### UNITED STATES ENVIRONMENTAL PROT ECTION AGE NCY WASHI NGTON, D.C. 20460 O FFICE OF CHEM ICAL SAFETY AND POLLUTIO N P REVENTIO N



### MEMO RAND UM Date : M ay 2 0, 2 010 S UBJECT : Limonenc : Re view o f H um a n Incident s PC Cod e: 07970 1 Decisio n No .: N A Pet ition No .: N A Ris k Assess ment Type: N A TXR No .: N A M RID No .: NA DP Barcode: D 374493 R egi str ati on No. : N A R egul at ory Actio n: NA Cas e No
. : N A CAS No.: 138

- 86 -3 40 CF R: N A
FROM :

T H ROUGH : S arah Winfield , B iologi s t

# .J**Fs;-:: ~N~~** **jJ:;. f.:::** **)Jo--** S hanna Reco re. Industrial 

### Hy i s t 

### K

hin 0 0 , M
. D ., M PH, En vi ronmental Health Scienti st Tox icology and Ep idemio logy B ranch 

# - =- - Health Effect D ivision (7509P) 

### Ma ry Manibu s an , Bran ch T oxicology and E pidemio log y Branc 

# t.. .,-c.--- ---.... Health EfTects Di vision (7 509P) V eT .A pr.l OIO



### TO: Geo rge Kr amer , Risk A sse s sor Ri s k A ssessme nt Br anch I 

### Health Effec t s Di vision (7509 P) a nd Ru ss ell W a s em , C RM Ri s k Manage ment & I mplem entation B ranch I 

### Pe st icide Re-evaluation Di vi s ion ( 7508 P) I. 

### CONCLUSION B ased on the lo w frequency a nd s eve ri ty o f i ncident c ases, there d oes n ot appear to be 

### a concern at thi s time th at w o uld warrant further investigation
. The Agen cy will continue to mo nitor th e inc ident inform ation and if a concern i s tri ggered , additi onal an a ly si s will be 

### in cluded in the ri s k a ssessment . Pa ge I o f 5II. A CTI O N REQ UEST ED Thi s review is i nte n ded to fu l fi ll o ur re q ui re me nt to docke t s umm aries o f inc i de n t data tha t w ere reported to t he A ge ncy, as w ell a s to e nsure hu m a n inci de nt data, a nd t he Ag r ic u ltura l He alth S tudy are 

### part of th e p rob l em f orm ulation ph ase o f regi s trati o n review
. Re port s of a dv ers e h ea lth eff ec t s alleged ly du e to a s pec i fi c pe s tic id e expo su re (i.e

. , a n " i nci d e nt ") are l arg el y sel f

- repo rted and the ref ore, gene ra lly s peakin g, ne i ther expo sure to a pe s ticide o r reported s y mp to m (o r the c on necti on be twee n the two) i s v alidated
. Typically , cau sat ion c annot be d etermined b a se d o n inciden t da ta . H o wever, incid ent i nfo rm a t ion c an be an i mportan t feedback loo p to the Agency

- i ncidents o f s eve re out c ome , or a s u ggested pa ttern or tre nd among less s eve re inc ident s ca n s ignal the Agency to fu rther inv es tigate a particul ar c hemical o r prod uct. Ob serva ti o nal epidem io logy s tu d ies re la te the ri s k o f d i s ea s e , 

### e . g ., can ce r, and e xposu re to an age nt s u c h as a pe s ticide p roduct in the gene ral popula tion o r s pecific su b- grou p s lik e pe sticid e applica tor s. Ill. BA CKGRO UND Fo r t hi s eval uation , bo th the O PP I nc id e nt D ata Sy s tem (I DS ) and th e Ce nters for Di sease C o ntro l a nd Prevent ionlNatio nal In s titute f o r Occ upationa l S a fet y and Health ( C DC IN IOS H) Se ntinel Eve nt No t i fication S ystem f or Occ upa tiona l R i sk -Pe s ticide s (SENSO R) d atabase w e re cons ulted fo r pe sti cide i nci d ent da t a o n the ac tive in g re die nt lim onene . Addi tionall y, th e Ag ency i s loo king to incl ude fi ndings fr o m th e A g ricult u ral H ea l th S tudy (A HS) , b eg innin g w i th t he p rob lem f ormula ti o n p ha se o f re gistratio n re view
. Th e p urpo se o f t he da taba se s e arc he s i s to identify p otentia l p attern s o n the ex ten t an d seve r ity o f the healt h e ffec t s a tt ri buted t o lim onene ex po s ure . T he I D S incl u de s report s o f alle ged hum a n he alth i nc id ent s from v arious s o urces , i ncludin g m and a tory F e d e ral In se cticide , Fung icid e a nd R oden ti cide Act ( F IFRA) Se ct ion 6 ( a) (2 ) re p ort s fro m r eg i s tra nt s, o th er fe dera l a nd s tate h ealt h a nd e nviro nm enta l a genc ies an d ind iv idu al co ns um er s. S inc e 199 2 , O PP c o mpi les th e s e rep o rts in I D S. ID S con tain s report s f rom acro ss th e U .S. an d m o st in cident s h ave a ll re levant p ro du c t inf o rmation re cord ed. Reports s u b mi tt ed to t he I DS r epre sent anecd otal rep o rt s or a ll ega tions o nl y, unl e ss o therw ise s ta te d in th e r e p ort . Th e N IOS H SENSOR d ataba s e co vers 1 2 s tates fro m 1 9 98

- 2006
. a lthough reporti n g varie s fro m s tate to s tate ( the data ba se includ e s a total o f 1 0 , 6 5 9 c ases). Pe sti cide-relat ed in cid e nt s are coll e cted f rom D epartm en t o f L a b or wo r ke r s' co mp e n sa tion cl aim s w hen rep ort e d b y p hysicians , re port s fro m St ate D e p artment s of A gr icu lture , fr om p o i so n co ntro l c e nter s a nd f ro m S t ate D epart ment s o f Health b a se d o n re p o rt s by p hysicia n s s uspe c tin g p e st icid e ex po s ure . A lthou g h bo th oc c u p ationa l a nd no n -occu pati o nal inc ident s are i ncluded i n th e d atabase , SENSOR f oc u s e s o n oc cup at iona l p e s ti c id e i nc ide nt s, an d i s of p articu lar va l ue in prov idin g that inf orm ati o n . A s t a te S ENSO R c o nta ct s pe c i a lis t d oe s f ollo w -up wi th wo rkers a nd o b t ains m edi cal re cor d s to v e ri fy s y mp toms, c i rc u ms t a nc e s s u rro u n d in g th e ex po s ure, s e v e rity , a nd o utco me . U s ing s t a n d ar d iz ed p ro to col a nd c ase defin i tions, de rived f rom p oi so n ce nt er repo rt ing , SENSO R coo r dina tors at S tate D epartm ents o f Hea lt h e nter the in cident i nterview d escrip t ion prov ided b y th e w orke r , m edical re port, p hysicia n and p atie nt into th e SE NSO R d a ta s yste m, acce ssi b le to pa rtic ipati ng sla te s a nd E PA
. Th e A HS i s a hi g h q ua l ity, pro s pect i ve e pidemiology s tud y ev a lu at ing th e li nk be tween p esticid e use a n d vario u s heal th o utcome s includ ing cance r . The A H S i ncl u d e s pri vate an d com mercia l pe s ticide ap plicator s and th eir s pous e s . I f th ere are AH S finding s re l evant to a p articular pe s ticide goi ng thr ough registration

P age 2 of 5re view, the A gency will ensure they are co n s idered in th e pr oblem fonnu lation/sco ping ph ase of the p roce ss and, if ap propriate , fu lly re viewed in the ri sk asses smen t ph ase of th e pro cess . The A H S include s info rma tion o n the u se o f 50 d iff eren t pe s ticide a ct iv e i ngredie nt s co m mo nly u s ed in a g ri cultur e . 

### IV. RESU LTS / DISC USS ION For I D S we id entifi ed 39 ca se s re ported for lim onene in th e U nited St ates f rom 2 0 0 2 to th e p re se nt. O f t he s e c a s e s, li v e were r evie wed b ecaus e i n th e se c ases li monen e w as u s ed a s a s ingle c hemic al o n ly a n d there for e th ese c ases p rovide m o re certai n inform ation abo u t th e p otent ial effe ct s of l imo nen e expo s ure . T hr ee o f the ca ses a ppe ar e d to involv e ex po s ure fro m u sin g a fle a and t ick s hampoo con taining li monene i n re s identia l s e tting s, and the rema ining two cas es involved po s tap plicatio n expo su r e in res id e ntia l s etti ngs (after p rofes si onal app lication)
. The m ost fre quently repon ed s y m p toms we re neurological ( 3 8% ) f ollo wed by d erma l ( 25 %) ; gas trointe s ti na l, ocu lar a nd mi sce llan eou s s ympto m s wer e re ported e qua lly ( 13 %) . P roport io n s re late to th e to tal n umber of sy mpto m s, n ot the to tal numb e r of cas es, 

### i .e . , a n in divi dua l m ay rep ort mu ltipl e s ymp to m s to t he d atabase
. S ee the t ab l e be low f or fu rther d et a i l s. For N I OS II SE NSOR , w e id entifi ed 4 c a ses reported that i nvo l ve the acti v e in g redient lim onene O f the s e c a se s, onl y on e wa s re v iewed b e c ause, in thi s case , lim o nene w as u se d as a s in g le c he mical o n ly and ha d a ce rt ai nty cl ass ifica t ion o f d efin it e . p robable, or p os s ib le . T he case w as a n un kn own a ge ma l e w h o h a d a pos tap plic a ti on e xposure to l imo nene wh e n h e e nte red a n o ffi ce that ha d ju s t b een tre a te d
. He e xpe ri enced oc u la r, re sp ira t ory. neurolog ica l an d ga str o inte st ina l s ym pto m s . Th i s cas e wa s ranked lo w seve rity
. Li mon ene is n ot included in th e AHS, an d therefore n ot co n si dered i n th i s re port . B as e d o n th e low f requ ency a nd se v erity of incident c ases , th ere d oes n o t a p p ea r to be a co ncern a t thi s ti me t ha t wou ld w a rrant f urther i n ve s ti g at ion
. A lth o u gh the re are in ci de nts re porte d th at re su lted in m o derate o ut come s, th e s y mptom s a nd s ettings we re v aried a nd d o n o t indi cate a trend or pa ttern that wo u l d tri gg er f o llow -up a na lys es . T he Ag e ncy will c ontinue to m onitor the inc ident in f orm ation a nd i f a c oncern i s tri gger ed, a ddi t ion a l a nalys is will b e includ e d in th e ri sk a ssess m ent.

Page 3 o f 5Adu lt (1 8 -64 yea r o ld ) fe m a l e ba thed he r pe l w ith t he p rod u ct w it hout gl ov es o n 3 s epa rate oc cas io n s . S h e rec ently dev e l o ped m emory d efi c it , c onfus io n , p a in in mu s c l es a n d j oints , and d iffi c ulty e xp ress ing h er t h ou gh t s i n w ords

. I ncident De s cr mn on Ex posure

Type · H C LA Sta le Ci t· · Human Incid ent s
R egistrati on

Nu mber 

### 004758001 4 1 Prod uct N a me A DAMS F L EA & T I C K S H AMPOO W ITH DL1 M O NENE t nctdcnt

Da le O

S

- Jan 

### 07 I ncident Num ber 

# ID S R eport Chemical : Limonene ",,,,,.. 

# "' 

# .. """'-'

01 8 34 4 I 001

0 18666 

### I 01 2 2 5-J u n

### 0 7 A DA MS F LEA & TI CK S H A M POO W ITH DL1M ONENE 

### 0 047580 0 141 N C H C A dult ( 1 8-6 4 year o l d) fe ma le wa s ex posed to t he produ ct d ermally 3 da ys ag o . S h e br o ke o ut w i th b umps f r om kn ees to t he to p of h er foot. She washed a nd a p pli e d G o ld B ond but le sions we re sti ll t here a nd not re s o l vi ng . Late r s he u sed h yd rocortis o ne oi n t m e n t, a nd t h e s ymp t oms g ot be tter
. 

### 019670 002 29 - M ar 

### 0 8 P RE SCR IPTI O N TR EATMENT B RA N D P ROC ITRA-DLTM CO NTACT 

### 0004 990049 7 G A H C Adu lt ( 1 8-64 y ear old ) f emale r e p o rte d that pes t co ntrol s p r ayed he r hom e ; t o ld he r t h a t i t was a lright f or her t o s t ay in t h e ar ea , The n e xt day s he s tarted f e e ling l et hargi c , a lso h ad h eada ch e , vom it ing a nd d iar rh ea , H er d og wa s a lso exp ose d t o the produ c t and d ev e l o p e d vo m i t ing , d eh y dra t ion , f at igu e , kid ney fa ilure , a nd ab n o rma l li v e r f unct i o n . Th e d og's pl a t e le t s l e v e l was lo w, b l ood s t o pped c lo tt i ng an d b egan h e mo rrhag i ng u nder t h e s ki n . DM V g ave t h e dog I V flu id s , ant i b i oti cs a nd a co rt iso ne sho t , but the d o g d ied

.



### Page 4 of 5

# IDS Report Chemical: Limun enc Human In cid ent s
In cid ent N umber , 

### 0 198 49 

### I 0 02

0 2 1 325 I 020

• Se ven . C a tc ones H ll 11 man II

-A Human Fa lahl' H-B Human Ma jor I ncident nate 25· Jun · 

### 08

20-Sep09 _ Product Na me PRESC R I PTION TREAT MEN T B RAND PR D C ITRA-DLT M C O N TACT

ADA M S D - L1 MO N E N E F LEA & T I CK S H A M P OO Regist ration Numbc r._ 

### 00049 900497

002724007 5 9 000270 Ci ty A NAHEIM Stale C A

AZ Expos ure

, T :y pe* H C

H C In ciden t Description A 73 year o l d ma l e w a s expo sed t o t he pr odu c t when a profess ion a l exterm i na t i o n co m pa ny spra yed hi s h ome w i th th e p r oduc t. H e deve loped he ad ache

. an d pa infu l l eft eye t he n ex t d ay . H e w en t t o h i s ph y s i c i an f o r trea tment. H e t oo k All eg r a D a n d t h e s y m p to ms

l o t b e tt e r . Ad ult ( 1 8-6 4 yea r s o l d) m a l e g ot t he p rodu ct o n hi s f eet, s to mach

. f o re ar m s and h an d s wh en w a shi ng th e do g wi th t he produ c t. Th e n ext day h e de veloped h ives a nd w elts o n h i s s tom ach a nd f ore arms . T h e d og w a s a lso d ro o li ng .

H-C Hu man M oderat e H-D H uman M irm r H- E Hu man Unspeci fied



### Pagc 5 0 f 5