## Page 2 of 51

to consider in its updated Chlorpyrifos Risk Assessment, and TEB was requested to provide an updated Tier II Incident Report.

The review considers a variety of types and sources of human observational information including human incident data, medical data/case report information, and epidemiological
information in an effort to inform the re

- evaluation of chlorpyrifos in this phase of Registration
Review. The human incident databases that were reviewed are:

OPP Incident Data System (IDS);

National Pesticide Information Center (NPIC);

NIOSH’s Sentinel Event Notification System for Occupational Risks (SENSOR);

California Pesticide Illness Surveillance Program Incident Data (CA PISP).

Together, these database s indicate that the number of incidents associated with chlorpyrifos declined post

- 2002, correlating well with the phase out/cancellation of the almost all chlorpyrifos residential products in December 2001. In addition, the Agency's findings are consiste nt with other incident cases investigations of American Association of Poison Control Centers ( AAPCC) data which have reported a decrease in the number of chlorpyrifos incidents that is temporally associated with the phase out/cancellation of most resident ial chlorpyrifos products.

While t he chlorpyrifos incidents are reported to have declined substantially (95%) among reside ntial users from 2002 to 2010, it is unclear if occupational incidents have also decreased. Specifically, chlorpyrifos occupation al incidents, reported in CA PISP and SENSOR databases, appear to be constant over time, despite risk mitigation implemented including reduced application rates and seasonal maximum limits, increased retreatment intervals, increased PPE and/or use of engin eering controls which were required as well as increased re

- entry intervals (REIs) for a number of crops. Overall, the NIOSH SENSOR database indicated that the largest
number of incidents are exposures due to actual application o f chlorpyrifos , but Calif ornia PISP data suggests that drift of chlorpyrifos to adjacent fields appears to be the largest contributor to occupational exposure . OPP has reviewed t he incidents reported and will continue to monitor these incidents and remain alert for any changes in trend or patterns.

In addition to the incident/poisoning data and medical case reports, epidemiological research can be an important source for human observational data and can potentially assist in identifying, characterizing, and (ideally) quantifying linkages between huma n exposures and resulting health effects. For chlorpyrifos, epidemiological data are available from both the Agricultural Health Study (AHS) and from a variety of university

- based research groups. While the AHS investigations currently published were hypo thesis

- generating in nature

, initial strength and consistency in the findings for lung cancer and colorectal cancer are notable, and warrant further
follow

- up and additional research

. Preliminary associations with breast and prostate cancer are weak, but a lso warrant monitoring the literature for additional publications on this association. There is no compelling evidence of an association with other cancer sites including pancreatic cancer, melanoma, brain, esophageal, kidney, all lymphohematopoietic cance rs combined and NHL, leukemia, and multiple myeloma ( Christensen, 06/16/2011

, D388167 ). These data alone

## Page 3 of 51

do not provide sufficient evidence to determine whether a causal association exists between chlorpyrifos exposure and these anatomical cancer sites. Information derived from animal toxicology data will continue to be used to evaluate cancer risk. However, EPA will continue to monitor this literature to determine if information provided in human epidemiology studies provide additional evidence as to th e carcinogenic potential of chlorpyrifos.

Finally, there are a number of ongoing university

- based epidemiologic studies that are examining the association between pre

- natal and early life c hlorpyrifos and OP pesticide exposures and

neuro developmental and neurobehavioral effects. EPA has concl uded from these studies that the observed association between chlorpyrifos and OP pesticide exposure s and neurodevelopmental and neurobehavioral deficits is compelling, as similar results were obtained across the thre e children’s health cohorts with respect to neurodevelopmental outcomes in neonates and young children. Notably , associations between chlorpyrifos and OP pesticides and these neurodevelopmental effects were pronounced in the time period prior to the volunt ary cancellation of the insecticide for the in

- home, residential environment, and the links were absent in studies conducted subsequent to the removal of chlorpyrifos use from the home pesticide market. EPA has concluded, with the input and concurrence of an external peer

- review panel (FIFRA SAP, September 2008), that chlorpyrifos exposure likely played a role in these adverse neurodevelopmental outcomes

. (See Appendix C “Epidemiological Research: Health Effects in

Children

, ” May 2011)

1. BACKGROUND

Chlorpyrifos ( O,O

- diethyl O

- (3,5,6

- trichloro

- 2

- pyridyl) phosphorothioate ) is an organophosphate insecticide, acaricide and miticide used to control a variety of insects

. Chlorpyrifos was first registered in 1965 for control of foliage and soil

- borne insect pests on a variety of food and feed crops. Currently

- registered uses include food and feed crops, golf course turf, greenhouses, non

- structural wood treatments such as utility poles and fence posts, ant bait stations, and as an adult mosquitocide.

In J une, 2000, the Agency released its revised human health risk assessment and entered into an agreement with the technical registrants to voluntarily cancel and phase out certain uses of chlorpyrifos. The agreement was established at that time in order to ex peditiously address food, drinking water, residential and non

- residential uses posing the greatest risks to children. An Interim Reregistration Eligibility Decision (IRED) was issued in February 2002. The IRED
included additional mitigation measures addres sing occupational and ecological risks not addressed in the June, 2000 agreement . Risk mitigation measures include eliminating use on tomatoes, restricting use on apples, phasing out termiticide use, canceling all homeowner use product registrations (excep t ant bait stations), and canceling uses in schools and parks where children may be exposed. To mitigate worker risks, a combination of reduced application rates and seasonal maximum limits, increased retreatment intervals, increased PPE and/or use of

eng ineering controls were required as well as increased re

- entry intervals (REIs) for a number of crops ( Drew, 02/09/2009, D361144)



## .

## Page 4 of 51

Chlorpyrifos is a pesticide being considered under the Registration Review program established in 2006 to review, on a 15 yea r schedule, pesticides for which a Reregistration Eligibility Decision has been made. During the problem formulation phase of Registration Review for chlorpyrifos, the EPA Office of Pesticide Program’s (OPP) Incident Data System (IDS) was queried to deter mine whether reported human incidents involving chlorpyrifos might be an important source of information to consider during the preliminary risk assessment phase of Registration Review for chlorpyrifos. Hawkins and Cordova (2008) found 126 incidents

repor ted from January 1, 2002, to March 2008 in IDS

. Based on the frequency and the effects
noted in the IDS

- reported human incidents involving chlorpyrifos identified during the problem formulation phase of Registration Review) the Agency determined these data are an important source of information to consider in its June 2011 risk assessment of Chlorpyrifos and TEB was requested to provide an updated Tier II incident report for use in preparation of the June, 2011
risk assessmen t.

It is important to recognize, however, that r eports of adverse health effects allegedly due to a specific pesticide exposure ( i.e

. , an “incident”) are largely self

- reported and therefore, generally speaking, neither exposure to a pesticide or reporte d symptom s (or the connection between the two) are validated. Therefore, only rarely can causation be determined or definitively identified based on incident data. However, incident information can provide important feedback to the Agency. Human incide nt data, in concert with other human observational information (medical case reports, general medical information, biomonitoring and epidemiological studies) and the human health risk assessment, can assist the Agency in determining the risk pesticides/pes ticide products are posing to the U.S population and can help characterize that risk. This review assesses human observational information regarding chlorpyrifos to inform the preliminary risk assessment phase of Registration Review.

2. TIER II REVIEW OVERV IEW

Generally, the Agency relies on toxicity studies conducted on animals and exposure information relevant to the pesticide’s use pattern when registering a pesticide. However, after a pesticide is registered, different types of human observational data about the effects and exposure of registered pesticides may be collected, analyzed and published. These are from a variety of sources including:

Human incident (poisoning) data from such sources as OPP’s Incident Data System (IDS) database, NIOSH SENSOR , the Agency

- sponsored National Pesticide Information Center (NPIC), California’s Pesticide Incident Surveillance Program (PISP), and summary data from the American Association of Poison Control Centers (AAPCC).

Human toxicological reviews and medical ca se reports from the literature

Epidemiological studies from the literature

As the Agency reevaluates pesticides during the Registration Review program, these additional sources of information are considered. Specifically, this review considers these diffe rent types and sources of human observational information and is intended to inform the re

- evaluation of chlorpyrifos in this phase of Registration Review.

## Page 5 of 51

3. HUMAN INCIDENT DATA

As indicated above, incident information can provide important feedback to the Agency

, assisting in determining actual real

- world exposures and risks posed by pesticides/pesticide products. Incident data are collected systematically, but differently

, across the different
databases used by the Agency with respect to such issues a s coverage, certainty/confidence, fields/parameters reported , and usability. T he aforementioned five pesticide incident data

sources (IDS, NIOSH/SENSOR, NPIC, California PISP, and AAPCC) were used in this chlorpyrifos report since they provide useful content and historical perspective. Various other comparable sources of data are available (e.g. the Bureau of Labor Statistics, emergency room outpatient surveillance, National Poison Data System (NPDS), etc.) but are believed to be of

lim ited additional utility and were not investigated

. B y looking across the five data sources which were used, the Agency is confident that we are considering adequate and appropriate information to discern trends and patterns in chlorpyrifos

- associated inci dent poisonings

.

3.1. OPP Incident Data System (IDS)

The OPP IDS includes reports of alleged human health incidents from various sources, including mandatory Federal Insecticide, Fungicide and Rodenticide Act (FIFRA) Section 6 (a) (2) reports from registrants and reports from other federal and state health and environmental agencies and individual consumers. Since 1992, OPP has compile d these reports in IDS. IDS contain reports
from across the U.S. and most incidents contained in the system have all relevant product
information recorded. C ase reports or “narratives” are provided for each incident, with varying levels of detail; however, there is no effort at validating or assessing how likely it is that the reported exposure is causally related to the reported outcome. Because IDS has such extensive coverage, it is useful for providing temporal trend information and determining whether risk mitigation has helped reduce potential pesticide exposure and decreased the number of potential incidents reported to IDS

.

For this evaluation, the OPP IDS w as utilized for pesticide incident data on the active ingredient chlorpyrifos (PC Code 059101 ). T h is database search was done to identify the frequency and severity of the health effects attributed to chlorpyrifos ex posure as well as potential patterns and
trends

. Reports submitted to the IDS represent anecdotal reports or allegations only, and are not necessarily confirmed, validated, or investigated by medical professionals unless otherwise stated in the report.

IDS records incidents resulting in high er severity outcomes, in a module called the Main IDS
module

. This system stores incident data for death and major and moderate incidents, and it includes more details about the location, date and nature of the incid ent. Main IDS incidents involving only one pesticide are considered to provide more certain information about the potential effects of exposure from the pesticide , and therefore these incidents are reviewed individually in t his assessment

.

The less seve re human incidents (those outcomes reported as “minor”, “unknown”, or “no effects”) are reported by registrants as counts called aggregate summaries and are recorded in a separate module called Aggregate IDS

. In A ggregate IDS, queried from January 1, 200 2 to May 27, 2010, there are 745 incident involving chlorpyrifos . Because it falls within the categories

## Page 6 of 51

reported as counts (which includes minor, unknown or no effects)

, there is no unique report that provides details about the incident and single chemical incidents are not distinguished from multiple chemical incidents ; however, a high frequency of incidents indicates there is a high potential for exposure and vice versa

. For the M ain IDS

-- which for this report was queried over the date range fro m January 1, 200 2 to February 1, 2011

-- there are 247 cases reported that involve the active ingredient chlorpyrifos

. Of these 247 cases, there are 141 cases reported for the single chemical chlorpyrifos in the database. Summaries of these 141 incidents are recorded in Appendix A. These incidents were mostly categorized as HCs (Human Moderates); however, there is one categorized as HA (fatalities) and 12 categorized as HBs (Human Majors). Fifteen
of these incidents were reported as affecting children 6 years old or under (2 HBs and 13 HCs). These latter incidents appear to be due to accidental ingestion and post application exposure to cancelled products.

Based on the IDS reports , symptoms most often reported were gastrointestinal, dermal

, neurological, respiratory, and ocular. Note that a patient could exhibit multiple symptoms. Gastrointestinal symptoms reported were nausea, vomiting, diarrhea, and abdominal pain. Dermal symptoms reported were rash, lesions , hives, burning sensation, irritation, and blisters. Neurological symptoms were tremors, headache s , dizziness

, confusion, memory dysfunction, numbness and tingling sensations, muscle weakness, muscle spasm, and seizures. Respiratory
symptoms were choking, coughing, shortness of bre ath, sore throat, and burning sensation in the
throat . Ocular symptoms reported were lacrimation, burning sensation, pain, and itchiness

.

Figure 1 shows the Main IDS

- reported chlorpyrifos incidents from 2002 to 2010. These appear to have decreased substantially in this period from 43 incidents in 2002

, to 2 incidents in 2010

. The initial large reductions generally coincide with the dates fo r which regulatory actions were
taken.

Figure 1. Main IDS Chl orpyrifos Incident Count (Chlorpyrifos

- only A.I.) , 2002

- 2010

0 5 10 15 20 25 30 35 40 45 50

2002 2003 2004 2005 2006 2007 2008 2009 2010 Incident Count



### Year

## Page 7 of 51

3.2. National Pesticide Information Center (NPIC)

NPIC is a cooperative effort between Oregon State University and EPA which is fu nded by EPA to serve as a source of objective, science

- based pesticide information and respon d to inquiries from the public and to incidents. NPIC functions nationally during weekday business hours through a toll

- free telephone number in addition to the in ternet (www.npic.orst.edu) and email

. Similar to Poison Control Centers, NPIC’s primary purpose is not to collect incident data , but
rather to provide information to inquirers on a wide range of pesticide topics, and direct callers for pesticide incident investigation and emergency treatment. Nevertheless NPIC does collect
information about incidents (approximately 4000 incidents per year) from inquirers and records
that information in a database

. NPIC is a source of national incident information ; but ge nerally receives fewer reports than IDS. Regardless, if a high frequency is observed in IDS, NPIC provides a source of information to see whether we can demonstrate consistency across national
data sets.

For NPIC from 2002 to 2010, there are 178 cases reported for chlorpyrifos in the database. Of these cases, 88 were reviewed because, in these cases, chlorpyrifos was used as a single chemical and had a certainty classification of probable, possible

, or unclassified; such classifications provide more rel iable information about the potential effects of chlorpyrifos exposure

. Eight of the chlorpyrifos cases were associated with children six years old or younger. The health effects reported include: neurological, gastrointestinal, respiratory, ocular, derma l, and cardiovascular.

As shown in Figure 2, chlorpyrifos incidents reported to NPIC appear to be decreasing over time, and show similar trends to those described above for IDS. Note that incidents reported in NPIC may overlap with incidents reported in other database systems such as those managed by
AAPCC and EPA’s IDS database.

Figure 2. NPIC Chlorpyrifos Incident Count , 2002

- 2010

0 5 10 15 20 25 30

2002 2003 2004 2005 2006 2007 2008 2009 2010 Incident Count



### Year

## Page 8 of 51

Stone et al . (2009) analyzed OP incident from NPIC's incident database for longitudinal trends, including incidents for chlorpyrifos, diazinon, and malathion reported to NPIC. The exposure incidents were grouped into pre

- (1995

- 2000) and post

- announcement of phase

- out (2001

- 2007) periods. The y reported that the number of ch lorpyrifos incidents decreased over
time. Similarly, the informational inquiries NPIC received regarding chlorpyrifos declined overtime following the phase

- out announcement.

Overall, the NPIC data suggest that incidents associated with chlorpyrifos are declining over time and in recent years have numbered only a handful each year. This is in general agreement with was has been seen in the Agency’s IDS reporting system.

3.3. NIOSH Sentinel Event Notification System for Occupational Risks (SENSOR)

The N IOSH SENSOR database covers 12 states from 1998

- 2006, although reporting varies from

state to state

. Pesticide

- related incidents are c ollected from Department of Labor workers’ compensation claims when reported by physicians, reports from Stat e Departments of Agriculture, from poison control centers and from State Departments of Health based on reports by physicians suspecti ng pesticide exposure. Although both occupational and non

- occupational incidents are included in the database, SENSOR focu ses on occupational pesticide incidents, and is of particular value in providing that information. A state SENSOR contact specialist performs
follow

- up with workers and obtains medical records to verify symptoms, circumstances surrounding the exposure, sev erity, and outcome. Using standardized protocol and case definitions, SENSOR coordinators at State Departments of Health enter the incident interview description provided by the medical report, physician and patient into the SENSOR data system,
accessible to participating states and EPA. I n

- depth investigations for case confirmation are performed giving the Agency high confidence in the information provided. Although SENSOR is not national in scope (it is limited to 12 states) the coverage does include most high

- production agricultural states and therefore covers the most states where agricultural pesticides are being
used. The ability to detect trends over time for SENSOR data is limited due to a generally small number of incidents and varying degrees with which the states track incidents.

For NIOSH SENSOR from 1998 to 2007, there are 635 cases reported for chlorpyrifos in the database. Of these cases, 348 were reviewed because, in these cases, chlorpyrifos was used as a single chemical only and had a certainty classification of definite, probable, or possible , as these cases provide more certain information about the potential effects of chlorpyrifos exposure

. There was one death due to suicide; eight cases were classified as high severity, 60 case s were classified as moderate severity, and 279 cases were classified as low severity

. Of the 348 cases chlorpyrifos

- only cases, 18 cases involved children six years old or younger. These latter incidents were mostly due to accidental ingestions, misappl ications around the home and drift from nearby properties. The health effects reported include: neurological, gastrointestinal

, respiratory , ocular , dermal, cardiovascular , and genitourinary

. Generally, chlorpyrifos incidents involved workers in agricult ural or professional application occupations, homeowners and individuals at work but their job was not related to pesticide application, and to individuals exposed through drift.

## Page 9 of 51

Chlorpyrifos SENSOR non

- occupational incidents appear to significantly dec rease after 2000 and continue to decrease until 2007 (see Figure 3). The increases in 2002 and 2005 each correspond to a single event involving several people. In 2002, chlorpyrifos was sprayed at a school to the exterior of nine buildings during school h ours. Twenty one employees working inside the buildings experienced symptom including dermal, gastrointestinal, ocular, neurological and respiratory symptoms. In 2005, eight workers in a field were sprayed with chlorpyrifos. They experienced gastrointest inal, neurological, and respiratory symptoms.

Figure 3

. NIOSH SENSOR Chl orpyrifos Incident Count , 1998

- 2007

On average, less than seven occupational incidents are reported per year for chlorpyrifos in the
NIOSH SENSOR database. The number of occupational incidents reported appears to remain steady from 1998 to 2007. Agricultural workers reported incidents that occurred due to drift from adjacent fields, post application exposure, chlorpyrifos application, mixing/loading chlorpyrifos, repair and maintenance of equipment, chlorpyrifos transportation and disposal, and spills/splashes/leaks of chlorpyrifos onto workers (see Table 1 ). Application of chlorpyrifos appears to lead to the largest number incidents, responsible for 46% reported to NIOS H
SENSOR from 1998 to 2007.

Table 1

. Chlorpyrifos o ccupational e xposure s cen arios reported to NIOSH SENSOR, 1998

- 2007

Exposure Scenario Count Percentage of Total Applying chlorpyrifos 19 46% Unknown if occupational or not. 10 24%

Workers in chlorpyrifos treated fields 8 20% Workers in chlorpyrifos treated fields 8 20% Spilling/splashing/leaking of chlorpyrifos onto worker 6 15% Occupational postapplication 2 5% Mixing/loading chlorpyrifos 2 5% Repair/maintenance 2 5% Transport /disposal of chlorpyrifos 2 5%

Total 41 100

0 10 20 30 40 50 60 70 80 90

1998 1999 2000 2001 2002 2003 2004 2005 2006 2007

occupational/agricultural non

- occupational

## Page 10 of 51

3.4. California Pesticide Illness Surveillance Program (PISP)

The Pesticide Illness Surveillance Program (PISP) maintains a database of pesticide

- related illnesses and injuries. Case reports are received from physicians and via workers’ compensation records. The local County Agricultural Commissioner investigates circumstances of exposure. Medical records and investigative findings are then evaluated by DPR technical experts and entered into an illness registry.

PISP contai ns both residential and occupational pesticide incidents. PISP has limited co verage (only California) and is not particularly useful for trend over time information. However, the
incident information is entered by professionals with expertise in pesticid es, with extensive
follow

- up on each reported case so there is a high level of confidence in the information provided for each reported incident.

One hundred and sixty four cases were identified that are attributable to chlorpyrifos

- only

exposures were re ported to the California Pesticide Illness Surveillance Program between 1999 and 2008. Of these cases, 87 were occupational incidents and 77 were non

- occupational incidents. The health effects reported include: neurological, gastrointestinal, respiratory , ocular, dermal, and cardiovascular.

Although there are some spikes in the data which are usually due to a single event affecting many people, the chlorpyrifos incidents appear to be decreasing over time for non

- agriculture related incidents and remaining steady for agricultural related incid ents. The spike for non

occupational incidents in 2005 is one event in which 12 office workers reported symptoms after a maintenance worker applied an outdoor chlorpyrifos product on office baseboards and under desks to control roaches. They reported exp eriencing neurological, respiratory, ocular and gastrointestinal symptoms including headache, sore throat, lightheadedness, itching or burning eyes and nausea. The first spike in agriculture incidents in 2000, is one event in which 17 postapplication work ers reported symptoms after unknowingly entering an orange plantation that had been treated with chlorpyrifos the day before. The chlorpyrifos REI for oranges is 5 days. The spike for the agriculture related incidents in 2007

, is one event in which 26 vi neyard workers reported symptoms after they were exposed to chlorpyrifos that was being applied on a neighboring almond orchard. The vineyard workers reported experiencing respiratory, gastrointestinal, neurological, ocular, dermal symptoms including coug hing and shortness of breath, nausea and vomiting, headache and dizziness, itchy and burning eyes, and itchy skin and
rash.

## Page 11 of 51 Figure 4 . California PISP Chlorpyrifos Incident Count , 1999

- 2008

On average less than nine agricultural incidents are reported per year for chlorpyrifos in the PISP database. The number of incidents reported appears to remain steady from 1999 to 2008. Agricultural workers reported incidents that occurred due chlorpyrifos drift from adjacent fields, postapplication, spil l/splash/leak, mixer/loader, and applicator exposure, misuse, equipment malfunction, and equipment cleaning ( See Figure 5 ). Unlike in SENSOR, where application was the most likely activity involved in incidents, drift of chlorpyrifos appears to be the cau se of the

most occupational incidents in PISP, being responsible for 56% of the cases reported to PISP
from 1999 to 2008

.

Figure 5 . Occupational Exposure Scenarios reported to PISP for Chlorpyrifos 0 5 10 15 20 25 30 35

1999 2000 2001 2002 2003 2004 2005 2006 2007 2008

Occupational Incidents Non

- occupational incidents

## Page 12 of 51 drift

56%

applicator

7% equipment cleaning

1% equipment

malfunction

5% mixer/loader/appli

cator

2% misuse

1% mixer/loader

2% postapplication

22% spill/splash/leak

4%

## Page 13 of 51

3.5. American Association of Poison Control Centers (AAPCC)

The American Association of Poison Control Centers (AAPCC) is a non

- profit, national organization founded in 1958 that represents the poison control centers of the United States and the interests of poison prevention and treatment of poisoning. All of the calls to a poison control center are answered by a medical professional trained to answer questions about poisons. Additionally, AAPCC reports provide clearly summarized information on pesticide incidents within the context of other poisoning events.

The Agency's findings with respect to decreases in CPY

- and O P

- associated poisonings

are consistent with other investigations of AAPCC data. These investigations reported that the regulatory restriction of access to pesticides may have a n impact on the number of human exposure incidents. Specifically:

B londell (20 07) examined Poison C ontrol Center data from 1995 to 2004. Rates were calculated for pesticide type and selected pesticide classes based on estimated total United States population and proportion of population served. Pesticides as a proportion of poisoni ng to all substances over the years and vital statistics on deaths
were examined to validate trends. Blondell found that from 1995 to 2004 there has been an overall 42% decline in estimated serious symptomatic exposures to pesticides reported to PCC in th e United States. At least 60% of this decline appears to be unrelated to any overall reporting bias. Specifically, organophosphate insecticides
declined 72%. The author noted that d eclines in PCC

- reported pesticide exposures are not fully understood becau se of the absence of denominator data on use and historical data on use patterns.

Sudakin and Power (2007) also utilized national Poison Control Center data to assess whether the risk mitigation decision had an impact on the number of incident cases
involv ing organophosphates in the United States. Organophosphate exposure incident data were extracted from Annual Reports of the American Association of Poison Control Centers for the years 1995 to 2004. They observed a reduction in incident

cases reported to poison control centers in the United States involving organophosphate insecticides. The reduction was temporally associated with risk mitigation decisions by the U.S. EPA to phase out the use of organophosphates from
residential environments.

An other inves tigation of PCC data by Power and Sudakin (2007) found that the restricting or banning of access to certain pesticides may have a significant effect on exposures to alternative clas ses of pesticides. They noted an increase in cases involving pyrethrins and pyrethroids associated with the US EPA’s regulatory decision to phase out organophosphate insecticides in residential environments.
Power and Sudakin extracted pyrethrin and pyrethroid insecticide exposure data from the AAPCC TESS annual reports from 2000 to 2005. They examined pyrethrin and pyrethroid incidents by total exposures for each year, and stratified exposures by age range, reason, number of cases treated in a health care facility, and medical outcome. Cases were examined as a proportion of all i nsecticide exposures. TESS data showed a clear increase in cases involving pyrethrins and pyrethroids. The increase was temporally associated with the phase out of organophosphates from residential uses.

## Page 14 of 51

AAPCC produces an annual summary report giving st atistics and information on all the poisonings reported to PCCs in a calendar year. The AAPCC annual summary data do not break
down the incident data in terms of chlorpyrifos per se but instead report it only as organophosphate incident data. The Agency examined the organophosphate data from 2002 to
2009 in order to update the Blondell (2007) examination of the PCC data from 1995 to 2004 and found that from 2002 to 2009, organophosphate exposures reported to the AAPCC ha ve continued to decline showing a 6 4% decrease in organophosphate exposures reported over that eight year period

.

3.6. Summary of Trends in Chlorpyrifos Incidents

Chlorpyrifos non

- occupational incidents appear to be decreasing over time across multiple
incident databases. In IDS, reports of incidents have decreased by 95% from 2002 to 2010. In NPIC reports of incidents have decreased by 92% from 2002 to 2010. This correlates well with the phase out/cancellation of the chlorpyrifos residential products

.

As of December 31, 2001, all products labeled for homeowner use, except containerized ant and

roach baits in child

- resistant packaging and all products labeled for use in schools and parks (both indoors and out) were canceled. However, there are still some homeowner/residential incidents reported as recently as May 2010 (IDS) and July 2010 (NPIC). Closer review of the most recent cases shows that they are due to eating food from a family owned farm without adhering to the pre

harvest interval, drift from a n eighboring farm, and residential misuse or spills and splashes from the use of cancelled products that had been stored in the home.

Chlorpyrifos occupational incidents appear to be constant over time in both the PISP and NIOSH
SENSOR databases. This co rresponds well with EPA’s agricultural market analysis that suggests that chlorpyrifos usage has remained relatively constant since 2001 (USEPA 2011).



## 4. Medical Toxicology and Medical Case Reports

Medical human observational data involving pesticides are another source of information that can be used to evaluate risks of chlorpyrifos. Medical case reports are evaluations of particular patients that describe the symptoms, signs, diagnosis, treatment, and follow

- up of an individual patient. Case series can be similar to case reports , but instead focus on multiple patients with similar exposure, treatment and/or symptoms/signs. Case reports and case series provide insight into the potential effects of pesticide exposure on humans assessed by health profession als. It is important to remember, however, that oftentimes, the exposure scenarios associated with medical case reports and series are extreme (suicides, attempted suicides, or non

- accidental ingestions) and bear little resemblance or similarity to more ty pical accidental or inadvertent exposures. Nevertheless, examining these cases can have value in that they illustrate the effects of frankly toxic doses and allow observation of what may be important sequella. In addition, examination of these cases can p ermit comparisons with the effects observed in laboratory animals in high dose toxicology studies. For pesticides where much information is available, there may be reviews and syntheses of information that professionals utilize to help diagnose and treat pesticide exposure (e.g., ATSDR

- Case Studies, Recognition and Management of Pesticide

## Page 15 of 51

Poisoning Manual). These reviews sometimes merge information from animal toxicity studies and in vitro studies in addition to human observational data to present a more complete picture of the toxicology of the pesticide.

Medical information on pesticides are found in many locations; however the Agency has relied on information obtained from databases for the period from 1993 to the present, querying the
National Libra ry of Medicine (PubMed, TOXNET), Google Scholar, as well as the CDC and ATSDR databases to identify relevant pesticide medical information. Specifically, the Agency looked across the following databases for this assessment:

PUB MED comprises more than 20 million citations for biomedical literature from MEDLINE, life science journals and online books.

TOXNET consists of HSDB (Hazardous Substances Data Bank) which contains comprehensive peer

- reviewed toxicology data for about 5,000 chemicals.

ATSDR Case

- Studies provide information regarding clinical findings, treatment and current knowledge regarding pesticides.

NHANES biomonitoring data provides information on environmental exposures
based on measures of environmental chemicals or metabolites in blo od or urine.

Google Scholar is a web search engine that indexes the full text of scholarly literature across an array of publishing formats and disciplines. It incl udes most peer

- reviewed
online journals of Europe and America's largest scholarly publishers.

Althoug h there may be other sources of medical information relating to pesticide exposures , the Agency is confident that considering the sources listed and described above captures the critical/impactful medical information, especially concerning human health ef fects of chlorpyrifos. A m edical literature search on chlorpyrifos was done, using the terms (or key concept) “chlorpyrifos poisoning” “chlorpyrifos AND health effects”, “chlorpyrifos toxicity”, “chlorpyrifos AND case study” to search Pub Med. Google adv anced search was used to retrieve full text articles. From PubMed 1044 citations were recovered but many of them were not specific to chlorpyrifos, or on human health effects. Twenty eight full text articles related to chlorpyrifos and human health effec ts, toxicokinetics and toxicodynamics were reviewed.

4.1. Medical Toxicology

Most of the toxic signs and symptoms presented by patients with chlorpyrifos poisoning are due to inhibition of acetylcholinesterase enzyme (AChE) which terminates the action of the neurotransmitter acetylcholine. Chlorpyrifos inactivates AChE by phosphor ylating the serine hydroxyl group located at the active site of AChE, resulting in an excessive accumulation of the neurotransmitter acetylcholine (ACh). This leads to overstimulation of muscarinic and nicotinic receptors in synapses and neuromuscular junc tions. Muscarinic and nicotinic receptors are acetylcholine receptors classified according to their response to Amanita muscaria mushroom
toxin and nicotine in tobacco. The clinical symptoms result from an interaction of parasympathetic, sympathetic, soma tic motor as well as central nervous effects ( Aaron and Howland, 1997 and Thompson and Richardson, 2004 ).

## Page 16 of 51

There are three generally described syndromes that result from organophosphates including chlorpyrifos exposure:

Acute cholinergic syndrome Intermediate syndrome (starts about 1

- 4 days after the acu te syndrome) Delayed neuropathy

Following the description of each of these syndromes, medical case reports obtained from the literature reflecting these three different syndromes are provided in Table 1. It is important to
note that these effects are obs erved only following severe poisoning incidents or intentional/ suicidal exposures and are only rarely reported in incident databases.

Acute Cholinergic Syndrome

Acute cholinergic syndrome can include the following central nervous system (CNS) effects: confusion, drowsiness, difficulty in concentrating, slurred speech, restlessness, bizarre behavior, ataxia, tremors, seizures, and coma. In severe intoxication, dea th can result from respiratory
failure . Respiratory failure is due to multiple factors: respiratory muscle weakness (particularly the diaphragm), central respiratory depression and pulmonary factors such as pulmonary edema, bronchoconstriction, bronchorrh ea (Singh G. et al

. , 2009).

Muscarinic mediated effects by organ systems include the following:

Cardiovascular

- b radycardia, hypotension Respiratory

- r hinorrhea, bronchorrhea, bronchospasm, cough, severe respiratory
distress

Gastrointestinal

– excessiv e salivation, nausea and vomiting, abdominal pain, diarrhea, fecal incontinence Genitourinary

– urinary incontinence

Ocular

- Blurred vision, miosis (constricted pupil)

Glands

- Increased lacrimation, diaphoresis (excessive sweating)

Nicotinic mediated si gns and symptoms by organ system include :

Cardiovascular

– may cause mild hypertension, and tachycardia Neuromuscular junctions

- may cause initial stimulation (muscle fasciculation, cramping), followed by weakness, and paralysis of muscles including diaphragm
muscle.

Dermal

– excessive sweating

Intermediate Syndrome

Intermediate syndrome is a development of weakness in respiratory muscles, proximal muscle groups of limbs, and neck flexor muscles after an episode of acute cholinesterase inhibitor pois oning

. It is so named because it can occur between 1

- 4 days after the acute cholinergic crisis

## Page 17 of 51

and the onset of organophosphate

- induced delayed neuropathy (OPIDN ) (Karalliedde and Senanayake 1989; Kwong 2002)

. Intermediate syndrome may occur from 20

- 70 % of p atients
and i t may last from 4

- 18 days. As discussed above, differing sensitivity is expected in the population. According to Aygun et al. (2002)

, intermediate syndrome may be due to damage secondary to over stimulation of nicotinic receptors withi n sympathetic ganglia and at skeletal myoneural junction. However, Katz and Brooks (2010) thought that it may be due to suboptimal treatment during the acute stage. R espiratory muscle weakness caus ing respiratory depression usually req uires ventilator su pport.

Chlorpyrifos has high lipoph il icity, and is able to readily access t he central nervous system (CNS). It is more likely to cause CNS effects such as extrapyramidal manifestations and Parkinsonism like syndrome (cogwheel rigidity of extremities, bradykinesia, resting tremor, choreoathetosis, and masked face) than other organophosphates (Kventsel et al., 2005). Hsieh et al. 2000 proposed that Parkinsonism like syndrome may be due to abnormal modulation of the nigrostriatal dopaminergic system. Som e cases exhibited Parkinsonism without antecedent or concomitant chlolinergic syndrome.

Salvi et al., 2003 state d that workers exposed to chlorpyrifos developed clinically significant extrapyramidal symptoms. Tremor was the predominant symptom; also mask

- like face and reduced pendular arm movement were commonly observed

.

Goel.et al., 2006 reported that a 21 year old female with a history of ingestion of heavy dose of organophosphate developed extrapyramidal symptoms (tremor, mask

- like face, cog wheel rigidity, hypokinesia, and occulo

- gyric crisis) on the 10 th 

## day. Magnetic resonance imaging (MRI) showed symmetrical hyper intensities in the Putamen and Caudate nucleus.

Delayed Neuropathy

Aygun et al. ( 2002) and Sennayake et al. (1993) mentioned that c hlorpyrifos poisoning may cause delayed neuropathy

, also known as organophosphate induced delayed neuropathy (OPIDN). It is a neurobehavioral and sensory

- motor distal axonopathy. It was mentioned that inhibition (phosphorylatio n) of neuropathy target esterase (NTE) enzyme in neurons leads to axonal degeneration and demyelination of the nerves (Nand et al. , 2007). According to Eaton et
al. , 2008, the severity of neuropathy correlates with the degree of NTE enzyme inhibition.
Gl ynn P., 2005 found that organophosphate inhibition of NTE causes disruption of neuronal cell membrane phospholipid homeostasis and endoplasmic reticulum functions which interferes with axonal transport of protein and other substances. The distal parts of long axons are particularly vulnerable to loss of these support functions.

Patients may suffer from impaired memory and concentration, disorientation, severe depression, irritability, confusion, headache, speech difficulties, delayed reaction times, nig htmares, drowsiness and insomnia (Cox

, 1994). Mostly patients presented 3

- 5 weeks after organophosphate poisoning with lower extremity weakness, a high stepping gait, calf pain, leg cramps, and glove and stocking type of sensory loss. Large distal neuron s tend to be affected first, causing atrophy of calf muscles, foot drop, and ataxia

. A n erve conduction study showed reduced or absent compound muscle action potential (CMAP) in motor nerves and reduced

## Page 18 of 51

conduction velocity in both motor and sensory nerves

. Residual sensory and autonomic dysfunction may persist for years after cessation of exposure (Senanayake, 1981).

## Page 19 of 51

4.2. Medical Case Reports

Table 2 : Medical Case Reports of Chlorpyrifos Poisoning

Article Title Author Year Summary

Medical Case Reports Regarding Acute Cholinergic Symptoms

Non

- accidental chlorpyrifos poisoning

- an unusual cause of profound unconsciousness Jiun

- Chang Lee Kuang

- Lin Lin
Jainn

- Jim Lin
et al. 2009 A 5 year 6 month old boy suffered from abdominal pain, excessive salivation, lacrimation, vomiting, shortness of breath, pin point pupils, prolonged pause in breathing, and deep unconsciousness, after being poisoned with chlorpyrifos by his
step

- mother. His plasma cholinester ase level was <84μ/l (normal range, 3,000

- 9,300 μ/l). Brain computed tomogram did not show focal brain lesion. One hour after the intravenous atropine treatment was started; pin point pupils, excessive salivation and lacrimation were improved. He regaine d consciousness after two days and the ventilator support was stopped on the fifth day.

Acute chlorpyrifos poisoning in pregnancy: A case report Solomon G.M. Moodley J. 2007 A 22 year old pregnant woman presented with generalized tonic

- clonic seizures, vomiting profusely with garlic odor, fecal incontinence, pinpoint pupils, muscle weakness, and secretions in lungs after drinking unknown amount of chlorpyrifos to commit suicide. Although her symptoms improved with atropine administration, she
went into premature labor two days after the initial event, and delivered a 1.2 kg live baby that died on day 2 due to prematurity. She was discharged from the hospital two
weeks later.

Chlorpyrifos poisoning treated with ipratropium and dantrolene: a case
report

. Shemesh, I., Bourvin, A., Gold, D. & Kutscherowsky, M. 1988 A 38

- year

- old man drank an undefined quantity of a 25% chlorpyrifos solution. He presented with stupor, respiratory distress, and had complete inhibition of serum ChE activity. The man was successfully treated with extensive antidote therapy and artificial respiration and was discharged from the hospital one month after the incident. His serum ChE activity was still undetectable at that time.

## Page 20 of 51

Medical Case Reports Regarding Intermediate and Extra

- Pyramidal Syndrome

Article Title Author Year Summary

Intermediate syndrome after exposure to chlorpyrifos in a 16

- month old girl Mattingly J.E.
Sullivan J.E. Spiller H.A.
Bosse G.M. 2003 A 16

- month old girl accidentally ingested chlorpyrifos and developed lethargy, difficulty in breathing and pulmonary edema. She was treated with pralidoxime and also put on the mechanical ventilator. At 24.5 hour post

- ingestion, the child had a normal neurologic examination, showed no signs of c holinergic symptoms, and was extubated. However, at 27.5 hour post

- ingestion she became flaccid, with slow heart rate and irregular respiration (temporary cessation of respiration). She was emergently

re

- intubated. This is consistent with the characteris tic of Intermediate syndrome (development of respiratory failure after recovering from the initial episode).

Scopolamine treatment for severe

extra

- pyramidal Signs following organophosphate (chlorpyrifos) ingestion Kventsel I.
Berkovitch M.
Reiss A.

Kozer E. 2005 A 17

- year

- old girl was admitted to the pediatric ward 2 hours after ingesting 150 mL of a household pesticide containing chlorpyrifos. Over the course of 36 hours, she gradually developed extra

- pyramidal signs and became comatose. Her plasm a cholinesterase level was 146 U/L (Normal value

- 5300

- 12900 U/L). She did not respond to questions and commands or to pain stimuli. She vomited four times but did not have other muscarinic signs and symptoms. She was treated with intravenous scopolamin e. Within few minutes, the patient started to respond to verbal commands and answered simple questions, rigidity subsided, and she was able to sit in bed. She was discharged after 4 days with no neurological sequelae. Scopolamine is able to
cross the blood brain barrier better than atropine and exerts its effects by acting as a competitive antagonist at muscarinic acetylcholine receptors. Her plasma cholinesterase level returned within normal range (8160 U/L) three months after the ingestion. This is one o f the chlorpyrifos poisoning cases presented with extrapyramidal effects with minimal muscarinic symptoms.

Medical Case Reports Regarding Delayed Neuropathy

Article Title Author Year Summary

## Page 21 of 51

Organophosphate induced delayed neuropathy Nand N. Aggarwal HK
Bharti K.
Chakrabarti D. 2007 A 19 year old male ingested 100 ml of chlorpyrifos in an attempt to commit suicide; he developed pin point pupils, and excessive secreti ons in lungs. After 24 hours he had respiratory paralysis and shock, and was put on mechanical ventilation for 16 days. He recovered except slight weakness of proximal muscles of lower limbs and was discharged from the hospital. After six days of discharg e, he developed distal weakness in the lower limbs which progressed in next 3

- 4 days to the extent that he could not walk without support. Electrophysiological examinations revealed markedly reduced CMAP (compound muscle action potential) and reduced moto r nerve conduction velocity in tibial nerve of both lower limbs. Sensory nerve action potential was mildly reduced. These findings were consistent with characteristics of OPIDN which has a predominant motor axonal neuropathy involving distal muscles of lo wer limbs.

Permanent paralysis at sites of dermal exposure to chlorpyrifos Meggs W. J. 2003 A case presented with OPIDN after a mixed dermal and inhalational exposure to chlorpyrifos. This case is unique because the neuropathy developed only in those regions with direct skin contact to chlorpyrifos. A 61 year old carpenter sprayed a nest of termites with the product containing 45% chlorpyrifos without protective equipment. The product got on his hands, lower arms, lower legs and feet. He developed n ausea, vomiting, abdominal cramps, weakness in arms and legs, bilateral shoulder pain, chest pain and numbness in the left hand and arm, 30 minutes after using the product. Although atropine and pralidoxime were given, electromyogram showed widespread

pe ripheral neuropathy which was progressing. Pralidoxime was repeated on the third day. However, he never regains use of his hands and has disturbed gait (unable to clear his left foot when walking). Follow up after ten years showed decreased grip strength

, inability to dorsiflex his left leg and hopping on his right foot to clear his left foot which has a marked foot drop. During the course of his illness, patient did not develop mental status change, or other neuropsychiatric disability. This case indic ates that exposure to chlorpyrifos can lead to permanent paralysis at the sites of dermal exposure in spite of a relatively mild systemic poisoning.

## Page 22 of 51

Severe and prolonged neurologic toxicity following subcutaneous chlorpyrifos self

- administration Soummer A.

Megarbane B.
Boroli F.
Arbelot C.
et al. 2011 An interesting case of prolonged coma (6 weeks), delayed cholinergic phase and prolonged neurologic toxicity following self injection with chlorpyrifos subcutaneously on both arms was reported. Although minimal muscarinic signs were found at the time
of a dmission, he developed respiratory failure after twenty four hours and was put on the ventilator. Large surgical wound debridement was done for extensive necrotizing fasciitis of both forearms; also daily wound debridement for necrosis and sepsis. On

var ious occasions, several minutes after wound care, muscarinic symptoms such as hypersalivation, bronchorrhea (excessive secretions in airways) and bradycardia occurred, were relieved by atropine. Authors thought these symptoms were due to prolonged and con tinuous release of chlorpyrifos from the body fat and forearm muscles acting as reservoirs (despite repeated wound debridement). They found chlorpyrifos in serum till Day 30, and metabolites in plasma and urine till Day 100. Chlorpyrifos concentration in the forearm muscle was 44 μg/kg on Day 50. Plasma butyrylcholinesterase activity remained low <500 IU/L (Normal range 8000

- 18,000) until Day 60. RBC cholinesterase level was 1138 IU/L (Normal range 2800

- 5200) on admission and became normal on Day 60. Pat ient was discharged at Day 120; he remained tetraparetic (weakness on all four limbs), but proximal muscle testing showed some improvement. However, distal muscle testing showed persistent severe deficits. At one year follow

- up, persistent severe muscle weakness was found indicating irreversible organophosphate related peripheral neuropathy.

Life

- threatening organophosphate

induced delayed polyneuropathy in a child after accidental chlorpyrifos ingestion. Aiuto, L.A., Pavlakis, S.G. & Boxer, R.A. 1993 A 3 year old child presented with cholinergic syndrome after chlorpyrifos exposure. Patient’s BuChE level got back to normal within 3 days of treatment. However, he developed bilateral vocal cord paralysis while he was in hospital

. Tracheostomy was performed and maintained for more than 50 days. Patients recovering from serious organophosphate poisoning should be monitored for the development of vocal cord paralysis which can be a fatal complication.

Isolated bilateral recurrent laryngeal nerve paralysis: A delayed complication of organophosphorus poisoning. Silva D Sanmuganathan P.S. Senanayake N. 1994 A 21

- year

- old man who ingested an unknown quantity of chlorpyrifos showed acute cholinergic effects comprising pupillary constriction, excess secretions, tachycardia, and impaired consciousness. He was treated with atropine and PAM (pralidoxime). Twenty

- eight days after exposure, bilateral vocal cord paralysis developed. The patient received prolonged intubation and ventilator support.

## Page 23 of 51

5. NHANES Biomonitoring Data

In a survey of a random sample of U.S. adults (n = 929) conducted in the late 1980s and early 1990s (Hill et al.

, 1995) estimated that detectable levels of a metabolite of chlorpyrifos (TCP y ) are present in the urine of 82% of U.S. adults, with a mean level of 4.5 μg /L. According to

NHANES 200 1

- 200 2 , urinary concentrations of 3,5,6

- TCPy were highest in 6

- 11 year old group, and the levels were 3.76 (50 th 

## percentile), 6.22 (75 th 

## percentile), 12 .2 (90 th 

## percentile) and 16.9 μg/g of creatinine (95 th 

## percentile). Adult (20

- 59) year old group levels were 1.64, 3.11, 5.50, and 7.44 μg/g of creatinine, respectively.

6. Epidemiological Data

Epidemiological data may be used to assist in the identificati on and characterization of human health hazards in the environment. Ideally, these data may be used quantitatively to estimate an

exposure

- response relation in the human population, as opposed to experimental animal models. In this assessment, the epidemio logic data related to chlorpyrifos exposure is used qualitatively to further describe potential human health hazards in certain study populations. Specifically, data from two distinct sources are considered: the Agricultural Health Study (AHS), and studies from three independent university

- based children’s health study populations (Columbia University, Mt. Sinai Hospital, and University of California, Berkeley ). Results of these investigations are briefly summarized below.

The AHS is a high quality

, pro spective epidemiology study evaluating the potential associations between pesticide use and various cancer and non

- cancer health outcomes among a large population of private and commercial pesticide applicators (N=57,310). The AHS chlorpyrifos carcinogen icity studies have been summarized in the memorandum “ Chlorpyrifos Carcinogenicity: Review of Evidence from the U.S. Agricultural Health Study (AHS) Epidemiologic Evaluations 2003

- 2009,” (Christensen , D388167 , 6/16/2011 )

. In the memorandum, two types of AHS studies were reviewed: studies which compare the proportion of chlorpyrifos users between those with and without certain cancers (referred to as nested case

control studies) and cohort studies which compare cancer incid ence between those exposed to chlorpyrifos and those not exposed to chlorpyrifos. Both the nested case

- control and the cohort studies published in the AHS to date are hypothesis

- generating in nature i.e.

, no a priori associations were hypothesized and mu ltiple analyses (comparisons) were performed in many instances, these investigations are among the first ever published examining a chlorpyrifos

cancer association and, as hypothesis

- generating studies, these results require replication to
confirm and full y understand the nature of the association between chlorpyrifos use and cancer

outcomes

, i.e.

, whether any observed statistical associations are in fact likely to be causal in

nature.

While all of these investigations were hypothesis

- generating in nature , initial findings for lung
and colorectal cancer are notable. In both of these investigations, the association is observed in
both cohort and case

- control studies at different points in time, and within both study st ates (NC, IA). In addition, researchers observed a monotonic, linear trend across exposure categories, and a statistically significant difference in cancer risk between upper

- and lower

- category exposure groups. H owever, these results represent initial reports only

, are the result of many diffe rent

## Page 24 of 51

statistical tests, and lack biological explanation at this time. Regarding hormonally

- modulated cancer sites, there is only limited evidence that chlorpyrifos may play a role in either prostat e

cancer , among men with a family history of prostate cance r, or breast cancer

, among female spouses of farmers/applicators. With regard to each of these afore mentioned anatomical cancer sites, additional research is needed to better define the nature of this association. There is n o evidence presented within th is occupational cohort that lifetime chlorpyrifos exposure is related to cancers of the pancreas, brain, esophageas, kidney, or cutaneous melanoma, lymphohematopoietic cancers combined or non

- Hodgkin’s lymphoma, leukemia, and multiple myeloma. EPA will con tinue to monitor the l iterature for additions to the chlorpyrifos cancer
database in the future.

In addition to evaluations of the carcinogenic potential of chlorpyrifos within the Agricultural Health Study (AHS), EPA is also considering the results of epidemiological evidence of the compound’s developmental neurotoxicity. Specifically, there are thre e major prospective epidemiology cohort studies evaluating pre

- and post

- natal pesticide (chlorpyrifos and/or OPs) exposure in mother

- infant pairs with birth outcomes, and childhood neurobehavioral and neurodevelopment outcomes in neonates, infants, and yo ung children. Two of the cohorts have also investigated the role of genetic susceptibility (PON1) in the association between pesticide exposure and adverse birth outcomes and neurodevelopmental effects. In 2008, EPA consulted
the SAP on the use of these three cohort studies in mothers and their children. Details of this analysis and discussion are provided in the chlorpyrifos docket (draft Appendix D Epidemology at http://www.epa.gov/scipoly/sap/meetings/2008/091608_mtg.htm.) EPA plans to finalize the

s cience documents reviewed by the SAP in the upcoming months. Funded by multiple Federal Agencies, including US EPA, the three studies originate from: (1) Columbia University, NYC, (2) Mt Sinai, School of Medicine, NYC, and (3) University of California at Berkeley (Center for Health Assessment of Mothers and Children of Salinas, CHAMACOS). The first two study populations include multi

- ethnic, urban low income mother

- infant pairs, and the latter reflects a farm worker/agricultural worker study population 1



## . The Columbia study focuses on chlorpyrifos
in cord blood and the latter two studies assess the non

- specific organophosphate (OP) metabolite dialkyl phosphates (DAPs) in maternal urine, and link these biomarkers of exposure with
associated health outcomes i n children that were exposed in utero

. The results and interpretation of these studies including the integration of the toxicological and epidemiological databases, are more fully discussed by EPA in the documents “ Chlorpyrifos Hazard and Dose Response
Ch aracterization,” as well as the risk assessment

. These results are briefly summarized here.

Briefly, researchers have evaluated the association between prenatal or perinatal chlorpyrifos exposure and developmental neurotoxic health effects observed in ne onates, infants, and children through age 7. In EPA’s review of the epidemiologic evidence concerning potential neurodevelopmental effects of prenatal or early postnatal chlorpyrifos and/or OP exposure, EPA noted consistency across the studies, i.e. delay s in cognitive achievement, motor control, social behavior, and intelligence measures that were reported in all three prospective cohorts (Columbia, Mt. Sinai and CHAMACOS) in children 2

- 3 years of age. However, the degree to which chlorpyrifos is implica ted in these outcomes varies.

1 

### The Mt Sinai study included inner city, black, Hispanic and white women, while the Columbia study evaluated inner city African American and Dominican. The Berkley study included homogenous Latino women from Agricultural communities.

## Page 25 of 51

More recently, in April 2011, these same researchers published results indicating that in utero chlorpyrifos and/or OP exposure may have persistent neurodevelopmental effects for school age children up to age 7 using the W eschsler Intelligence Scale for Children

- IV. Since these studies were recently published, EPA has not conducted a full evaluation of these recent publications (of the same cohort), but will consider these human epidemiological studies along with the availa ble empiricial data in a full weight of evidence analysis in the final assessment.

There are several strengths of the epidemiological database linking prenatal chlorpyrifos and other OP exposure with neurodevelopment effects in neonates, infants, young children and school aged children. Specifically, the measurement of the neurodevelopmental outcomes (e.g., Brazelton index, Bayley scale, and the Weschlar Intelligence Scale) are accepted valid and
reliable measurement tools in clinical and epidemiologic r esearch. In addition, the use of biological markers of exposure [i.e., cord blood concentration of chlorpyrifos or maternal urinary dialkylphosphate (DAPs)], are more accurate and reliable measures of prenatal exposure than other forms of exposure assessm ent such as self

- report questionnaire. Notably, the exposure measurements (biomonitoring and/or personal air monitoring) were well coordinated with the exposure period of interest (third trimester for birth outcomes). The Columbia study measured chlorpyr ifos in umbilical cord blood at delivery, and maternal blood measurements during pregnancy and delivery. The researchers in each of these cohorts utilized robust and appropriate statistical analysis methods to model the exposure

- response association includ ing adjustment for potentially confounding variables.

All three cohort studies have limitations that include multiple chemical exposures and exposure to other organophosphates. The exposure classification is based on maternal spot urinary samples for the Mt. Sinai and CHAMACOS studies and maternal and cord blood samples in the Columbia Study that may not necessarily represent total chlorpyrifos or OP exposure throughout pregnancy because these pesticides have short half

- lives. However, the prevalence of exposure among these cohorts based upon a one

- time sample indicates the total exposure may be greater than measured (exposure measurement error likely exists), and results of meconium analyses in the Columbia cohort indicate chlorpyrifos exposure occurred throughout pregnancy. Meconium is considered to be an integrative measure of exposure throughout pregnancy. In addition, the Mt. Sinai and CHAMACOS studies associate increased maternal urinary DAP levels with increased mental delays in children. DAP met abolites are non

- specific metabolites that result from several OP pesticides, so it is difficult to determine which OP compound may be contributing most to the adverse findings.

7. CONCLUSION

This review considers different types and sources of human obser vational information (human incident data, medical data/information, and epidemiological information) in an effort to consider different lines of evidence that may inform the re

- evaluation of chlorpyrifos in this phase of Registration Review. The symptoms reported in the medical human observational data and human incident data reviewed for this report are mutually supportive. Specifically, the symptoms reported for both types of observational data include cardiovascular, respiratory,

## Page 26 of 51

gastrointestinal, ner vous system and ocular symptoms. The Agency’s risk mitigation measures including canceling all homeowner use product registrations (except ant bait stations), and canceling uses in schools and parks where children may be exposed appears to have led to a
d ecrease in the number of incidents reported in residential areas. The databases that were reviewed (OPP Incident Data System, National Pesticide Information Center [NPIC], NIOSH
Sentinel Event Notification System for Occupational Risks [SENSOR], and Calif ornia Pesticide Illness Surveillance Program Incident Data [CA PISP]) showed the number of incidents associated with chlorpyrifos significantly declined post

- 2002 and this correlates well with the phase out/cancellation of the almost all chlorpyrifos resid ential products as of December 31,

2001. In addition, the Agency's findings are consistent with other incident cases investigations
of American Association of Poison Control Centers ( AAPCC) data which have reported a decrease in the number of chlorpyrifos incidents that is temporally associated with the phase out/cancellation of most residential chlorpyrifos products. For AAPCC data, the mean annual number of reports for chlorpyrifos in th e pre

- and post

- announcement phases was 214 and 39.3, respectively (Stone et al. 2009). In IDS, there were 43 incidents reported in 2002 and only six reported in 2009.

C hlorpyrifos occupational incidents, reported in CA PISP and SENSOR databases, appear to be constant over time, despite risk mitigation implemented including reduced application rates and seasonal maximum limits, increased retreatment intervals, increased PPE and/or use of engineering controls were required as well as increased re

- entry int ervals (REIs) for a number of

crops. However, a number of these incidents appear to be due to accidents and misuse. In NIOSH SENSOR applying chlorpyrifos appears to lead to the most incidents, being responsible for 46% reported to NIOSH SENSOR from 1998 to 2007; in PISP, drift of chlorpyrifos from adjacent fields appears to be the cause of the most incidents, being responsible for 56% of the cases reported to PISP from 1999 to 2008.

The chlorpyrifos incidents reported have declined substantially (95%) a mong residential users from 2002 to May 27, 2010, but the occupational incidents reported remain the same. The incidents reported have been reviewed and, overall, the numbers and severity of incidents associated with chlorpyrifos use are not of public hea lth concern, but we will continue to monitor these incidents and remain alert for any changes in trend or patterns.

The Agency examined epidemiologic data from two distinct sources to support this risk assessment: the AHS and results from three university

- based children’s health cohorts. Regarding the AHS studies, EPA notes that the results for the potential link between occupational use of chlorpyrifos over the lifetime and both lung and colorectal cancers are notable, given the strength and consistency o f the association; however as preliminary, hypothesis

- generating studies, additional research and follow

- up is needed to clarify and verify
the nature of the association. EPA will continue to monitor the literature for additions to these
two databases. Reg arding other cancer sites, there is li mited, preliminary evidence that chlorpyrifos may play s a role in eit her prostate or breast cancer, and no evidence to suggest that chlorpyrifos is associated with pancreatic cancer, melanoma, brain, esophageal, kidney , all lymphohematopoietic cancers combined and NHL, leukemia, and multiple myeloma. Regarding the putative association between prenatal chlorpyrifos exposure and neurodevelopmental effects

## Page 27 of 51

in neonates, and young children, EPA will continue to follow to thi s issue and further evaluate
the associated epidemiological and toxicological science in the coming months.

## Page 28 of 51

8. References

AIUTO, L.A., PAVLAKIS, S.G., & BOXER, R.A. 1993. Life

- threatening organophosphate

induced delayed polyneuropathy in a child after accid ental chlorpyrifos ingestion. J. Pediatrics, 122, 658

- 660.

AARON, C.K., HOWLAND, M.A. 1997. Insecticides: Organophosphates and carbamates. Appleton & Lange, 1429

- 1449.

ALBERS, J.W., G ARABRANT, D.H., STANLEY, B., RICHARDSON R.J. 2010. Paraoxonase status and plasma butyrylcholinesterase activity in chlorpyrifos manufacturing workers. Journal of Exposure Science & E nvironmental E

pidemiology

, 20 (1),79

- 89

ATSDR, 1997. Toxicological Profile for Chlorpyrifos

. http://www.atsdr.cdc.gov/toxprofiles/tp.asp?id=495&tid=88

AYGUN, D., DOGANAY, Z., ALTINTOP, L.ET AL. 2002. Serum acetylcholinesterase and prognosis of acute organo phosphate poisoning. Journal of Toxicology, vol40, No7, 903

- 910.

BICKER, W., LAMMERHOFER, M., GENSER, D., KISS, H. & LINDNER, W. 2005. A case study of acute human chlorpyrifos poisoning: Novel aspects on metabolism and toxicokinetics derived from liquid c hromatography

- tandem mass spectrometry analysis of urine samples. Toxicology Letters, 159
, 235

- 251.

BLONDELL, J. M. 2007. Decline in pesticide poisonings in the United States from 1995 to

2004. Clinical Toxicology, 45
, 589

- 592.

BOUCHARD 2011 Maryse F. B ouchard, Jonathan Chevrier, Kim G. Harley, Katherine Kogut, Michelle Vedar, Norma Calderon, Celina Trujillo, Caroline Johnson, Asa Bradman, Dana Boyd Barr, and Brenda Eskenazi. “Prenatal E xposure to
O rganophosphate Pesticides and IQ in 7

- Y ear

- O ld C hildren”; http://ehponline.org/article/info:doi/10.1289/ehp.1003185.

BOUCHARD, M. F., BELLINGER, D. C., WRIGHT, R. O. & WEISSKOPF, M. G. 2010.
Attention

- Deficit/Hyperactivity Disorder and Urinary Metabolites of Organophosphate
Pesticides. Pediatrics, 125
, E1270

- E1277.

CDC, 2010

. National Report on Human Exposure to Environmental Chemicals

. http:/ /www.cdc.gov/exposurereport/data_tables/Trichlorophenols_ChemicalInformation.
html

CDC. The Fourth National Report on Human Exposure to Environmental Chemicals, 2009. http://www.cdc.g ov/exposurereport/pdf/FourthReport.pdf

COX, C. 1994. Chlorpyrifos, Part I: Toxicology. Journal of Pesticide Reform, 14
, 15

- 19.

EATON, D. L. ET AL. 2008. Review of the Toxicology of Chlorpyrifos with an Emphasis on Human Exposure and Neurodevelopment. Critical Reviews in Toxicology, S21

- 125.

ENGEL, S.M., Wetmur, J., Chen, J., Zhu C. , Barr , D.B. , Canfield , R. L.

, & Wolff , M. S. 2011

. Prenatal Exposure to Organophosphates, Paraoxonase 1, and Cognitive

## Page 29 of 51

Development in Childhood

. Environmental Health Perspectives. http://ehponline.org/article/info:doi/10.1289/ehp.1003183.

ENGEL, S. M., BERKOWITZ, G. S., BARR, D. B., TEITELBAUM, S. L., SISKIND, J., MEISEL, S. J., WETMUR, J. G. & WOLFF, M. S. 2007. Prenatal organophosphate metabolite and organochlorin e levels and performance on the Brazelton Neonatal Behavioral Assessment Scale in a multiethnic pregnancy cohort. American Journal of Epidemiology, 165
, 1397

- 1404.

ESKENAZI, B., MARKS, A. R., BRADMAN, A., HARLEY, K., BARR, D. B., JOHNSON, C., MORGA, N. & J EWELL, N. A. 2007. Organophosphate pesticide exposure and neurodevelopment in young Mexican

- American children. Environmental Health Perspectives, 115
, 792

- 798.

FARAHAT F.M., ELLISON C.A., et al. Biomarkers of Chlorpyrifos Exposure and Effect in Egyptian C otton Field Workers. Environmental Health Perspectives, January, 2011.

FOXENBERG, R. J., MCGARRIGLE, B. P., KNAAK, J. B., KOSTYNIAK, P. J. & OLSON, J. R. 2007. Human hepatic cytochrome P450

- specific metabolism of parathion and chlorpyrifos. Drug Metabolis m and Disposition, 35
, 189

- 193.

GLYNN, P. 2006. A mechanism for organophosphate

- induced delayed neuropathy. Toxicology
Letters, 162
, 94

- 97.

GOEL, D., SINGHAL, A., SRIVASTAV, K., VERMA., ET AL.2006. Magnetic resonance imaging changes in a case of extra

- pyra midal syndrome after acute organophosphate poisoning. Neurology India , 54:207

- 209.

HAWKINS, M. & CORDOVA, J. 2008. Updated Review of Chlorpyrifos Incident Reports. In: HEALTH EFFECTS DIVISION, OFFICE OF PESTICIDE PROGRAMS, OFFICE OF CHEMICAL SAFETY AND POLLUTION PROVENTION, US ENVIRONMENTAL
PROTECTION AGENCY. Memorandum dated 10/15/2008.

HILL, R.H.J.,HEAD, D.L., BAKER S. ET AL. Pesticide residues in urine of adults living in the
United States: Reference range concentrations. Environ. Res. 71:99

- 108.

HSIEH, B.H., DENG, J.F., GER, J., TSAI, W.J. 2000. Acetylcholinesterase inhibition and the extrapyramidal syndrome: A review of the neurotoxicity of organophosphate. Neurotoxicology, 22, 423

- 427.

KATZ, K.D., BROOKS, D.E. 2010. Toxicity, Organophosphate. eMedicine Emergency
Medicine. http://emedicine.medscape.com/article/167726

- overview

KVENTSEL, I., BERKOVITCH, M., REISS, A., BULKOWSTEIN, M. & KOZER, E. 2005. Scopolamine treatment for severe ext ra

- pyramidal signs following organophosphate (chlorpyrifos) ingestion. Clinical Toxicology, 43
, 877

- 879.

LEE, J. C., LIN, K. L., LIN, J. J., HSIA, S. H. & WU, C. T. 2010. Non

- accidental chlorpyrifos poisoning

- an unusual cause of profound unconsciousness. E uropean Journal of Pediatrics, 169
, 509

- 511.

MEGGS, W. J. 2003. Permanent paralysis at sites of dermal exposure to chlorpyrifos. Journal of Toxicology

- Clinical Toxicology, 41
, 883

- 886.

## Page 30 of 51

NAND, N, AGGARWAL, H.K., BHARTI, K. & CHAKARABARTI, D. 2007. Organophosphate Induced Delayed Neuropathy. J Assoc Physicians India , 55,72

- 73

POWER, L. E., SUDAKIN, D. L. & GIFFIN, S. L. 2007. Longitudinal trends in spatial and temporal clustering of pesticide exposure incidents: Applications o f GIS. Clinical Toxicology, 45
, 115.

RAUH, V., ARUNAJADAI, S., HORTON, M., PERERA, F., HOEPNER, L., BARR, D. B. & WHYATT, R. 2011. 7

- Year Neurodevelopmental Scores and Prenatal Exposure to Chlorpyrifos, a Common Agricultural Pesticide. Environ Health Pers pect

. h ttp://ehponline.org/article/info:doi/10.1289/ehp.1003160.

RAUH, V. A., GARFINKEL, R., PERERA, F. P., ANDREWS, H. F., HOEPNER, L., BARR, D. B., WHITEHEAD, R., TANG, D. & WHYATT, R. W. 2006. Impact of prenatal chlorpyrifos exposure on neurodevelopm ent in the first 3 years of life among inner

- city
children. Pediatrics, 118
, E1845

- E1859.

SALVI, R. M., LARA, D. R., GHISOLFI, E. S., PORTELA, L. V., DIAS, R. D. & SOUZA, D.
O. 2003. Neuropsychiatric evaluation in subjects chronically exposed to organophosphate pesticides. Toxicological Sciences, 72
, 267

- 271.

SHEMESH, I., BOURVIN, A., GOLD, D. & KUTSCHEROWSKY, M. 1988. Chlorpyrifos Poisoning Treated With Ipratropium and Dantrolene

- A Case

- Report. Journal of Toxicology

- Clinical Toxicology, 26
, 495

- 498.

SENNAYAKE, N., SILVA, D. 1993. Scale to assess severity in organophosphorous intoxication. Human Exposure Toxicology

, 12, 297

- 299.

SINGH, G., KHURANA, D. 2009. Neurology of acute orga nophosphate poisoning. Indian Perspective , vol: 57, 119

- 125.

SINGH H, S. 2000. Delayed Neuropathy after Organophosphorus Insecticide Poisoning

– A Case Report

. Neurology India ; 48:308

- 13.



## SOLOMON, G. M. & MOODLEY, J. 2007. Acute chlorpyrifos poisoning in p regnancy: A case
report. Clinical Toxicology, 45
, 416

- 419.

STEENLAND, K., DICK, R. B., HOWELL, R. J., CHRISLIP, D. W., HINES, C. J., REID, T. M., LEHMAN, E., LABER, P., KRIEG, E. F. & KNOTT, C. 2000. Neurologic function among termiticide applicators expose d to chlorpyrifos. Environmental Health Perspectives, 108
, 293

- 300.

STONE, D. L., SUDAKIN, D. L. & JENKINS, J. J. 2009. Longitudinal trends in organophosphate incidents reported to the National Pesticide Information Center, 1995

- 2007. Environmental Health, 8.

SUDAKIN, D. L. & POWER, L. E. 2007. Organophosphate exposures in the United States: A longitudinal analysis of incidents reported to poison centers. Journal of Toxicology and
Environmental Health

- Part a

- Current Issues, 70
, 141

- 147.

TANG, J., CAO, Y., R OSE, R. L., BRIMFIELD, A. A., DAI, D., GOLDSTEIN, J. A. & HODGSON, E. 2001. Metabolism of chlorpyrifos by human cytochrome P450 isoforms

## Page 31 of 51

and human, mouse, and rat liver microsomes. Drug Metabolism and Disposition, 29
, 1201

- 1204.

THOMPSON, C. M. & RICHARDSO N, R. J. 2004. Anticholinesterase Insecticides, Chichester, John Wiley & Sons, Inc.

TIMCHALK, C., KOUSBA, A. & POET, T. S. 2002. Monte Carlo analysis of the human chlorpyrifos

- oxonase (PON1) polymorphism using a physiologically based pharmacokinetic and ph armacodynamic (PBPK/PD) model. Toxicology Letters, 135
, 51

- 59.

USEPA 2011. Pesticide Industry Sales and Usage 2006 and 2007 Market Estimates. In: BIOLOGICAL AND ECONOMIC ANALYSIS DIVISION, OFFICE OF PESTICIDE PROGRAMS, OFFICE OF CHEMICAL SAFETY AND POLLUTI ON PROVENTION.

WHYATT, R.B., GARF I NKEL, R., HOEPNER, L.A., ANDREWS, H., ET AL.2009. A Biomarker Validation Study of Prenatal Chlorpyrifos Exposure within an Inner

- City Cohort during Pregnancy. Environmental Health Perspectives , vol 117, no.4.

YOUNG, J. G., ESKENAZI, B., GLADSTONE, E. A., BRADMAN, A., PEDERSEN, L., JOHNSON, C., BARR, D. B., FURLONG, C. E. & HOLLAND, N. T. 2005. Association between in utero organophosphate pesticide exposure and abnormal reflexes in neonates. Neurotoxicology, 26
, 199

- 209.

## Page 32 of 51



# Appendix A : Chorpyrifos Main IDS Report

Main IDS Report Chemical: Chlorpyrifos (PC code 059101) Human Incidents

Incident
Number Incident

Date Product Name Registration
Number City State Exposure Type* Incident Description

12570 11 4

- Jan

- 02 RAID ANT BAITS (DISCONTINUED IN 2001) 482200335 OXFORD MI HC A 3 year old Female Child reported Ear
Infection

12639 23 9

- Jan

- 02 DURSBAN MONKTON MD HC Unknown Adult (18

- 64 years old) Male, Symptoms Not
Mentioned

12694 1 4

- Feb

- 02 LORSBAN WEST
MONROE LA HB A 23 month old Male Child reported Muscle weakness, Tachycardia, Drowsiness/Lethargy

12694 4 7

- Feb

- 02 DURSBAN TC 6271900047 TALLAHASSE
E FL HC A 11 month old Female Child reported Edema,
Lacrimation

12729 5 12

- Mar

- 02 DURSBAN MIDDLEBERG GA HC A 73 year old Female reported Shortness of Breath, Dizziness/Vertigo, Coughing/Choking,
Bronchitis

12754 3 26

- Mar

- 02 AFFRONT GEL
INSECTICIDE 272400487 BURLINGTON VT HC A 47 year old Female reported Irritation/Pain,
Lacrimation

12796 16 22

- Mar

- 02 ORTHO

- KLOR SOIL
INSECT AND
TERMITE KILLER (CONCENTRATE) 23902513 PA HC A 66 year old Male reported Lacrimation, Diarrhea, Pneumonia, Congestion

12855 2 30

- Jan

- 02 LORSBAN (NON

SPECIFIC) ARCADIA FL HC Unknown Adult (18

- 64 years old) Male reported Rash developing on different parts of skin all over his body

12855 7 25

- Apr

- 02 LORSBAN 15G 6271900034 INVER GROVE
HEIGHTS MN HC Unknown Adult (18

- 64 years old) Male reported Dizziness/Vertigo, Memory Loss

12875 42 12

- Apr

- 02 ANT

- STOP ANT KILLER DUST (DC'D
CHLORPYRIFOS FORMULA) 23902517 ELYRIA OH HC A 55 year old Male reported Seizure

## Page 33 of 51

Main IDS Report Chemical: Chlorpyrifos (PC code 059101) Human Incidents

Incident
Number Incident

Date Product Name Registration
Number City State Exposure Type* Incident Description

12875 176 24

- Apr

- 02 HOME DEFENSE
ORTHO

- KLOR
INSECT & TERMITE
KILLER 23902513 FARMERSVILL
E TX HC Unknown Adult (18

- 64 years old) Male reported No Symptoms Described

12937 7 23

- Jan

- 02 DURSBAN TARMA OH HC A 77 year old Female reported Irritation/Pain, Headache, Dizziness/Vertigo, Hypertension

12937 13 29

- May

- 02 LORSBAN (NON

SPECIFIC) CORNELIUS OR HC A 56 year old Male reported Mental Status Changes

12937 14 3

- May

- 02 LORSBAN (NON

SPECIFIC) AUSTINVILLE VA HC A 76 year old Male reported Nausea, Vomiting, Diarrhea

12989 1 2

- May

- 02 CYREN TC 6776000010 MCALLEN TX HC A 2 month old Female Child reported Drowsiness/Lethargy, Respiratory Depression and Eyes rolling around
in Head

13008 17 6

- May

- 02 ORTHO

- KLOR SOIL
INSECT AND
TERMITE KILLER (CONCENTRATE) 23902513 HARTFORD CT HC A 36 year old Male reported Diarrhea, Vomiting

13008 36 14

- May

- 02 ANT

- STOP ANT
KILLER DUST 23902517 AMARILLO TX HC A 34 year old Male reported Shortness of
Breath

13099 1 28

- Jun

- 02 TERMITE KILL II 138600615 RICHMOND IN HC Unknown Adult (18

- 64 years old) Female reported Shortness of Breath, Bronchospasm

13099 2 16

- Jun

- 02 TERMITE KILL II 138600615 WEST
ALEXANDRIA OH HC A 45 year old Female reported Coughing/Choking , Dyspnea , Shortness of
Breath

13135 5 2

- Jun

- 02 ANT

- STOP ANT KILLER DUST (DC'D
CHLORPYRIFOS FORMULA) 23902517 JACKSONVILL
E FL HC Unknown Adult (18

- 64 years old) Female reported Respiratory
Irritation

13135 17 2

- May

- 02 ORTHO

- KLOR SOIL
INSECT AND
TERMITE KILLER (CONCENTRATE) 23902513 STAFFORD VA HC A 26 year old Female reported Headache, Fever/hyperthermia, Enlarged Tonsils

## Page 34 of 51

Main IDS Report Chemical: Chlorpyrifos (PC code 059101) Human Incidents

Incident
Number Incident

Date Product Name Registration
Number City State Exposure Type* Incident Description

13135 50 22

- Jun

- 02 ANT

- STOP ANT KILLER DUST (DC'D
CHLORPYRIFOS FORMULA) 23902517 LEXINGTON KY HC A 57 year old Female reported Pruritus, Rash
on her Neck and
Shoulders

13135 128 1

- Jun

- 02 ANT

- STOP ANT
KILLER DUST 23902517 THOUSAND
OAKS CA HC Unknown Adult (18

-- 64 years old) Male, Symptoms Not
Mentioned

13243 27 28

- Jun

- 02 ANT STOP ANT KILLER (TRIGGER SPRAY) 23902490 SAYER PA HC Unknown Adult (18

- 64 years old) Female reported Rash, Bullae/Blisters, Pruritus

13241 3 1

- Jun

- 02 SPECTRACIDE
TERMITE AND ANT
CONTROL 0627190005

6 008845 BERLIN NJ HC Unknown Adult (18

- 64 years old) Female reported Tingling in her Hands, Muscle Pain in Calves and Shoulders, Pain in right Eye, Muscle Twitching, Nervousness, Loss of Appetite, Difficulty Sleeping, Memory Problems, Squeezing feeling in Neck, Vibrating insid e her body, Tingling in Legs below Knees and Feet,

13241 10 19

- Jul

- 02 DURSBAN PRO 6271900166 ID HC A 31 year old Female reported Dyspnea/Shortness of
Breath

13281 4 1

- Jul

- 02 LORSBAN

- 4E 6271900220 AMARILLO TX HC Unknown (2

- 6 years old)
Male Child reported a young boy drank the product and it was in a
Gatorade bottle in the garage or house where the boy had access to the
material.

13281 15 21

- Aug

- 02 DURSBAN TC 6271900047 BIRMINGHAM AL HC Unknown Adult (18

- 64 years old) Male reported Vomiting, Loss of
Consciousness

## Page 35 of 51

Main IDS Report Chemical: Chlorpyrifos (PC code 059101) Human Incidents

Incident
Number Incident

Date Product Name Registration
Number City State Exposure Type* Incident Description

13331 3 3

- Jul

- 02 DURSBAN LAWN
INSECT SPRAY 23902633 NAPA ID HC A 59 year old Male reported Headache, Nausea, Drowsiness/Lethargy,
General Aches and Pains

13331 20 9

- Aug

- 02 ANT STOP ANT KILLER DUST (DC'D
CHLORPYRIFOS FORMULA) 23902517 OKLAHOMA
CITY OK HC A 23 year old Female reported Rash on Legs,
Chest and Neck

13331 28 8

- Aug

- 02 ORTHO

- KLOR SOIL
INSECT AND
TERMITE KILLER (CONCENTRATE) 23902513 HINCKLEY OH HC A 14 year old Female reported Rash all over her body and today the
Rash is just on her Joints.

13364 3 24

- Sep

- 02 ORTHO DURSBAN
LAWN INSECT
SPRAY 23902633 MARINA CA HD Unknown Adult and
Children evacuated from daycare reported, Nausea, Headache and Burning Throat from fumes; adults had Dizziness, Chest
Pressure.

13386 5 9

- Sep

- 02 DURSBAN TC 6271900047 IN HC Unknown Families (2

- 64 years old) All Females reported Diarrhea, Coughing/Choking, Ear Infections, Abdominal Pain, and Allergy.

13419 6 1

- Jan

- 02 K

- GRO HOME PEST
INSECT CONTROL 4651500013 GREENSBOR
O NC HB Unknown Adult (18

- 64 years old) Families reported Headache, Other Miscellaneous, Daughter has a Seizure

13458 2 27

- Jun

- 02 ORTHO

- KLOR SOIL
INSECT AND
TERMITE KILLER (CONCENTRATE) 23902513 FARMINGTON NM HC Unknown Adult (18

- 64 years old) Female reported Edema, Irritation/Pain, Joint Pain

13458 25 2

- Sep

- 02 FLEA

- B

- GON
OUTDOOR FLEA
AND TICK KILLER 23902423 MARIETTA GA HC Unknown Adult (18

- 64) years old) Male reported Dizziness/Vertigo, Vomiting

## Page 36 of 51

Main IDS Report Chemical: Chlorpyrifos (PC code 059101) Human Incidents

Incident
Number Incident

Date Product Name Registration
Number City State Exposure Type* Incident Description

13509 12 29

- Sep

- 02 DURSBAN PRO 6271900166 CONSHOHOC
KEN PA HC Unknown Adult (18

- 64 years old) Female reported Dyspnea, Coughing/Choking, Congestion

13509 14 14

- Sep

- 02 DURSBAN (NON

SPECIFIC) SUNNYVILLE CA HC A 3 year old Female Child reported Diarrhea, Fever/hyperthermia

13510 10 4

- Oct

- 02 ORTHO

- KLOR SOIL
INSECT AND
TERMITE KILLER (CONCENTRATE) 23902513 TITUSVILLE FL HC A 70 year old Male reported Tachycardia, Hypertension

13669 13 18

- Nov

- 02 DURSBAN TC 6271900047 WHITTIER CA HC Unknown Adult (18

- 64 years old) Male, Female reported Byron: Prostate Cancer, Bronchial Spasms and white spots
on his Brain.

Laura: Immune deficiency of the Liver, Swollen Liver, Elevated level of Liver Enzymes, Mark:
Elevated level of Liver Enzymes

13829 14 22

- Feb

- 03 RAID FIRE ANT
KILLER FORMULA 2 482200264 RICHARDSON TX HC A 59 year old Female reported Dermal Irritation/Pain, Oral Irritation, Dyspnea, Throat Irritation, Nausea, Headache, Tingling, Edema, Bad Taste, Nasal Irritation, Back Pain

13945 1 5

- Mar

- 03 CYREN TC 6776000010 JUPITER FL HC Unknown Adult (18

- 64

years old) Male reported Burning Skin, Dry Mouth, Numbness of Lips and
Tremors.

13959 26 25

- Mar

- 03 ANT STOP ANT KILLER DUST (DC'D
CHLORPYRIFOS FORMULA) 23902517 CALDWELL ID HC Unknown Adult (18

- 64 years old) Female reported Respiratory Irritation, Congestion

## Page 37 of 51

Main IDS Report Chemical: Chlorpyrifos (PC code 059101) Human Incidents

Incident
Number Incident

Date Product Name Registration
Number City State Exposure Type* Incident Description

14093 14 18

- May

- 03 LORSBAN

- 4E 6271900220 TX HD Unknown Age Family reported Product being sprayed and says that husband, 2 kids and self
were outside and wind picked up and blew product on them. She
and 1 child never had symptoms. Today 1 child is having Diarrhea and
husband was it with
Pneumonia and ha s Rash on his back.

14178 15 2

- Jul

- 03 LORSBAN 4E
INSECTICIDE 6271900220 MINOT ND HC Unknown Adult (18

- 64 years old) Male reported Burning Eyes, Some
Shakiness of Hands.

14190 19 20

- Jun

- 03 SPECTRACIDE
CARPENTER ANT &
TERMITE KILLER
INSECT SPRAY
CONCENTRATE 0465150005

1 008845 HINSDALE IL HC A 72 year old Male reported Fever/hyperthermia, Nausea, Muscle Cramps, Aches, Tremors, Shaking, Vomiting

14190 27 24

- Jun

- 03 SPECTRACIDE
DURSBAN MULTI

PURPOSE INSECT
SPRAY
CONCENTRATE 884500030 HUDSON FL HC Unknown Adult (18

- 64 years old) Male reported Chest Pain, Dizziness/Vertigo, Dypsnea

14198 21 27

- Jun

- 03 ORTHO

- KLOR SOIL
INSECT AND
TERMITE KILLER (CONCENTRATE) 23902513 LONG ISLAND NY HC A 47 year old Female reported Wheezing,
Diarrhea

14198 22 26

- Jun

- 03 ORTHO

- KLOR ANT
KILLER DUST 23902517 STUART
TOWN PA HC A 11 year old Male reported Throat Irritation

14198 73 22

- Jun

- 03 ANT STOP ANT
KILLER DUST (DISCONTINUED) 23902517 APACHE
JUNCTION AZ HC Unknown Adult (18

- 64 years old) Female reported Dermal Irritation/Pain, Rash

14219 1 30

- May

- 03 CYREN 2E 6776000006 CLAIREMOOR
E OK HC A 55 year old Male reported Pneumonia

14339 1 1

- Jun

- 03 CHLORPYRIFOS
PRO 2 AZ HE Unknown Adult (18

- 64 years old) Male No Symptoms Mentioned

## Page 38 of 51

Main IDS Report Chemical: Chlorpyrifos (PC code 059101) Human Incidents

Incident
Number Incident

Date Product Name Registration
Number City State Exposure Type* Incident Description

14317 45 17

- Jul

- 03 ANT STOP ANT KILLER DUST (DC'D
CHLORPYRIFOS FORMULA) 23902517 CENTER
POINT TX HC A 88 year old Male reported Nausea, Weight
Loss

14419 6 17

- Aug

- 03 CHLORPYRIFOS (UKN PRODUCT) CLIFTON TX HB Unknown Adult (18

- 64 years old) Male reported Stopped Breathing and
Convulsions

14428 24 2

- Aug

- 03 DURSBAN LAWN
INSECT SPRAY (CONCENTRATE) 23902633 ATLANTA GA HC A 39 year old Female reported Respiratory Irritation, Abdominal Pain, Diarrhea, Headache, Coughing/Choking

14568 1 23

- Sep

- 03 DURSBAN TC 6271900047 CA HB A 46 year old Male reported Nystagmus, Dizziness/Vertigo,
Inflamed Sinus

14697 2 1

- Oct

- 03 ANT STOP KILLER
DUST (DISCONTINUED FORMULA) 23902517 TERRENCE CA HC A 39 year old Female reported Muscle Spasms

14719 7 23

- Jun

- 03 LORSBAN

- 4E 6271900220 ND HC Unknown Adult (18

- 64 years old) Male reported Lost sense of Taste, Insomnia, Depression

14737 5 21

- Dec

- 03 REAL KILL FIRE ANT
KILLER GRANULES 0495850001

6 000478 JACKSONVILL

E FL HC Unknown Adult (18

- 64 years old) Male reported Coughing/Choking, Fever/hyperthermia

14959 2 25

- Apr

- 03 DURSBAN 2E 6271900065 MI HB Unknown Age Male Child accidentally drank an
unmarked container and
left it on child grandmother’s porch. The Child was playing on the porch, picked up the bottle, and drank the product. Child suffered severe and permanent injuries and damages.

14959 6 4

- Aug

- 03 LORSBAN PRIOR LAKE MN HC A 66 year old Male reported Rash on his Legs

## Page 39 of 51

Main IDS Report Chemical: Chlorpyrifos (PC code 059101) Human Incidents

Incident
Number Incident

Date Product Name Registration
Number City State Exposure Type* Incident Description

15031 2 19

- Aug

- 03 LORSBAN CALEDONIA MN HC A Male (40 year old) Female (39 year old) Male Child (15 year old) reported Headache, Severe Stomach Ache, Cramping, Diarrhea, and Difficulty sleeping during the night of alleged

exposure.

15148 18 17

- May

- 04 DURSBAN TC 6271900047 PONCA CITY OK HC A 51 year old Female reported Headache, Dizziness/Vertigo, Respiratory/Irritation, Malaise, Confusion

15207 47 21

- May

- 04 ANT STOP ANT KILLER DUST (DC'D
CHLORPYRIFOS FORMULA) 23902517 NJ HC A 33 year old Male reported Vomiting, Diaphoresis, Joint Pain

15207 58 25

- May

- 04 OUTDOOR ANT,
FLEA AND CRICKET
SPRAY 23902423 LA HC Unknown Adult (18

- 64 years old) Female reported Rash all over her body

15401 4 19

- Jun

- 04 SPECTRACIDE
CARPENTER ANT &
TERMITE KILLER
INSECT SPRAY
CONCENTRATE 0465150005

1 008845 WICHITA

FALLS TX HC A 48 year old Female reported Irritation/Pain,
Other Miscellaneous

15419 112 7

- Jul

- 04 ORTHO

- KLOR
INSECT AND
TERMITE KILLER 23902513 TUCSON AZ HC Unknown Adult (18

- 64 years old) Female reported No Symptoms
Mentioned

## Page 40 of 51

Main IDS Report Chemical: Chlorpyrifos (PC code 059101) Human Incidents

Incident
Number Incident

Date Product Name Registration
Number City State Exposure Type* Incident Description

15453 2 2

- Dec

- 02 DURSBAN TC 6271900047 WEST
LAFAYETTE IN HB A Family Age Unknown
The mother and children reported Rhinorrhea,
Increased Mucus Production, Drooling, Nausea, Vomiting, and
Diarrhea. The father had minimal symptoms. They
also claim to have had Headaches, Mood Disturbance, Tension, Focus and Learning
Pr oblems, Increased Fatigue with Muscle
Weakness and Sleepiness.

15453 11 5

- Aug

- 04 LORSBAN

- 4E 6271900220 GREAT FALLS MT HC A 54 year old Male reported Myalgia, Joint Pain, Headache

15453 18 27

- Aug

- 04 DURSBAN PRO 6271900166 NATIONALCY CA HC A 42 year old Male reported Coughing/Choking, Anorexia, Diarrhea

15419 528 17

- Jun

- 04 ORTHO

- KLOR SOIL
INSECT AND
TERMITE KILLER (CONCENTRATE) 23902513 TN HC Unknown Adult (18

- 64 years old) Male reported
Rash on his Stomach

15483 5 1

- Aug

- 04 ORTHO

- KLOR SOIL
INSECT AND
TERMITE KILLER (CONCENTRATE) 23902513 ROCHESTER MI HC A 48 year old Male reported Nausea, Dizziness/Vertigo

15507 1 27

- Jul

- 04 DRAGON HOME
PEST KILLER 1600139 HUTCHINSON KS HC A 53 year old Female reported Headache, Breathing Problems, Dizziness/Vertigo

15519 8 17

- Aug

- 04 DURA GUARD ME
MICROENCAPSULA
TED INSECTICIDE 49900367 ST CHARLES MO HC Unknown Adult (18

- 64 years old) Female reported Rash

15602 29 16

- Sep

- 04 ORTHO

- KLOR SOIL
INSECT AND
TERMITE KILLER
CONC 23902513 CA HC A 58 year old Male reported Nausea, Tremor, Vomiting

## Page 41 of 51

Main IDS Report Chemical: Chlorpyrifos (PC code 059101) Human Incidents

Incident
Number Incident

Date Product Name Registration
Number City State Exposure Type* Incident Description

15637 1 3

- Nov

- 04 SURRENDER TC BRADENTON FL HB Unknown Adult (18

- 64 years old) Female reported Blood Pressure Elevated, Muscle Weakness, Headache, Swelling, Diarrhea, Nausea, Blurred Vision

15669 4 1

- Aug

- 02 DURSBAN NON

SPECIFIC TULSA OK HC Unknown Adult (18

- 64 years old) Female reported Health Problems, Mastectomy, Possible Constipation

15784 10 9

- Nov

- 04 ORTHO ANT STOP
TRIGGER SPRAY (MEXICO) 23902517 FL HC A 63 year old Male reported Rash on Under arms, Legs, Stomach, Back, Head and Arms

15837 4 1

- Jan

- 04 CHLORPYRIFOS GRANITE CITY IL HB Unknown Adult (18

- 64 years old) Male reported No Symptoms Described

16009 4 9

- Feb

- 05 LORSBAN 15G
GRANULAR
INSECTICIDE 6271900034 MARYSVILLE CA HC A 45 year old Female reported Diaphoresis, Vomiting, Other
Miscellaneous

16126 15 12

- Mar

- 05 ANT STOP ANT KILLER (TRIGGER SPRAY) 23902490 MINNEAPOLIS MN HC A 81 year old Male reported Shortness of
Breath

16352 35 17

- May

- 05 ORTHO

- KLOR SOIL
INSECT AND
TERMITE KILLER (CONCENTRATE) 23902513 TULSA OK HC A 35 year old Male reported Dizziness/Vertigo, Vomiting

16396 62 23

- Jun

- 05 ANT STOP ANT
KILLER DUST (DISCONTINUED) 23902517 GRAND
JUNCTION CO HC A 3 year old Male Child reported Abdominal Pain, Vomiting

16633 6 5

- Aug

- 05 DURSBAN TC
TERMITICIDE
CONCENTRATE 6271900047 BIRMINGHAM AL HC Unknown Adult (18

- 64 years old) Male reported Nausea, Throat Irritation, Vomiting

## Page 42 of 51

Main IDS Report Chemical: Chlorpyrifos (PC code 059101) Human Incidents

Incident
Number Incident

Date Product Name Registration
Number City State Exposure Type* Incident Description

16633 10 14

- Aug

- 05 DURSBAN PRO
INSECTICIDE 6271900166 BOAZ AL HC Unknown Adult (18

- 64 years old) Male reported Bradycardia, Diaphoresis, Agitated/Irritable, Confusion, Other
Miscellaneous

16652 64 27

- Aug

- 05 HOMEDEFENSE
INDOOR AND
OUTDOOR INSECT
KILLER 1 23902490 ROMEOVILLE IL HC A 32 year old Female reported Vomiting, Diarrhea, Chest Pain

16689 26 27

- Aug

- 05 DURSBAN

- OTHER/UNKNOWN PHILADELPHI
A PA HC A 63 year old Male reported Irritation/Pain, Pruritus, Other
Miscellaneous

16738 8 9

- Feb

- 05 LORSBAN

- 4E INSECTICIDE (NAF

163) 6271900220 YUBA CITY CA HC Unknown Adult (18

- 64 years old) Female reported, Vomiting, Headache, Dyspnea

16754 28 20

- Sep

- 05 RID

- A

- BUG FLEA
AND TICK KILLER LIQUID 884500031 FAIRBURY NE HC A 34 year old Female reported Hives/Welts, Pruritus, Rash

16763 1 7

- Oct

- 05 LORSBAN* 75WG 0627190030
1 010163 OXNARD CA HC (6) Male Trucking Company Employees reported Burning Eyes, Nausea, Tremors

16890 8 8

- Oct

- 05 DISC ZODIAC
FLEATROL YARD
AND KENNEL
SPRAY 272400327 TX HC A 55 year old Male reported Stomach Swelling

16940 33 19

- Aug

- 05 CHLORPYRIFOS 4E
AG 6622200019 CA HC (10) Field Workers employees reported Headache, Vomiting, Nausea, Shortness of Breath, Dizziness, Stuffy
Nose and Pressure on
the Chest. The employees were indoors working under evaporative coolers. Two additional employees had symptoms of Headache
and Vo miting when they started working in the box yard.

## Page 43 of 51

Main IDS Report Chemical: Chlorpyrifos (PC code 059101) Human Incidents

Incident
Number Incident

Date Product Name Registration
Number City State Exposure Type* Incident Description

16940 45 1

- Nov

- 05 DURSBAN PRO 6271900166 MERCED CA HC Unknown Adult (18

- 64 years old) Male and Female reported (5) Individuals Employees had short term Symptoms of Itchy and Burning Eyes
and Nausea.

17056 2 1

- Oct

- 03 DURSBAN TC
TERMITICIDE
CONCENTRATE 6271900047 REEBLEY CA HC A 6 year old Male Child reported Abdominal Pain,
Other Miscellaneous

17300 3 1

- Jun

- 05 DURSBAN R 6271900044 WILLOUGHBY,
MAYFIELD
HTS OH HB A 45 year old Female reported Numbness, Difficulty Swallowing,
Shortness of Breath

17298 34 24

- Apr

- 06 ANT KILLER SANTA ANA CA HC A 4 year old Male Child reported the child grandmother had put
some ant killer in a water
bottle. The child drank
from the bottle and started to have breathing difficulty and experienced stomach ache, The child was taken to a hospital and was hospitalized.

17581 1 28

- Jun

- 06 MOSQUITOMIST
TWO ULV 832900018 LAMONT IL HC A 39 year old Female reported Shortness of Breath, Headache, Memory Problems, Erythema/Flushed, Dermal Irritation/Pain,
Tremor

17585 6 6

- Jun

- 06 LORSBAN

- 4E INSECTICIDE (NAF

163) 6271900220 MAZOMANIE WI HC A 57 year old Male reported Nausea, Malaise, Ocular
Irritation/Pain

17701 6 14

- Jul

- 06 SPECTRACIDE
TERMITE & ANT
CONTROL
CONCENTRATE 0627190005

6 008845 BATON

ROUGE LA HC A 21 year old Male reported Diaphoresis, Fasciculation, Hallucinations, Delusion

17837 4 29

- Jun

- 06 DURSBAN PRO
INSECTICIDE 6271900166 KNOXVILLE TN HC Unknown Adult (18

- 64 years old) Male reported Hives/Welts, Rash,
Throat Irritation, Drowsiness/Lethargy,
Headache

## Page 44 of 51

Main IDS Report Chemical: Chlorpyrifos (PC code 059101) Human Incidents

Incident
Number Incident

Date Product Name Registration
Number City State Exposure Type* Incident Description

17837 5 29

- Jul

- 06 LORSBAN

- 4E INSECTICIDE (NAF

163) 6271900220 WOODLAKE MN HC A 48 Year old Male reported Malaise, Dizziness/Vertigo, Fever/hyperthermia

17837 9 7

- Aug

- 06 LORSBAN

- 4E INSECTICIDE (NAF

163) 6271900220 GROVE OAK AL HC Unknown Adult (18

- 64 years old) Male reported
Diarrhea

17863 32 15

- Aug

- 06 DURSBAN LAWN
INSECT SPRAY (CONCENTRATE) 23902633 BAKERSFIELD CA HC A 18 year old Male reported Vomiting

18233 1 1

- Jun

- 06 MOSQUITOMIST
ONE U.L.V. 832900024 AURORA MO HA A 58 year old male was reportedly exposed to a ULV product five to six
times. Each time he was taken to the emergency room with difficulty breathing and an upset
stomach. He was diagnosed with and
treated for COPD. The last time he was exposed
to the ULV product, he fell while taking a shower after the exposure. He was subsequently hospitalized and died about 10 days later. He
also suffered from peeling skin.

18287 1 23

- Jul

- 06 MOSQUITOMIST
ONE ULV 832900024 AURORA MO HB A 7 year old Male reported severe Asthma

18428 55 24

- Mar

- 07 LORSBAN SANTA PAULA CA HC A 6 year old Male Child reported has been hospitalized after ingesting an unmarked
water bottle the father
used for Ant Control. The
child started to foam at
the mouth and became
unconscious. No Symptoms mentioned.

18599 56 26

- May

- 07 ORTHO

- KLOR SOIL
INSECT AND
TERMITE KILLER (CONCENTRATE) 23902513 FLEMINGTON NJ HC A 45 year old Male reported Shortness of Breath, Respiratory
Irritation

## Page 45 of 51

Main IDS Report Chemical: Chlorpyrifos (PC code 059101) Human Incidents

Incident
Number Incident

Date Product Name Registration
Number City State Exposure Type* Incident Description

18732 3 31

- May

- 07 DURSBAN LAWN
INSECT SPRAY (CONCENTRATE) 23902633 FL HC Unknown Adult (18

- 64 years old) Male reported Dizziness, Diarrhea

18732 7 1

- Jun

- 07 DURSBAN READY

SPRAY OUTDOOR
FLEA AND TICK KILLER 1 (HOSE

END SPRAYER) 23902633 FL HC Unknown Adult (18

- 64 years old) Male reported Dizziness, Vomiting,
Nausea

18732 16 31

- May

- 07 DURSBAN LAWN
AND GARDEN
INSECT CONTROL (GRANULES) 23902570 CA HC Unknown Adult (18

- 64 years old) Male reported Dermal Irritation, Other Neurological

- Drooping Lip

18732 36 7

- Jun

- 07 DURSBAN LAWN
INSECT SPRAY (CONCENTRATE) 23902633 VA HC Unknown Adult (18

- 64 years old) Male reported Hives/Welts, Pruritus

18759 1 2

- Jul

- 05 MOSQUITOMIST
TWO ULV 832900018 WAYNE IL HB Unknown Adult (18

- 64 years old) Female reported Aneurism, No Symptoms Mentioned

18839 2 11

- Jul

- 07 LORSBAN

- 4E INSECTICIDE (NAF

163) 6271900220 FIREBAUGH CA HC A 28 year old Male reported Nausea, Dyspnea, Shortness of
Breath

18913 1 25

- Aug

- 07 MOSQUITOMIST
TWO U.L.V. 832900018 GILBERT IL HC A 69 year old Female reported Diarrhea, Tremor, Lacrimation, and
Other Renal

- Urinary Frequency.

18930 19 23

- Dec

- 06 DURSBAN TC
TERMITICIDE
CONCENTRATE 6271900047 CHARLOTTE NC HC Unknown Adult (18

- 64 years old) Female reported Nausea, Diarrhea, Arthralgia, Drowsiness/Lethargy, Headache, Muscle Weakness, Blurred Vision, Nasal Discharge, Nasal Irritation, and Respiratory Irritation.

18930 33 23

- Apr

- 07 LORSBAN 15G
GRANULAR
INSECTICIDE 6271900034 OREGON IL HC A 68 year old Male reported Respiratory

- Dyspnea/Shortness of
Breath

18930 46 1

- Oct

- 06 DURSBAN (UNSPECIFIED) WALKERTOW
N NC HB A 43 year old Male reported Dermatological

## Page 46 of 51

Main IDS Report Chemical: Chlorpyrifos (PC code 059101) Human Incidents

Incident
Number Incident

Date Product Name Registration
Number City State Exposure Type* Incident Description

Rash

18966 2 17

- Aug

- 07 LORSBAN

- 4E INSECTICIDE (NAF

163) 6271900220 STOCKTON CA HC A 67 year old Male reported Neurological
Headache

18984 21 10

- Jul

- 07 LORSBAN

- 4E 6271900220 CA HE Field Farmworkers reported ill, No Symptoms Mentioned.

19025 6 3

- Sep

- 07 ANT STOP ANT KILLER DUST (DC'D
CHLORPYRIFOS FORMULA) 23902517 OH HC Unknown Adult (18

- 64 years old) Female reported Blurred Vision,
Visual Defect

19218 20 22

- Nov

- 07 ORTHO

- KLOR SOIL
INSECT AND
TERMITE KILLER (CONCENTRATE) 23902513 FL HC A 81 year old Male reported Dermal Irritation,
Pruritus

19218 23 25

- Nov

- 07 ORTHO

- KLOR ANT
KILLER DUST 23902517 CHICAGO IL HC A 3 year old Female Child reported Abdominal Pain, Vomiting, Diarrhea

19293 2 18

- Dec

- 07 DURSBAN

- OTHER/UNKNOWN
PRODUCT PAOLI IN HC A 52 year old Male reported Confusion, Nausea, High Blood Pressure, Shaking, Muscle Tightness, Throat
Irritation

19499 1 17

- Feb

- 08 SPECTRACIDE
CARPENTER ANT &
TERMITE KILLER
INSECT SPRAY
CONCENTRATE 0465150005

1 008845 HILLSBORO OH HC A 63 year old Male reported Coughing/Choking, Erythema/Flushed, Irritation/Pain, Blistering on Face, Pruritus, Irritated Breathing

19681 164 21

- Mar

- 08 ORTHO

- KLOR ANT
KILLER DUST 23902517 CA HC A 52 year old Female reported Oral Irritation, Rash, Seizure, Confusion, Agitated,
Pruritus

## Page 47 of 51

Main IDS Report Chemical: Chlorpyrifos (PC code 059101) Human Incidents

Incident
Number Incident

Date Product Name Registration
Number City State Exposure Type* Incident Description

19758 6 1

- May

- 08 ORTHO

- KLOR SOIL
INSECT AND
TERMITE KILLER 23902513 WINDSOR
LOCKS CT HC A four year old male was playing in an area that
was treated with the product 4 hours earlier.
He broke out in a diffuse rash. He was given a bath and Benadryl. The symptoms did not clear
so he was taken to the
ER. It could not be
determined if the rash was from the product or
antibiotics that the child had been taking. He
discontinued the antibiotics and was given
steroids.

19742 1 27

- May

- 08 NUFOS 4E 6776000028 CA HC Unknown age adult male reported product sprayed back into his face by wind
for approximately one hour. He was not wearing appropriate PPE. He experienced nausea, vomiting, difficulty breathing and felt as if his throat was closing.

19758 65 27

- May

- 08 ORTHO

- KLOR SOIL
INSECT AND
TERMITE KILLER (CONCENTRATE) 23902513 FL HC Unknown age (18

- 64 years old) female developed headache, dermal irritation (within 12 hours) and a cold (within 24 hours) after her husband empty three bottles of product around
the house. She saw an MD who prescribed
antibiotics. The husband developed a headache
and dermal irritation (within 12 hours).

## Page 48 of 51

Main IDS Report Chemical: Chlorpyrifos (PC code 059101) Human Incidents

Incident
Number Incident

Date Product Name Registration
Number City State Exposure Type* Incident Description

19837 17 6

- Jun

- 08 SPECTRACIDE
CARPENTER ANT &
TERMITE KILLER
INSECT SPRAY
CONCENTRATE 0465150005

1 008845 SELMA AL HC Unknown age adult female applied product in yard. Next day she developed fever, tongue irritation, fever, pain, rash, throat irritation, and vomiting. She was weak
and fell and hit her head. She was hospitalized and given antibiotics, breathing treatments, and
steroids. She has a history of COPD, emphysema and hypertension.

20065 4 26

- Jun

- 08 DURSBAN PRO
INSECTICIDE 6271900166 LAKE GENVA WI HC 42 year old male professional applicator was working with product for 3 hours without using PPE. He experienced tingling and numbness in his arms, back and head and tachycardia. He went
to ED an d was cleaned in the shower. CBC, RBC and plasma
cholinesterase levels
were done. No SLUDGE symptoms were experienced. CXR performed.

20065 9 16

- Jul

- 08 LORSBAN 4E 6271900023 ECHO MN HC 56 year old male was flattening pesticide boxes, picking up
container lids and labels to be recycled and was not wearing PPE. There
was some minor amount of liquid left in materials. After about one hour, he experienced a rash on his
wrist. Later he felt nauseated, had no appetite, the left side of
his face swelled and the rash spread up his arm. He went to the hospital. He was given blood work
some medication and
released.

## Page 49 of 51

Main IDS Report Chemical: Chlorpyrifos (PC code 059101) Human Incidents

Incident
Number Incident

Date Product Name Registration
Number City State Exposure Type* Incident Description

20725 40 6

- Oct

- 08 REAL

- KILL
DURSBAN 0096880009

5 000478 OXNARD CA HC Five year old male ingested unknown amount of product. He was taken to the hospital,
treated and released 13 hours later. The only symptom reported was
sore throat.

21148 9 1

- Jan

- 09 LORSBAN

- 4E INSECTICIDE (NAF

163) 6271900220 MAQUOKATA IA HC A 31 year old male applied the product two times a year for about 1
to 2 weeks at a time in a cemetery using a groundboom. He did not
use PPE and did not wash product off until the end of the day. He
suffered from shortness of breath, abdominal cramping, and now has allergies.

20997 49 13

- Jun

- 09 ORTHO

- KLOR SOIL
INSECT AND
TERMITE KILLER (CONCENTRATE) 23902513 IL HC A 48 year old male applied product in his garage. He experienced
tremors and dizziness. He saw his physician who did not run any tests or prescribe and
medications.

20997 52 15

- Jun

- 09 ORTHO

- KLOR SOIL
INSECT AND
TERMITE KILLER (CONCENTRATE) 23902513 BROADVIEW IL HC 58 year old male applied product in his garage
over the weekend. Monday he worked in the garage. Tuesday he experienced dizziness
and nausea and Wednesday he saw his physician. By the following Tuesday he was feeling better.

21209 8 1

- Jul

- 09 LORSBAN

- 4E INSECTICIDE (NAF

163) 6271900220 NORWALK CT HC An 81 year old female applied product in backyard. In an unknown
amount of time later she experienced shortness of
breath and cough/choking. She saw
an MD and was prescribed an inhaler.

## Page 50 of 51

Main IDS Report Chemical: Chlorpyrifos (PC code 059101) Human Incidents

Incident
Number Incident

Date Product Name Registration
Number City State Exposure Type* Incident Description

21092 62 10

- Jul

- 09 ANT STOP ANT KILLER DUST (DISC CHLORPYRIFOS) 23902517 SILVER
SPRING MD HC An 84 year old female was exposed to a product she applied 2 to 3 years ago when she lifted up a board in her yard. She experienced lesions on
her arms. She saw her physician.

2118 1 17 24

- Aug

- 09 HOT SHOT
MAXATTRAX
ROACH BAIT 0096880006

7 008845 ROCKPORT TX HC Adult postpartum female experienced a fever, chills vomiting and could smell poison on her hand. She put a bait product in the cupboard in the morning.

22051 1 24

- May

- 10 WARHAWK 3470400857 SOUTH
GLASTONBUR
Y CT HC A 67 year old male's
home is located 25 feet
from five rows of trees that were sprayed with the product. The doors and windows were open
and the caller was home at the time of application.
The caller detected a
chemical odor and one
and a half to two hours later he developed a headache, ocular irritation, numbness in his cheek, vomiting, lower back aches, throat irritation, and weakness.
He saw an MD and was given an unknown injection and the MD said he had sign s of chemical poisoning. Symptoms persisted more than six days.

## Page 51 of 51

Main IDS Report Chemical: Chlorpyrifos (PC code 059101) Human Incidents

Incident
Number Incident

Date Product Name Registration
Number City State Exposure Type* Incident Description

22005 53 26

- May

- 10 DURSBAN LAWN
INSECT SPRAY (CONCENTRATE) 23902633 OH HC Unknown age (18

- 64) adult male spilled the product on his hand and
wrists. He rinsed it off
about an hour later. The next day he has hives
and a rash in those
areas. He went to a health care facility and his MD gave him a
cortisone shot and a prescriptio n salve to apply. His symptoms lasted three days.