### UNITED STATES ENVIRONMENTAL PROTECTION AGENC Y WASHINGTON , D

. C. 20460 OFF I C E OF CH EMI CA L SAFE T Y AND PO LL UT I O N PRE V ENT ION 

### MEMORANDUM
Date: 12 / 1 5 / 2015 SUB J ECT: Stryc hnin e . 

### Hum a n H ea l th Assess m e nt Sco pin g Doc ument in S up po rt of Reg is trati on Review

FROM:

T H RO U GH:

T O: P C Co d e : 

### 07690 1 Decis i o n No
. : 

### 508056 P etiti o n No
. : NA 

### R isk Asse ss m ent Ty p e: NA 

### TXRNo.: NA 

### MRIDNo
. : NA 

### D P Barco d e: 

### D428699 Reg i s t ra ti o n No.: 

### Re g Rev-3 1 33 -1 Reg ul a t ory Acti o n : 

### Reg i s tr ati o n Rev iew Case No.: 3 1 1 3 

### CAS No.: 

### 57-24-9 40 

### CFR : NA 

### J ai m e D ' Ago s tin o, Ph
. D ., Toxico l og i s t Matthew Crowley, Biol ogist

**~~::_....A&..L.>-A** 

### Ri sk Assess m e nr Branch li 

### H

ea lth Effects Div ision (7509 P) Office of P es ti cide Pro g ra ms Chri st ina Swart z, Bran ch



# hi **ef~~** Ri s k Assess m ent Bran c h II \ , $> 

### J ess Rowland , De puty Div is io n Dir ec t o r



### ~Q-..:::lo J e ff D aw so n , Ac tin g D eputy Di v i s io n Direc tor H

ealth Effects Di vis io n (7509 P ) Office of P est icide Programs S usan B artow , C h e mical R ev iew Manage r Cathryn Britton , Team Leader Kevin Coste ll o, Acti ng Br anch Chief Risk Management a nd Impl em e ntati o n Bra nch IV P

es ti c ide Re- Eva lu ation Divi s io n (7508P) Office of P es ti c ide Prog ra ms At tac h e d is th e Hea lth Effec ts Divis ion 's ( H ED) hum a n h ea lth ri s k assess m e nt sco pin g d oc um e nt for s tr yc hnin e to s upp ort Re g i s tr ation Review.

P

age 1 

### of 11Exec uti ve S ummary T h e H ea lth Eff e c t s Di v i s ion ( H E D ) s tr yc hnine R eg i s trati o n R ev iew Tea m ha s eva lu a t e d th e da ta b ase a n d th e m os t rece nt human h ea lth ri s k assess me nt fo r s tr yc hni ne. H E O pe r f orm e d thi s e valuati o n in ord e r t o d e t e rmin e th e sco p e o f w o rk n ecessar y t o s upp o rt th e ex i s tin g reg i s tr a ti o n s durin g reg i s trati o n r e vi e w. Th e primary so urc e o f inf o rm a ti o n for thi s e valuation wa s th e m os t r ece nt H E D c h a pte r o f th e R e reg i s trati o n Eli g ib i li ty D e ci s io n ( RED ) d oc um e nt 

### (J
. S mith ; 1/ 22 / 1 996). S trychnin e i s · a ro d e nti c id e th a t was fir s t reg i s t e re d fo r no n - f ood u ses in th e U
. S. in 1947. S tryc hnin e i s a t e r pe n e ind o le a lk a lo i d w hi c h ac t s a s a co n v ul s ant by a n tago ni z in g g lyc in e rece pt o r s. Gl y cin e i s an imp o rt a nt inhibit o r y tra n s mitt e r t o m o to r n e ur o n s. S tr yc hnin e i s c urre ntl y f o rmulat e d as a 0
. 5 % g rain-ba se d bait or g ranu le appli e d und e rg round t o c ontrol gop h e r s in p as tu res , r an ge l a nd , c r o pland , ir ri gati o n ditch es/ ca nal s , and h o m e law n s. B ase d o n la b e l d esc ript io n s , a ppli cati o n can b e b y s p oo n s , c up s, hand pro b e di spe n se r s , m ec h a ni ca l b u rrow build e r s , a nd hand d i s p e rs a l. S ome but n o t all pr o du c t s ar e res trict ed-u se . The r e i s al s o a s p ec i a l loca l n ee d (S LN) re g i s tration in Nev ada f o r contro l o f y ell ow -b e lli e d m a rm o ts a nd g r o und s quirre l s in a dditi o n to pocke t go ph e r s th a t i s a 3
. 2 % pas t e res tri c ted u se pr o du c t ( R U P )
. T he toxi co lo g y dat a ba se for s tr ychnin e i s c o n s id e re d adequ a t e fo r ri s k a ss essm e nt e xcept f o r the req uire m e nt o f an inh a la ti o n t ox ic it y s tud y as d e t e rmin e d b y l-I E D 's H aza rd a nd Sc ie n ce P o li cy Co un c il (TXR # 0057269; J
. L es hin). H oweve r , labe l c han ges ( i .e. , u se of res pir a t o r s fo r some sce nari os), i f a g ree d to b y th e reg i s trant , c ould a ll e viate th e n ee d for th e s tud y as d es crib e d in th e HASPO C d oc um e nt . HED 's HASPO C a l so det e rmin ed th a t a r e peat d ose d e rm a l to xicit y s tud y, p re natal deve lo pm e nt a l s tudi es (rat an d rab bit ) , a 2

- gen e r a ti o n re pr o du c ti o n s tu dy , an a c ut e n e ur o t ox ic it y batte ry , a s ub c hro ni c n e ur o t oxi ci ty batt ery, a n immun o t ox ic it y s tud y , a nd th e ge noto x ic it y batt e ry o f s tudi es a re not re quire d for s tr ychnin e (TXR # 00 5 7 2 69; 

### J. Les hin )
. In the 1 996 RED ( J. S mith ; 1 / 2211996) , du e t o th e non- foo d u s e pr o fil e , P o int s o fD e p a rtures ( POD s) and t ox ic it y e ndp o int s of co n ce rn we re n o t es ta b li s h e d ; h oweve r , HED w ill r e a ssess th e n eed fo r POD s and t ox ici ty e ndpoint s of co nc e rn durin g R eg i s trat ion R ev i e w . Stry c hnin e i s a p o t e nt ac ute t ox ic ant res ultin g in clini c al s ig n s re la t e d to n e urot ox ic it y an d morta li t y f o ll ow in g ac ut e o r a l , oc ular , a n d inhal a ti o n ex p os ures. 

### In co ntr as t , n o t ox ic i ty i s o b se rve d fo ll owin g acute d e rmal expo s ure t o v e r y hi g h do ses o f s tryc hnin e, like l y du e t o lo w d e rmal a b so rpti o n . Limit e d d ata i s ava il a bl e for r e p eat do se ex p os ure to s tryc hnin e du e t o it s po t e n t ac ute t ox ic it y. S try chn in e i s a non-f oo d u se ro d e nticid e and it s limit e d and ta rge t e d und e r g round u ses do n o t w arrant es tim a ti o n o f co n ce ntra ti o n s in d rinkin g wa t er; th e re f o r e , a di etary ex p os ure assess me nt i s n o t a p p li cab le. S try chnin e produ c ts ar e int e nd e d f o r u se in und e rg ro und burro w s o n h o m e la wn s , but r e quire ce rt a in c lo thin g a n d/o r p e r so n a l protec ti ve eq uipm e nt ( PP E) to be wo rn (lo n g s leeve s hirt , pants , g l oves , a n d fo r so m e pr o du c t s , a res pir a t o r). A res id e nti a l h a ndl e r assess m e nt w ill no t b e c ond u c t e d for Re g i s tration R ev i e w b e cau se standa rd H E D a ss umption s f o r re s id e ntiaUcon s um e r a ppli cat o r s p ec ifi c assess m e nt s , s uch as wear in g s h o rt s and a t- s hirt w i th o ut PP E like c h e mi ca lPag e 2 of 

### 11

### resistant g lo ves or respirators , would represent non-complianc e with curre nt stryc hnin e products. If products containing strychnine are meant to be marketed towards and performed by consumers/ homeowners , H E D recommends that label requirements for clothin g and / or PPE be reeva lu ated or separate cons um er - specific labels be developed and a separate residential handler assessment using standard HED assumptions be conducted to eva lu ate suc h products. A postapplication residential exposure assessment w ill also not be conduc ted due to its underground use. Additiona ll y, neither exposure via drift o r vo latili zation i s expected due to its formulation as solids/ pastes and it s underground use. During Registration Review , HED will cond uct a quantitative risk assessmen t for occupational handler inh alation exposure. The occupational exposure database is adequate to support Registration Review of strychn in e with the use of surrogate datasets for non-standard app li cation scenarios. Furthermore, an objective of Registration Review will be to reconcile handler work attire and PPE w ith corresponding end -u se acute toxicity-based requireme nt s and potential requirements based on the Registration Rev iew occupational handler ri sk assess m ent due to the varying requirements for wo rk clothing and PPE on product labels. No post-application exposure assessment w ill be conducted as contact with residues fo llo w in g applicat i on is not antic ipated based on the product formulations and underground use. Introduction 

### Strychnine is a rodenticide that was first registered for non-food uses in the U.S
. in 1 947
. Strychn in e is a terpene indole alka loid which acts as a conv ul sant by antagon i zing g l yci ne receptors. Glycine i s an important inhibitory transmitter to motor neurons. Strychnine was a l so used as a therapeutic agent in humans between the 16th and mid-20th century but no longer ha s any medical uses. The Health Effects Division (HED) evaluated the most recen t HED chapter of the Reregistration Eligibi lit y Decision (RED) document (J. 

### Smi th ; 1/22 / 1 996) for strychnine in association wit h updates to it s toxicity, exposure, and u sage databases to determine i f s uffi cient data are ava ilabl e, and if further updates are needed , to suppo r t Registra tion Review. The structure and c hem ica l names can be found in the chem i ca l identity table in Attachment 1
. Hazard ldentificationrroxicology 

### While no mechanism of action stud ies were submitted for s trychnine, the mechanism for mammal ian toxicity is we ll known for this compou nd based on its previous medical uses and a significant body of lit erature. Please see the U.S. Department of Agr iculture (USDA) Forestry Services human health and ecological ri sk assessment for strychn in e (P
.R. Durkin, 20 1 0) for a comprehe n s ive li st of r efe rences for the proposed mechanism of action of strychn in e. The follow in g is a brief summary based on the inf ormat io n presented in that document. Strychnine acts as an antagonist fo r glycine r ecep tors, wh ich is a li gand

- ga ted ch l orid e channel in n euro n s. Glycine i s a neurotransmitter critical to the norma l function of the nervous system. When glyc in e binds to the g l ycine receptor on neurons it increas es the flow of chlorid e ions int o motor neurons which results in inhibition of motor neuron act ivity. In contrast , binding of strychnine to
P age 3 ofllchloride channels d oes not result in an i nc reased fl ow of c hl o ri de ion s a nd interferes wit h th e normal inhibitory f un c ti on of glyc in e. The n e t res u lt i s that s trychnin e leads to hyper exci tab il ity by p reve nting g lyc in e f ro m inhi b itin g th e act iv it y of th e m o tor n e ur o n s. At ve r y low doses , stryc hnin e ac t s as a s timul a n t o r p e rf o rm ance e nh a n cer, h oweve r at hi g h e r d oses thi s lead s to spast ic muscl e con tr ac ti o n s, re s ulting in deat h b y asp hyxiation. The toxicology database fo r s tryclmine consists o f o nl y the acute six pack s tudi es f o r the t ec hnical compound and its for mulations. However , ther e is a significant body o fliterature on th e toxicity of stryc hnine based on its medic a l u ses , acc id e ntal or s uicidal human poi so ning s, a nd experim e ntal stud ies in m a mmals
. T hi s body of li t e rature was recent ly r ev iewed and s ummarized as part of th e US D A Forestry Se rv ices human h ea lth a nd eco log ica l ri sk assess m ent for s tr yc hn ine (P.R. Durk in , 20 1 0) and th ese studi es were co n s id ered in th e h azard c h aracterizati o n of s tryc hnin e. HED 's H aza rd and Sc ience Polic y Co un c il ( H AS POC) determined that a repeat dose derma l to x ic ity s tud y, pre n atal d eve lop m e nt a l s tudi es ( rat and rabbit) , a 2

- ge n erat io n re production st ud y, a n ac ute n eurotoxicity batt e ry, a s ub c hro nic n e urotoxicity battery , a n immunotoxicit y s tud y , a nd the geno tox ici t y battery of studies are n o t required fo r strychni n e (TXR # 0057269; 

### J
. Leshin). Ho weve r , H E D ' s H ASPOC decided that an inh a lat io n study i s required unl ess the r egistra nt ag rees t o labe l chan ges ( i .e. , u se of respirat o r s for so m e sce n arios) deve lo ped and incorpor ated i nt o c urr e nt labels w hi c h wo uld reduce inhalation exp os ures t o a p oi nt w h ere th e mar g in s of ex posu re ( M OEs) ba se d o n the H ASPOC sc ree nin g c rit e ria wo uld n o lon ge r b e of conc e rn. T h e tox icolo gy dat abase for s tr yc hnin e i s co n s id ered adeq u ate for ri s k assess m ent , exce pt fo r a r eq uir e d inh a lat io n s tud y, ba se d o n th e s ig nificant bod y of lit e r a tur e ava ilabl e and th e acu t e s ix pack st udi es. T h e primar y toxicit y of s tr y chnine i s manife s t e d as ac ut e effects du e to th e potent toxicit y of th e c h e mical. T his includ ed potent acute toxicit y f o ll owi n g oral , ocu lar , and in h a latio n exposure. Th e primary effects obse rve d we re cl i nical s ign s co n s i ste n t wi th n e ur o to x ic effec t s (s uch as tremors ) o r m orta lit y. In co ntrast, s trychn in e do es not appear to be acute l y tox ic by the derma l ro ut e . No irritatio n , m o rta lit y , or s i gns o f toxic it y were observed in th e acu t e r abb it dermal le th a lit y s tud y with t ec hni ca l s tr yc hnine up t o a d ose of2000 mg/ kg. T hi s i s lik e ly due to a very low derma l ab so rpti o n of s tryc hnine. Whi le n o direc t m eas ure m e nt of th e d e nn a l absorpt i o n fo r s tryc hnin e i s ava il ab le , a d e rm a l absorpt io n va lu e of 0.25% ove r a n 8 ho ur p e ri od wi th a dermal l oad of 1 J..L g/cm 2 was es tim a t e d using th e Nationa l In s titute for Occupational Hea l th an d Safet y (N I OS H ) finite dose sk in pe rm eat i o n calcu l ato r ( http: //www . cdc.gov/ ni osh/ t o pi cs/ s ki n/ finite Sk inP e rmCalc.htm l ) wh ich predicts a chemical ' s dermal absorption based o n it s physica l chemistry para m eters . Th e re i s limit ed data o n th e repea t do se toxic it y of s tr yc hnin e due to the p ote nt ac ut e toxi c ity o b se rve d. For exa mpl e , o n e study in the li teratu re set o ut to determin e a m axima ll y to lerated d ose of s trychnin e in r a t s fo ll ow in g gavage d os in g (Se idl and Zb ind e n , 1 982). Co n s i ste nt with th e L D so va lues d e t e rmin ed in the g uid e lin e ac ut e l e thality s tud y, so me numb e r of the rat s in eac h sex died at th ese do ses s h owi n g tonic mu sc l e co ntractions and re s pirat o ry paral ys is. Th e a nima l s that s u rv i ved s ho wed inc reased mu sc le to ne or a s li g ht tre m or 1 0 t o 20 minutes following do s in g th a t reso l ve d wit hin 60 minut es.

P age 4 o f 11

### In 1 996 , 

### because of the seve r e ora l tox i ci ty o f this chemica l and the no n food use s t a tu s, ri sk assess m ent s were n ot conducted (J. 

### Smit h ; 1 / 22/ 1996). 

### Si nce l-I E D p lans to pe rform a qua nti tat ive occ up at ional inha lat io n expos ure assess m ent during Registration R eview , an inhalation endpoint will be chosen durin g Re g istration Rev iew. No other endpoints are anticip ated to be needed as there is n o ant ic ip ated expos ur e to c hildr en , there is no dietary ex po s ur e , and the co mbin ation of the es timat ed lo w d erma l absorption a nd th e lack of acute de t mal toxicity s upports that a quantitative dermal occ upati o na l dermal assessment is n ot needed. Th e acute tox ic ity profil e of s tr ych nin e is s ummari zed in Attachment 2. Co nclu s ions for H az ard Id e ntifi cat ion/Toxico l ogy The toxicity databa se is adequate for the purpose o f registration review , except for the lack o f an inhalati o n s tudy w hi c h is r equire d at thi s tim e. Durin g R eg is tration Rev iew , HED will se l ect an inhalation en dpo int for u se in occupatio na l ri s k assessments. R es idu e C h e mi s t ry a nd Di e t ary Ex p os ur e 

### Str ychnine i s a non-f oo d use rodenti cide and it s limite d and tar gete d undergr oun d u ses do not warrant es tim atio n of concentrations in drinking wa t er; the r e fore , a dietary exposure assess ment is not applicable. Co nclu s ion s for R es idue C hemistry and D ieta r y Exposure H

ED does no t anticipate cond ucting a dietary risk assessme n t duri ng R eg istration R ev iew . Res id e nti a l Ex p os u re 

### Stryc hnin e products a r e intended for use in underground burrows o n ho m e lawns , but require ce t1ain clothing and / or personal protective equipment ( PPE) to be worn (long s l eeve s hirt , pants , g loves , and , for so m e products , a respirator). A r eside nti a l hand l e r assessment will not be co ndu c t ed for Regi s tration Revi ew because standard H ED assumptions for r es identi a l / consumer applicato r sp ec ifi c assessments, s uch as wearing sh orts and at
- shirt without PPE lik e c he micalr es istant gloves or r esp irators , wou l d r e pr ese nt non-compl iance with current s tr y chnine pr o duct s. An exposure assess m e nt for occ up at io na l handlers/ app licators assuming co mplianc e w ith labe l r eq uir e ment s for work clothing and/or PPE wi ll be conducted. If product s containing str yc h n in e a r

e meant to be mark eted towards and pe rf o r med by co n sum ers/homeowners , HED recommend s that lab el r equi r eme nt s for clothing and / or PP E be r eevaluated or se parate consume r- s pecific labels be d eve l oped an d a sepa r ate r esidentia l handl e r assessment using standard l-I ED a s sump ti o ns (co nsume r applicators wi ll wea r ju st s h o rts a nd a s hort
- s l eeve s hirt) be co ndu c t e d t o eva l uate suc h products. Additi o na ll y , a re s ide ntial post -ap pl ication expos ure assessme nt will n ot be conducted as contact with o r ingestion of residues is not expected due to the underground nature of the app licati o ns. S

pray Drift and Volatilization



### Page 5 of 11

### Becau se strychnine i s app li ed as eithe r a granule/ bait or paste v ia hand or h a nd- o p erate d eq uipment in und e rg round burr ows, ne ith e r expo s ur e via drift o r vo la tili zat io n i s expected
. Co n c lu s io n s for Res idential Exposure T h e re a r e s tr yc hnin e products fo r us e in re s id e nti a l se ttin gs in underg round go pher burrows of h ome lawns. For R eg i s tra tion R eview , h owever, res id en tial handler assessme nts wi ll not be co ndu cted ba s ed o n lab e l re quir e m e nt s fo r clot hin g and PPE n or will a po s t- ap pli cation exposure assess m e nt be conducted due to its underground u se. Additio n a ll y, ne ither ex po s ure v ia drift o r vo lati li zatio n i s expected due to it s formulation as so lid s / pastes a nd it s unde rg round use. Occupation al Exposure S try ch nin e i s c urre ntl y for mul ated as a 0.5% g rain-bas ed bait or g r a n ule and can be a ppli e d by profe ss ion al app li cators to control gophe rs in pas tures , ra n ge la nd , cropland , and h o me lawns. Ba sed on l abe l descriptions, application can be b y spoo n s, cups , hand probe dispensers , m echa ni cal burrow build e rs, and h and disp e r sal. So me but n o t all products are r es trict ed- u se. Produ cts s t a t e that ap proximat e ly 1 

### t ab les p oo n of produ c t s hould be placed in each burrow / tunnel a nd that 1- 3 lb s of product wi ll tr eat an ac re dep e ndin g o n th e numb er of b urro ws (at 0.5% s tr yc hnin e that is approx im a tely 0.0 15 lb ai/acre). T here i s also a s p ee iall oca l n ee d (S LN ) registr atio n in Nevada for control o f yellow-be lli e d marm ots a nd gro und squ irrel s in addit ion to pocket gophe rs that i s a 3.2% paste restricted use product (R U P). Th e labe l for th e SLN paste product in s tructs u se rs to mix the p aste in a la rge plast ic ba g at a rate of7 fluid ounces of paste per p ou nd of a l falfa o r cu t vegetables (e.g. , carrots or pars nip), o r approximatel y 0.0 15 lb s trychnin e p e r p o und of bai t (7 

### fl oz prod / lb veg bai t * 1 g a l/ 128 fl oz 

## * 8 .34 lb/ ga l *3.2 % ai). A teaspoon of b ait i s th en placed in the burr ows by h and o r with a lon g- h andl e d s poon. 

### Occup ation a l Han dle rs Th e m os t rece nt H E D ri s k assessme nt in 19 96 did not id e n ti fy s hort- , interm e diat e- , or lo n g t e rm / c hr o ni c toxicologi ca l endpoint s for stryc hnin e and did not quantitatively ass ess ri sk for occupati o n a l handl e r exposu re. H oweve r , th e evaluation c oncluded th at there we re ri sks of co nc e rn for applic a tors a nd outlined potential miti gation opt ions in c ludin g limitin g access to and u se of s tryc hnine e nd-u se products to professional appli cato r s who ca n b e r eq uir ed per so nal protec tive e quipm e nt , includin g res pir ato rs , as we ll as res tricti o n s on powder and paste fonnulations. As a re s ult. th e 1 996 RED r eq uired certain PP E r e quir e ment s bas ed on th e product fonnu lation. C urre ntl y, req uireme nt s for wo rk cl o thin g a nd PP E vary o n pr oduct labels. So m e o nl y require base lin e wo rk attire ( lo n g s l eeve s hirt , long pant s , s h oes/ soc ks) w ith co tton g lo ves , w hil e others req uir e chemical/water- res istant g loves and dust/m ist filtering r espirators . An 

### objecti ve of Re g i s tration Re view wi ll be to reconcile h and le r work attire and PPE w ith co rre s p o ndin g e nduse acute toxic i ty-based req uire me nt s a nd potential requ ir e men ts based on th e R eg istra ti o n R

ev iew occupatio n al h andler ri s k assess m e nt.
P age 6 of 

### 11Based on the currently registered uses, Regi stratio n Review w ill include an inhalation occupat ional handl er ex po s ure assessment o nly; based o n the es timated low dermal absorpt ion (0.25% at a derma l loading of 

### 1 f.1g/cm 2 ) , a dermal exposure assessment w ill not be conduc ted
. Exposures are ant i c ipated to be s h ort-te rm on ly; intem1ed iate- t erm a nd c hronic expos ures a r e n ot expected. The occupational h andler assessment should be conducted for the following sce nari os: • Loadin g/ applying granul es (0.0 15 lb a i /acre) 

### o By hand 

### o With a spoo n or cup 

### o With a mechanical bu rrow b uild er 

### o With a hand probe dispenser • Mixing/ load in g/ apply in g paste s ( 0.0 1 5 lb a i / lb vegetables) Some of these sce nario s arc not sta ndard app li catio n scenarios therefore s urro ga te datasets w ill be used to complete the r isk asse s sment. For mixing/loading and applying via mechanical burrow bu ild e r , datase ts for assessme nt of tr ac tor-drawn granu le spreade r s are recommended. Assessment of application via hand probe d ispenser d oes not need to be quantified as the a pplication is done by the p robe under gro und

- exposu r e during loading of th e probe is adequate l y covered by assessment of hand d i s per sa l or spoo n or cup applicatio n exposure. For assess m ent of expos ure during mixi n g of th e paste fo rmu lat io n w ith vegetable baits , datasets for mixing/loading liquid formulations is recommended. 

### Occupational Post-application Exposure Due to its formulation as a solid or pa s te and i ts targeted und ergrou nd use, no inhal a tion expos ure o r de rma l co nta ct w ith re s idu es are expec ted fo ll ow i ng app li catio n s. Th erefo r e , when applicable, restr icted entry int ervals (REis) wi ll default to the stand a rd active i ngredie n t ac u te tox ic ity-b ase d r eq uir e m e nt s. Conclus ions for Occupationa l Exposure Through use of su rr ogate datasets, th e occ up a tion a l exposure database i s adequate to suppo rt Regi s trati on Review of strychn i ne. The most recent occupational assessments are not reflec ti ve of cu rr ent policies and data , so th ese assessments should be updated. Occupationa l hand ler exposure will be quantitatively assessed for the sce n arios as ou tlin ed above. No po s t-applicati o n expos ure assessmen t wi ll be conducted.


### Ri s k Assessme nt Updates, Data Deficienci es, and Label Revisions The following study i s required to s upp ort Registration Revi ew of s trychnine: • An inJ1 a lat ion study to address occ up at ion a l expos ure by this rout e or label cha n ges ( i .e. , use of respirators fo r so m e scenarios) , th at could alleviate th e need for the s tudy. Due to th e high ac ut e toxicity of the compound , a g uid e lin e 90 -day stud y i s not recommended. Instead , a subacute inh alation s tud y that i s we ll desig n ed to iden tify th e key n e urotoxic Page 7 of 11effects (cl ini ca l s i g n s) a t the criti ca l time of peak effec t , in ad diti o n t o th e t y pical eva l uat ions of a g uide li n e inha lat io n study , i s rec o mm e nded.
E PA anticip a te s conducti n g th e followin g risk assessment update s dur in g R eg i s tration R ev iew : Toxicology: • HED w ill chose an inhalation endpoi nt for u se in occ up at iona l expos ur e as s ess m e nt s. Dietary Exposure: • No n e. Occ up ation al / R es id entia l Exposure: • H E D anticipates conducting a quantitative occ up at io na l exposure assessment for i nh a lat ion exposure for the reg i stere d u ses.
Publi c H ea lth a nd Pes tici d e E pid e miol ogy D a t a For thi s eval uati o n , th e Agency consulted the OPP In c id e n t D a ta System ( ID S) , the Ce nt e r s for Disease Co ntr o l and Prev e nti on/National In s titute for O cc upat iona l Safety and Hea l th (C D C/N I OSH) Se nt i nel Eve nt Notification System for Occupation a l Ri sk -P es ticid es (SENSO R ) , and the Nat io n a l Pe stici d e I nformati on Center (N PI C) d a t a ba ses for pesticide incid e nt d a ta on th e active ingr e dient s trychnin e ( D4 30 17 6 ; S. R eco re ; 11 / 17/ 20 15 ) between the p e riod of 1998

- 20 11 , w h ich i s fo ll ow in g implementation of th e miti gatio n reco mm e nd ed in th e R E D. Based o n th e low frequency and seve rit y of th e in c ident s re ported in I D S and SENSOR-Pesticides, there d oes not a pp ear to be a co n cern that warrants furt h er in v e stigation. Strychillne is n ot i ncluded in th e Agricultura l He a lth S tud y (A H S) ; th e r e fore , that st ud y d oes n o t provide info r mati on for thi s document. T ol e ran ce 

### Assess m e nt a nd In te rn at io n a l Harm o ni z ati o n Ther e are n o tol e ran ces fo r s tryc hnin e as it i s a non-f ood u se rode nti c id e. E nvir o nm e nta l Ju s ti ce P o te nti a l areas of environmental ju s ti ce co ncerns , t o th e ex tent po ss ib le, will be considered in R eg i strati o n R ev iew , in accordance w ith U
. S. Exec uti ve Order 1 2898 , "Federal Act io n s to Address Environmen ta l Ju stice in Minority P op ulati o n s a nd L ow - I nco m e P op ul a ti o n s," (http: // w \ Yw .ar c hi ves . gov / fc d c r a l- rcg i stc r h:xcc u ti ve-o rdc r s / pdfi'l2898
. ptlf). As a part of every pesticide ri sk as s essme nt , OPP conside r s a large varie ty of conswner subgro up s according t o well-establ i s hed pro ce dures. In l ine with OPP poli cy , H E D es tim a tes ri sks to pesticide exposures that are based on act i vities in and around the h o m e that in vo lve p esticid e use in a res id e ntia l sett in g . Whenever a ppropriate , th ese non-di e tar y ex po s ure s are calculated b ased on hom e u se of pesticide products a nd associated risks for adult applicators and fo r toddlers , youths , an d ad ult s en t e r ing o r playing o n trea ted areas post-app l ica tio n are ev aluated
. Pag e 8 of 

### 11

### C umulative Risk Assessments Un li ke other pesticides for which EPA has followed a cu mul ative risk approach based on a co mmon mechanism of toxicity , EPA has not mad e a com m o n m ec h a ni sm of toxicity finding as t o strychnine and any other substances and strychnine does n ot appear t o produce a toxic metabolite produced by oth e r substances. For informati o n regarding E PA 's efforts to determine which ch e micals h ave a co mmon m ec hani sm of tox ic ity and to eva luate the cumu lative effects of s uch chemicals , see the polic y stateme nt s released by EPA ' s Office of P es ti cide Pr ograms co n ce rnin g common m ec h a ni sm determination s and procedures for cum ul at in g effects from substa nce s found to have a commo n mechanism o n EPA 's webs ite at http: // www.epa.gov/ pe s ticides/ c umul at ive /
. 

### Reference s Author Barco de Date Titl e J. S mith NA 1/22/ 1996 Stryc hnine : HED chapter of the reregistration e li g ibility decision document, Case #3133 J. Lc s h in T XR#0057269 NA Strychnine: Summary of Hazard and Science P olicy Co uncil ( H ASPOC) Meeting of Dec e mber 3, 2015: R ecomme nd ation on the R equirement for a non-food use database of toxicity st udi es P. Durkin NA 3/27/ 20 10 S trychnine Hum a n H ealth and Eco l ogica l Ri sk Assess ment Fina l Report S. Recore D4 30 176 1 1 / 1 7/ 20 15 Stryc hnin e: Tier I (Scoping) R ev iew of Human I nc id ents and Epidemiology Se idl and Arc h ive s o f 1982 Subchronic Oral Toxicity of stry chnine in Rats Zbinden T ox ico logy. 5 1 : 26 7- 2 7 1 

### Attachments A ttachment I. Chemical Id ent ity T able for Strychnine A ttachm ent 2. S u mmary of Ac ut e Tox ic ity Profile fo r Stryc hnin e fo r Use in Human H ea l th Ri sk Assess m ents

Page 9 of J1Att a c hm e nt 1. 

### S tr yc hnin e C hemi ca l Ide ntity.

T a b le Al S try c hnin e No me ncl a tur e. Ch emical st r uctu r e 

# fN H

..

# ' ··
..



### ~ 

### H 

# " I 

# ' H 

# ' N H 0 

### H 0 Comm o n name S t rychnine Company experimen tal None na m e IUPAC name s tr yc hnidin-1 0-one CAS name st ryc hni di n- 1 0-o n e CAS reg is try number 57

- 24-9



### P age 10 

### of 11Attachment 2. Summary of Acute To x ic it y Pr ofi le for Stryclm in e for Use in Human Health Ri sk Assessme nt s.

Table A3.1. Acute Tox i city Profile - Strychn i ne technica l Guideline Study Type MRID(s) Results Toxicity 

### No. Category 870.1100 Acu te oral

- rat 40908901 LD so I 41210701 M 

## = 6.4 m g!kg F 

## = 2.2 m g/ kg 870.1200 Acute dermal

- rabbit 40908902 LD so > 2000 III 412 1 0702 m g/kg No s igns o f toxicity observed. 870.1300 Acu t e inh a lat ion - rat Study not submitted 870.2400 Acute eye irritation

- rabbit 4090894 Irritation an d 

### I 41210704 mortality 870.2500 Acute dermal irritati on- 40908903 No irritation, 

### IV rabbit 410 I 0703 mortality , or signs of toxicity observed 870.2600 Skin sensitization- gu in ea Not a sens iti zer NA pig 44684601

Pa ge 11 of 11