### UNITED STATES ENVIRONMENTAL PROTECTION AGENCY WASHINGTON , D.C

. 20460 OFFICE OF CHEM I CAL SAFETY AND POLLUT I O N PREVENTION



### MEMORAND UM Date: December I , 20 1 5 

### SU BJEC T : A ldi carb: T ie r 

### I Update of Hum an Incid e nt s for Draft Ri s k A ssess ment

P C Co de: 09 8 30 1 OP Barco d e: 0430435 De c is ion No
. : 498310 Petition No .: 1A R egi s t r ati o n No .: NA R egula t ory Acti on: 1 A C a s e N o.: ' A Ri s k Assess ment T ype : /I. TXR N o . : A C A S N o.: 116

- 06

- 3 .tO C FR: NA MRID No .: ' A 

### FROM:

THROUGH:

TO: V**~r.Apr.08** Elizabeth Evans, E n vironmental Protec tion Specia li s t .

# ~ To x ic o logy and Epide mi o log y Branch 

# c;,,t.,,..**~ ~**  H ealth E ffect s Di v i s i o n ( 7509P) V' 

# ff - - · - and Shanna Reco re. Indu stri al Hyg ie ni s t . 

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. - A. • T ox ico logy a nd Epidemi o logy B ranch
. 

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## ~**~** He a l th Effec ts Di v ision (7509 P ) 

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### .I. Miller , Acti ng Branch C hi ef .;;/ A Tox ico logy a nd Ep id em iology Bran c h Health Effec ts Division (7509 P ) Matt h ew Llo y d. Ri sk Assessor Ri sk Assess m e nt Branch 

### V II H ea lth Effec t s Di vis ion (7509 P ) a nd Sue B a rtow. C h e mical Re v i ew Manage r Ri s k Manage m e nt & Implem e nt a ti o n Branch 2 Pe s ticid e Re -eva lu ation Di v i s io n (75 08P) S ummary and Conclu s io n s Ald icarb was previously rev iewe d in 20 1 2 (S. Re co re 3 / 14 112
. 0 398569). At the time. I DS wa s queried from January I
. 2006 to Dece m be r 

### l 4. 20 

### I I and th ere we re 1 5 repo rted incidents in Main ID S in vo l v in g th e s in g l e active ingred ie n t a nd ten reported in cidents in vo lving a ldicarb in Agg r egate ID S
. The r e was o n e incident clas s ifi e d as min o r severity, 11 incide nt s classified a s Page I o f 8

### moderate severity. and two incidents classified as major severity and one fatalit y . Upon review of these incidents , it was conc luded that there wa s not a concern warranting further investigation. Since the time of the 2012 scop ing memo (from January 1 , 20 12 to Apr iI 15, 20 1 5) there hav e been three additional ald ica rb incidents reported in Main I DS, including one hi g h seve rity incident. There are two add itional aldicarb cases reported in aggregate IDS. SENSOR

Pesticides was not review ed in 2012 and for thi s review. an all-year query of SENSOR

Pesticides , from l 998-20 I I. was conducted and 63 s ingle ai case report s inv o lv ing aldicarb were identified. One case was high in severity. Twenty-six cases were moderate in severit y and 36 cases were low in seve rity. In sum. this updated re v i ew of aldicarb incidents finds that the frequency of aldicarb incident reports remain s low. There are two high seve rity incidents involving aldicarb both of which are a result of misuse or use of illegal products. In the 20 12 scoping memo. a review of the Agricultural Hea lth Study litera ture involv in g aldicarb identified finding s of interest regarding aldicarb and it s potential association with colon cancer and farmer's lung. These findings arc included in this memo: however the studies were preliminary and EPA concluded at that time that continued monitoring of follow-up ep idemiolog y studies were to be evaluated as the y became available. As of ovember 2015, the Al IS has not publi s hed s ubsequent papers with findings on aldicarb and cancer or non-cancer outcomes. Further, EPA is not aware of other recent epidemiology studies that focus on aldicarb exposure and health outcomes. Therefore this a ldi ca rb update memo doc s not include additional or updated epidemiological find in gs.
Detailed Review
I. 

### ACTION REQUESTED Aldicarb is being cons id ered under the FQPA-mandated Registration R eview program es tabli shed to review. o n a 15 year cycle, pesticides for whic h a Re- registrat io n El ig ibility Decision ha s been made. One component of the Age ncy's Registration Review Program is cons iderat ion of human incident data. In conjunction with a human health ri s k assessme nt based on other data sou rces. s uch human incident data can assist the Agency in better defining and characterizing the ri sk of pesticides/pesticide products. Reports of adverse health effects allegedly due to a s pecific pesticide exposure (i.e
.. 

### an ··incident ") are largely se lf-reported and therefo re. ge nerally speaking, ne ither exposure to a pesticide or reported sy mptom (or the connection between the two) is va lid ated or otherwi se confi rm ed
. Typically , ca usati o n cannot be determined based on incident data. However , incident informati on ca n be an important source of feedback to the Agency: incidents of severe outcome. or a suggested pattern or trend among less severe incidents. can s ig nal the Agency to further investigate a particular chemical or product. Ob se rvational epidemiology s tudies relate th e risk of disea se . 

### e.g. . cance r. and exposure to an age nt such as a pe sticid e product in the ge neral population o r spec ific s ub-groups like pesticide applicators. Page 2of8I. 

### BA C KG RO UN D Aldi carb is registered for use as a systemic in sect ic ide and nematicide on ag ri cu ltural crops. For this evaluation. both OPP I ncident Data Sys t em (ID S) and the Centers for Di sease Control and Prevention/National In s titute for Occupational Safety and Health (CDC/NIOSH) Sentinel Eve nt ' otification System for Occupational Ri sk- Pesticides (SE SOR) databases were consulted for pesticide incident data o n the active in g redient a ldicarb (PC Code: 09830 l )

. 

### The purpose of the databa se search is to identif y potential patterns in the freque ncy and severity of th e health effects attributed to aldicarb exposure. I n addi tion , findings from the Ag ricultural Hea lth S tud y (AHS) were reviewed. The AHS is a hi gh quality , prospective epidemiology s tud y eva lu a tin g the link between pesticide use and var ious health outcomes including cancer. A ldi ca rb is included in the A HS and the findings are s ummarized in this report.


### II . R ES UL TS/ DISCUSS IO N a. ID S ( In c id e nt Data System) O PP 's 

### ID S includ es r eports of alleged human hea lth incidents from vario us so urces, includin g mandatory Federa l I nsecticide. Fungicide and Rodent ic ide Act (FIFRA) Section 6(a)(2) reports from registrants, o th er federal and state health and environmen ta l agencies, and individual co n s umers. 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 recorded. Reports submitted to the IDS represent anecdotal report s or a llegations only. unless o therwise stat ed in the report. ID S records incident s in one of two modules: Main ID S and Aggregate I DS:
o 

### Main ID S conta in s incidents r e s ulting in hi g her severity ou t comes and provides more detail with regard to case spec ific. This system stores incident data for death. major and moderate incident s. and it includes information about the location. date and nature of the incident. Main I OS incid en ts involving only one pesticide are considered to provide more certain information abo ut the potential effects of exposure from the pesticide.

o 

### Aggregate ID S contain s in cidents r esu ltin g in less seve r e human incidents (m in o r, unkn ow n . or no effec ts outcomes). T hese are reported by r eg istra nt s only as counts in what are agg r egate summa ri es . For the Main IDS. from January I. 2012 to April 28. 20 15. there were three incidents reported for al dicarb in the database. 1 

### One incident was classified as major severi t y. I n 

### this case, a 61

1 There were three addit ional incidents reported to IDS that were not reviewed further. One moderate seve rity incident that was a self-harm a tl ernpt. and two deaths that were the result of suicides. 

### Page 3 

### of 8

### year old male was in a comatose condition after experiencing a severe migra i ne headache that lasted for about 24 hours. The son of the patient had brought in a label for Temik stating that hi s father ha s a history of using this product off-label to control wild animals on hi s farm. At the time the incident was reported, no one kne·w how recentl y th e pat ient had handl e d Temik. The other two incidents were classified as moderate severity. The incident detail s are found in Appendix/\. Aggregate IDS , from January I , 2012 to April 28, 20 1 5. there were 2 incident s reported involvin g aldicarb. These incidents were classified as minor severity. O verall. there are few incidents reported to IDS involving aldicarb. 

### b. SEN SOR

- Pes ti c id es A query of SENSOR-Pesticides from 1998- 20 11 identifie s 79 s ingle ai cases invol v ing aldicarb (pc code 098301 )
. Sixteen of these 79 cases have been rem oved from this anal ysis because they were inte nti onal exposures. therefore this me mo reviews 63 s ingle ai case reports. Thirty-eight cases involved various Temik p r od u c ts. 19 case s had unknown products and six cases involved the i llega l ly distributed Ch ine se Chalk, aka ''T res Pasitos". Svmptoms and Severity The most commonly reported sy mptom s were gastrointestinal including diarrhea. vo miting and abdominal pain , followed by neurological sy mptoms including sweating and di zz iness. Also of note is that n i ne cases experienced cardiova sc ular symptoms including c hes t pain and slow heartbeat.

Table 1. SENSOR

- Pesticides 1998-2011 Single Al/Unintentional Aldicarb Cases n=63 Health Effects Co u nt Gastrointestinal 44 Nervou s Svs t cm 42 Respiratory 18 Ocular 15 Cardio\'ascu lar 9 Dermal 8 Renal I**Ca~es** m ay n.:nort multiple symptoms One case was high in severi ty. Twenty-six cases were moderate in severity and 36 cases were low in severi ty. The single high severity case occurred in ew York in 2008 and in vo lved a two
- year-old child who was eating potato chips off a floor th at had been treated with Tres Pasito s . The child develop e d seve ral symptoms: fever , vomiting, sweating. tremo r (shaking and falling down) , limp , diarrhea. pinpoint pupi ls, and star ing off to space . With r egard to the 26 moderate severity cases. I 0 cases involved ingestion , 9 invo lved application / handling. 2 inv o lved transport. one field exposure , and 4 cases bystander cases. Agricultural cases (n=34) Page 4of8Thirty-four cases occurred on a fa rm . Of th e ag ri cu ltu ra l cases, seven cases occ urred in o rth Ca r o lin a in 2009 w h e n h e farmworkers ate wa te rm e lon from a fi e ld where fly bait (a ldic ar b ) h ad rece ntl y been app li ed
. Five agr icultural cases in vo lve d cases where th e h a ndl e r did not wea r PP E. The 21 re mainin g ag ricultural cas es inv o l ved variou s exposure sce nari os. Non -a gric ultural cases (n = 29) • Of th e 29 cases that did not occur on a farm
. 1 6 cases occ urred in o r around pri vate residence s includin g: 7 home garde n cases a n d 9 ro d e nt bail cases. • Two tran spo rtati o n exposure case s • Two paramedic seco nd a r y exposure cases • T wo re s id e nti a l drift 2 cases (O ne of th ese cases was apply in g Tem ik a nd the wind blew the product into hi s face; the second case did not include narrativ e d e ta il. ) • Two forest worker s mad e ill from Temik w hil e in ves ti gat in g the d ea th of a p o isoned bear • One case r ece i ved T e mik from a friend lo co ntrol coyotes (and in adve11e ntl y ingested some) • Jn fou r cases th e expos ure scenar ios were not known. Of the 63 cases de sc rib ed above, 1 9 cases involv e d th e acc ide ntal inge s tion o f a ldi carb: these cases a re describ ed in Appendix 2
.



### c. Agr icultura l Health Stud y (AHS) T he A H S i s a high quality . prospect ive epidemi o logy s tudy evaluatin g the lin k be t\ vee n pestic ide use and variou s health o utc o me s includ i ng cancer. The /\HS include s private and co mmerc ial pesticide applicator s an d their spouses. 

### If there arc A l I S findings rel evant to a partic ul ar p es ticide going throu g h r eg i s trati on r eview, th e Age n cy w ill ens ure th ey a rc cons id e r ed in the prob le m formulation / sco ping phase of th e proce ss a nd , if appropriate , fully rev i ewe d in the risk assess m e nt ph ase o f th e proce ss . The AHS in clud es in formation on u se of 50 diff e r

ent pesticide ac tiv e ingredient s commonly u se d in agricu lture. In ves tigators with th e Agricu ltura l He a lth Study (A l I S) (Lee et al. (2007)) perfom1ed an an a lysis o r colorecta l cancer . loo kin g at colon cancer. rect a l cancer and co l o rectal (co l o n + rectal ) cancer a m o ng AHS study part icipant s. Cancer incidence was ide ntifi ed from s t a te cancer registrie s fro m the time of stud y enro llmen t ( 199 3- 1 997) thro u g h D ecembe r 3 1. 2002. The st ud y in c lud ed 305 colo rec tal cancer cases (2 12 colon , 93 r ectu m). Pes ti c ide exposure was eva lu ate d throu gh va lidated se lf-re p o rt que s ti o nn a ires, Th e re we re 40 a ldi ca rb- ex po se d co lo rec ta l cancer cases a nd 195 non-expo se d case s ge n e rating an OR of 1. 6 (95% C T: 1. 0, 2.4) when cases were c lassified b y eve r / ne ve r u se. Wh e n co l o n a nd rectal cancer cases we re considered separa te ly, assoc iate d OR s we re 2. 1 (95% CI: 1. 3. 3.4) and 0.8 (95% Cl: 0.4. 1 .8). respectively. Th e a uth o rs a l so conducted a n expos ure -r esponse assessmen t by di viding expos ures into 

### 4 level s ( a n o n- ex posed refere nt le ve l and three tertilc exposure le ve ls) for co lorec t al. colon. a nd rectal can cers. but the numbers

2 SE SO R-P esticid es define s drift as "off-target m oveme nt of a pesticide"' and this include s both drift and vo la tiI ization. Page 5of8of cases in each category were small, rang in g from a low of I to a hi gh of 8. For the highest exposed gro up s ORs for colorectal can cer were 2.6 (95% C I : 0.9, 7.6: n = 5, p-tre nd 0
. 0 14) and fo r co lon cancer 4 .1 (95% C l 1.3, 1 2 .8 ; n = 5, p for tre nd 0.001 ); howeve r a uth ors note the l ack of a n 

### a p riori hypoth es is to exp lain thi s observation. a nd l ac k of ex p e rim e nt a l s tudi es to s upp o rt a possible m ec h anism of ac ti on . While authors we re ab le to control fo r known co lon cancer ri sk factors related to diet and exerc ise, the A H S study was not designed to cap ture detailed informat ion concerning diet and exerc ise and thus residual confoundin g may be reflected in these escimates
. Overa ll. authors noce the significance of the finding , but suggest caution due to small numbers, the role of chance, and lack of biological explanatio n . Also w ithin the A H S, in vestigato rs reported a link be twee n aldicarb u se a nd farrner·s L un g, a non-cancer resp i ratory hea lth o utcome (Hoppin et a l. (2007))
. Us ing se l f-repo rt incid e nc e of Farm er's Lun g amo n g private appl icato rs and their s p o u ses, authors observed e leva te d odds of this outco me with carbamates as a gro up (approximate 40% increase in risk among both farmer s and spouses), and an odds ratio of 1.65 (95% C I 1.04. 2.61) reflective of25 farmer's lun g cases who reported use of aldicarb. Authors suggest again that these preliminary findings could be due to chance. Therefore a s t rong causal link cannot be made based on the se findings. As of Nove mber 2015, the AHS has not pub li s hed s ubsequent papers with findings on aldicarb and cancer or non-cancer o utco m es . Further, E P/\. is not aware of o th er r ecen t ep id e mi o logy s tudie s that foc u s o n a ldi ca rb expos ure and hea lth ou tco m es. III. Concl u s i o n Based on the low frequenc y and generally low severity of incident cases rep o rted for aldicarb and the current statu s of the AHS epidemiolog ical re search
. the re doc s not appear to be a concern that would warrant further investigation at thi s time. The Agency will continue to monitor the in cident information and /\HS results and i f a concern is tri gge r ed. addit iona l a na lysis w ill be included in th e ri sk assessmen t a nd fo ll ow- up st udi es from the Al-IS w ill be eva lu a ted if avai la bl e at the tim e o f th e ri s k assessme nt.
Ci tations: L ee WJ
. Sandle r DP. Blair A, Samanic C, Cross AJ, Alavanja MC. Pesticide use and colorectal cancer risk in the Agricultural Hea lth Study
. 

### Int J 

### Cancer. 2007 J ul I 5;121 (2):339-46
. PubMed P M ID: 1 7390374; Pu bMed Ce ntral P M C JD : PMC2928992. Hopp in , J. A., U mbac h , D.M, Kullman , G .J. , I l e nn eberge r , P.K. , London. S ..J ., A lavanja , M. C., Sa ndl e r , D.P. Pesticide s a nd o th er Ag ricultu ra l fac to rs Associated w ith Se l f-reported Farn1er's Lung among Farm Re s idents in the Agricu ltura l Hea lth Study
. 

### Occupational and Environmental Medicine 2007. 64:334-342

Page 6 of 8App endix I. M a in ID S in cid e nt · lv in l! A id ' b

Hum an In c id en ts 

# I C h em i cal: Aldicarb 

# I PC Code: 09830 1
I ncid ent Pa c ka ge Reg is tration Exposure Rep ort Incid e nt Date Location Number Pr oduct Na me S eve ri ty * I n cid e nt Des c ription Two aduh female came in contact with aldicarb when their dog go t into the nei ghbors garbage and ingested bones with aldicarb 02 4 05 1

- TEMIK BRA ND o n them
. The dog died that night
. The dog \\ US necropsied and

00002 4/10/ 2012 MOLTEN. 1 \I. N 1 \ (NON

- SPECIFIC) Moderate te sted positive for Temik
. One female experi e nced nau sea. difficuhy breathin g. tin g l in g . sal i vation. wa terin g eye s . anorexia. a nd dia rrh ca . She we nt 10 th e**.** The o t her fema l e cxpcric nccd nausea. vomiti ng. waterin g cye s . s aliva t ion. runn y nose and kidnev pain
. TEMIK BRAND 15 G A 39 year old male used the product outdoors
. About 30 025612

- 6115/ 20 13 R UPERT. ID 00026 4-00330 J\LDICARB minutes after \\Ork i ng \\ ith it. he began to fi:cl "poo rly
. " He 00009 PEST I CIDE Moderate experienced vomiting a nd lethargy
. Three ''eek s later. he was hosp itali ze d for three day with evidence of pulmonary cmboli o n film. as well a s pneumon i a . t\ 6 1 yea r old mah: wa s in a comatose co nd it ion <1ftc r expe rienci ng a severe mi g ra ine headache that l as ted fo r nbou l 02578 1

- 000264- 00330 TEM IK BRAND I 5 2, 1 ho urs . The so n of the paticlll had broug ht inn label for

00006 8 119/2013 JONESBORO. AZ G Major Te mik s taling that hi s father ha s a hi story of using thi s product**otl~labcl** to control\\ ild ani mals on hi s form
. At the time the incident was reported
. no o ne knew hO\\ recently the patient had handled Tcmik
.



### P

age 7of8Appendix 2.
' Tabl e 2. SENSO R -Pesticides Accide n ta l In ges tio n Cases fo r A ldica rb



## . N = l 9 Ca se ID Age Year Case Des cription Sev erity Reg # NYOl703 2.3 2008 Child played on the floor of a bodega \\hen he consumed potato chips off the floor or a High L3odega that had heen treated with 'Trcs Pasitos
. " NY00897 29 .8 2004 Subject ace i dently ingested Tres Pasi t os on bread l eft on t he kit chen cou nter as ra t bai t. Moderate NY00890 0.8 2004 A 9 month old chi l d inge s ted "tres pasitos" {aldiearb) that she found in a dish on the floor. Moderate Child \\as hospitalized
. NY002 15 12 1998 Child inge sted cake mixed with illegal rat poi son in his home
. ivloderate NC02237 27 2009 7 Mexica n form workers at..: watermelon in field whe r e lly bait/carbamate had bee n scattered. Moderate 00026400330 He was exposed while p l ac ing the pesticide into a sp reader. I le go t hit on th e face with the \VA.00309 33.2 20 1 1 pesticide
. The poison center indicated he had a mouthful of the product. DOI I was not able to Modaatc 00026400330 locate the \\Orkcr for inten ie\\
. Good MD information
. FL0 1 602 51.7 2006 Patient ate Tcmic mixed \\ ith peanut buner that \\as used to bai t rat traps. Moderate 00026400322 NCO l 98 1 45.3 2009 Man. wife & s t ep dau ghte r ate sq ua sh from home garden t ha t had been grown in so i l treated Mod erate 00026400330 wi th Temik and all became very i ll. NC02232 38.1 2009 7 Mexican farm workers ate watermelon in field where fly bait/carbamatc had been scattered
. Moderate 00026400330 NCOJ983 38 2009 Man. \\Oman & stepdaughter ate squash from home garden soil that had been treated \\ ith Moderate 00026400330 Temik and all became very ill. NCO l 982 15 2009 Man. win: & s tepdaugh t er ate s quash that hnd been g r ow n in home ga rden so il treated with Moderate 00026400330 Tcmik and all became very ill. NC02235 22.5 2009 7 Mexican farm workers ate watcnnelon in !ield \I here lly bait/carbarnate had been seauered. LO\\ 00026400330 FL0 1023 2002 No description provided Low 00026-10033 1 FL0 1255 32.2 2003 No desc r ip t

ion provided L ow 0002640033 1 FL0 1 022 2002 Workers exposed lo temik and dorex in\'e stignt ing cause of death of a bi:ar. Low 00026400331 NC0223.t 53..J 2009 7 Mexican farm workers ate 1\atermclon in lield where lly bai t/c arbamatc had been scaucrcd. Low 00026 -1 00330 NC02236 28.1 2009 7 l'vlcxican farm workers ate 11 -. 11crmelon in lield where lly bait/carbarnate had been scaucrccl
. Low 00026400330 NC0223 8 23.2 2009 7 Mexican farm worke rs ate watenm: lon in fie l d where ll y bait /car bamale had bee n scatte r ed. Low 00026400330 NC02233 3 4 .3 2009 7 Mexican farm workers ate 1\ at ermelon in field where ll y bait/carbarnatc had been scaucred
. Low 00026400330 

### P age 8of8