# Page 2 of 6 II. ACTION REQUESTED

This review is intended to fulfill our requirement to docket summaries of incident data that were

reported to the Agency, as well as to ensure hum an incident data and th e Agricultural Health

Study (AHS) are part of the problem formulati on phase of registrati on review. Reports of

adverse health effects allegedly due to a specific pesticide exposure ( i.e. , an “incident”) are

largely self-reported and therefore, generally speaking, neither exposur e to a pesticide or

reported symptom (or the connectio n between the two) is validate d. Typically, causation cannot

be determined based on incident data. However, incident information can be an important source

of feedback to the Agency – incidents of severe outcome, or a suggested pattern or trend among

less severe incidents, can signal the Agency to further investigate a particular chemical or

product. Observational epidemiology studi es relate the risk of disease, e.g. , cancer, and exposure

to an agent such as a pesticide product in th e general population or specific sub-groups like

pesticide applicators.

III. BACKGROUND

For this evaluation, the OPP Incide nt Data System (IDS) was utili zed for pesticide incident data

on the active ingredient al dicarb (PC Code 098301). Aldicarb is registered for use as a systemic

insecticide and nematicide on agricultural crops



# . The purpose of the database search is to identify

potential patterns in the frequency and severity of the health effects attributed to aldicarb

exposure. The IDS includes reports of allege d human health incidents from various sources,

including mandatory Federal Insecticide, F ungicide and Rodenticide Act (FIFRA) Section

6(a)(2) reports from registrants, other federal and state health and environmental agencies, and

individual consumers. Since 1992, OPP has compiled these reports in IDS. IDS contains reports

from across the U.S. and most incidents have a ll relevant product inform ation recorded. Reports

submitted to the IDS represent anecdotal reports or allegations only, unless otherwise stated in

the report.

The AHS is a high quality, prospective epidemio logy study evaluating the link between pesticide

use and various health outcomes including can cer. The AHS includes private and commercial

pesticide applicators and their spouses. If there are AHS findi ngs relevant to a particular

pesticide going through registration review, the Ag ency will ensure they are considered in the

problem formulation/scoping phase of the process a nd, if appropriate, fully reviewed in the risk

assessment phase of the process. The AHS include s information on use of 50 different pesticide

active ingredients commonly used in agriculture.

IV. RESULTS/DISCUSSION

Incident Data System:

IDS records incidents resulting in higher severity outcomes in more detail, in a module called the

Main IDS module. This system stores incident data for death, major and moderate incidents, and

it includes more details about the location, date and nature of the incident. Main IDS incidents

involving only one pesticide are considered to provide more certain information about the

potential effects of exposure from the pesticide. The less severe human incidents (minor,

# Page 3 of 6 unknown, or no effects outcomes) are reported by registrants as counts called aggregate

summaries and are recorded in a separate module called Aggregate IDS.

In Aggregate IDS, from January 1, 2006 to D ecember 14, 2011 there were 10 reported incidents

involving aldicarb.

For the main IDS, from January 1, 2006 to D ecember 14, 2011, there were 15 reported incidents

reported involving the single chemical aldicarb in the database and 2 incidents reported that

involve more than one chemical (including aldica rb). For the single chemical incidents, there

was one incident classified as minor severity, 11 incidents classified as moderate severity, and

two incidents classified as major severity and one fatality. The incident s classified as major

severity and the fatality are described below in Table 1. Overall, there are few incidents

involving aldicarb reported to IDS.

Agricultural Health Study:

Investigators with the Agricultural Health Stud y (AHS) (Lee et al. (2007)) performed a nested

case control analysis of colo rectal cancer among AHS study pa rticipants and observed an

elevated odds of colon cancer among lifetime us ers of a aldicarb (OR 4.1 (95% CI 1.3, 12.8), p

for trend 0.001); however aut hors note the lack of an a priori hypothesis to explain this

observation, and lack of experi mental studies to support a possi ble mechanism of action. The

study included 305 colon cancer cas es identified through state cance r registries between the 1993

enrollment period and 2002. Pesticide exposur e was evaluated through validated self-report

questionnaires, and authors were able to contro l for known colon cancer risk factors related to

diet and exercise. There were 29 aldicarb exposed colon cancer cases which is a moderately

small number of exposed cases, and the AHS study was not designed to capture detailed

information concerning diet a nd exercise;therefore, residual confounding may be reflected in

these estimates. Overall, authors note the si gnificance of the finding, but suggest caution due to

small numbers, the role of chance, and lack of biological explanation. Additional follow-up is

on-going.

Also within the AHS, investigators reported a link between aldicarb use and Farmer’s Lung, an

important non-cancer, respiratory health outc ome (Hoppin et al. (2007)). Using self-report

incidence of Farmer’s Lung among private app licators and their spous es, authors observed

elevated odds of this outcome with carbamates as a group (approximate 40% increase in risk

among both farmers and spouses), and an odds ra tio of 1.65 (95% CI 1.04, 2.61) reflective of 25

Farmer’s lung cases who reported use of aldicarb. Authors suggest again that these preliminary

findings could be due to chance and are unexpect ed given previously conducted research, but

also note that there is some evidence of aldicar b adversely affecting imm une-response. At this

time, TEB notes these preliminary findings and suggests risk assessment teams consider this

information when compiling hazard characterizati on and exposure scenarios; however the data

are too preliminary to infer str ong causal links at this time.

Based on the low frequency and generally low seve rity of incident cases reported for aldicarb

and the current status of the AHS epidemiological research, there does not appear to be a concern

that would warrant further investigation at this time. The Agency will c ontinue to monitor the

incident information and AHS results and if a co ncern is triggered, additional analysis will be

# Page 4 of 6 included in the risk assessment and follow-up studies from the AHS will be evaluated if

available at the time of the risk assessment.

REFERENCE:

Lee WJ, Sandler DP, Blair A, Samanic C, Cross AJ, Alavanja MC. Pesticide use

and colorectal cancer risk in the Agricultural Health Study. Int J Cancer . 2007 Jul 15;121(2):339-

46. PubMed PMID: 17390374; PubMed Central PMCID: PMC2928992.

Hoppin, J.A., Umbach, D.M, Kullman, G.J., Henneberger, P.K., London, S.J., Alavanja, M.C.,

Sandler, D.P. Pesticides and other Agricultural F actors Associated with Self-reported Farmer’s

Lung among Farm Residents in the Agricultural Health Study . Occupational and Environmental

Medicine 2007, 64:334-342.Page 5 of 6Table 1: Main IDS high severityincidents involving AldicarbHuman IncidentsChemical: AldicarbPC Code: 098301IncidentPackageReportIncidentDateLocationRegistrationNumberProduct NameExposureSeverity*Incident Description017388‐000015/19/2006LESLIE,GANATEMIK(UNSPECIFIEDPRODUCT)HAA31yearoldmaleappearedtohavediedinhissleepafterusingTemikearlierintheday.TherewerenoapparentoutwardsymptomsofTemikpoisoninginthiscase.Anautopsyhasbeenperformed.Themedicalexaminerwhoperformedtheautopsysaidthatitwasnothisimpressionbasedonthehistoryprovidedtohim,orthepost‐mortemexam,thatthe31yearoldmalediedofanexposuretoAldicarb.Themedicalexaminerfurtherstatedthatthe31yearoldmale'spost‐mortemexamwasremarkableforanenlargedheart.018718‐000156/24/2007IDAHOFALLS,IDNATEMIKBRAND(NON‐SPECIFIC)HBA59yearoldfemaleaccidentallyatetheproductbecauseshethoughtitwaspepper.Itwasinapeppershakerforapplicationinthegarden.Sheexperiencedbradycardia,hypertension,hypotension,salivation/drooling,renalfailure,diaphoresis,coma,fasciculations,miosis,andrespiratorydepression.ShewastakentotheER.019734‐000025/13/2008SHAWNEE,KS000264‐00322TEMIKBRAND10GALDICARBPESTICIDEHBA47yearoldmaleappliedproducttosweetpotatoes.Hewasfullyclothed,andworeamaskandgoggles.Hemayhavespilledproductonhimwhilemixingit.Heexperiencedbradycardia,abdominalpain,diarrhea,nausea,vomiting,diaphoresis,legcramps,andlethargy.HewastakentothehospitalandtreatedwithIVfluidsandatropine.* Severity Categoriesna – not availableH-A Human Fatality Death (if the person died)H-B Human Major Major (if the person alleged or exhibited symptomswhich may have been life-threatening, or resulted in adversereproductive effects or in residual disability)H-C Human Moderate Moderate (if the personalleged or exhibited symptoms more pronounced, more prolonged or of a more systemicnature than minor symptoms; and involved some formof treatment, even though symptoms were not lifethreatening and the person returned tohis/her pre-exposure state of healthwith no additional residual disability)H-D Human Minor Minor (if the person alleged or exhibited somesymptoms, but they were minimally traumatic; the symptomsresolved rapidly and usually involveskin, eye or respiratory irritation)H-E Human Unspecified Unspecified (if symptoms are unknown, unspecified or are alleged to be of a delayed or chronic nature that mayPage 6 of 6appear in the future)H Human Undetermined (an undetermined severity)from 40 CFR § 159.184