### UNITED STATES ENVIRONMENTAL PROTECTION AGENCY WASHINGTON, D.C. 20460
OFFIC E OF C HEMICAL SAFETY AND POLLUTION PRE VENTIO N



### M E MORANDUM Date : Jun e 

### 18, 20 1 5 

### SUBJECT: Diquat 

### Dibromide : Tier 

### I R eview of Hum an In c idents fo r D raft Risk Assessment

PC Co d e: 03220 1 DP Barcode: 0427720 D ecis io n No.: 482019 P et iti on No.: A R isk Asse ss ment T y p e: A TXR No.: A MRIO No.: NA Re gistrat io n No.: NA Reg ul a t ory Action: A Case No.: A CAS No.: 85-00- 7 40 C FR: NA Vcr.Apr.08 

### FROM: Elizabeth Evans, Environmental Protection Specialist Toxicology and E pidemiol ogy Branch 

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# ~';hA/J/**c;\At~**

# ~~~ Health Effects Division 

### (7509P) and S h a nna R ecore , In dustrial H yg i e ni s t Toxicology and Ep idemiol ogy Branch



### T HRO UGH:

TO: Health Effects Di v ision 

### (7509 P) /,) David J. Mill e r , Acting Branch C hief 

# J 

# _A;. 

# J**~If..** Toxicology and Epidemiology Branch Heal th Effects Division 

### (7509 P )
Thurston Morton , Ri sk Assessor Risk Assessment Branch I Health Effect s Division 

### (7509 P) and Bonnie Ad le r, Che mical R ev iew Manager Ri sk Management 

### & Implementation Branch 

### 3 Pesticide R e - eva lu ation Divi s ion 

### (750 8P) Summary and Conclusions Diquat dibrom ide incide n ts were prev io u s l y reviewed on June 

### 11 , 2009

. Thi s inc iden t review found th at "

... 

### the evaluation of incident data for diquat dibromid ejinds a relativ e ly loiv volum e of incidents

... only 5 7 incidents , symptoms appear generic and not confirmed to be re lated to exposu r e. th e re is no clear ev id ence of a trend or expos ur e pallern. Therefore. at this time, there are no re markable case r epo rts which sugges t a plausible association between a mod e rate or 

### Page 1of6

### seve re health outcome and exposure 10 

### pesticide diqua t dibromide nor can we discern any s ugges tion of a trend or pattern rega rding th e he alth effects due to th e alleged exposu re t o pesticide diquat dibromide. The current rev iew of th e incident data does not warrant further investigations at this time. "( Hawkins, 2009)
T he current ID S analysis, from January I , 20 I 0 to M ay 28 , 20 1 5, found 18 incidents repor1ed to Main ID S involving the s in gle active ingredient , d iquat di bromide. Fourteen of these incid ents were class i fied as moderate severity and four in ciden t s were class ifi ed as major severity

. Th ere a r

e 85 a dditional incid e nt r e porte d to Main IDS th at in v olve multiple ac ti ve ingre di e nts , including diquat di bromide. In Agg re gate IDS , from January I , 20 I 0 to May 28. 2015, th e re are 1121 incidents reported invo lvi n g diquat dibro m ide.
T he query of SENSO R-Pe s ticide s 1998-20 11 id e ntifi es 11 9 cases in vo lv in g diqu a t di bromid e, 32 of which involve a s in g le activ e ingredient. Detailed R ev iew I. 

### ACTION REQUESTED Oiquat dibrom ide is b e in g considered und e r the FQPA- mandate d Re g i s tr ation R ev iew prog ra m estab li shed to review , on a 15 year cycle. pestic ide s for wh ich a Re-regi s tration E li gibi li ty Decision ha s been made. One component of the Agency ' s Registration Review Program is consideration of hum a n incident data. In co njuncti o n with a human h ea lth risk assessment based o n other data sources , s uch hum an incident data can ass ist the Age nc y in better d efin ing and characteri z ing the ri sk of pesticides / pesticide p roducts

. Reports of a d ve r se hea lth effects a ll egedly due to a s p ec ific pesticide ex po s ure 

### (i.e. , a n
" inc iden t'") a re large ly se lf-reported and th e refore , ge nerally spea king , ne ither exposure to a pesticide or reported symptom (o r the connection between the two) is va lid ated or otherwise confi rm ed

. Typ icall y, ca us ati o n cannot b e determined based o n incid e nt data. H oweve r, in cide nt information ca n be an important so urce of feed back to th e Age n cy: incid e nts of severe o utcome. or a suggested pattern or trend among less sever e incidents , can s ignal the Agenc y to further inve s tigate a particu lar chem ical or product. Observational e pid e mi o logy s tudies relat e the ri sk of disease , 

### e.g., cancer, a nd expos ure to an age nt such as a pe s ti c id e produ ct in th e ge neral popu lat ion or s pecific s u b

- gro ups like pesticide app li cato rs.



### II. BACKGROUND Oiquat dibromide is a non - se l ective contact herbicide , a lg icide , desiccant , and defoliant. As an he rbicide/ a lg icid e, it is u sed to co ntrol bro ad leaf and g rass y w eeds in non- c rop (inc ludin g res id e nti a l) an d aquatic a r eas. As a de siccant/ defoliant , it i s u se d in seed crops and potatoes. It s largest u se i s as a de s iccant on po tato crops. Diquat dibrom id e is formu la t e d as a soluble co ncent rate and ready-to use li qu id. As an herbicide , it is applied using a h a nd-h e ld or mechanical sprayer; as an algicide , it is inj ecte d below the water surfa ce to co ntrol s ubmer ged

Page 2of6weeds. When used as a desiccant , it may be applied by a ircraft or ground equipment. App licati o n s in crop a reas are made fiv e days to two weeks before harv es t.
For this evaluation , both OPP Incident D ata System (IDS) and the Centers for Di sease Control and Prevention/National Institute for Occupational Safety and Health (CDC/NIOSH) Sentinel Event Notification System for Occupationa l Risk-P es ticides (SENSOR) databases were consulted for pesticide incident data on th e act ive ingredient diquat dibromide (PC Code: 03220 I). The purpose of the database search is to identify potential patterns in the frequency and sever ity of the h ealth effects attributed to diquat dibromide exposure.



### II I. RES UL TS! DI SCUSS I ON a. IDS (In ci de n t D a t a Syste m ) opp · s IDS includes reports of alleged human health incidents from various so urc es , includin g mandatory Federal Insecticide , Fungicide and Rod enticide Act (FIFRA) Section 6(a)(2) reports from registrants, other federal and s tat e health and env ironm enta l agencies. and indi vidua l consumers. Since 1 992. OPP has compi led these reports in IDS. IDS contains reports from across the U.S. and most incidents have a ll relevant product information recorded. Reports submitted to the ID S represent anecdotal reports or a ll egations on ly, un less otherwise stated in the report. IDS records incidents in one of two modules: Main I DS and Aggregate IDS:



### o Main IDS contains incidents resulting in higher seve rit y outco m es and provides more detail with regard to case specific. This system stores incid ent data for death , major and moderate incident s , and it includes information about the loc ation , date and nature of the incid ent. M ain ID S incid ents invol ving only one pesticide are considered to provide more certain information about the potential effects of exposure from the pesticide.



### o Aggregate IDS conta in s 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 s ummaries.
From January 1 , 2010 to May 28. 2015 , there were 18 incidents reported to Main IDS in volv in g the single active ingredient, diquat di bromide. Fourteen of these incidents were classified as moderate seve rity and four incid e nts were classified as major seve rity. Two of th e major severity incidents were the result of unintentional ingestion of the product that had been repacked in a beverage container. The details of the incidents classified as major seve rity are found in Tab le l. There are 85 a ddition al incid ent reported to Main ID S that involve multiple active ingredients , includin g diquat dibromide.
From January I, 2010 to May 28, 2015, there are 1 1 2 1 incidents report ed to Aggregate IDS involving diquat di bromide. Three of these incidents had no or unknown effec ts and 1 1 18 of these incidents were classified as minor severity. For minor severity incidents, the effec t s Page 3of6

### experienced were generally minimally traumatic and r es olving rapidly and usuall y involve skin. eye o r r es piratory irritation

.

In c id e nt P ac ka ge**Re t**  In ci d en t Reg Da te Lo cat io n Num ber Produ c t Na me In c id e nt Desc ripti o n A 56 year old male applied th e product to a body of water on a windy da y and he inhal ed so me of the pro duct. He exp eri ence d hypothermia , per s is ting pulmona ry 02 18 07

- REWARD infiltrates with a ssoc iated shortn ess of 00007 SHREVEPORT , (NON- breath and low 02 s aturation, 3/ 15 / 2 0 I0 LA NA SPE C IFI C) re spiratory fai l ure and sweating. A 2 ye ar old boy s uffered a severe asth ma anack and had to be REG LO E ho s pitalize followin g application of 023289

- (NON- thi s product to ne ig hboring potato 00004 8 / 30 /2 011 NE NA SPECIF I C) fi e ld. An adult male put s ome product in a so da bottle with the intention of REWARD applying it to a field. He accidentall y LANDSCAPE drank about one o unce of th e product. AND He ex perienced vomiting , throat 024186

- 000 100- AQUATIC irritation , burn s to hi s throat and lip s . 00200 5 / 16 / 20 12 

### MS 0 109 1 HERB I C IDE increa se d creatinin e. A 3 y ear old boy acciden tall y in ges ted product th at was sto r ed in a Gatorade bo11le. H e expe r ienc e d REWARD burned lips , b li stered tongue and r e na l 0 2522 1

- AQ UAT I C damage

. He was hosp italized for I0 00005 2 / 4/ 20 11 CA NA HERB I CIDE da ys . 

### The most impl icate d product is RoundUp Weed & Gra ss Kille r Concentrate P l us ( Reg . No. 71995-29). It is imp li cated in 50% of the diquat d ib rom ide inc i dents reported to IDS. This product contain 0.73% diquat dibromide and 18 % g ly ph osate . 

### It i s u se d around flowerbeds , land s capes , tr ees, driveway , wa lkways, and a long fence s to control weeds. 

### b

. S EN SOR-Pes ticides
The SENS OR- P est ic ides databa se covers 12 s tates from 1998-2011 , a lthough reporting varie s from s ta te to state. Cases of pesticide

- related illnesse s arc ascertained from a vari e ty of sources , including: report s from local Po iso n Contro l Ce n ters , state D epar tment of Labor wo rke rs ' compensation claims when r epo rted by phy s ic ians , repo rt s from State Department s of Agriculture, and physician reports to state D e partm en t s of Health. Although both o ccupatio n al and non-occupational incident s are included in the databa se, SENSOR focuses on occ upation a l pe s ticid e incident s, and is of particu l ar value in providing that info r mat ion. A state SENSO R contact specialist attempts to fo ll ow-up w i th cases and obta in s m ed i ca l r ecords to ve ri fy symptoms , circum s tances surTounding the exposure , severity , and outcome. Us in g s tandardi zed protocol and case definitions derived from poison center reporting , SENS OR coordinators at
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### State Departme nt s of Health e nter the incid e nt interv iew d es cripti o n pro v ided by th e case. m edica l rep ort , physician and patient into the SENSOR da ta sys te m . The SENSOR data sys t e m i s access ible to p a rti c ipatin g s ta t es and EPA. SENSO R-Pe s ticid es identified a total of 116 cases in vo lv in g diquat dibromid e (pc co de 0 3220 1 )

. Of these. 32 cases in vo l ve a s in gle active in g re dient wh ich w ill be a n alyzed in thi s memo. S ixtee n cases we re work-related and 16 cases we re not wo rk-related

. Ex ample s of diquat application tar ge ts that result ed in cases mad e ill in clude landscapi ng ( n = 5) , aquatic ( n = 6) , and weed co ntrol (n =4). While half of th e cases were appl y in g the produ c t at th e tim e the y were exposed , 13 bystander cases were reported as well (the remainin g four cases had no re ported applicatio n target). Produ cts m os t imp l icated among cases we re : 10 cases in vo l ved Reward La nd scap e and Aq ua tic H e rbi c ide (mainly und e r reg. # I 00-109 l ); 7 cases invol ved Moss-Out ( Re g 

### # I 1694-40)
T wo cases were high in severit y , four cases we re moderate in seve ri ty and 26 cases were low in seve rit y. The m ost co mm o nl y reported hea lth effects we r e dennal ( n = l 9) mainl y ras h and irri ta ti o n , followed by ocular ( n = 11) includ ing eye irritation. 

### It is notable , howe ver , that of th e fo ur moderate seve rity ca ses. sy mptom s in c luded: corneal abrasion. burning of s kin , a nd blistering skin. B oth hi g h severit y cases reporte d ren al hea lth effects a nd one a lso repo rt ed cardiovascular symp tom s . 

### ln o ne high seve rit y case the cases made an aquatic ap pli c ation to a lake o n his prop er ty and proceeded to rake the s hore for several h o urs. T he ca se deve lop ed a headach e and troubl e breathin g and was admitted to th e E R w ith respiratory, gastrointesti n a l , neuro log ical , re n al a nd cardiovascular sy mpt o m s. Th e seco nd hi gh seve rity case was occupational ; a vegetation managemen t s up erv iso r was in a chemical sto rage room takin g in ventory. Some 2.5 ga llon containers we r e improperly sto red on the top s helf and the employee decided to relocate them

. Wh e n he r eached up to mov e a co ntain e r, the lid wa s not o n it and the material s pilled into hi s face. Th e per son swa ll owed so me of the he rbi ci dal de s i ccant. H e immediately took a full body shower a nd was take n for m edical care. T he n ext day he was hospitalized due to progressive respirat o ry a nd gastro intes tinal symp to m s and discharged after 10 days.

c. Ag ricultur a l H ea lth Study (AHS ) The AHS is a hi g h quality, prospective epidemiology s tud y evaluatin g the link between pe st ic id e u se a nd vari o u s h ea lth outcom es inc luding cancer. Th e AHS includ es pr i vate and commerc i a l pesticide applic ato rs and t h e ir spo u ses . If th e re are AHS finding s relevant to a particular pesticide goi n g through reg i stratio n r ev iew. the Agen cy w ill e n s ure they are considered in the problem fo rmul atio n / scop in g phase of the process and , if a ppropri ate , fully re v iewed in the risk assessment pha se of the proc ess. The AH S includes in fo rm ation on u se of 50 diff e rent pesticid e act ive in g r e dient s common l y u se d in agriculture. Diquat dibromid e is not includ e d in the AHS and the refo re this st ud y does not provide information for thi s rep o rt. CONCLUS IO N Agg regate IDS identities a m ode rate frequency of min o r seve ri ty cases ( n=l 1 2 1 ) inv o lvin g diquat dibrom ide: w he re as ID S Ma in id en tifi es o nl y 18 cases ( m ode rate and h ig h severi ty)

Pa ge 5of6involving diquat dibromide. Diquat i s registe red for homeowner us es a nd available a t ga rd e n ce nters and is often mixed with other chem icals s uch as glyphosate. W ith regard to moderate and hi g h severit y diquat case rep o rts , there is a low frequency of cases in both ID S ( n = l 

### 8 ) a nd SENS OR-P es ticide s ( n = 6) . H owever, th e sy mpt oms of the se high and moderate cases are genera ll y se rious

. Further, it is n otable that two of th e four hi g h severity incident s r e port in I OS invo lve th e acc identa l ingestion of diquat from a rep urpos e d beverage container. The Agency will continue to monitor the diquat incid ents.

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