### UNITED STATES ENVIRONMENTAL PROTECTION AGENCY WASHINGTON , 

### D

. C. 20460 OFF I CE OF CHE MI CA L SAFETY AND POLLUTION PREVENT I O N



### MEMORAN D UM Date: Sep temb e r 1 5, 20 15 

### SUB.JECT: Difeno co naz olc: T ier 

### I (Scoping) Rev iew of Human Incid e nt s a nd Epide miol ogy

P C Co de : 12884 7 DP B a r codc: 04290&1 De c is io n No .: 50897 1 Petition No.: NA Ri s k A ss essment T y pe: A T XR No. : ' A

HUD No .: , A Regi s tration ' o . : NA Re g ulat ory Action: NA C a se N o.: NA C A S o.: I 1 9

.. 46 - 68 - 3 -' O C FR: t A Vcr.Apr.08 

### F ROM : Shanna Re co re, industrial H yg ieni st 

### O " °' f\, , Toxicol ogy and Ep id emio lo gy Branch

### ~**~** He a lth Effec t Divi s ion (7509P) , a nd

## ~ El izabeth Eva ns , E nvironm en ta l Pro tect io n Speciali s t

## <"'~~**~** Toxic o logy a nd Epidem iology Bra nch ,, 

# U
- -- - He a lth Effec ts Di v ision (7509P) 

### THROUGH: 

### Da vid Mill e r, 

### Acting Branch

# hi**~,_//t;!l.l_** )<J'J

# '1.ai~tkj To x ic o logy and E pidemiolo gy Bran c h 

# /-17 () /)

TO: He a lth E ffe c t s Division (7509 P) l van N ieves . Ri s k Assessor Ri sk Assess m e nt Branch IV H ea lth Effec t s Di v ision (7509 P) a nd Ke ll y Ball a rd , C he mical Rev ie w Manager Ri sk M a n ag ement & Impl e ment ati o n Branch 1 Pes ticid e Re-evaluat ion Di v is ion (7508 P) S ummary a nd Conclu s io n s Based on the low frequ e ncy and seve rity of in ciden t cases repo rted fo r di fe noco n azo le in both I OS a nd SE SO R-P estic ides there does not appear to be a co nc e rn a t thi s t i m e th at would war ra nt further in ves ti ga ti o n. The Age ncy w ill co ntinu e to monitor the inci d en t info rn1ation a nd if a co nc e rn i s tri ggere d , add iti o n a l a nal ys is w ill b e included in th e ri sk assess m e nt.

Pa ge 

### I of 4Detailed Review 

### I. ACTION R E QUESTED This review is intended to fulfill our requirement to docket summaries of incident data that were r epo rted to the Agency , as we ll as to e n s ure hum a n incident data and the Agricultural H ea lth Study (A HS) are part of the problem formulation phase of registration review. Reports of adverse health effects allegedly due to a s pecific pe s ticide exposure 

### (i.e . . an " incident ") arc large l y sc i f- repo rted and therefore, generally speaking , neither exposure to a pesticide or reported symptom (o r the connection between th e t\· VO) is va li dated or ot he rwi se confirmed. T ypically , causation cannot b e determined based on incident data. However , incident information can be an important source of feedback to the Agency: incidents of s evere outcome , or a suggested pattern or trend among less seve re incidents, can signal the Agency to further i nvestigate a particular chemical or product. Observational epide mi ology studie s relate the risk of disease , 

### e.g. , can cer, and exposure to an agent s uch as a pe s ticide product in the general population o r specific sub-groups like pesticide applicators. 

### II

. BA C KGRO UN D Difenoconazole is a broad spectrum fungicide belonging to the triazo lc group of fungicide s . ll is current ly registered fo r use as a seed treatment on a number of cereal gra in crops , co tton , potato s eed piec es and canola and for fo li ar app li cation to numerous food crops and ornamental s a nd for post -h arvest u se on tuberou s and corm vegetab les subgroup IC. Difenoconazole acts by blockin g demethylation dur in g stero l b iosy nthe s is which, in turn , di sr upt s membran e synt hesis. Difenoconazole is available as emulsifiable concentrate , soluble concentrate , emu lsion [oil) in water , flowable su s pension , and ready-to-use formulations. As a seed treatment , it is applied with commerc ia l g rade seed treatment eq uipment. As a foliar treatment , it is applied to field and vegetab l e crops , landscape orname ntal s and golf cou rse turf by commercial applicators using aeri a l and ground app lication methods and equ i pment. It is applied to ornamentals by re s idential applicators using hand held spraye rs. For this evaluation , both the OPP Incident Data System (IDS) and the Centers for Disease Control and Prevention /N ational Institute for Occupational Safety and Health ( CDC IOSH ) Se ntin el Event Not ifi cation System for Occupational Ri sk-Pest icide s (SENSOR) database s were cons ulted for pesticide incid en t data on the active ing redient difenoconazole (pc code : 128847). The purp os e of the database s earch is to identif y potential patterns in the frequenc y and s everit y of the health effects attributed to difenoconazole exposure. Difenoconazole is not included in the AHS, and therefore this study does not prov ide information for this report. 

### III. 

### RE SU LT S/DIS CUSS IO N

a. 

### ID S ( In cid ent Data 

### System) OPP's IDS includes reports of alleged human health incident s from various sources , including mandatory Federa l In sectic id e , f-ungicide and Rodenticide Act (FIFRA) Sect ion 6(a)(2) reports from registrants, other federal and state hea lth a nd environmenta l agencies , and individual

Page 2 of 4consumers. Since 1992, OPP has compiled these reports in IDS. IDS contains reports from across the U.S. and most incidents have all relevant product information r ecorded. Reports s ubmitted to the IDS represen t anecdotal rep o rt s or allegations only , unle ss othe rw ise stated in the report. IDS records incidents in one of two modules: Main IDS and Aggregate ID S:



### o Main IDS contai n s incidents resulting in higher severity o ut comes and provides more deta il with regard to case specifics. This system stores incident data for death , major and moderate incidents , and it includes in format ion about the location , date and nature of the incident. Main IDS incidents involving only one active ingredient (as opposed to pesticide products with multiple act ive ingredients) are conside red to provide more certain information about the potential effec ts of exposure from th e pesticide

. 

### o Aggregate IDS contains incident s resulting in less severe hum a n incidents (m in or. unknown. o r no effects outcome s). These are reported b y re g i s trants only as coun t s in what are aggregate summaries. For the Main IDS , from January 1 , 2010 to May 27, 2015, there were 0 incidents reported for the s ingle chemical difenoconazole on ly in the database. There were 6 incident s reported involving more than one chemica l. Five of these incidents we r e class ifi ed as moderate seve rity and one was classified as minor seve rity. In Aggregate IDS. from .J a nuary 1, 2010 to Ma y 27, 20 15 , there were 14 incidents reported involving difenoconazo le. These incidents were cla ss ified as minor severity. Overall. there arc few incidents reported to ID S in vo lving difenoconazo le. 

### b. SENSOR-Pesticid es The SENSOR-Pesticide s database covers 12 s tat es from 1998-20 11 , although reporting varies from state to state. Cases of pesticide- re lated iII ne sses are ascertained from a va ri ety of sources , including: report s from local Poison Control Cen te rs, s tate Department of Labor workers' co mpensation claims when reported by physician s, reports from State Departments of Ag ri c ulture , and ph ys ician re ports to s tate Departments of Health. Althou g h both occupat ional a nd non- occ upational incidents are included in the database , SENSOR-Pe s ticides focuses on occu pational pesticid e incidents , and is of particular value in providing that infom1ation. The s ta te coordinator at each of the 12 respective s tat e Departments of Health conducts case followup activit ie s s uch as ob ta inin g medical record s to verify symptoms and seve rit y. Using s tandardized protocol a nd case definitions derived from poison center repo rting , the state SENSO R-Pesticide coordinator enters the incid e nt information into the s tate-bas e d system which is se nt to N IOSH annually to be aggrega ted. A query of SENSOR-P es ticides 1998-2011 identifi es one case involving dif e noconazole**~** code 128847). This case in vo l ve d multipl e active in g r ed ients a nd was low in severit y. This case was re p o rted in 

### 1999.

Page 3 of 4c. Ag ricultura l Health S tud y (A H S) 

### The AHS is a high quality , prospective epidemiology study evaluating the link between pesticide use and various health outcomes includin g cancer . The AHS includes private and commercial pes ti cide app li cators and their spo uses. If there are AH S findings re levant to a particular pesticide go in g through regis tration re view , the Agency wi ll ensu r e they are conside r ed in the prob lem formulation / scoping phase of the process and , if appropriate. fully reviewed in the risk assessment phase of the process. The A l IS includes information on use of 80 different pesticide ac ti ve ingred ien ts co mm o nl y u sed in agriculture

. Di fenoco nazo le is no t incl ud ed in the A l IS, and therefore this s tudy docs not provid e information for this r eport. 

### IV. CONCLUS IO N Based on the low frequenc y and severity of incident cases reported for difenoconazole in both IDS and SENSOR-Pesticides there does not ap pea r to be a concern at this time that wou ld warrant further in ves ti gation. T he Agency will continue to monitor the incident information and if 

### a concern i s tri gge red, additiona l analysis will be included in the risk assessment.

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