelines, U.S.
EPA Office of Prevention, Pesticides, and Toxic Substances, July
27, 2006. Viewed on August 1, 2006.
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Hazard Assessment vs. Risk
Assessment
The data presented in
the PAN Pesticide Database is strictly based on the inherent hazards
posed by a particular chemical. Actual risks to humans and the environment
can only be evaluated by knowing both the inherent hazards of a
chemical and actual exposures to the chemical. If a pesticide is
used in accordance with the label instructions, the risks to the
user associated with the chemical can be reduced, but never fully
eliminated. A problem with the risk management process that U.S.
EPA uses for pesticides is that compliance with label instructions
is assumed when calculating "acceptable" risks. In fact,
people often do not read the label on a pesticide product and even
if they do, they may not follow the label instructions. People who
are unaware that a pesticide has recently been applied in a particular
area will not know to take precautions. Thus, the "acceptable"
exposures produced by risk assessment are based on fundamentally
flawed assumptions about pesticide user behavior.
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Weight-of-the-Evidence Evaluations
A toxicity
evaluation based on the weight of the evidence is one where
a panel of experts evaluates all available laboratory studies for
a particular type of toxicity (cancer, birth defects, reproductive
harm, etc.), as well as any epidemiological or occupational data,
to determine a consensus rating for the hazard posed by that chemical.
Most "official" toxicity rankings (e.g., U.S. EPA, World
Health Organization (WHO), etc.) are determined in this manner.
This is the best system we currently have for objectively evaluating
the intrinsic hazards of chemicals. Unfortunately, even this system
can fail to protect human health and the environment.
There are many
obstacles to an objective and timely evaluation of chemicals. For
such an official ranking to be possible, the following must be true:
- A decision
must be made by the evaluating organization that the particular
chemical will be evaluated. Because of the expense and time involved
in the process, not all chemicals are evaluated in this manner.
In theory, those chemicals producing harmful effects in preliminary
studies or those in widest use are given highest priority for
evaluation. In practice, this process is often politicized, and
some toxic chemicals remain unevaluated because of industry efforts
to prevent listing of a particular chemical.
- There must be sufficient
data available for review. It is unfortunately true that there
are many chemicals for which the data gaps are substantial. Even
though the U.S. EPA requires the manufacturer to conduct a certain
minimum
set of studies (1) before a chemical can be registered, these
studies only evaluate a limited number of effects of the chemical
on laboratory animals and do not provide enough information to
defnitively say the chemical will not, for example, be carcinogenic
in humans or will not harm the environment. More complete information
often only appears after the chemical has been in use for years
and chronic effects have had time to become evident---DDT is a
good example of a pesticide that people once thought was "harmless"
but in fact had and continues to have devastating impacts on ecosystems.
Independent studies (not conducted or funded by the manufacturer)
are critical to an objective analysis, yet these kinds of studies
are rarely conducted until after the chemical has caused enough
damage to raise suspicion that it is more hazardous than the initial
evaluation revealed.
Reference:
- OPPTS
Harmonized Test Guidelines,
U.S.
EPA Office of Prevention, Pesticides, and Toxic Substances, July
27, 2006. Viewed on August 1, 2006.
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Last updated
August 1, 2006
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