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across the U.S. and most incidents have all relevant product information recorded. Reports 

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

the report. 

IDS records incidents in one of two modules: Main IDS and Aggregate IDS:

 

o Main IDS contains incidents resulting in higher severity outcomes and provides 

more detail with regard to case specific. This system stores incident data for 

death, major and moderate incidents, and it includes information 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. 

o Aggregate IDS contains incidents resulting in less severe human incidents (minor, 

unknown, or no effects outcomes). These are reported by registrants only as 

counts in what are aggregate summaries. 

For the Main IDS, from January 1, 2007 to September 13, 2012, there was 1 incident reported for 

involving EPTC in the database. This incident was classified as major severity (Table 1). 

Overall, there are few incidents involving EPTC reported to IDS. 

In Aggregate IDS, from January 1, 2007 to September 13, 2012, there were 5 reported incidents 

involving EPTC. 

b. NIOSH SENSOR

The NIOSH-led SENSOR-Pesticides database covers 11 states from 1998-2008, although 

reporting varies from state to state. Cases of pesticide-related illnesses are ascertained from a 

variety of sources, including: reports from local Poison Control Centers, state Department of 

Labor workers’ compensation claims when reported by physicians, reports from State 

Departments of Agriculture, and physician reports to state Departments of Health. Although both 

occupational and non-occupational incidents are included in the database, SENSOR-Pesticides 

focuses on occupational pesticide incidents, and is of particular value in providing that 

information. A state SENSOR contact specialist attempts to follow-up with cases and obtains 

medical records to verify symptoms, circumstances surrounding the exposure, severity, and 

outcome. Using standardized protocol and case definitions, derived from poison center 

reporting, SENSOR-Pesticides coordinators at State Departments of Health enter the incident 

interview description provided by the case, medical report, physician into the data system. In 

order to be included in the database, all SENSOR-Pesticides cases, including low severity cases, 

must have at least two adverse health effects.

In SENSOR-Pesticides from 1998 to 2008, ten case reports, stemming from seven events are 

identified. All ten cases involve a single active ingredient. Eptam is the product implicated in six 

cases. One case is moderate in severity and 9 cases are low in severity. The moderate severity 
Page 4 of 8

case experienced multiple symptoms reported as follows, “numbness, tingling, muscle weakness, 

lumps on scalp/hip; immediate: nausea, headache, throat irritation, diarrhea”. 

The most commonly reported health effects among cases were nervous system and 

gastrointestinal symptoms. A summary of symptoms is provided in Table 2 below.

Table 2: Reported Symptoms

Respiratory 3

Nervous System 6

GI 6

Eye 4

Dermal 3

Cardiovascular 1

All ten cases are work-related. In one event that occurred in Louisiana in 2000, four individuals 

were made ill after an Eptam application, the incident description for all four cases states “A 

carpentry crew worked in a flowerbed during/after herbicide application”. These cases 

experienced a variety of symptoms but all reported gastrointestinal distress.

c. AHS

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

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

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

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

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

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

active ingredients commonly used in agriculture.

Researchers with the AHS have performed several epidemiologic investigations that have 

included evaluation of occupational exposure to S-Ethyl-N,N-dipropylthiocarbamate (EPTC). 

Research results mainly relate to the carcinogenic potential of EPTC; however investigators have 

also evaluated the role of pesticide exposure, including EPTC, and respiratory health (wheeze). 

A summary of these findings follows: 

Cancer: 

A number of studies have evaluated EPTC for its carcinogenic potential given its ability to form 

nitrosamines and its role in inter-cellular oxidative stress. No significant positive associations 

were observed with prostate, lung, and breast cancers or with cutaneous melanoma (Alavanja et 

al., 2004; Alavanja et al., 2003; Dennis, Lynch, Sandler, & Alavanja, 2010; Engel et al., 2005; 

Lee et al., 2007). However, several authors have identified statistically significant associations 

between EPTC use and leukemia, colon, and pancreatic cancer, as well as prostate cancer among 

those with a family history of prostate cancer (Alavanja et al., 2003; Andreotti et al., 2009; Barry 

et al., 2011; van Bemmel et al., 2008). These findings are discussed in more detail below: 
Page 5 of 8

Leukemia and Colon cancer Investigators completed a cohort analysis of cancer risk 

by EPTC exposure status and reported significant, positive associations with both 

leukemia and colon cancer (van Bemmel et al., 2008). Among 48,378 participants in the 

AHS and controlling for known and suspected risk factors for cancer, researchers 

observed an approximate 30% increased risk of colon cancer, and two-fold increased risk 

of leukemia, comparing the upper-half of the exposed group to the non-exposed group 

[colon: OR 1.28 (95% CI 1.09, 1.50); leukemia: OR 2.09 (95% CI 1.16, 4.84)]. These 

study results persisted using alternate exposure metrics, i.e. lifetime exposure days, and 

referent group. Additional sensitivity analyses did not alter the conclusions from these 

final models, including simultaneous adjustment for correlated pesticides. Nevertheless, 

the authors caution that although EPTC was associated with colon cancer in the highest 

tertile of both lifetime exposure days and intensity-weighted lifetime days (RR = 2.09; 

95% CI, 1.26-3.47 and RR = 2.05; 95% CI, 1.34-3.14, respectively) and the trend test 

was < 0.01 for both, the pattern of RR was not monotonic with increasing use and state 

that - given the relatively small number of cases in the highest exposure tertile (n<5) 

results should be interpreted with caution and further investigations are needed. A 

previous study using AHS data investigating the association between pesticide use and 

colorectal cancers (Lee et al. (2007)) also explored the relationship between EPTC and 

colon cancer, but did not find a significantly increased risk using an ever/never exposure 

metric. In this latter study, the authors estimated odds ratios of 1.1 (95% CI: 0.8, 1.5), 

1.2 (95% CI: 0.8, 1.8) and 0.9 (95% CI: 0.4, 1.7) for colorectal (n = 305), colon (n=212) 

and rectal (n=93) cancers, respectively, suggesting no evidence of association between 

EPTC and colorectal cancers. 

Pancreatic cancer: Andreotti et al. (2009) examined pesticide exposure among 

pancreatic cancer cases in the AHS cohort in two case-control studies within the AHS, 

and observed an increased risk among male applicators who reported use of EPTC. 

Controlling for the influence of age, smoking, and diabetes, those who were most highly 

exposed to EPTC had 2.5-times greater odds (risk) (95% CI 1.1–5.4, p-trend, 0.01) than 

participants who reported never use of EPTC. The use of other pesticides did not alter 

the risk estimate with pancreatic cancer. Due to limitations of data collection, the authors 

state that they were not able to control for a family history of pancreatic cancer in the 

analysis; family history is an established risk factor for pancreatic cancer. In addition, the 

authors caution in discussing their results that this is the first ever investigation of 

pancreatic cancer and pesticide exposure and that no a priori hypotheses were offered. 

The authors hypothesize that since EPTC forms N-nitroso-compounds, which are known 

animal carcinogens, this may play a role in carcinogenesis; however, they state that the 

biological mechanisms have not been clearly defined at this time. 

Prostate cancer in those with a family history of prostate cancer: Researchers have 

extended earlier studies within the cohort in which prostate cancer risk was nonsignificantly elevated among EPTC users who also reported a family history of prostate 

cancer (a stratified analysis) (Alavanja et al., 2003). The more recent study investigated 

genetic variability in base excision repair genes, pesticide exposure and prostate cancer 

risk (Barry et al., 2011). In this study, authors found increased risk of prostate cancer 

among EPTC users with less than two copies of the dominant alleles at a specific genetic 

locus known to encode proteins involved in base excision repair mechanisms; although 
Page 6 of 8

the estimated OR was statistically significant, the authors state that the estimate was not 

statistically significant after adjusting for multiple statistical comparisons. 

Overall, authors caution that these are among the first ever investigations of these anatomical 

cancer sites with occupational EPTC exposure; that few a priori hypotheses were offered, and 

that additional biological support is needed to identify mechanisms of action. However, with a 

large, prospective sample, motivated hypotheses (prostate cancer), and elimination of several of 

the major non-causal hypothesis (i.e. biases in the study can explain the positive association), the 

results are notable and should be considered as part of hazard characterization. Additional studies 

will help elucidate these preliminary findings, and possible discount current findings. 

Respiratory Health

Farmers generally report having higher rates of respiratory illness such as asthma, chronic 

bronchitis, and farmers lung than the general population and report higher rates of wheeze, 

cough, and shortness of breath (see http://aghealth.nci.nih.gov/pdfs/NCWheeze2005.pdf). 

Hoppin et al (2002) investigated self-reported wheeze among farmers and EPTC was among the 

pesticides tested that was associated with wheeze over the previous reporting year in the AHS 

(Hoppin, Umbach, London, Alavanja, & Sandler, 2002). The authors hypothesized that that use 

of OP, carbamates or thiocarbamates may be associated with wheeze based upon previous 

literature, and studied this question in a cross-sectional analysis among pesticide applicators in 

the Agricultural Health Study (AHS). Researchers measured pesticide use with both an evernever exposure metric and - for those pesticides positively associated with wheeze using this 

exposure metric or for which authors proposed a priori hypotheses - days of use over the past 

year were categorized. Authors compared use of certain pesticides between those who did and 

did not report episodes of wheeze in the previous year. Models were adjusted for age, state, 

smoking and presence of asthma or atopy. Of the 40 pesticides evaluated in association with 

wheeze, 34 had odds ratios greater than 1 of which 11 were significantly associated with the 

outcome. Participants who reported use of EPTC in the last year had a 30% increased risk of 

wheeze as compared to those who reported no use of EPTC in the previous year using 4-levels of 

exposure-days [OR 1.32 (95% CI 1.05, 1.65) (p for trend<0.01)]. Neither adjustment for 

correlated pesticides nor for corn or grain dust exposure changed the observed results. No 

difference in the association between EPTC use and wheeze was observed between those who 

did and did not report diagnosis of asthma or allergy. Authors hypothesized that the cholinergic 

potential of EPTC as a thiocarbamate may lead to bronchoconstriction which may contribute to 

symptoms of wheeze; however the cholinesterase inhibiting potential of EPTC and 

thiocarbamates in general is known to be low. While a hypothesized mechanism of action is 

unclear at this time, several other non-AHS epidemiological investigations have identified a link 

between carbamates and respiratory symptoms

While the above AHS findings are only preliminary in nature and the authors caution about the 

study limitations, further analyses should be conducted. The HED HIT recommends that a more 

detailed (Tier II) review be conducted at the time of the risk assessment of EPTC which focuses 

on the epidemiological aspects of exposure to this pesticide. 
Page 7 of 8

IV. CONCLUSION

Based on the low frequency and severity of incident cases reported for EPTC to both IDS and 

NIOSH SENSOR-Pesticides, there does not appear to be a concern at this time that would 

warrant further investigation. However, based on current AHS findings we intend to further 

evaluate follow-on studies from the AHS. In addition, the Agency will continue to monitor the

incident information and if a concern is triggered, additional analysis will be also be included at 

that time. 

Works Cited

Alavanja, M. C., Samanic, C., Dosemeci, M., Lubin, J., Tarone, R., Lynch, C. F., . . . Blair, A. 

(2003). Use of agricultural pesticides and prostate cancer risk in the Agricultural Health 

Study cohort. Am J Epidemiol, 157(9), 800-814. 

Andreotti, G., Freeman, L. E., Hou, L., Coble, J., Rusiecki, J., Hoppin, J. A., . . . Alavanja, M. C. 

(2009). Agricultural pesticide use and pancreatic cancer risk in the Agricultural Health 

Study Cohort. Int J Cancer, 124(10), 2495-2500. doi: 10.1002/ijc.24185

Barry, K. H., Koutros, S., Berndt, S. I., Andreotti, G., Hoppin, J. A., Sandler, D. P., . . . Alavanja, 

M. C. (2011). Genetic variation in base excision repair pathway genes, pesticide 

exposure, and prostate cancer risk. Environ Health Perspect, 119(12), 1726-1732. doi:

10.1289/ehp.1103454

Hoppin, J. A., Umbach, D. M., London, S. J., Alavanja, M. C. R., & Sandler, D. P. (2002). 

Chemical predictors of wheeze among farmer pesticide applicators in the agricultural 

health study. American Journal of Respiratory and Critical Care Medicine, 165(5), 683-

689. doi: 10.1164/rccm.2106074

van Bemmel, D. M., Visvanathan, K., Beane Freeman, L. E., Coble, J., Hoppin, J. A., & 

Alavanja, M. C. (2008). S-ethyl-N,N-dipropylthiocarbamate exposure and cancer 

incidence among male pesticide applicators in the agricultural health study: a prospective 

cohort. Environ Health Perspect, 116(11), 1541-1546. doi: 10.1289/ehp.11371
Page 8 of 8

Table 1: Main IDS Incident involving EPTC

Human Incidents Chemical: EPTC PC Code: 041401

Incident 

Package 

Report

Incident 

Date Location

Registration 

Number Product Name

Exposure 

Severity* Incident Description

021976 -

00001 4/21/2010 SAGINAW, MI 010163-00283

EPTAM 7-E SELECTIVE 

HERBICIDE 

EMULSIFIABLE LIQUID

HB

A 59 year old male was applying the product at 

work on a windy day. He got some of the 

product on his skin and inhaled some of the 

blown back product. He went to the hospital 

and presented SLUDGE symptoms at the time 

of admission. He was treated as having 

cholinergic manifestation of carbamate 

poisoning secondary to inhalation and dermal 

exposure to this product. He was intubated 

and placed in ICU. He was treated with 

atropine to control secretions. No 

cholinesterase testing was performed. Three 

days later he was extubated. At the time of the 

call and was still hospitalized, he was no longer 

manifesting the signs of cholinergic crisis, and 

his prognosis was very good.

* Severity Categories

H-A Human Fatality Death (if the person died)

H-B Human Major Major (if the person alleged or exhibited symptoms which may have been lifethreatening, or resulted in adverse reproductive effects or in residual disability)

H-C Human Moderate Moderate (if the person alleged or exhibited symptoms more pronounced, more prolonged 

or of a more systemic nature than minor symptoms; and involved some form of treatment, 

even though symptoms were not life threatening and the person returned to his/her preexposure state of health with no additional residual disability)

H-D Human Minor Minor (if the person alleged or exhibited some symptoms, but they were minimally 

traumatic; the symptoms resolved rapidly and usually involve skin, 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 may appear in the future)

H Human Undetermined (an undetermined severity)

from 40 CFR § 159.184