UNITED STATES ENVIRONMENTAL PROTECT I ON AGENCY WASHINGTON, D.C. 20460
OFFICE OF CHEMICA L SAFETY AND POLLUTION PRE V E N T ION

MEMORANDUM Date: January 23, 2014 SUBJECT: Imazapyr: Tier I Review of Human Incidents
PC Code: 128821 , 128829 Deci s ion No.: 486732 Peti tio n No.: NA DP Barcode: 04 17421 Registration No.: NA Regulatory Action: NA Case No.: NA Ri sk Assessment Type: NA TXR No.: NA CAS No.: 81334-34-1 , 81510

- 83-0 40CFR: NA MRID No.: NA


### FROM : Shanna Recore, Industrial Hygienist Toxicology and Epidemiology Branch Health Effect Division (7509P) and E li zabeth Evans, Environmental Protection Speciali st Toxicolo gy and Epidemiology Branch Health 

### Effects Division (7509P) 

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THROUGH: David Miller, Acting Branch Chi6, :). Toxicolo gy and Epidemiolo gy Branch Health Effects Division (7509P) TO : Mohsen Sahafeyan, Risk Assessor Risk Assessment Branch VT Health Effects Division (7509 P) and Wilhelmena Livingston, Chemical Review Manager Risk Management & Imp lementation Branch 2/4 Pesticide Re-evaluation Division (7508 P) Summary and Concl usions Ver.Apr.08

Based on the low severity and relatively low freq uency of incident cases reported for imazapyr in both ID S and SENSOR-Pesticides, there does not appear to be a concern at this time that would warrant further investigation. Ortho® GroundClear® Vegetation Killer Concentrate (Reg No 239-2657) does appear to be implicated in a disproportionate amount of incidents which may be attributable to high use of this product by consumers. The Agency will continue to monitor the Page 1 of 5incident information and if a concern is triggered , additional analysis will be included in the risk assessment. Detailed Revi ew 

### I. ACTION REQUESTED Thi s review is intended to fulfill our requirem ent to docket summaries of incident data that were reported to the Agency , as well as to ensure human incident data and the Agricultural Health Study (AHS) are part of the problem formulation phase of registration 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 exposure to a pesticide 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. Ob servational epidemiology studies relate the risk ofdisease, e.g., cancer, and exposure to an agent such as a pesticide product in the general population or specific sub

- groups like pesticide applicators

. 

### II. BACKGROUND Imazapyr is part ofthe imidazolinone chemical class. Imazapyr is a systemic, non-selective, preand post-emergent herbicide used for the control of a broad range of terrestrial and aquatic weeds, and contro ls plant growt h by preventing the synthesis ofbranched-chain amino acids. 1 For this evaluation, both the OPP Incident Data System (IDS) and the Centers for Disease Control and Prevention/National Institute for Occupational Safety and Health (C DC/NIOSH) Sentinel Event Notification System for Occupational Risk-Pesticides (SENSOR) databases were cons ulted for pesticide incident data on the active ingredien t Imazapyr (PC codes: 128821 and 128829). The purpose of the database search is to identify potential patterns in the frequency and severity of the health effects attributed to Imazapyr exposure. Imazapyr is not included in the AHS , and therefore this study does not provide information for this report. 

### Ill. 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. ID S contains reports from across the U.S. and most incidents have all relevant product information recorded. Reports submitted to the IDS represent anecdotal reports or allegations only , unles s otherwise stated in the report.

1 Excerpt from Imazapyr R ED, found online at: http ://www.epa.gov/oppsrrd 1 / REDs/ imazapyr red .pdf Page 2 of 5IDS re cord s incidents in one of two module s: Main ID S and Aggregate IDS :



### o Main ID S contains incidents resulting in higher severity outco mes and provides more detail with regard to case specifics. This sys tem stores incident data for death, major and modera te incide nts, and it includes information about the location, date and nature of the incident. Main IDS incidents involving only o ne active ingredient (as opposed to pesticide products w ith multiple active ingredients) are consi dered to provide more certai n information abo ut the potential effects of exposure f rom the pesticide.

o Aggregate IDS contains incidents resulting in less severe human incidents (minor, unknown, or no effects outcom es)

. These are reported by registrants only as co unt s in what are aggregate summaries. For the Main ID S , fro m January I, 2008 to January 9 , 2014 , there w ere 3 incidents reported for s ing le chemical only in the database. These incidents were classified as moderate severity. There were 75 additio nal incidents reported involving mo re than one chemical. Two of these incidents were classified as major severity. Two incidents were classified as major severity; however, upon further review these incidents could not be directly linked to the product used (Table 1 ). The other 73 incidents were classified as moderate severity. 

### T b l I M . IDS M

. I 'd

a e a m aJOr nc1 ents Descnpt10ns 

### fi Im or azapyr . Homan Incide nt 

## I Chemica l : Tmazapy r 

## I PC Codes: 12 8821 and 128829 Incident Package Incident Reg Report Date Location Nu mb er Product Name Incident Descriptjon An adult male s prayed th e produc t. He does not recall having any ocular exposure to the so lutio n at the time of the application and he did not experience any ocular ir rit ation or redness at the t ime of the exposure. A week later, he began to GROUNDCLEAR lose some vision in his right eye. The TRlOXTOTAL patient was evaluated by an unsp ecified 0 19978- 000239

- VEGETATION ocula r s pecialist who found a probl em with 0044 1 7/12/200 8 fL 02657 KILLER I the p at ient's blood flow to his optic nerve. An adult male used product. Two or 3 days later, he went to ICU a nd was diagnosed as GROUNDCLEAR having Pneumonia a nd was placed in a TRIOX TOTAL medically induced coma. No background 024071- 000239- VEGETATION in formation of the patient's exposure to AI 00147 4/15 /2012 VA 02657 KILLER I was provided. In Aggregate IDS , from January 1, 2008 to January 9, 2014, there were 279 reported incidents involving imazapyr. One incident was classified as unknown or no effects and 278 incidents were class ified as mi no r severity. Ortho ® GroundClear® Vegetation Killer Concentrate (Reg No 239

- 2657) appears to be implicated in a large number of incidents in both Aggregate (71 %) a nd Main IDS (77%). This Page 3 of 5product i s used on residential control of unwanted vegetation in areas such as driveways, walkways, patios and fence rows. In addition to Imazapyr (0.8%), this product contains the active ingredient Glyphosate (5%). This may be potentially attributable to the high use of this product by consumers. 

### b. SENSOR-Pesticides The SENSOR-Pesticide s database covers 11 states from 1998-2009, 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. The state coordinator at each ofthe 11 respective state Departments of Health conducts case followup activities such as obtaining medical records to verify symptoms and severity. Using standardized protocol and case definitions derived from poison center reporting, the state SENSOR-Pesticide coordinator enters the incident information into the state-based system which is sent to NIOSH annually to be aggregated. A SENSOR-Pesticides query from 1998-2009 identifies a total of49 cases involving imazapyr, stemming from 38 events. A total of21 out of 49 cases were drift-related. Of these, 46 cases involved multiple active ingredients and three cases involved a single active ingredient. Two single active ingredient (ai) cases were exposed to Arsenal Herbicide (EPA reg# 241-273) and one case was exposed to Arsenal 5

- 0 Herbicide (EPA reg# 241-308). One of these cases was work-related and two were not work-related. Two of the cases were low in severity and one case was moderate in severity. The moderate severity case occurred in Florida in 2002 and involved a 14-year old; unfortunately the narrative for this case is blank therefore exposure scenario is unknown. One case reported dermal symptoms , two cases reported gastrointestinal symptoms , and all three cases reported nervous system symptoms such as headache, weakness and dizziness. It may be of note that of the 46 multiple ai cases, 14 were related to aerial application to forest lands , 13 of which were drift-related. One aerial application to a forest was an event that involved six occupationa.l cases, the event occurred in Louisiana in 2006 and the event description states "Six loggers were exposed to herbicides from a helicopter application while logging in pine forest". Another multiple exposure event from aerial application to forest resulted in four bystander cases; the event occurred in Texas in 1998 and the event description states, "Residents live next to forest land. The land was sprayed with pesticides. The family was exposed through drift and mist."



### 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
Page 4 of5problem formulationlscoping phase ofthe 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. Imazapyr is not included in the AHS, and therefore this study does not provide information for this report
.


### IV. CONCLUSION Based on the low sever ity and relatively low frequency of incident cases reported for imazapyr in both IDS and SENSOR-Pesticides, there does not appear to be a concern at this time that would warrant further investigation. Ortho® GroundCiear® Vegetation Killer Concentrate (Reg No 239-2657) does appear to be implicated in a disproportionate amount of incidents which may be attributable to high use of this product by consumers. The Agency will continue to mo ni tor the incident information and if a concern is triggered , additional analysis will be included in the risk assessment.

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