### UNITED STATES ENVIRONMENTAL PROTECTION AGENCY WASHINGTON , D.C. 20460 OFFICE OF CHEMICAL SAFETY AND POLLUTION PREVENTION



### MEMORANDUM Date: April 15 , 2015 SUBJECT: Manco zeb: Tier I (Scoping) Review of Human Incid e nts

PC Code : 0 145 04 DP Barcode: 0426276 Deci s io n No. : 499273 Pe t iti on No.: NA Ri s k Assess m e nt Type : NA TXR N o.: NA MRID No .: NA Re g i s tration No
. : NA Re g ulatory Act i o n: NA Case No. : NA CAS No.: 8018-01- 7 40 CF R: NA



### FROM: Elizabeth Evans , Env ironmenta l Protection Special i st Toxicology a nd E pidemiology Branch H ealth Effects Divi s ion (7509P) and Ver.Apr.OS



### Shanna Recore , Industrial Hygienist 

### f /J

### ~ • . _ 

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. • 

### Toxicology and Epidem iology Branch**~~**



### THROUGH:

TO: Heal th Effect Division (7509 P) and
. /} 

# Il e Caro l Christensen ,**Epidemiologis ~**  

### ""' "' ""'""' " Tox icology and Ep id em iology Branch Health Effects D ivision (7509 P) 

# ,· 1**}~** 

## /'9ofi'/GulS David Mi ll er, Acting Branch Chief

## v'c//11~ Toxico logy and Epidemiology Branc Health Effects Division (7509P) Matthew Lloyd , Risk Assessor VII 

### R isk Assessment Branch Health Effects Division (7509P) and Steven Snyderman, Chemica l Review Manage r Risk Management & 

### Imp l ementation Branch 3 Pesticide Re-eval u ation Division (750 8P)
Pagelo f 9Summary a nd Co nclu s ion s With re gard to incident data reported to ID S, SENSO R-P es ti cides. and N PIC there is a relati ve ly low to moderate frequency and severity fo r manco zeb cases overall. Th e re are, h oweve r , a num ber of e pidemiologica l fi ndin gs regarding manc ozeb that will be thoroughly reviewed and co n s id e r ed prior to reregistratio n. These includ e both the re s ult s o f the Agricultural Health Study (A H S) and a sys tematic review of the human health effects o f mancozeb ( r epro ducti ve toxicity s p ec ifically) prod u ced by a consort ium of sc ie nce -p o li cy in vestigato rs under the RE AC H pro g ram. For thi s rea so n , HED will per fo rm a Tier II asse ss m en t of the human h ealth effects of manco zc b
. in c ludin g the synthes is of informati o n ava il able in th e human population regardin g manco ze b ex posure , to s upport the inte grati o n o f thi s information with th e experimental toxicolo g ica l data ava ilabl e . D e t a il e d R ev i ew I. 

### AC TI ON RE Q UESTED Thi s rev ie>vv is intended to fulfill our requireme nt to docket s umm a ri es of in c id e nt data that we re report ed to th e Agency , as we ll as to ensure human incident data and the Agric ultural Health Study (A HS ) particularl y are part of the problem formu la ti o n phase of reg istratio n review. Repor t s o f adve rse hea lth effects a llegedly due to a s pecific pes ti c ide exposur e 

### (i.e., an

.. incide nt .. ) are la rge l y se lf-reported and therefore. ge nerall y s p eaki ng. ne ith er exposure to a pesticide o r rep o rted sy mptom (o r th e co nn ec ti on between the two) is va lid ated o r o th erw ise confirmed. T y picall y. causat io n cannot be definiti ve ly determ in ed based so lel y on incide nt data. Howeve r. incide nt in fo rm ation can be an imp o rt an t so urce of feedback to the Agency : incidents of seve re o utcome s -- or a s u ggeste d pattern o r tre nd a m ong less severe incident s -- can s i g nal to the Age ncy a nee d to further inv estigate a particular c he mi ca l o r prod u ct. Ob servationa l e pid e mi o logy s tudie s relate the risk of di sease, 

### e.g.. ca nc e r , a nd expos ure to an agent s uch as a pest ic id e product in the general population or s pecifi c s ub- g r o up s 

### Iike p es ticide applicators. I n ad dit io n , th is m e morandum inc lu de s a brief re v iew of a vo lunt a rily s ubmi ss ion of a syste matic rev iew to th e d ocke t 

### of "'An U pdate d Look at Mancozeb: Concern s about Farmworke r Rep roduc ti ve H e alth " ( D425202)
. by participant s in the " R e ach th e D ec is ion Makers Program ( R EAC H ) con so rtium co nc ern ing the reproducti ve tox ic ity of ma ncoze b 

### II. BAC K G R OUN D Manc ozeb is a memb e r of the ethylene bisdit hi oca rb amate (E BD C) gro up of fungicides , which inclu d es the relat ed active in gredie nt s maneb and m e tiram. Mancozcb i s used in agricultw-e , profess ional turf management. and ho rti culture and is u sed o n a wide vari ety of food/feed crops , includin g tree fruits
. vegetable crops , field crops. and grape s. o rnam e ntal pl a nt s, and sod farm s. Other uses includ e g ree nhouse grown flo we rs a n d ornamentals. a nd seed a nd seed piece treatment. Ap prox imatel y 

### 5
. 6 million pounds of manc ozeb a re u sed a nnu a ll y, w ith the greatest u s e o n potatoes and apples. Mancozeb is also used ex te n s i ve ly o n g rape s, onions , p ea rs, to mat oes. s qua s h , and melon s . M ancozeb is not a Res tri cted Use Pes ti c id e .

P age 2 of 9For th is eva lu at io n , both the OPP In c ident D ata System (IDS) and the Cen ters for Di sease Control and Prevention/National In s titute fo r Occupational Safety and Health (CDC/N IOSH ) Se nti nel Event ot ification System for Occupational Ri sk-Pestic id es (SENSO R ) databases we re consu lt ed for pes ti ci d e incident data on th e ac ti ve in gredient mancozcb (pc code: 

### 014504)
. Add iti ona ll y . EPA reviewed for this memo the in ciden t report on mancozeb provided by th e

at ional Pesticide In formation Ce nter (N PI C). The purpose of the database sea rch is to id e nti fy potential pa tt erns in the freq u ency and seve rity of the heallh effec t s attributed to m ancozeb exposure. Mancozeb is includ ed in the AHS and a brief compi lat ion of findings from the Agricultu ra l H ealt h S tud y regarding man cozeb is provided in thi s document. A co n so rtium of advocate-scient is t-po l icy professionals prepa red a sys te matic rev iew of the open l ite ra ture regardin g th e developmental and reprodu c t ive tox icit y and e ndocrin e effects of m a ncozeb, e ntitl e d , 

### An Upd ate d Look at Mancoze h : Conce rn s abo ut Farmworker R eproductive Health''. EPA plans to conduct a more in-depth rev iew th e ex p e r im e ntal and obse rvational studi es id e nt i fied by E P A as well as member s of the pub lic 

### (e.g. th e R EACH syste matic review) as part of an a n alys is to be performed at the tim e of the hum a n hea lth risk assess ment for mancozeb.


### 111. I NC I DENTS RESULTS /DI SCUSS IO N

a. ID S (Incident D a t a Sys t e m ) opp· s ID includes reports of allege d human health incidents from various sou rc es, including mandatory Federal In secticide. Fung icid e and Rodenticide Act (F I FRA) Sect ion 6(a)(2) r epo rt s from registrants, other federal and sta te health and env iro nm e nt a l agencies, and indi v idual consume rs . Si nc e 1992, OPP has compiled th ese repo rt s in IOS. ID S con t ai n s r epo rt s from across th e U.S. a nd most incid e nts ha ve all re le vant produ c t inform at ion r eco rded
. R e p011s s ubmitted to the I D S rep rese nt anecdotal re po r t s or allegations only, unl ess o t herwise stated in th e re p o rt. IDS reco rd s incidents in one o f two modul es: Main ID S and Agg r egate I DS :


### o Main ID S co ntains incident s res ultin g in hi g he r seve rity outcomes and pro v ides more deta il with re g ard to case s p ecifics
. This syste m sto res incident data for death. major and moderate incidents, a nd it includes infom1ation about the locat ion, date and nature of th e in c id en t. Ma in ID in c id ents involving o nl y o ne active ingredient (as opposed to pesticide products with multiple acti ve ing redients) are conside red to provide more certain information abo ut the potential effects of exposure from th e pesticide.


### o Aggregate IDS co nt a in s incidents resulting in less severe human incidents ( min or . u nkn own . or no effects outco m es). These are reported by registrants only as co unt s in what are aggregate s umm ari es.

Page 3 of 9

# ' For th e Main ID S, from January I, 2010 to December 30, 20 14
. th e re we re 0 incidents reported for the s in g le chemical o nl y in the datab ase. There we r e 4 in c id e nt s reported in vo lving than one ac ti ve in gre dient. Thr ee of these in cidents were classified as m oderate seve rity and one incident was class i fied as ha v in g .. no or unkno w n sy mptom s :· rt sho uld be noted there we re two add iti o n a l incid e nt s th at were reported as laws uit s to ID S that a r e n o t cons id ered in this report. In Aggregate ID S. from January l , 2010 to D ece mb er 30, 20 14. th e re were 26 incid ents rep o rt ed inv o lv ing m a ncozeb
. These incident s were classified as minor seve rity . Overall there are few incidents in vo lv in g mancozeb reported to IDS. In addi ti on to th e ID S query performed , a s tudy , ent itl e d
.. Health and En v ironmental Assessment of S it io Ca moc aa n , Hago noy , Davao D e l Su r ," (M RTD 4775 30 -01) was s ubmitted by D u P ont to co mpl y with 40 CF R § 1 59 (co ncern i ng reporting req uire m e nt s by regi s trants on r isk/benefit information). Th is study covered incident s occurring prior to 2009. It was r ece ntl y rec e ived by E P A and wi ll be added to o ur IDS a nd rev iewed by H E D a t a la t e r date for incorporation into OPP' s Hum a n Tl ea lth Ri s k Assess m ent ( HHRA ) fo r manco ze b.


### b. SENSO R- Pes ti c id es The SENSO R-P es ti c id es database co ve rs 12 s t a te s from 1998-20 11. a lthou g h reporting v aries from s t a te to s t a te. Cases o f pesticide

- related illnesses a re ascerta in ed from a variety of sources, inc l uding: repor t s from local Poi so n Con trol Ce nter s, s tate Department of Labo r workers' co mp e n sa tion c la im s when reported b y physicians, r epo 11 s from S t ate D e partments of Ag ri cu lture. a nd p hys ic ian reports to state D e p a rtment s of H ea lth
. A lth o u g h both occupationa l a nd non-occupati o nal incidents are included in the database, SENS OR-P es ticides focuses on occ upati o n a l p est ic id e incident a nd is of particular va lue in prov idin g that information. The state coo rdin a to r at eac h of the 12 res p ect ive state D e p artm e nt s o f" H ea lth cond u c t s case fo llow-up act iv iti es s uch as obtaining medical records to ve rif y sy mp toms a nd seve rity . Usi n g s tandardi zed protocol a nd case d efi nition s deri ved from poison ce nte r re portin g . th e s tate SENSOR

- Pesti c id e coord in ato r e nters the incident infom1ation into the s tate-b ased sys t e m which is se nt to N I OSH a rnrn a ll y to be aggrega t ed. A qu e r y of SENSO R-Pesticides 1998- 20 11 identifie s a total o f 84 cases involving mancozeb. Of th ese, 35 in vo lve the s in g le acti ve ingredient for a nal ys is . The 35 s in g l e ai cases stemmed from 24 eve nt s. evera l (5) multiple case events we r e id e ntifi ed. Thirty
- o ne cases (9 4 % ) were workre la ted. E l eve n cases (33%) we re directl y exposed from a n ae rial ap pli ca ti o n s in process. Seventeen of th e 35 cases (49%) in vo l ved fe m ales
. With rega rd to severi ty of cases: n o fatalities we re reported. two hi g h severity cases were repo11ed, four moderate severity cases we re reported and 29 low seve rit y cases w ere report ed
. B o th of the hi g h seve 1i ty cases ( and one moderate case) we re expose d to mancozeb fro m the sam e ae rial ap pli cat io n overhead while th e indi v idual s were co ndu c tin g routine farm wo rk. One hi g h severi t y case r epo rtedl y lost 75 work da ys fo ll ow in g thi s expos ure event (C alifornia, 2004). These two hi g h seve rity cases and the mod e rat e seve rit y case in th e same exposure event reported multipl e sy mptom s in vo lvin g resp ira tory, gas trointes tinal a nd ca rdi ovasc ular effects. Page 

### 4 of 9

### All three of these cases ex p e rienced a slow hear tb eat ( bradyca rdi a). Two of them also had chest pain an d o ne h ad palpitations. A su mm ary of sy mpt oms r epo rted is pro v id ed in Table I. Table 2 provides case details for eac h of the 35 s in g le ai cases in vo l ving manco zeb r epo rt ed to SE SOR-Pest icide s from 1998

- 2010. The most com m o nl y reported body system effected was nervous syste m (p rimaril y headache) fo ll owed by dermal then ocular sy mptom s . 

### It is n o tab le th at a to ta l of e i g ht cases experienced cardi ovasc ul ar symp toms. S pecificall y , fo ur cases (a ll cases from eve nt # N Y01353 that occurred in New York in 20 I 

### 0) h a d chest tightne ss and presented '"abnormal e lec trocardiograms "; three cases h a d s low heattbeat (bradycard ia); and two had c hes t pain.

T a bl e l. SENS OR-P es ti c id es 1998

- 2011 R e p o rte d H ea lth Eff ects fo r Mancoze b Cases ( N = 3 5 )
He a lth Effect # ofTimes Reported Nervou s S ys t em 1 6 Dermal 15 Ocular 14 Re s pirator y 11 Ga s trointe s tinal 9 Cardiova s cular 8 Renal 0 • Ca s e s ma y report multiple health effec t s 

### Multipl e Case Expos ure and Illness Eve nt s I. 

### Eve nt # NYO 1 353 in 20 I 

### 0 : Five cases becam e ill**a~er** 

### the cherry trees outside of the ir office buildin g were sprayed with the product P e ntathl o n 

### LF ( re g # 6769

- 38)
. Cases were ex po se d whi le conducti n g dail y work practice s and they inhaled the pest ic ide fume s thro ug h the venti lation system . One case was modera t e seve r ity and fo ur we re low seve rity. These fiv e cases were coded as ha v in g '"no l a b e l v iol a ti o n identi fied but p e rson s till became ill" ' 2. Eve nt # CA 1706 in 2004: Three cases were co ndu ct in g farm wo rk and were s praye d b y a n ae ri a l ap pli catio n overhead. Two hi g h seve rity a nd o ne mod era t e severity case. 

### 3. Eve nt # CA 171 0 in 200 4: Three cases we re exposed to drift; two fannworkers working in a lield a nd their s uper viso r who e ntered the area to evac u ate th e wo rker s . A ll three cases were low in severity
. 

### 4. Eve nt # TX02016 in 200 

### I : Three cases were ex p o s ed from 

### an ae ri a l application that fl ew ove r the fi e ld they we r e in: all three were low in severity . 5. Eve nt # TX02060 in 200 1: T wo cases we r e ex p osed to the pesticide from an aerial appl ic at ion that h ad leaking equipment: both we re low in seve rity .

Page 5 of 9Violation C it a ti o n s A tot a l of 1 7 of the cases involved FIFRA inspection s after the eve nt. Twe lve of these cases Jed to violations c ited. N ine cases with v iolation s c ite d we re in Florida w he re the agricultural e mpl oyer was c it ed for fa ilure to provide PPE
. inc o mpl e te appli cati o n records , and failure to post pesticide in fo rmation. In the remaining five cases in spec t ed
. no v io l a ti on was found
. These fi ve

.. no v i o la ti o n s found
.. were the office wo rkers exposed v ia the ve ntil a ti o n sys tem in ew York in 20 10. Summary o f SENSOR F inding s There a r e 35 s in g le ai manco ze b cases r eported in SEN OR ; 82% were low in severity. I lowevc r . e ig ht cases expe rienced cardiovascular sy mptom s (i ncludin g fo ur low- severit y cases , three that h ad "abno rmal electrocardiogram s")
. Five multiple case ex posu r e eve nt s are recorded (involvi n g a to tal of 16 cases) involving mancozeb. T he majo rity (67%) of t hese cases occurred in agr icu ltural se ttings , yet 15 % happ e ned in an office se tt in g after a n app li cat ion to the tre es outside aro und th e parame ter building.



### c . Na tional P est icid e Information Ce nte r (N PI C) Th e Na ti o n a l Pesticide In fo rmation Center or P IC is a coopera ti ve e ffort between Oregon State U ni ve rsi t y and EP A which is f unded by EPA to ser ve as a so urce o f object ive, sc ience-based pesticide inform at io n and re s pond to inquirie s from th e publi c a nd to in cide nt s. N PI C functions nationally during weekday business hours through a to ll-free te l ep h o ne number in addition to the internet ( '-'vww.npic.orst.edu) and email. S imilar to Po ison Con tro l Ce nters . PIC's primary purpose is not to collect incident data. but rather to pro v id e in formati o n to inquirers on a w ide range of pe s ti cide top ic s, a nd direct caller s fo r pesticide in c id e nt in ves ti gation and emergency treatme nt. Neve rth e less PI C does collect informati o n about incid ents (a pproximately 4000 incid e nt s p e r yea r) from inquirers and record s that inform a ti o n in a database
. N P I C is a source of n ational in c id e nt in for mation but generally receives fewer re port s than IDS
. R egardless, if a hi g h fre qu e ncy i s obse rved in IDS , N PIC provides an addi ti onal so urce of information to see whethe r th e r e is evidence of consistency across national data se t s o r possibly dup li cation a n d addit ion al information about the same incident(s). From 1/1 / 10 to 1 2/3 1 / 14 , s i x incidents we re re port e d to NP I C in vo lvi n g mancozeb
. Of the six re porte d incid e nt s, 4 were reported as symptoma ti c and two we r e asy mptomatic exposures. N PI C es timates a certa in ty index as to whether an incid e nt ( in clud in g re p o rte d sy mptoms) was e ith er definitely, probably, poss ibl y . or unlike ly to ha ve been ca u sed by th e reported exposure to a pesticide, or w he th er the incident was unrelated to pesticides or if th e incident w as un class ifi ab le . One incident was clas s ified as pro b a bl e w ith min o r seve rity (oc u lar irritation); one case was class ifi ed as unlike ly w ith m o d e rat e but atyp ica l symp to m s; o ne case was class i fied as p oss ibl e ' ith moderate severit y ( dermal irritati on); o ne cases was c la ss ifi ed as possible with minor seve rit y; and two cases we re unclassifiable/ asy mpt omati c. The probable case with minor severity invol ve d a caller who go t a mancozeb product in her eyes from a bottle th a t was n ot properly closed. Caller reported it bumcd a littl e and s he immediately rin sed as per the lab el in s tructions
.

P age 6 of 9The possible case with moderate severity in vo lv ed a caller that reported he was exposed to mancozeb while golfing and wanted to report the incident lo NP I C. Caller r eported that the course where he plays golf sprays mancozeb every Wednesday evening and th at during the week prior to his call lO P IC he played a game of go l f on Thursday morning while the course vegetation was still wet. Caller reported th at two days later he developed an itchy. blistering. poison-ivy like rash on his ankles , legs , hands and face and that thi s rash was persisting at the time of his call to PIC.

II. Hum a n Hea lth E ff e cts in th e Hum a n P o pulati o n (E pid e mi o l ogy St udi es) At this time, EPA i s aware of several diff ere nt epidem iological in vest igat ion s of potential human h ea lth effects of mancozeb use and exposure in th e human popu lat ion. Th is includes the Agricultural I lcalth Stud y (AHS) and a vo luntarily s ubmi ss io n by a consortium of science in vesti gato rs and policy advisors of an analysis of th e r eprod u ct ive toxicity of mancozeb under the auspices of the R eac h the Decision Makers Fellowship program (t he REACH program). These data will be co m p rehens ivel y identifi ed and thoroughly reviewed in the development of the human health risk assessment ( HHRA ) for mancozeb, 

### i.e., E PA will develop a Ti er II human incident and epidemiology report at the time of the HHRA. Briefl y . the analys i s submitted by REACH,
.. 

### An Upda ted look at Manco::eb: Concerns about Farmworker Rep roductive Health" was a comp rehensive systematic id e n tification , evaluation and integrati o n of 

### in vitro. in vivo, and ep id emiology studies regarding the potential reproductive toxicity of manco zeb, and include s REACH policy recommendations. Regarding the epidemiology da t a. REACH researchers id entified 

### 14 studies publ ished between 

### 2001 and 

### 2007 investigating the potential reproductive toxicity of mancozeb. Most of these epidem iological eva lu at ions were case-control studies in design. but there were three co hort st udie s identified. , . These eva lu at ions of reproductive toxicity in cl ud ed assessmen t of hea l th o utc omes s uch as fetal loss (Arbuckle. Lin , & Mery, 

### 2001; Garry c t al., 

### 2002), bi11h defects (Rull, Ritz, & Shaw, 

### 2006) and female r eprod uct i ve effects (Farr et al., 

### 2006; Farr , Cooper, Ca i, Sav itz , & Sandler, 

### 2004; Laca sa na e t al., 

### 2006) amo n g other reproductive toxic ity e ndp o int s . Although EPA has not yet evaluated the R EAC H report and will do so for the H ll RA of mancozeb, th e R EACH authors app li ed systemati c review techniques to id e nti fy. evaluate a nd synthesize information ( i
. e., critically evaluating an d rating individual study quality to inform overall sy nth es is and combining information from laboratory -based. an im al expe rim e nt al data , and human epidemiology data). EPA will evaluate the REACH report methods and results. including an EPA assessment of each study, as well as update the literature review, as needed, at the time of the HHRA for mancozeb. In addition to information regarding reproductive toxicit y . the epidem iolog ic al database for thi s chemical include s information as to potential carcinogenic effects and other non-cancer effects of mancozeb as s tudi es in the Agricultural H ealth Study (Al IS). The AHS i s a high quality , prospective epidem iology study eva luatin g the link between pe s ticide use and variou s health outcomes including cancer. The AHS includes private and commerc ial pesticide applicators and their spouses. The A II S includes information on use of 80 different pesticide active ingredients commonly used in agriculture. Mancozeb is included in the AHS. Page 7 of 9

### There are several 

### AHS epidemio log ical in vestigations which identified a potential ro le for m ancozeb, amo n g othe r compo und s, in spec ific cance r and non-cancer hea lth o utcomes . Within t he A I-IS , Denni s (20 1 0) co mpare d th e incidenc e of c ut ane o u s me lan oma by pesticide exposure in a nes ted case cont ro l s tudy
. Co ntrolling for age, sex a nd other related pe s ti c ides , a uthors reported an elevated odds of melanoma: odd s rat io 2.4 (95% confidence inte rval (95% CI) 1 .2 , 4
. 9) (p=0
. 006) among 27 1 cases of melanoma a nd 24,704 non-cases. G o ldn e r an d colleagues (20 10) reported a n e le va ted odds of thyro id disease ( both hyper- and hy po-thyroidism) among female participant s in the A H S (N= l 6, 529): in thi s cross - secti onal analysis (expos ure and disease asce rt ained s imultan eo usl y; temporal occurrence cannot be determin ed w ith certainty) re searchers report ed a s tati s tically significant 2 -fold elevated odds of th yroid d i sease (both hype r- and hypo-th yro id di sease) amon g fema le mancozeb users. In vestigatin g further the p ubli shed link betwe e n (any) fungicide u se a nd re tinal degeneration ( RD ), 

### Kirrane et al. (2005) reported a non- s tati st ica ll y s i g nificant 40 % increased odds of RD among fema le participant s in the 

### AHS (N=3 l , 173) co mpa rin g those w ho report e d u se of manco ze b to th ose who reported no u se of man cozeb. La s tl y, Farr et al. (2004) repo rted s tat istically sig nifi can t ev id e nc e of men s tru a l cyc le disruption a m o ng female 

### AHS participant s who repo rted exposure to mancozeb or maneb (no est im ate of m ancozeb

- o nl y e pid emio log ical ri s k). Among users of m an cozeb OR maneb , th e author s reported odds of a long- or mi ssed cyc le increased 2.5 to 4.5-fold. afte r co ntro llin g for age . bod y mas s ind ex, smo king , and ph ys ical ed uc at ion. E PA note s th at the s tudy b y Farr (2004) were included in the R EAC H m ate rial s pre se nte d to E PA in A pril 20 14.


### IV. CONCLUS I ON The incident data re p o rt e d to ID S, SE SOR- P estic id es, a nd PI C id e ntifi es a re la ti ve ly low / moderate frequency and sever ity for mancozeb cases overall. T h ere a re . however , a number of e pidemiol og ica l findin gs regarding manco zeb that w ill be th orough ly rev iewed and co n s idered at the tim e of th e developme nt of th e HHRA 

### for m ancozeb. Th ese include s tudi es of th e potential reproduct i ve toxicity of manco ze b s ummarized b y p arti cipants of the REACH program and s ubmitted to E PA voluntarily as we ll as the findings of a numbe r of s tudies published under th e au s pi ces of th e AHS , a m o ng o ther informati on. Th ese data will be co n s id ere d with othe r in fo rm at ion reg ardin g hum a n hea lth effec t s, and integ rated with the experime nta l toxicol og i ca l data fo r manc ozcb w ithin the HHRA.

Page 

### 8 of9

### Refer en ces A rbu ck le, 

### T. E
.. Lin. Z. 

### Q., 

### & Mery. L. S. 

### (200 1). A n exp l o ratory ana lys i s of the effect of pe s ti cide exposure on the risk of spontaneous abort ion in an Ontario 

### fa1m population. 

### Environmental Health P e r

spectives. 109(8) , 851-857. De nni s, 

### L. K
.. Ly nch. 

### C. F. , Sandler , D. P. , & Alavanja. M. 

### C. (20 I 0). Pe s ticide use and c ut a ne o u s mel a noma in pesticid e applicators in th e agricultural h eath study. 

### Environ Ile a/th P e r spectives
. 118(6). 812 -8 17. F a rr , S., Ca i , J. , Sav itz, D. , Sandler , D. , Hoppin , 

### J. , & Cooper , G. (2006)
. Pe s ticide exposure and timin g of menopause: the Agricultural Health Study. 

### A m. 

### .J. Ep id e miol.
. 163(8), 731-742. Farr, S
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