US Environmental Protection Agency
Office of Pesticide Programs
A Review of the Relationship between
Pyrethrins, Pyrethroid Exposure and
Asthma and Allergies
June 2009
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A Review of the Relationship between Pyrethrins,
Pyrethroid Exposure and Asthma and Allergies
Abstract
In the current review, EPA used a weight of evidence approach to determine
whether an association exists between pyrethrins/pyrethroid exposure and asthma and
allergies. More explicitly, the current review included data from both animals and
humans. The Agency considered animal data regarding mode of action; target organ of
toxicity; acute inhalation and dermal irritation; and sensitization. The Agency also
considered human data including incident data from several sources and epidemiology
studies. In the weight of evidence analysis, EPA considered consistency, reproducibility,
temporal and dose concordance, and biological plausibility of the effects reported in each
data set and across all data sets. Comparisons of health effects profiles were also
conducted between pyrethrins/pyrethroid products and other insecticides when possible
to determine whether exposure to this class of pesticides elicits a heightened or unique
respiratory response compared to other insecticides. This approach is predicated on the
premise that an integrative assessment is more informative than what any single dataset
or study could provide; and that fundamental biological mechanisms of disease outcome
are concordant across species.
Based on the current analyses, the Agency concluded there is no clear and
consistent pattern of effects reported to indicate conclusively whether there is an
association between pyrethrins/pyrethroid exposure and asthma and allergies. The
Agency is not requiring additional warnings or label statements specific to asthmatic or
allergic individuals on pyrethroids and pyrethrins end-use products, nor is the Agency
requiring additional data from pyrethroid registrants at this time. However, in order to
clarify the issue of possible correlation between use and incidents, the pyrethrins
registrants have committed to a product stewardship program that will include a
prospective in-depth follow-up of reported pyrethrins incident cases. The Agency will
review the pyrethrins incident data as it is submitted. If the Agency identifies
discrepancies or trends in the data that differ from the incident data considered in this
review, the Agency will consider requiring additional or similar data from the pyrethroid
registrants.
I. Introduction
On July 30, 2008 the Center for Public Integrity (CPI) published an article titled
'Safe' Pesticides Now First in Poisonings, which focused on human incidents and
exposure to pyrethroid and pyrethrins pesticide products. The article asserts that human
incidents associated with pyrethroid and pyrethrins products have increased sharply over
the past decade in both number and severity. CPI cites the Environmental Protection
Agency's (EPA or Agency) Incident Data System in support of their assertion that 50
fatalities are associated with pyrethroids and pyrethrins since 1992, of which 20 occurred
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between 2003 and 2007. The authors attribute the increase in pyrethroid and pyrethrins
incidents largely to increasing use of the active ingredients since the phase-out of
organophosphates in residential areas, beginning in 2000.
The article further states that "(d)espite the common belief that these insecticides
are less toxic than organophosphates and that fatal incidents are rare, some scientists and
physicians have begun to question their safety — especially for people with asthma or
allergies."
The CPI report prompted EPA to conduct its most recent review of pyrethrins and
pyrethroid incidents to identify any trends in the data. To determine whether there is an
association between pyrethrins and pyrethroid products and asthma and allergy effects,
EPA performed a thorough review of the animal and human incident and epidemiological
data1. The process and conclusions of this evaluation are discussed in Sections III and IV
below.
Before the recent review, various offices within EPA had considered the potential
relationship between pyrethrum, pyrethrins, and pyrethroids and allergic/asthmatic
effects. EPA's Office of Pesticide Programs' (OPP) "Recognition and Management of
Pesticide Poisonings" manual states that crude pyrethrum is a dermal and respiratory
allergen, probably due mainly to non-insecticidal ingredients. However, there are no
pyrethrum end-use products currently registered with the Agency. The Agency does
have over 1,200 registered end-use products containing pyrethrins, which is refined
pyrethrum. In the production of pyrethrins, impurities such as sesquiterpene lactones
(chemicals found in many plants that are known to cause allergic reactions) are removed
from pyrethrum, which removes the allergic component (Osimitz, 2006). Pyrethroids are
synthetic insecticides similar to pyrethrins, but have been modified to increase their
insecticidal potency and their stability in the environment (Bradberry, 2005; Casida,
1980). There are approximately 2500 pyrethroid end-use products registered with the
Agency. Neither pyrethrins nor pyrethroids have been characterized by EPA as allergens.
In 2000 the EPA's Office of Radiation and Indoor Air (ORIA) commissioned a
review by the National Academy of Sciences' Institute of Medicine (IOM) of published
data on the relationship between asthma and exposure to various substances commonly
found in indoor air. Based on the results of this review, the Agency's risk reduction
guidance for indoor asthma triggers focuses on secondhand smoke, dust mites, mold,
cockroaches and other pests, household pets, and combustion byproducts. The IOM
review considered pesticides as a potential asthma trigger, but found the information
available to be inconclusive. Therefore the Agency has not listed pesticides as an indoor
environmental trigger of asthma symptoms. The Agency has stated, however, that proper
use of some pesticides as part of an exposure control program may yield benefits to some
individuals with asthma, through the elimination or reduction of sources of allergens,
such as cockroaches and other pests (IOM, 2000).
1 The human studies described do not constitute "research involving intentional exposure of a human
subject" under EPA's Rule for the Protection of Human Subjects.
Page 2 of 27
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The EPA does not require additional warning statements for individuals with
respiratory allergies or asthma on registered pyrethrins or pyrethroid end-use pesticide
products. However, in 1982 the Food and Drug Administration (FDA) required the
following warning statement to appear on pediculicide products containing the
combination of pyrethrum extract and piperonyl butoxide: "Use with caution on persons
allergic to ragweed" (21 CFR § 358.601). According to FDA, the decision to add this
statement was based on conflicting reports on the allergenicity of ragweed-sensitive
individuals to pyrethrins formulations.
A scabicide cream product containing 5% permethrin (a type I pyrethroid) has
been available with a prescription since 1989 and does not contain a specific asthma or
allergy warning statement. It has a general statement warning of possible
hypersensitivity to any of its components. A pediculicide cream product containing 1%
permethrin is available over the counter (OTC). In 1990 when the product was changed
from a prescription to OTC, labels warned consumers that the product may cause
breathing difficulty or an asthmatic episode in susceptible persons but did not mention
ragweed.
With the publication of the "Drug Facts Labeling" rule in 1999 (64 FR 13254),
FDA standardized all OTC labels. In 2003, the allergy warning statements on all OTC
pediculicide drug products was expanded and revised to the following: "Ask a doctor
before use if you are allergic to ragweed. May cause breathing difficulty or an asthmatic
attack" (68 FR 75414, published December 31, 2003).
The Reregi strati on Eligibility Document (RED) for pesticide products containing
pyrethrins was published by OPP in 2006. During reregi strati on the association between
pyrethrins products and allergy/asthma effects was considered. The Agency reviewed
pyrethrins incidents to determine if they signaled a need for label language warning
consumers of a possible association between exposure and allergy/asthma effects. Due to
uncertainty in the data, label language similar to that required by the FDA was not
considered necessary. Instead, as a condition of reregi strati on the EPA required the
Pyrethrins Joint Venture (PJV), an industry task force, to institute a product stewardship
program involving a prospective in-depth follow-up of reported pyrethrins incidents to
clarify any possible correlation between pyrethrins product use and adverse health
consequences. The product stewardship program also requires outreach to physicians and
Poison Control Centers, and provides them with better guidance and diagnostic standards.
As part of the PJV stewardship program, an annual report submitted to the Agency will
be required for at least 5 years.
While the data collected by the PJV is expected to clarify whether pyrethrins
exposure is associated with allergy and asthma effects, these new data won't be available
for another 1-2 years. Therefore, the Agency has reviewed the current available animal
studies, human incident data and epidemiological studies to evaluate whether there is a
potential relationship between exposure to pyrethrins/pyrethroids and allergic/asthmatic
responses.
Page 3 of 27
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II. Background
A. Definition of Asthma and Allergies
An allergy is an immunologically mediated adverse reaction to a particular
substance, also called an allergen (common allergens include ragweed, peanuts, house
dust mites). Allergic reactions can be expressed in many ways, such as a rash, an
asthmatic response, swelling and/or shock. (NIH, 2006)
Asthma is a chronic inflammatory disease of the airways. Symptoms include
wheezing, breathlessness, chest tightness and coughing (and are often episodic).
Although research has indicated that there are both genetic and environmental
components involved in the development of asthma, the etiology of asthma continues to
be researched. Additionally, asthma lacks a universal definition, which adds to the
overall complexity of evaluating this disease when there are such vast differences in
medical diagnoses and multiple allergic triggers. Asthma triggers include pet dander
from cats and dogs, cockroaches, house dust mites, environmental tobacco smoke,
fungi/molds, rhinoviruses and nitrogen dioxide. (IOM, 2000; NIH 2007).
B. Prevalence of Asthma and Allergies
Based on statistics from the Centers for Disease Control and Prevention (CDC) in
2005 8% and 9.3% of U.S. non-institutionalized adults and children, respectively, were
diagnosed with hay fever (a specific and widespread allergy), and 7.3% and 9.4%,
respectively, were diagnosed with asthma (CDC, 2007b; CDC, 2007c). Overall the
asthma rate in the U.S. increased towards the end of the 20th century, and the increase
affected all ages, racial groups and geographic areas. However, more recently, evidence
suggests asthma morbidity and mortality are leveling off or decreasing (CDC, 2007a;
ALA, 2007). Regardless, asthma remains a public health concern. Public health
surveillance indicates that the prevalence of asthma differs among various demographic
subpopulations (e.g., blacks, Puerto Ricans, children, Northeasterners, those living below
the federal poverty level) (CDC, 2007a).
C. Pyrethrum, Pyrethrins and Pyrethroids
Pyrethrum is an extract (and mixture of substances) derived from chrysanthemum
flowers with insecticidal properties. Pyrethrins is a more refined pyrethrum extract,
intended to further isolate the insecticidal components of pyrethrum. EPA regulates
pyrethrins as one active ingredient, however, the refined extract contains a mixture of six
isomers. Pyrethroids are a class of synthetic insecticides that are structurally similar to
pyrethrins and act in a similar manner to pyrethrins, but have been modified to increase
their environmental stability and their insecticidal properties (Bradberry, 2005; EPA
1999; Casida, 1980). In general, pyrethrins/pyrethroids are less toxic to mammals and
are considered good candidates for replacement of the more toxic organophosphate
insecticides. As discussed in Section I, pyrethroids and pyrethrins are not expected to
Page 4 of 27
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contain the allergic component found in pyrethrum. However, there have been reports
asserting a potential association between pyrethrins/pyrethroid exposure and
allergic/asthmatic effects, based on human incident data.
D. Previous Reviews and Analysis
In 2005, the Agency reviewed pyrethrins incidents from the OPP Incident Data
System (IDS), American Association of Poison Control Centers (PCC), Pesticide
Telecommunications Network (NPTN), and the National Institute of Occupational Safety
and Health's Sentinel Event Notification System for Occupational Risk (NIOSH
SENSOR). The resulting report concluded that direct exposure to pyrethrins can cause
skin, eye, or respiratory irritation. The literature review found evidence that persons may
become sensitized or have cross-reactivity due to exposure to other allergens. Evidence
that pyrethrins products may be involved in producing asthma-like reactions is suggested
from a number of cases identified in the literature review. However, it was
acknowledged that there is strong evidence for other causes of asthma, such as pet
dander, cockroach allergens, and dust mites. Applications that can result in direct
exposure to bystanders (e.g., automatic insecticide dispensers) can be expected to result
in skin, eye, or respiratory effects in some sensitized individuals. (Blondell, 2005).
In 2004 the Agency reviewed Poison Control Center data covering the years 1993
through 1998, and concluded that there was a greater risk of moderate or major
symptoms among those exposed to products containing pyrethrins and piperonyl butoxide
(PBO) than those exposed to pyrethrins alone. PBO is a pesticide synergist, which is
often co-formulated with the pyrethrins active ingredient to increase the insecticidal
potency of the active ingredient. The data also indicated that respiratory symptoms
(bronchospasm, coughing or choking, or dyspnea) and selected dermal symptoms (dermal
irritation, pain, itching, or rash) were more likely if the exposure included PBO (Blondell,
2004).
In a Master's thesis (Mosby, 2003) analyzing PCC data, Jacqueline Mosby
concluded that pyrethrins and pyrethroid exposure increased the likelihood of asthma or
allergies. Mosby found that the effect is greater for pyrethrins than for pyrethroids.
Mosby also noted that national pesticide poisoning surveillance is poor, and many cases
may go undiagnosed or unreported.
In response to Mosby's work, Dr. Jerry Blondell acknowledged that there was
some evidence of an association between dermal effects and exposure to
pyrethrins/pyrethroid products. However, the associations were slight. Mosby concluded
that EPA should "consider improving their labels to warn applicators and users with a
history of ragweed allergy or asthma about the potential consequence of inhalation
exposure when using products that contain pyrethrins/pyrethroids." (Mosby, 2003). Dr.
Blondell supported similar label language.
During pyrethrins reregi strati on, EPA considered requiring a label warning for
those with asthma or ragweed. However, due to uncertainty in pyrethrins incident data it
Page 5 of 27
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was unclear whether those with asthma or ragweed allergies reacted more strongly to
products containing pyrethrins than the general population. Instead of adopting the
suggested restrictions for these specific populations, the pyrethrins Reregi strati on
Eligibility Decision (RED) includes precautions for all consumers, including
requirements for ventilation when these products are used in enclosed areas. In addition,
the RED requires registrants to conduct a stewardship program, cited above and
described in detail in the RED2.
III. Current Data Review and Analysis
In the current review, a weight of evidence approach was utilized to determine
whether an association exists between pyrethrins/pyrethroid exposure and asthma and
allergies. The current review considered animal studies addressing mode of action, target
organ of toxicity, acute inhalation and dermal irritation, and sensitization. The review
also considered human incident data from several sources and human epidemiology
studies. In the weight of evidence analysis, several criteria are used to determine whether
an association exists; they include consistency, reproducibility, temporal and dose
concordance and biological plausibility of the effects/outcomes.
A. Animal Data
Animal studies show that pyrethrins and pyrethroids have low acute toxicity and
the active components are rapidly and extensively metabolized with no significant
accumulation, and they pose relatively low hazard to mammals. Available animal data do
not indicate that pyrethrins or pyrethroids significantly affect organ systems other than
the nervous system, although changes in liver weight and metabolism of chemicals have
sometimes been used as an index of adverse effect levels for pyrethroids (Schoenig,
1995). Signs of respiratory irritation were reported in laboratory animals acutely exposed
to aerosols of pyrethroids at lethal or near-lethal airborne concentrations (Curry and
Bennett, 1985; Flucke and Thyssen, 1980; Hext 1987; Pauluhn and Thyssen, 1982).
Intermediate-duration (90-day) repeated exposures of rats to mean analytical pyrethrins
concentrations >30 mg/m3 resulted in clinical and microscopic evidence of respiratory
irritation (Schoenig, 1995). These tested concentrations in animals are much higher than
those to which humans are likely to be exposed.
No animal studies were available in which inhalation exposure to pyrethrins or
pyrethroids could be associated with immunological effects such as hypersensitivity (i.e.,
allergy or asthma). In contrast, immunosuppressive effects were observed in various
pyrethroids via oral exposure such as decreased humoral immune response, reduced cell-
mediated immune response and leukopenia (Lukowicz-Ratajczak and Krechniak, 1992;
Demian, 1998; Varshneya et al., 1992).
The primary mode of action for pyrethrins and pyrethroid exposure is prolonging
the open phase of the sodium channel gates of nerve cells (Cassida et al., 1983; Coats,
' The pyrethrins RED can be found at http://www.epa.gov/pesticides/reregistration/pyrethrins/.
Page 6 of 27
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1990; Narahashi, 1986; Sattelle and Yamamoto, 1988; Soderlund, 1995; Soderlund et al.,
2002; Valentine, 1990; Vijverberg and van den Bercken, 1990). Using a variety of
methods, including voltage clamp and patch clamp techniques, pyrethrins and pyrethroids
have been shown to slow the closing of sodium channel gates following an initial influx
of sodium during the depolarizing phase of an action potential, resulting in a prolonged
sodium tail current (Narahashi 1986; Vijverberg and Van den Bercken 1982). The
prolonged opening of the sodium channel in the nervous tissue causes repetitive firing of
sensory nerve endings, resulting in a hyperexcitable state. In rodents, effects such as
tremors are induced if the open state is prolonged for brief periods; effects such as
sinuous writhing (choreoathetosis) and salivation occur if the open state is prolonged for
longer periods.
There are two types of pyrethroids, types I and II, which differ in basic structure
and in the symptoms of poisoning (Coats, 1990; Verschoyle and Aldridge, 1980). Type I
pyrethroids do not include a cyano group, and their effects in rodents typically include
rapid onset of aggressive behavior and increased sensitivity to external stimuli, followed
by fine tremor, prostration with coarse whole body tremor, elevated body temperature,
coma, and death. Type II pyrethroids include a cyano group in the alpha position, and
their effects in rodents are usually characterized by pawing and burrowing behavior,
followed by profuse salivation, increased startle response, abnormal hindlimb
movements, and coarse whole body tremor that progresses to sinuous writhing
(choreoathetosis). Almost all systemic effects of exposure to pyrethrins and their
derivatives are targeted to the nervous system.
B. Human Incident Data
Human incident information is mainly self-reported, and typically neither
exposures to a pesticide nor reported symptoms (nor the connection between the two) are
easily verifiable or reliable. Incident information, however, does provide important
feedback to the Agency. Incidents with severe outcomes, or other clear patterns or
trends, can signal a need to further investigate a particular chemical or product.
The following table summarizes the strengths and limitations of various sources
for human incident data for pesticides available to OPP. These sources differ in purpose,
in scope, in key definitions, and in methods of data acquisition and database maintenance.
These differences must be understood in order to accurately interpret the data.
Page 7 of 27
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Table 1: Strengths and Limitations of Human Pesticide Incident Data Sources
Data Source
OPP Incident
Data System
(IDS)
American
Association of
Poison Control
Centers (PCC)
National
Pesticide
Information
Center (NPIC)
Sentinel Event
Notification
System for
Occupational
Risk
(SENSOR)
California
Pesticide Illness
Surveillance
Program (PISP)
Years
1992-present
1993-2005
1978- present
1998-
present
Standard
collections
from 1982;
Methods
revised 1992
Strengths
-Centralized system
-Incident reports from various
sources
-Case reports
-National scope
-Able to summarize fields/organize
information
-Clinically oriented
-Over 1.5 million records
-National scope
-Best available data for
occupational incidents
-Includes data from multiple
sources
-Standardized information
-Unique infrastructure for follow-
up
-Strong baseline information;
longest history
-Includes all types of pesticides
-Provides detailed information
Limitations
-Uneven level of detail
-Labor intensive; not fully automated
-Largely anecdotal reports/allegations
-Focus on incidents in residential
settings
- Focus on incidents in residential
settings
-Limited scale; small sample size
-Covers only 12 states
-Reporting varies from state to state
-Focus on occupationally -related
cases
-Limited to California
-Occasional lag time between incident
and report
This review focused on the IDS, PCC, and NPIC databases, because their
coverage is the most nearly national. To gain an additional regulatory perspective on
pyrethins and pyrethroid products we also considered FDA's incident database covering
incidents associated with pharmaceutical use of pediculicides and scabicides containing
pyrethrins and permethrin.
1. OPP Incident Data System (IDS) Data
OPP Incident Data System (IDS) contains incident reports submitted to OPP since
1992 from various sources including registrants, other federal and state health and
environmental agencies, and individual consumers. These reports are typically anecdotal
with low to moderate levels of detail. Often, it is difficult to draw clear conclusions
implicating any pesticide as a cause of any of the reported health effects. Nevertheless,
the data can be helpful in describing potential health effects from exposure to a pesticide.
The graph below shows the number of incidents reported to IDS each year from
1993-2005 involving products containing pyrethrins or pyrethroids. Among the total of
2,279 incidents there is no apparent temporal trend during this time period.
Page 8 of 27
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400-r
350
300-
250-
200
150
100
50
0
Figure 1
Pyrethrins and Pyrethroids Incidents in IDS
1993 1994 1995 1996 1997 1998 1999 2000 2001 2002 2003 2004 2005
year
The Agency also examined reported deaths following exposure to products
containing pyrethrins or pyrethroids from 2003 to May of 2008 to see if the information
available about these incidents suggested a relationship between exposure to
pyrethrins/pyrethroids and respiratory symptoms or allergic reactions. When available,
the following information was extracted from IDS for each reported death associated with
pyrethrins/pyrethroids: age and sex of the victim, the chemical the person was exposed
to, time of exposure to initial onset of effects, the duration of exposure, symptoms, pre-
existing conditions, and other circumstantial or exposure-related information.
Initially, 24 reports of deaths were identified in IDS appearing to be potentially
related to exposure to pyrethrins and/or pyrethroids. Upon further examination, 16 of
these reports were set aside for one or more of the following reasons:
1. Duplicate report of previously counted cases
2. The death was a suicide or homicide, or resulted from intentional misuse
3. Exposure was to other active ingredients as well as to pyrethrins/pyrethroids,
and attribution to pyrethrins or pyrethroids is unclear.
Of the eight deaths that may be attributable to exposure to pyrethrins and/or
pyrethroid products, four victims showed respiratory symptoms, two showed other
symptoms such as feeling ill and headaches, and burning hands, and no particular
symptoms were reported for the remaining two victims. The eight deaths involved
exposures to one or a combination of the following pyrethrins and pyrethroid active
ingredients: pyrethrins, permethrin, cyfluthrin, cyhalothrin, bifenthrin, and esfenvalerate.
No apparent link between the symptoms and the deaths, or between the type of pyrethrins
and pyrethroids and the deaths, can be hypothesized.
2. American Association of Poison Control Centers (PCC) data
The American Association of Poison Control Centers database includes reports of
over 200,000 pyrethrins and pyrethroid total incidents recorded from 1993-2005. Figures
Page 9 of 27
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2 and 3 below show pyrethrins and pyrethroid total incidents increasing gradually over
time, both in crude count and as a percentage of all pesticide incidents.
Figure 2
Pyrethroids and Pyrethrins Incidents over Time
30000 -,
25000 -
20000-
15000 -
10000 -
5000 -
• pyrethroid/pyrethrin PCC incidents
by year
n
1993 1994 1995 1996 1997 1998 1999 2000 2001 2002 2003 2004 2005
year
Figure 3
Pyrethroids and Pyrethrins incidents compared to all Pesticide
incidents
1 \J\J\J\J\J -
140000 -
120000 -
100000 -
80000 -
60000 -
40000 -
20000 -
0
1
09
i '
&
', '
i—i
39
i 1
-
39
i '
—
49
) '
—
49
'< 1
49
' '
—
49
i 1
69
', '
79
i 1
89
', ''
—
99
i '
-
29',
1993 1994 1995 1996 1997 1998 1999 2000 2001 2002 2003 2004 2005
year
All Pesticide incidents
Pyrethrins and Pyrethroid
incidents
PCC information also shows total incidents involving organophosphates (OPs)
decreasing over time, again both as crude counts and as a percentage of all pesticide
Page 10 of 27
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incidents. The decline in OP incidents coincides with an expected decline in usage
following the phase-out of residential uses of OPs beginning in 2000 (Power, 2007).
Figure 4
Organophosphate Incidents Compared to All Pesticide Incidents in
PCC
180000
160000 -
140000 -
•£ 120000 -
o>
T3
1 100000 -
Z 80000 -
A
I 60000 -
c
40000 -
20000 -
0
14!
0
n
1
1
16
%
3
'o
11
%
11
Yo
ro
Yo
95
75
0
65
S'/o
1993 1994 1995 1996 1997 1998 1999 2000 2001 2002 2003 2004 2005
year
PCC data support OPP hazard assessments showing OPs to be more toxic than
pyrethrins and pyrethroid insecticides. The tables below report all deaths and "major"
incidents, those in which the patient has exhibited symptoms as a result of the exposure
which were life-threatening or resulted in significant adverse health effects for
pyrethrins/pyrethroids, organophosphates, and carbamates. Although there were roughly
a third more incidents overall from 1993-2005 involving pyrethrins/pyrethroids than
involving OPs, more of the OP incidents resulted in serious health outcomes or death.
Table 2: Total Incidents in PCC Database by Insecticide Class, 1993-2005
Insecticide Class
Pyrethrins/Pyrethroids (P/P)
Organophosphates (OP)
Carbamates (C)
Total Incidents in PCC*
234,206
178,705
78,085
Ratio
P/P:C~3
OP:C~2.3
C:C=1
*See Appendix I for further information about queries
Page 11 of 27
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Table 3: Annual Deaths and Major Incidents by Insecticide Class
Major Incidents
P/P
16
20
19
18
22
28
33
21
23
30
24
35
35
OP
39
43
46
35
48
31
61
61
46
43
30
35
26
C
11
8
10
9
10
12
8
5
11
14
6
7
7
1993
1994
1995
1996
1997
1998
1999
2000
2001
2002
2003
2004
2005
Incidental Deaths
P/P
1
0
0
1
0
0
1
0
0
0
1
0
3
OP
0
2
1
3
3
2
2
1
0
4
3
0
2
C
0
0
0
2
0
0
0
0
0
0
1
0
0
A chemical's 'related-effect profile' or symptom signature refers to the different
symptoms or effects that are reported to be related to exposure to the chemical. The
Agency reviewed all reported incidents in the PCC database for pyrethrins and six
pyrethroid active ingredients (bifenthrin, deltamethrin, permethrin, resmethrin, sumithrin,
and tetramethrin) selected based on their usage information and use patterns. The
Agency considers these six to be representative pyrethroids since they are among the
most commonly used and encompass the full range of approved residential uses for
pyrethroids. Results of this analysis are shown in Table 4 below.
The reported related effects are summarized by category, such as cardiovascular,
dermal, gastrointestinal, etc., in Table 4 for each of the seven active ingredients.
Although PCC does not capture information about asthma or allergies directly, EPA
believes the PCC categories of respiratory and dermal effects may be correlated to
potential asthmatic or allergic responses.
Page 12 of 27
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Table 4: Analysis of Related Clinical Effects Reported in PCC for Pyrethrins and Select Pyrethroids
Category of
Effects
Cardiovascular
Dermal
Gastrointestinal
Heme/Hepatic
Neurological
Ocular
Renal
Respiratory
Miscellaneous
Total Related
Effects
Total Incidents
Bifenthrin
%
(Count)
2%
(49)
26%
(506)
18%
(361)
0%
(5)
15%
(285)
21%
(403)
0%
(1)
7%
(141)
11%
(212)
1963
2,058-2,827
Deltamethrin
%
(Count)
1%
(19)
37%
(627)
17%
(300)
0%
(1)
11%
(195)
14%
(232)
0%
(0)
9%
(148)
11%
(193)
1715
1,844-2,396
Permethrin
%
(Count)
2%
(446)
21%
(5619)
24%
(6301)
0%
(14)
13%
(3394)
18%
(4904)
0%
(14)
13%
(3437)
10%
(2611)
26740
30,156-
47,422
Pyrethrins
%
(Count)
1%
(811)
16%
(9359)
23%
(13199)
0%
(14)
10%
(5556)
26%
(14935)
0%
(37)
14%
(8071)
8%
(4819)
56,801
60,081-
94,337
Resmethrin
%
(Count)
2%
(83)
16%
(679)
24%
(992)
0%
(3)
13%
(557)
22%
(918)
0%
(3)
12%
(514)
9%
(381)
4130
3,987-6,127
Sumithrin
%
(Count)
2%
(197)
19%
(2109)
23%
(2557)
0%
(2)
11%
(1261)
21%
(2324)
0%
(15)
14%
(1576)
11%
(1186)
11227
11,591-
17,830
Tetramethrin
%
(Count)
2%
(224)
17%
(2382)
24%
(3355)
0%
(3)
12%
(1665)
19%
(2736)
0%
(11)
17%
(2416)
10%
(1469)
14261
14,231-21,414
The reported health effects associated with these chemicals do not show a
disproportionate number of respiratory or dermal effects reported for pyrethrins or
pyrethroid exposures compared to other categories of effects. The most frequently
reported symptoms for these seven chemicals were gastrointestinal, except for bifenthrin
and deltamethrin, which are the only type II pyrethroids included in the table. Type II
pyrethroids have a specific dermal effect called the "pyrethroid effect" characterized by
burning and tingling of the skin. Even though it is a dermal effect, the pyrethroid effect
is not considered an allergic reaction, but rather an indication of local skin irritation. No
trend of pyrethrins/pyrethroids respiratory/allergic effects was identifiable, but the
"pyrethroid effect" is potentially reflected in that the most frequently reported related
effects are dermal effects for bifenthrin and deltamethrin.
To put those individual chemical 'related effects profiles' in Table 4 into a larger
context, the effects reported for the pyrethrins/pyrethroids class as a whole were
compared to reported effects for other major classes of insecticides, organophosphates
(OPs) and carbamates. As shown in Table 5 below, the symptom profiles for these three
insecticidal classes are fairly similar. The most frequently reported related effect for all
three insecticide classes is gastrointestinal. The second most frequently reported related
effect is ocular (although for OPs neurological effects, and for carbamates dermal effects
were reported as frequently as ocular effects). Even though there are slight differences
among the classes between the frequency of related effects (e.g., gastrointestinal effects
are reported more frequently for OPs and carbamates [29% and 30%, respectively] than
Page 13 of 27
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for pyrethrins/pyrethroids [23%]), these differences are secondary to their similar
symptom signatures (i.e., gastrointestinal is reported most frequently,
ocular/neurological/dermal is reported second frequently, dermal/neurological is reported
third frequently, and respiratory/miscellaneous is reported fourth frequently).
Table 5: Analysis of Related Clinical Effects Reported in PCC for
Pyrethroid/Pyrethrins, OPs and Carbamates3
Related Effects
Cardiovascular
Dermal
Gastrointestinal
Heme/Hepatic
Neurological
Ocular
Renal
Respiratory
Miscellaneous
Total Related
Effects
Pyrethroid/Pyrethrins
%
(Count)
2%
(2178)
19%
(27141)
23%
(32222)
0%
(44)
11%
(14810)
21%
(29907)
0%
(87)
15%
(20884)
9%
(12680)
139953
Organophosphates
%
(Count)
3%
(3563)
13%
(15792)
29%
(33445)
0%
(91)
17%
(20724)
17%
(20267)
0%
(328)
10%
(11832)
11%
(13129)
119171
Carbamates
%
(Count)
3%
(941)
16%
(5269)
30%
(9529)
0%
(24)
15%
(4869)
16%
(5291)
0%
(64)
10%
(3241)
10%
(3266)
32494
3. National Pesticide Information Center (NPIC) data
In addition to IDS and PCC, the NPIC database was also evaluated. Unlike IDS
and PCC, NPIC can be searched for the key terms "allergy" and "asthma". NPIC queried
their database for pyrethroids, pyrethrins, OP, and carbamate incidents from 1995-2007,
and found these key terms associated with about 14% of the NPIC pyrethroid incidents,
about 17% of the pyrethrins incidents, 7% of OP incidents, and 8% of carbamate
incidents.
4. FDA Adverse Event Reporting System (AERS)
Information from FDA was obtained on incidents related to the use of
pediculicide and scabicide products they regulate. FDA provided EPA with a report from
their AERS incident database for permethrin and pyrethrum extract (i.e., pyrethrins-
related incidents). The summary table of symptoms (Table 6 below) provided by FDA
3 These percentages are not absolute values, and reflect the lack of certainty associated with self- reported
human incident data. For example, a difference of 5% should not be interpreted as an absolute value given
the lack of precision and reliability of the underlying data.
Page 14 of 27
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indicates a low incidence of respiratory effects and anaphylactic reactions, despite the
more direct application of pediculicides, which may increase the likelihood of exposure
via the dermal and inhalation routes. The table includes information on permethrin
prescription cream (5%) for scabies and over-the-counter cream (1%) for lice, and
pyrethrins over-the-counter shampoos (0.33%) for lice.
Table 6: Crude Counts of Selected Adverse Event Terms for Pediculicide and Scabicide Products
System Organ Class
Immune System Disorders
Respiratory, Thoracic, and
Mediastinal Disorders
Skin and Subcutaneous
Tissue Disorder
Preferred Term
Anaphylactic Reaction
Anaphylactoid Reaction
Drug Hypersensitivity
Hypersensitivity
Multiple Allergies
Asthma
Hyperventilation
Laryngospasm
Respiratory Disorder
Respiratory Distress
Respiratory Failure
Throat Tightness
Wheezing
Angioedema
Dermatitis
Dermatitis Bullous
Dermatitis Contact
Dermatitis Exfoliative
Photosensitivity Reaction
Rash
Rash Erythematous
Rash Generalized
Rash Maculo-Papular
Rash Papular
Rash Pruritic
Rash Vesicular
Skin Exfoliation
Stevens Johnson Syndrome
Toxic Epidermal Necrolysis
Urticaria
Permethrin
Drug Products
(n=340)
0
2
3
23
2
18
1
2
1
1
0
1
1
2
181
25
5
23
3
4
7
1
40
2
3
1
2
1
2
30
Pyrethrum
Extract Products
(n=8)
1
0
0
0
0
0
1
0
0
1
1
0
0
0
3
0
0
0
0
0
0
0
0
0
0
0
0
0
0
1
The "preferred terms" listed in Table 6 were selected by FDA reviewers as those
keywords in the AERS system best describing the adverse events of concern to EPA in
this review. One or more of these adverse events of interest was reported for 348 of the
total 6,998 reports for permethrin and pyrethrum products—just under 5%. Summation
of the columns would exaggerate the number of incidents, because one report may have
been assigned more than one of the coded terms.
Figure 5 shows the distribution by FDA receipt year of the total of 6,998 reports
for permethrin (6,908) and pyrethrins (90) products.
Page 15 of 27
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Figure 5
Combined # of Permethrin + Pyrethrum Extract Adverse Events Reports
2500
2000 -
1500 -
1000 -
500 -
2136
957
578 564
10 9
49
98
77
5 Z n n
1970
274
26
55 35 18 33 27 24
11 12
FDA Report Year
As outlined in the introduction, FDA first included a warning statement on
pyrethrins labels in 1982, added language warning of breathing difficulty for asthmatics
handling permethrin products in 1990, and expanded asthmatic and allergy warnings to
all over the counter pediculicide products in 2003. If the changes in required warning
labels in 1982 and 2003 had an effect, it cannot be identified from this data, which is
overwhelmed by the dramatic peak in incident reporting during the mid-1990s.
C. Other Human Incident and Epidemiological Data Available in Published
Literature4
There are many human studies available in the literature related to the health
effects of pyrethrins and pyrethroids. Although multiple human studies were considered,
the following studies are highlighted, as they reflect the information most relied on in this
analysis.
1. Population Based Case Study of West Nile Virus Treatment
(Karpati et al., 2004)
The Agency is aware of published studies involving human subjects intended to explore the relationship
between exposure to pyrethroids or pyrethrins and allergic and asthmatic responses. The Agency will
submit these studies to the Human Studies Review Board for review and consideration. Pending the
outcome of review, the Agency will determine whether to include those studies in the weight of the
evidence consideration.
Page 16 of 27
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The analysis conducted by Karpati et al. (2004) showed that spraying a product
containing 10% sumithrin (a type I pyrethroid) and 10% PBO for West Nile Virus control
in New York City was not followed by population-level increases in public hospital
emergency department (ED) visit rates for asthma. Possible associations between
exposure to this pyrethroid product and increased rates of asthma-related public hospital
ED visits in vulnerable populations were also examined. No association between the
spraying of this pesticide and an increased rate of asthma-related ED visits was seen in
children or in those with chronic obstructive pulmonary disease in this study population.
This study did find an association between known asthma triggers (ozone levels,
particulate matter [PMi0] and temperature) and asthma-related ED visits.
2. Agricultural Health Study (Hoppin et al., 2002, 2006, and 2008)
The Agricultural Health Study (AHS) is an ongoing prospective cohort study
involving over 89,000 private and commercial pesticide applicators and their spouses.
The goals of the project are to investigate the effects of environmental, occupational,
dietary, and genetic factors on the health of the agricultural population. In a cross-
sectional analysis of the AHS cohort 1993-1997, Hoppin et al. explored the association
between 40 individual pesticides, including OPs, carbamates, and permethrin (a type I
pyrethroid), and respiratory outcomes (wheeze) by studying both farmers and commercial
applicators. Among approximately 20,000 farmers and 2,000 commercial applicators,
incidence of increased wheeze was associated with individual OP and carbamate
pesticides. Permethrin use on crops was not associated with increased wheeze in farmers
or commercial applicators. However, permethrin use on poultry was associated with
wheeze (permethrin was the only insecticide reported separately for crop and animal use
in the AHS data). Among asthmatic subjects, however, five chemicals, including
permethrin [poultry] showed significantly lower odds ratio of wheeze (2002, 2006).
Further, in their analysis of 25,814 farm women in the Agricultural Health Study,
Hoppin et al. (2008) used self-reported history of doctor-diagnosed asthma with or
without eczema and/or hay fever to create two case groups: patients with atopic asthma
and those with nonatopic asthma. Atopic asthma, or allergic asthma, occurs when an
individual is exposed to items in their environment to which they have an allergy. Other
individuals with nonatopic asthma have no allergies, and the cause of their airway
inflammation is unclear. Hoppin et al. found pesticide use overall (any pesticide use) was
associated with atopic or allergic asthma (2006, 2008). A total of 7 of 16 insecticides, 2
of 11 herbicides, and 1 of 4 fungicides were significantly associated with atopic asthma;
only permethrin use on crops was associated with nonatopic asthma (2008).
3. Pyrethrins and Pyrethroid Illnesses in Pacific Northwest: A Five-
Year Review (Walters et al., 2009)
This study reviewed pesticide surveillance data from 2001 through 2005 for the
Washington State Department of Health and Oregon Public Health Division. Based on
this evaluation, the report concluded that of the 407 total reported incident cases, 92%
were categorized as low severity illnesses, while 8% fit into the moderate/high category
Page 17 of 27
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with 1 death potentially attributable to pyrethrins/pyrethroid exposure. Similar to EPA's
analyses, this article acknowledges that the increase in incidents reported for
pyrethrins/pyrethroids could potentially be explained by the phase-out of the
organophosphates beginning in 2000/2001. While the article notes that 52% (of the 407
cases) were reported with symptoms of respiratory illnesses (210 cases), these symptoms
include a majority of coughing (n=l 12), dyspnea (n=88) and respiratory irritation (n=98),
but only a small number (n = 45) of asthmatic attacks. There were also a majority of
neurological symptoms (n=162) and gastrointestinal cases (n=134). Multiple symptoms
could be from the same individual, which could contribute to double counting of effects,
but it is also interesting to note that not all respiratory symptoms lead to asthmatic
attacks. The article states that "there is also a potential for false positives because
nonspecific symptoms may have been coincidental and not actually caused by pesticide
exposure" (Walters et al., 2009).
The authors also conclude that there is a significant association between pre-
existing conditions (asthma, allergy, multiple chemical sensitivity) and case severity, but
state that incident data are usually incomplete, with limited documentation in the
literature. Interestingly, only 10 asthmatics were reported in the medium severity
category, while 50 asthmatics reported in the low severity category (defined as <3 work
days missed and no medical treatment necessary). If asthmatics were more sensitive a
higher frequency of moderate or severe responses would be expected, but this is not
shown to be the case.
In addition to reviewing incident data, the authors also point out that there are
inconsistencies between human studies available in the literature. They mention the West
Nile virus study discussed above (Karpati et al., 2004), and note there was no association
between mosquito control spraying of pyrethroids for West Nile virus and emergency
department asthma visits in New York City in 2000. However, the authors also describe
a report on flight attendants who experienced health effects after aircraft deinsection,
some of which were respiratory effects (Sutton et al, 2007).5 Subsequently, the authors
state that the inconsistencies in the available human studies may be reconciled through
the collection of more robust incident data for pyrethrins/pyrethroid exposure and asthma,
better public education on the appropriate use of pesticides, and heightened awareness
that many aerosols and foggers may be respiratory irritants of potential health concern for
those with hyper responsive respiratory airways like asthmatics (Walters et al., 2009).
IV. Conclusion
A. Weight of Evidence Data Conclusion
Unlike previous reviews, this assessment used a weight-of-evidence approach,
integrating both animal and human incident and epidemiological data, seeking to
5 Other effects experienced by the flight attendants after pyrethroid spraying on airplanes included
confusion, weakness and heart palpitations. The respiratory effects were no more frequent than other health
symptoms. Additionally, the flight attendant study was limited as it included only six completed interviews
out of 17 flight attendants; eight declined participation, and three could not be reached.
Page 18 of 27
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determine whether exposure to products containing pyrethrins and/or pyrethroids is
associated with asthma and allergies. This approach was selected because an integrative
assessment with animal and human data is more informative than an analysis of any
single dataset or study, and because fundamental biological mechanisms of disease
outcome are assumed to be concordant across species.
The animal data show that pyrethrins and pyrethroids have low acute toxicity to
mammals via oral, dermal and inhalation routes of exposure and are not skin sensitizers.
While these animal studies were not specifically designed to identify potential asthmatic
responses, it does provide dose response information and severity of acute responses via
the inhalation route of exposure. Animal data taken alone, however, does not form the
bases of the overall conclusion.
The IDS incidents did not indicate an association between exposure to
pyrethrins/pyrethroids and asthma/allergies. No causal relationship between exposure to
pyrethrins or pyrethroids and asthma or allergic effects can be established using IDS
incident data alone. PCC pyrethrins/pyrethroid incident data do not demonstrate a
heightened respiratory or dermal response compared to other symptom categories.
Furthermore, the PCC data show effects profiles for pyrethrins and pyrethroids—e.g., the
distribution of reported effects by category—quite similar to those for organophosphates
and carbamates. NPIC data reports higher frequencies of incidents indexed for "allergy"
or "asthma" for pyrethrins and pyrethroids as compared to OPs and carbamates. FDA
adverse event data did not support an association between use of pyrethrins or permethrin
pharmecutical pediculicide and scabicide products and allergic or asthmatic responses,
despite the more direct method of application and associated high human exposure levels.
Incident databases do not consistently show trends or patterns potentially
indicative of allergies/asthma consequent to exposure to pyrethrins or pyrethroids. If
there were a strong relationship, the Agency would expect to find a clear and consistent
pattern of increased respiratory and allergic effects reported across multiple human
incident databases.
The review article by Walters et al. (2009) articulates some of the limitations of
human incident data: incomplete information, lack of information about pre-existing
health conditions, potential for misclassification or false positives and underreporting.
These limitations make it difficult to assess a causal relationship between asthma and
exposure to pyrethroids or pyrethrins using incident data. Human incident databases may
simply be inadequate to identify any relationship between exposure to pyrethrins or
pyrethroids and allergy or asthma responses. These databases are crude, varying in
quality, level of detail, and type of information.
Human data are inconsistent. Although there are studies indicating an association
between asthma/allergies and pyrethrins and/or pyrethroids exposure, there are also
similar studies that do not indicate an association. More robust studies, such as the
population-level study (Karpati et al., 2000) did not find a higher number of hospital
visits for subjects with asthma following wide-area exposure to pyrethroids. The cross-
Page 19 of 27
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sectional AgHealth study did not report a clear association between respiratory symptoms
(wheezing) and exposure to permethrin (Hoppin, 2002 & 2006), but follow-up
investigation of this potential relationship is ongoing.
Based on its assessment of the available animal experimental data, human
incident data, and human epidemiology studies, EPA concludes that there does not appear
to be a clear relationship between exposure to products containing pyrethrins or
pyrethroids and allergic or asthma responses.
B. Regulatory Conclusion
As discussed in Section II above, previous evaluations of incident data have
recommended warning statements on pyrethrins/pyrethroid product labels such as "Ask a
doctor before use if you are allergic to ragweed. May cause breathing difficulty or an
asthmatic attack for sensitive subpopulations." However, our evaluation of the FDA's
data indicated that the inclusion of similar warning language on labels of FDA-regulated
pyrethrins products was unrelated to the frequency of reported incidents. Although the
nature of the use of the FDA-regulated pyrethrins products generally results in relatively
high direct human exposure, the symptoms reported to the FDA Adverse Events
Reporting System do not suggest an association between exposure and respiratory effects.
Based on the weight of the evidence discussed above, the Agency concludes there
is not a clear relationship between pyrethrins/pyrethroid exposure and asthma and
allergies. Therefore, the Agency is not requiring additional warnings or label statements
specific to asthmatics on pyrethroids and pyrethrins end-use product labels at this time.
As noted above, during pyrethrins reregi strati on the Agency required the
Pyrethrins Joint Venture to institute a product stewardship program involving a
prospective in-depth follow-up of reported pyrethrins incidents to clarify any possible
correlation between pyrethrins pesticide product exposures and adverse health incidents.
The Agency will review the pyrethrins incident data as it is submitted. If these new data
provide new insights or evidence of trends in the data that differ from the incident data
considered in this review, the Agency may consider imposing a similar stewardship
requirement on registrants of products containing pyrethroids.
Page 20 of 27
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2009. "Pyrethrin and Pyrethroid Illnesses in the Pacific Northwest: A Five-Year
Review." Public Health Reports; 124:149-159.
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Appendix I: Incident Databases
1. Incident Data System (IDS)
IDS is maintained by OPP and incorporates data submitted by registrants under FIFRA
section 6(a)(2), as well as other incidents reported directly to EPA. FIFRA allows the
aggregation of individual events in some circumstances. IDS includes information on
incidents involving humans, plants, wild and domestic animals where there is a claim of
an adverse effect, as well as detects of pesticides in water. The vast majority of reports
are received in paper format. IDS entries act as a pointer to copies of original reports,
retained on microfilm and scanned images in OPP's Information Service Center. Many
companies use standardized, industry-developed Voluntary Incident Reporting Forms.
While IDS reports are broad in scope, the system does not consistently capture detailed
information about incident events, such as occupational exposure circumstances or
medical outcome. In most cases data going into IDS is not validated or verified, though
some reports are collected from calls to contract poison control centers.
2. American Association of Poison Control Centers (PCC)
The National Poison Data System (NPDS), formerly the Toxic Effects Surveillance
System (TESS), is maintained by the American Association of Poison Control Centers
(PCC), with funding from several federal agencies. NPDS is a computerized information
system with geographically specific and near real-time reporting (for bioterrorism
detection purposes). While the main mission of Poison Control Centers is helping callers
respond to emergencies, and not collecting specifics on incidents, NPDS data helps
identify emerging problems in chemical product safety. Hotlines at 61 PCC's nationwide
are open 24/7, 365 days a year, with many bilingual centers in high Spanish speaking
areas, and the capability to translate 80 languages. Hotlines are staffed by specially
trained nurses to provide poisoning information and clinical care recommendations to
callers with a focus on triage to give patients appropriate care. Using computer assisted
data entry, standardized protocols, and strict data entry criteria, local callers report
incidents that are retained locally and updated in summary form to the national database.
Since 2000 nearly all calls in the system are submitted in a computer-assisted interview
format by the 61 certified Poison Control Centers, adhering to clinical criteria designed to
provide a consistent approach to evaluating and managing pesticide and drug related
adverse incidents. Information calls are tallied separately and not counted as incidents.
The PCC system covers nearly all the US and its territories and is undergoing major
computer enhancements post 9/11.
• There are 1,546,503 records of "incidents" in the PCC database for pesticides,
algicides and disinfectants. Not all of these records are complete
• Some analyses were conducted searching by chemical, but the broader queries were
done using the Major_Category and/or Minor_Category fields, searching for all
records that identified *pyre*, *organophosphate* or *carbamate* in one of these two
fields.
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o Major/Minor Category queries
Major Category
*organophospate*
*carbamate*
*pyre*
*pyre*
*organophospate*
*carbamate*
*pyre*
Minor Category
*pyre*
*pyre*
*organophospate*
*carbamate*
*organophospate*
*carbamate*
*pyre*
Associated # of records
0
0
0
5709§
178,705
78,085
234,206
O
o
These 5,709 records of incidents are called up due to the Minor_Category designation
"PIPERONYL BUTOXIDE & PYRETHRINS (WITHOUT CARBAMATE OR O.P.)";
not because they involve exposure to both a pyrethrins/pyrethroid product and a
carbamate
Table 3 - Query details
Major/Minor Categories - queried for pyre/pyre,
organophospate/organophosphate, carbamate/carbamate
(see table above)
Medical outcome — queried for designation 4 and 3
4 - death [definition: the patient died as a result of the exposure or as a direct
complication of the exposure where the complication was unlikely to have occurred had
the toxic exposure not preceded the complication. Only include those deaths which are
probably or undoubtedly related to the exposure.]
3 - major [definition: the patient has exhibited symptoms as a result of the exposure
which were life-threatening or resulted in residual disability or disfigurement. Follo9w-
up is required to make this determination unless the initial poison center call occurs
sufficiently long after the exposure that you are certain the clinical effect(s) will not get
worse. Symptomatic patients must be followed until symptoms have resolved or nearly
resolved, unless the symptoms are anticipated to be long-term or permanent.]
Reason for Exposure — excluded designations 9-14
o
Reason for exposure
Unintentional-General
Unintentional-Environmental
Unintentional-Occupational
Unintentional-Therapeutic error
Unintentional-Misuse
Unintentional-Bite/Sting
Unintentional-Food poisoning
Unintentional-Unknown
Intentional-Suspected Suicide
Intentional-Misuse
Intentional-Abuse
Intentional-Unknown
Other-Contamination/tampering
Other-Malicious
Adverse rxn-Drug
Adverse rxn-Food
Adverse rxn-Other
Unknown reason
Other-Withdrawal
Code
1
2
3
4
5
6
7
8
9
10
11
12
13
14
15
16
17
18
19
Table 4 - Query details
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o PCjCode — queried for record of incidents with particular pc codes
associated with them
(done using EPA/OPP generated table associated PDX_ID with PC codes)
o Total incidents: the higher number represents the total number of
incidents associated with a particular PC code, the lower number
represents the number of incidents associated with a particular PC code
and with clinical effects reported in the incident record. The total related
effects can be lower than the lower number of total incidents because
some reported clinical effects are designated as not related to the exposure
or as unknown if related to the exposure.
• Table 5 - Query details
o Major/Minor Categories — queried for pyre/pyre,
organophospate/organophosphate, carbamate/carbamate
(see table above)
3. National Pesticide Information Center (NPIC)
NPIC is funded by EPA to serve as a source of objective, science-based pesticide
information in response to inquiries and to respond to incidents. NPIC functions
nationally during weekday business hours, under a cooperative agreement between
Oregon State University and EPA. Similar to Poison Control Centers, NPIC's primary
purpose is to provide information and not to collect incident data. NPIC does collect
information about incidents from inquirers and reports that information to EPA (about
10% of NPIC's annual calls are considered "incident" related). The Center's main role is
to provide information to inquirers on a wide range of pesticide topics, and direct callers
for pesticide incident investigation and emergency treatment.
4. FDA Adverse Effect Reporting System (AERS)
The FDA AERS provides crude count data. For any given report, there is no certainty
that a suspected drug/biologic product caused the reported event, because physicians are
encouraged to report suspected events. However, the event may have been related to the
underlying disease being treated, may have been caused by some other drug/biologic
product being used concomitantly, or simply may have occurred by chance at that time.
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