UNITED STATES ENVIRONMENTAL PROTECTION AGENCY 

WASHINGTON, D.C. 20460 

OFFICE OF CHEMICAL SAFETY AND 

POLLUTION PREVENTION 

MEMORANDUM 

Da te: May 12, 2015 

SUB.JECT: Chlorimuron-ethyl: Tier I Review of Human Inc idents for Draft Risk Assessment 

PC Code: 128901 DP Barcode: D-126223 

Decision No.: 5021 75 

Petition No.: NA 

Registration No.: NA 

Regulatory Action : NA 

Risk Assessment Type: NA Case No.: A 

TXR No.: IJ\ CAS No.: 90982-32-4 

.MRIO No.: NA 40 CFR: NA 

FROM: 

THROUGH: 

TO: 

Shanna Recore, Industrial Hygienist 

Toxicology and Epidemiology Branch 

Health Effects Di vision (7509P) 

and 

Elizabeth Evans, Environmental Protection Specialist 

Toxicology and Epidemiology Branch 

Health Effects Division (7509P) c 

Carol C~~·1s se , Epidemiologist i Toxicology and Epidemiology Branch 

Health Effects Division (7509P) /} y//~ 

David J. Miller, Acting Branch hief } Toxicology and Epidemiology Branch 

Health Effects Division (7509P) 

Karlyn Middleton, Risk Assessor 

Risk Assessment Branch fl 

Health Effects Division (7509P) 

and 

Wilhelmena Livingston, Chemical Review Manager 

Risk Management & Implementation Branch 4 

Pesticide Re-evaluation Division (7508P) 

Page 1 of 6 

Vcr.J\pr.08 
Summary and Conclusions 

Chlorimuron-ethyl was previously reviewed in 20 I 0 (K. Middleton ct al., 08/1912010, 0380339). 

At the time, there were no incidents reported for the single chemical chlorimuron-ethyl only in 

Main IDS and three incidents reported to Aggregate IDS from January 1. 2000 to May 25. 20 l 0. 

In addition, there two cases reported for chlorimuron-ethyl to NIOSH SENSOR-Pesticides from 

1998 to 2007. Upon review of these incidents. it was concluded that ·'Based on the low frequency 

and severity of incident cases, there does not appear to be a concern at this time that would warrant 

further investigation." 

The current IDS analysis from January 1, 20 10 through March I 0, 2015, shows one incident 

reported involving chlorimuron-ethyl in Main IDS involving multiple chemicals and six 

incidents reported to Aggregate lDS. There were no single chemical incidents reported to IDS. 

The query of SENSOR-Pestic ides I 998-2011 identifies the same two cases. both involving 

multiple active ingredients, that were previously identified in 20 10. 

Based on the low frequency and mostly low severity of incident cases reported for chlorimuronethyl in both IDS and N lOSH SENSOR-Pesticides. there does not appear to be a concern at this 

time that would warrant further investigation. Several initial investigations within the AHS have 

made an epidemiological risk estimate of the association between chlorimuron ethyl and various 

anatomical cance r endpoints; however, these cancer sites were either not related to use of 

chlorimuron ethyl (prostate or lung cancers, NHL, and cutaneous melanoma), or the association 

measured was non-statistically significantly modest in size (< I .5) (breast, colorectal, pancreatic 

cancers). The Agency will continue to monitor the incident information and if a concern is 

triggered, additional anal ysis will be conducted. 

Detailed Review 

J. ACTION REQUESTED 

Chlorimuron-ethyl are being considered under the FQPA-mandated Registration Review 

program established to review, on a 15 year cycle, pesticides for whi ch a Re-registration 

Eligibility Decision has been made. One component of the Agency"s Registration Review 

Program is consideration of human incident data. ln conjunction with a human health risk 

assessment based on other data sources. such human incident data can assist the Agency in better 

defining and characterizing the risk of pesticides/pesticide products. 

Reports of adverse health effects allegedl y due to a specific pesticide exposure (i.e., an 

·'incident'') are largely self-repo1ted and therefore. generally speaking, neither exposure to a 

pesti cide or reported symptom (or the connection between the two) is validated or otherwise 

confirmed. 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 studies relate 

the risk of disease. e.g., cancer. and exposure to an agent such as a pesticide product in the 

general population or specific sub-groups like pesticide applicators. 

Page 2of6 
II. BACKGROUND 

Chlorimuron-ethyl is a sul fonylurea class herbicide with a mode of action of inhibiting 

acetolactate synthatase. Chlorimuron-cthyl controls grasses and broadleaf weeds. Chlorimuronethyl is registered for use on soybeans, field com, peanuts, low growing berries and non-crop 

areas such as fence rows and roadsides. Soybean is the predominant agricultural usage. There 

are no registered residential uses for chlorimuron-ethyl methyl. 

For this evaluation, both OPP Incident Data System (IDS) and the Centers for Disease Control 

and Prevention/National Institute for Occupational Safety and Health (CDC/NIOSH) Sentinel 

Event Notification System for Occupational Risk-Pesticides (SENSOR) databases were 

consulted for pesticide incident data on the active ingredient chlorimuron-ethyl (PC Code: 

128901). The purpose of the database search is to identify potenti al patterns in the frequency 

and severity of the health effects attributed to chlorimuron-ethyl exposure. 

In addition. findings from the Agricultural Health Study (AI-IS) were reviewed. The AHS is a 

high quality, prospective epidemiology study evaluating the link between pesticide use and 

various health outcomes including cancer. Chlorimuron-ethyl is included in the AI-IS and the 

findings are summarized in this report. 

lll. RESULTS/DISCUSSION 

a. IDS (Incident Data System) 

OPP's 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, 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 all relevant product infom1ation 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 arc aggregate summaries. 

Page3of6 
From January 1. 2010 to March 18. 2015. there were no incidents reported to Main IDS 

involving the single active ingredient, chlorimuron-ethyl. There was one incident reported to 

Main IDS. involving multiple active ingredients including chlorimuron-ethyl. thifensulfuronmethyl, flumioxazin, s-metolachlor, and sodium salt of fomesafen. This incident involved a 54 

year male who died five days following inhalation exposure to two products (Registration 

numbers 100-1 268 and 352-756). He was loading the products into a truck and it blew back into 

his face. His initial symptoms included fever, no appetite, body aches, and difficulty walking 

which were followed by renal failure. and hypovolemic shock. The patient required intubation. 

but eventually died. The radiologist's reading of the case·s chest x-ray indicated "suspicious for 

multi-lobular pneumonia." No autopsy was conducted and causation cannot be determined based 

on the incident data provided. 

From January I, 20 I 0 to March 18, 2015. there were six incidents reported to Aggregate IDS 

involving chlorimuron-ethyl. These incidents were classified as minor severity. Overall there 

were few incidents reported to IDS involving chlorimuron-ethyl. 

b. SENSOR-Pesticides 

The SENSOR-Pesticides database covers 12 states from 1998-2011. 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 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 sun-ounding the exposure, seve rity, and outcome. Using standardi zed 

protocol and case definitions derived from poison center reporting. SE SOR coordinators at 

State Departments of Health enter the incident interview description provided by the case, 

medical report, physician and patient into the SENSOR data system. The SENSOR data system 

is accessible to participating states and EPA. 

A query of SENSOR-Pesticides from 1998-2011 identifies a total of two cases involving 

chlorimuron (pc code 12890 I); no single ai cases were identified. Both cases were low in 

severity. One case experienced dermal irritation and redness and the other case was a bystander 

in his car who saw and was sprayed by an aerial application and reported cough and headache. 

c. Agricultural Health Study (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 

acti ve ingredients commonly used in agriculture. 

Page 4of6 
Authors with the AHS have reported risk estimates regarding the association between 

chlorimuron-ethyl and several specific anatomical cancer sites. Tn nested case control analyses of 

breast. colorectal and pancreatic cancer. authors estimated the association between chlorimuron 

ethyl and cancer. Regarding breast cancer. among 30,434 wives of AHS applicators there were 

309 cases. Chlorimuron-ethyl use modestly non-statistically significantly increased the odds of 

breast cancer by 30% ( 1.3 (95% confidence interval (95% CI) 0.6. 2.8), among only 7 

chlorimuron-ethyl exposed cases (Engel et al., 2005). In a study of pancreatic cancer risks, ever 

use of chlorimuron-ethyl was related to a 40% increased odds of pancreatic cancer (l.4 (95% CI 

0.7, 3.0), among I I exposed cancer cases (Andreotti et al., 2009). Among 56, 813 AHS 

applicators. there were 305 cases of colorcctal cancer: however. use of chlorimuron-ethyl was 

not related to this cancer (0.80 (95% CI 0.6. 1.2)) (Lee et al., 2007). Overall, from these 

preliminary, hypothesis generating studies within the AHS, chlorimuron-ethyl is not strongly 

linked to these anatomical cancer sites. For other anatomical cancer sites evaluated within the 

Af IS including prostate. lung, non-Hodgkin lymphoma and cutaneous melanoma, authors did not 

present an epidemiological risk estimate for chlorimuron-ethyl because a risk estimate with this 

compound was not calculated (too few exposed cases) or not presented (Alavanja et al., 2004: 

Alavanja et al.. 2014; Alavanja et al., 2003: Dennis. Lynch, Sandler, & Alavanja, 2010; Koutros 

et al.. 2013). 

Hoppin et al. (2002) evaluated the association between agricultural pesticide use and wheeze 

among 20.468 applicators within the AHS. Using self-reported information concerning pesticide 

use and physician diagnosis of wheeze, authors reported a significantly increased odds of wheeze 

among chlorimuron-ethyl users ( 1.14 (95% CI 1.02, 1.29), p for trend 0.0 I across four exposure 

categories. Several other pesticides were also related to this outcome; however the plausibility 

for a role of this chemical in adverse respiratory outcomes remains unclear. 

IV. CONCLUSION 

Based on the low frequency and mostly low severity of incident cases reported for chlorimuronethyl in both IDS and NIOSH SENSOR-Pesticides. there does not appear to be a concern at this 

time that would warrant further investigation. Several initial investigations within the AHS have 

made an epidemiological risk estimate of the association between chlorimuron ethyl and various 

anatomical cancer endpoints; however, these cancer sites were either not related to use of 

chlorimuron ethyl (prostate or lung cancers, NHL, and cutaneous melanoma), or the association 

measured was non-statistically significantly modest in size (<1.5) (breast, colorectal, pancreatic 

cancers). The Agency will continue to monifor the incident information and if a concern is 

triggered, additional analysis will be conducted. 

Page 5of6 
Citations: 

Alavanja, M. C., Dosemeci, M., Samanic, C., Lubin, J., Lynch, C. F., Knott, C., ... Blair, A. (2004). Pesticides 

and lung cancer risk in the agricultural health study cohort. Am J Epidemiol, 160(9), 876-885. doi: 

10.1093/aje/kwh290 

Alavanja, M. C., Hofmann, J. N., Lynch, C. F., Hines, C. J., Barry, K. H., Barker, J., ... Beane Freeman, l. E. 

(2014). Non-hodgkin lymphoma risk and insecticide, fungicide and fumigant use in the 

agricultural health study. PLoS One, 9(10), e109332. doi: 10.1371/journal.pone.0109332 

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 

Dennis, l. K., Lynch, C. F., Sandler, D. P., & Alavanja, M. C. (2010). Pesticide use and cutaneous 

melanoma in pesticide applicators in the agricultural heath study. Environ Health Perspect, 

118(6), 812-817. doi: 10.1289/ehp.0901518 

Engel, l. S., Hill, D. A., Hoppin, J. A., Lubin, J. H., Lynch, C. F., Pierce, J., ... Alavanja, M . C. (2005). 

Pesticide use and breast cancer risk among farmers' wives in the agricultural health study. Am J 

Epidemiol, 161(2), 121-135. doi: 161/2/121 [pii]10.1093/aje/kwi022 

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 

Koutras, S., Beane Freeman, l. E., Lubin, J. H., Heltshe, S. L., Andreotti, G., Barry, K. H., ... Alavanja, M. C. 

(2013). Risk of total and aggressive prostate cancer and pesticide use in the Agricultural Health 

Study. Am J Epidemiol, 177(1), 59-74. doi: 10.1093/aje/kws225 

Lee, W. J., Sandler, D. P., Blair, A., Samanic, C., Cross, A. J., & Alavanja, M . C.R. (2007). Pesticide use and 

colorectal cancer risk in the Agricultural Health Study. International Journal of Cancer, 121(2), 

339-346. doi: 10.1002/ijc.22635 

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