### EPA REGISTRATION DIVISION **- COMPANY NOTICE OF FILING FOR PESTICIDE**  **PETITION Docket ID Number: EPA**  **- HQ**  **- OPP**  **- 2012**  **- 0010**  **EPA Registration Division contact: Sidney Jackson, (**  **703 )**  **30 5**  **- 761**  **0 I**  **nterregional R**  **esearch Project Number 4**  **(IR -**  **4) Pesticide Petition**  **Nu mber**  **: PP**  **- 1E7957**  21 U.S.C. 346 EPA has received a pesticide petition , **PP -**  **1E7957** from **IR -**  **4 Project Headquarters, Rutgers, The State University of NJ**  **, 500 College Road East, Suite 201 W,**  **Princeton, NJ 08540** proposing, pursuant to section 408(d) of the Fed eral Food, Drug, and Cosmetic Act (FFDCA), 21 U.S.C. 346a(d), to amend 40 CFR part 180. 463 by establishing a tolerance for residues of **the herbicide q uinclorac, 3,7**  **- dichloro**  **- 8**  **- quinolinecarboxylic acid**  **, including its metabolites and degradates,**  **in or on the raw agricultural commodity**  **rhubarb at**  **0.4 parts per million (ppm) and**  **Berry, low growing, except strawberry, subgroup 13 -**  **07H at**  **1.1 ppm.**  EPA has determined that the petition contains data or information regarding the elements set forth in section 408(d)( 2) of the FFDCA; however, EPA has not full y evaluated the sufficiency of the submitted data at this time or whether the data support granting of the petition. Additional data may be needed before EPA rules on the petition. A. Residue Chemistry 1. Plan t metabolism. **The qualitative nature of the residues in quinclorac in plants is well understood.**  **Based on a nature of the residue studies in wheat and supported by similar**  **studies in rice and sorghum, the residue of concern from quinclorac use consists on ly of the**  **parent compound.**

2. Analytical method. **As per the document “**  **Quinclorac. Human Health Risk Assessment for the Proposed Food/Feed Use of the Herbicide (Associated with Section 18**  **Registration) on Cranberries in Massachusetts ”**  **, docket ID number EP**  **A -**  **HQ -**  **OPP -**  **2009 -**  **0528: Adequate analytical**  **m ethods,**  **utilizing gas chro**  **m atography**  **with electron**  **capture detection**  **( G**  **C/ECD), are**  **available to**  **enforce the**  **tolerance expression**  **on plant (BASF**  **Method A8902; MRID# 41063537) and ani**  **m al**  **(BASF M e**  **thod 26**  **8 /1;**  **MRID# 41 063536)**  **com m**  **odities. Both m**  **ethods have**  **undergone successful**  **Agency m**  **ethod validation**  **trials, and**  **have been sub**  **m itted**  **to FDA for publication**  **in PAM II as t**  **h e**  **tolerance enforce**  **m ent**  **m ethods.**  **The li**  **m it**  **of quantitation (LOQ) for both**  **m ethods**  **is 0.05 ppm**  **in all**  **m atrices.**  **Furthermore, FDA has reported**  **that quinclorac**  **can be**  **d e**  **tected by Multiresidue**  **P rotocol**  **B.** 3. Magnitude of residues. **Field trials were carried out in order to determine the magnitude of residues in rhubarb and cranberry. Four rhubarb field tr**  **ials were conducted**

### in rhubarb growing regions of the United States. Five cranberry field trials were conducted

**in cranberry growing regions of the United States. Cranberry is the representative crop for**  **th e Berry, low growing, except strawberry, subgrou**  **p 13 -**  **07H. Field trials were carried out using the maximum number of applications, the maximum label rate and shortest pre**  **- harvest**  **interval (PHI).** B. Toxicological Profile **As per the document Quinclorac. “**  **Human Health Risk Assessment for the Proposed Foo**  **d/Feed Use of the Herbicide (Associated with Section 18 Registration) on Cranberries in Massachusetts**  **” , docket ID number EPA**  **- HQ**  **- OPP**  **- 2009**  **- 0528:**  **Ha z**  **ard Characteri z**  **ation and Ass e**  **ssment** For detailed infor

m ation, please refer to th e hum an health risk assess m ent conducted f or quinclorac’s use on i m

ported barley (D325790; M.A. Doherty; 13 September 2007). The database adequatel y characterizes quinclorac as having low acute oral, der m al and inhalation toxicity

. It is Toxicity Category IV for acute inhalation to xicity , and Toxicity Category III for acute oral toxicity , acute der m al toxicity , pri m ary der

m al irritation, and pri m ary eye irritation. It is a der m al sensitizer. The database for quinclorac is considered i n co m p lete at th is ti m e. ARIA/RD and HED have det ermined that a 90
- day inhalation t o xicity study (OPPTS Guid e line 870.3465) is required to assess potential toxicity from inhalation exp o sures during spray applications. This is a new require m ent since the previous Section 3 risk assess m ent (D238399; M.J. N elson; 15 Dece m ber 1998). An oral toxicity endpoint is available for assess m ent of inhalation risk pen ding receipt of the inhalation study

. A waiver request has been submitted by the registrant. Additionall y , rece nt chan ges to 40CFR §158 m ake acute and subchronic neuroto x icity testing (OPPTS Guideline 870.6200), and imm unotoxicity testing (OPPTS Guideline 870.7800) required for pesticide registration. The available data for quinclorac do not show the potential for immunotoxic nor neurotoxic effects

. T herefore, an additional 10X database uncertainty factor (UF) has not been warranted. The 870.3465 inhalation, 870.6200 neurotoxicity and 870.7800 immunotoxicity studies were also a requirement in the document “ **Quinclorac. Human Health Risk Assessment for the Proposed**  **Food/Feed Use of the Herbicide (Associated with Section 18 Registration) on Cranberries in Massachusetts”, docket ID number EPA**  **- HQ**  **- OPP**  **- 2009**  **- 0528.**  An immunotoxicity study was submitted in 2010 (MRID 48346101). The registrant, BASF, plans to c onduct acute and 90 day neurotoxicity

studies in 2012. The registrant, BASF has submitted a waiver request for the inhalation study

. The m ode of action for m ammalian toxicity from quinclorac, an herbicide structurall y related to the py ridinoxy and pico linic acid herbicides, has n o t been characterized at this ti m e. Following single or m ultiple o ral do s es, quin c lora c was well

- a bsorbed and excr e ted ra

p idly , but was very poorly m etabolized. Inrat m etaboli s m studies, m ost of an admi nistered dose was excrete d unchanged, and al m ost all (91

- 98% b y day 5 post
- dosing) in the urine. Sign i f icant biliary excretion (up to 15%)

### was observed. Tissue retention was low in both sexes, b ut slightly higher in fe m ales. Less than 0.45% of the dose was retained in tissues, with the highest levels in thy roid, bone m arrow, and adrenal gl ands. Two mi nor m etabolites have been isolated but not identified. Subchronic or chronic oral exposure to quinclorac caused decreased body weights in all species tested (rat, dog, mouse). In the dog, kidney , blood and liver were target organs following chronic exposure. Hydropic degeneration of the kidney , and increased kidney weight were observed at relativel y high doses (about 500 mg/kg/day). Liver weights were also increased, although no mi cros copic findings or clinical changes were s e en. Several red blood cell param eters were decreased. In the rat, quinclorac affected th e pancreas in m ales only following chronic administration, with an i n crease in the incidence of pancr e atic acinar cell hyperpl asia at relativel y high doses (500 m g/kg/day). Subchronic exposure at appro x imately li mit doses (1000 mg/kg/day) caused increased water intake in both sexes; in m a les, increased serum glutamic oxaloacetic transami nase (SGOT), serum glut am ic py ruvic transami nase (SGPT), and focal chronic int er stiti a l nephritis were o bs erved, as w e ll. Inte r stitial nephritis was also observed in parental females in the reproductive toxicity study

. Although th e m ouse was the m o s t sensitive species in th ese stu dies (based on the chronic toxicity / carcin o genicity study), a target organ was not identified in mi ce; decreased body

weight was the only effect reported at doses exceeding the li mit dose. No toxicity was observed in a 21
- day der m al toxicity study in the rabbit, which tes ted up to the li mit dose. There are no data on the effects of quinclorac via i nhalation exposure. Studies on the effects of quinclorac on devel op m ent do not show increased susceptibility of offspring. In the rabbit, increased rates of early resorption and post - implantation loss, decreased live fetuses, and reduced f etal body w e ight were observed at doses that caused signi f i cant m aternal to x i city , in c luding m ortality

. No develop m ent a l effects were rep orted in the rat even at m aternall y toxic doses. Howeve r, in the rat reproductive toxicity study , offspring effects at m aternall y toxic doses included dec r eased pup weight, delay s in pinna unfolding and eye opening, and a possible m arginal reduction in pup viability

. There were no effects on reproductive param eters. Evidence for carcinogenicity of quinclorac is considered equivocal, and insufficient for clas s i ficati o n. A m arginal increa s e in the incid e nce of pancreatic aci n ar adeno m as was seen in m ale rats. No tum ors w e re observed in fe m ale rats, or in mi ce. Q uinclorac was negative in a co m plete battery of genotoxicity studies. For all exposure scenarios a UF of 100X was used (10X for intraspecies variation, and 10X for interspecies extrapolation). An acute dietary reference dose (RfD) of 2.0 m g/kg/day was se lected for f e m ales age 13 to 49, based on the develo p m ental no - observed

- a dverse

- effect level (NOAEL) in rabbits (200 mg/kg/day) for effects (increa s ed resorption and post - i m plantation loss, d ecreased li v e fetuses and fetal weight) at 600 mg/kg/day that are presum ed to occur following a single exposure. There was no appropriate endpoint representing potential toxicity from a single exposure for the general population, including children and adults. A chronic dietary RfD of 0.38 mg/kg/day was deter mined for all populations, including children

### and f

e m ales age 13 to 49, based on the N OAEL in mi ce (37.5 m g/kg/day) for decreases in body weight gain observed at 150 mg/kg/day

. NOA E Ls f r o m other species (rat and dog) were significantl y higher than the m ouse. Assess m ent of incidental oral exposure of young children to quinclorac is required because there are resi d e ntial uses of quincl o rac. T he point of d eparture ( P OD) selected for short

- and inter m e diate

- term e xposure (both residential and occupational) was the rabb it m aternal toxicity NOAEL of 70 mg/kg/day

. This POD is based on reduced m aternal body weight gain and food consum ption (and increased water con s um ption) at 200 mg/kg/day

. Other studies assessing effects from dietary exposures of 3 to 6 months duration gav e higher NOA E Ls. No effects were observed in a 21
- day der m al toxicity study in the rabbit at doses up to the li mit dose (1000 m g/kg/day). A dermal assess m e nt is therefore not required because an endpoint has not been identified. Inhalation studies are no t available for quinclorac. An oral endpoint (the rabbit m aternal toxicity NOAEL of 70 mg/kg/day based on body w e i ght decreases at 200 m g/kg/day) for short

- and inter m e diate

- term e xposure was selected, with an assum ption of 100% inhalation absorption relat ive to oral absorpti o n. Lo ng - term inhalation endpoints w ere not selected because long

- term exposure is not anticipated und e r current use patterns. Quinclorac is classified as "Group D, not classifiable as to carcinogenicity in hum ans" under the A gency ’s 1 986 cancer classification gui d elines. Available carcinogenicity studies indicate th at there was equivocal evidence of an increase in the incidence of pancreatic acinar cell adenomas in th e m ale rat, b ut no tre at

m ent - a s sociated increases in tumors were obse rved in fe m ale rats, or in mi ce. A quantification of cancer risk is n o t warranted b ecause the chronic RfD of 0.38 mg/kg/day is approxi m ately 1200
- fold lower than the dose (487 mg/kg/day) that induced the benign p ancreatic tumors. Thus, the chron i c RfD will a d equatel y account for all chronic effects (including the observed adeno m as) likely to result from exposure to quinclorac. Additionall y, if quinclorac were evaluated under the current 2005 Guidelines for Carcinogen Risk Assessment , quinclorac would be cla ssified as "not likely to be carcinogenic to hum ans" since only benign tum ors were seen in only one sex, and in one species. There is no qualitative evidence of increased pre - and/or postnatal susceptibility and, due to the m arginal nature of the effects observed on pup viability in the m ultigeneration reproductive toxicity study , no residual uncertainti e s with regard to pre n atal toxicity following in utero exposures of rats or rabbits to quinclorac (develop m ental toxicity studies), and pre - and/or postnat al exposure of rats to quinclorac (reproductive toxicity study). Further m ore, the doses selected for use in risk assess m ent from th e rabbit develop m ental study are lower than the NOAEL from the m

ultigeneration study , and pro t ective of the pup effects note d therein. Therefore, it is recomm ended that the FQPA saf e ty factor (SF) be reduced from 10X t o 1X, and that no additional safety factors beyo nd the standard 100X are needed. A summ ary of the LOCs for risk assess m ent is li s ted in Ta b le 1 (below). The toxi c o logical doses and hazard end

p oints selected for use in dietary and non - occupational hum an health risk assess m ents are summ arized in Tab l e 2 (below), while those for use in occupational hum an health

### risk a s ses s m ents are summarized in Table 3 (below). The acute toxicity profile and the

subchronic/chronic toxicity profile for quinclorac are provided in Appendix A.

**TABLE 1 Sum**  **m a**  **ry of Levels of**  **Concern (LO C**  **s) for Quinclo**  **r ac**  **Risk Ass**  **e ss**  **m ent.**  **Route of**  **E x**  **posure Sho**  **r t**  **- Term**  **( 1**  **- 3**  **0 D**  **ay s**  **) Interm**  **e diat**  **e -**  **Term (**  **1 -**  **6 M**  **o n**  **t h**  **s )**  **Long -**  **Term (>6**  **M o**  **n t**  **h s**  **) Occupat**  **i onal**  **( W**  **orker) Exposure** Dermal 1 0 0 1 0 0 NA * I nha lati on 1 0 0 1 0 0 NA

**Residenti a**  **l E**  **x p**  **o sure**  Dermal 1 0 0 1 0 0 NA I nha lati on 1 0 0 1 0 0 NA Inc i dental Oral 1 0 0 1 0 0 NA * NA = N o t A

pp licab le. 

### LOCs of 100 are used f

or all short

- and inter

m e diate

- term e xposure scenarios, based on 10X factors for intra

- and interspecies varia b ility , and reduction of the FQPA SF to 1X. Long
term exposure is not anticipat ed under current use patterns. **FQ PA Safety Factor**  **C onsiderations**  ARIA/RD and HED recomm end that the FQPA SF be reduced to 1X based on the f ollowing c o nsideratio n s: 1. The available toxicity data do not s h ow evidence of increased susceptibility in offspring, 2. T here is no evidence of neurotoxicity from exposure to quinclorac, 3. T he to x i col o gy databa s e f or quinclo rac is su ff

i ci e ntly co m

plete f or purposes of this risk a s s e ss m ent (the Agency is r e questing ad d itio n al data to m ore appropriately evaluate risk, per recent changes to 40CFR§158), and 4. E sti m ates for dietary intake (f ood + water) are based on conservative assum ptions, resulting in high

- end exposure esti m ates. For food, the exposure esti m ates assum e tolerance

- level residues, and 100% crop treated (%CT); for drinking water, m odeled values were used. By using these conse rvative assess m ents, acute and c hronic expo s ures and ris k s will not be underestimated. The residential exp osure assess m ent utilizes residential SOPs to assess incidental oral ingestion by toddlers. The residential S O Ps are based on reasonable worst - case as sum ptions, and will not likely underesti m ate exposure or risk. These assess m e nts are unlikely to underesti m ate the potential exposure to infants and children resulting from the use of quinclorac. Based on these data, the quinclorac risk assess m ent team co ncluded that no additional SF is needed to account for exposure considerations.**TABLE 2 Summ**  **a ry of**  **Quincl o**  **r a**  **c T**  **ox i**  **c o**  **lo g**  **i c**  **a l**  **D o**  **ses a**  **n d Endp**  **o i**  **nts f o**  **r Use in Diet a**  **r y**  **a n**  **d N o**  **n**   ** Occu** **p a**  **t i**  **o n**  **al Hu**  **m a**  **n Health Risk**  **Asses s**  **ments. Exposure**  **Scenar i**  **o Point of** 

**Departure Unce**  **r tai**  **n ty**  **a nd** 

**FQPA S**  **a f** 

**e ty**  **Factors R** **f**

**D, P**  **A D,**  **LOC for**  **Risk Assessm**  **e nt**  **Stu d**  **y a**  **n d**  **T o**  **x i**  **co lo**  **g i**  **cal E**  **f f**  **ects**
Ac ute dietary (g e n eral US p op ulati o n) Not app li cable. An en dp o i nt f o r acute dietary expo s ure of th e ge n e ral p op ulati o n was n o t selected because th e r e wa s no av ailable endpoint th at was appropr i ate for this sc e n ar i o ( e ffects observ e d in the avail able studies are presumed to re quire mo re than o n e exp o s ur e ). Ac ute dietary (fe males 13
- 4 9 ) N O AE L =

2 0 0 mg/kg/ day UF A = 10X UF H

= 10X FQ P A SF

= 1X Ac ute RfD = 2 .0

mg/kg/ day aP AD = 2
. 0 mg/kg/ day De v e l op me ntal stu dy in rab b its.

LO AEL = 60 0 mg/kg/day , b a s ed on increas e d e arly

re s o rptions an d pos t i m p lantati o n loss, d ecreased l i v e fetu ses, decreas e d fetal weight. T h ese fetal effects are pre s umed to occur a fter a single dose. C hr onic dietary (all p op ulati on s ) N O AE L =

3 7 .5 mg/kg/ day UF A = 10X UF H

= 10X FQ P A SF

= 1X C hr onic RfD =

0
. 38 mg/kg/ day cPAD = 0.38 mg/kg/ day Dietary carc i nog e nicity study in mi ce.

LO AEL = 15 0 mg/kg/day , b a s ed on decreas e d body weight.

Inc i dent al oral ( s h o rt and i nterme d iate

term ) N O AE L = 70

mg/kg/ day UF A = 10X UF H

= 10X FQ P A SF

= 1X Resi d e ntial LOC

f o r MO E = 10 0 De v e l op me ntal stu dy in rab b its. LO AEL =

20 0 mg/kg/day , b a s ed on decreas e d maternal body we ight ga i n an d f oo d c on s um p ti on ( and i n cr ea sed wat er co n s um p ti on)

. Dermal (all durati o ns) Not applicable. A d e rmal en dpo int wa s not s e l ected bec au s e an ap propriate endpoint wa s not

avai l ab l e (n o d ermal t ox i ci ty at l i mi t dose o f 1 0 0 0 mg/kg/d ay i n a 2 1
- d ay dermal t ox i ci ty s tu dy). Inh alati o n (s h o rt - an d i nterme d iate

term ) N O AE L = 70

mg/kg/ day UF A = 10X UF H

= 10X FQ P A SF

= 1X Resi d e ntial LOC

f o r MO E = 10 0 (Same as for incidental oral.) Also

s u pp o rte d b y s ub chr o ni c an d c hro nic dietary data on mice. Inh alati o n absor

p tion rate = 1 0 0%. Inh alati o n (l o n g - term) N o t ap p licab le. L o n g - term i nh alati o n exp o s ure is n o t antici p ated un d e r c urrent use scenarios. Cancer (oral, derma l , i nh alatio n) C lass i fication ( last assess ment wa s p e r f ormed un d e r th e 19 8 6 A ge n cy Cancer Assessm e n t Gu id elin es ) wa s “not cl assifi ab le as to car ci n og e nicity to humans,” based o n an e qui vocal i n crease in p an c reatic aci n ar cell a d en o mas in th e ma le rat o n ly, an d no i n creases in fe male rats no r in mice. Ther ef ore, c ancer ri s k from exp o s ure to qui n cl o r ac is not o f c onc e rn . AR IA/RD an d H E D do n o t anticip ate th at a ree v al u ation un d e r th e 20 0 5 re v i sed gui d e l i n es wo ul d sig n ificantly alter th e b a sic conc lu s io n s o f th e ex i s tin g d e c i s i on. Po i nt o f Dep art

ure ( P O D ) = a data po int or e s t i mat ed po i nt der ived f r om o b se rv e d d o se - r es p onse data, whi c h is us e d to mark th e b e gi nni n g of extr apolati o n to d e termi n e risk a s sociated with l o w e r env iro nme ntally rele v ant human e xp o s ur es. UF = Unc e rtainty Factor. U F A = e xtrap o lati o n fr o m ani ma l to human (interspecie s ). U F H = p o te ntial variati o n i n se n siti v ity amo n g me m

b ers o f th e human po pulation (i ntras p ecies). U F DB = d atab a se un c ertai nty factor to account for the absence of key data ( s uch as th e lack of a c ritical study)

. F Q PA S F = F Q P A Safety Factor. NOAE L = No Obs e rved Adverse E ffect Level. L OAE L = Lo we st Obs e rv ed Adv e rse Effect Le v el. PAD = Pop ulati o n A d j u sted Dose (a = ac ute, c = chronic). RfD = Re fer e nce Dose. MOE = Margin Of Exposure. LO C = Level Of Conc e rn.**TABLE 3 Summ**  **a ry of**  **Quincl o**  **r a**  **c T**  **ox i**  **c o**  **lo g**  **i c**  **a l**  **D o**  **ses a**  **n d Endp**  **o ints f**  **o r Use in Occupation**  **a l**  **Hu m**  **a n**  **Health Risk Asses**  **s me**  **nts. Exposure**  **Scenar i**  **o Point of** 

**Departure Unce**  **r tai**  **n ty** 

**Factors LOC**  **for Ri**  **s k** 

**Assessm e**  **nt Stu**  **d y**  **a n**  **d T**  **o x**  **i co**  **lo g**  **i cal**  **E f**  **f ects**  Dermal (all duratio n s ) Not applicable. A d e rmal en dpo int wa s not s e l ected bec au s e an ap propriate endpoint wa s not

avai l ab l e (n o d ermal t ox i ci ty at l i mi t dose o f 1 0 0 0 mg/kg/d ay i n a 2 1
- d ay dermal t ox i ci ty s tu dy). I nhalati on (s h o rt - an d i nterme d iate

term ) N O AE L = 70

mg/kg/ day UF A = 10X

UF H = 10X Occu

p atio n al LOC f o r MO E = 10 0 De v e l op me ntal stu dy in rab b its. LO AE L =

20 0 mg/kg/day , b a s ed on decreas e d maternal body we ight ga i n an d f oo d c on s um p ti on ( and i n cr ea sed wat er co n sum p ti on) . A l so s u

pp o rte d by s u bchro n ic an d chr o nic d ietary d ata on mice. Inh alati o n absor

p tion rate = 1 0 0%. Cancer (oral, derma l , i nh alatio n) C l ass i fication ( last assess ment wa s p e r f ormed un d e r th e 19 8 6 A ge n cy Cancer Assessm e n t Gu id elin es ) wa s “n ot c l ass i f

iab l e as to car c in og e ni c ity t o humans,” based o n an e qui vocal increase i n p ancreatic acinar c ell adeno mas in the male rat on ly, and n o increases i n fe male rats n o r in mice. Ther e f

o re, canc e r ri s k f

r om exp o s ure to qui ncl o rac is n o t of c onc ern. AR I A/RD an d HED do n o t anticip ate t h at a re e v aluatio n un d e r th e 20 0 5 r e v i sed gui d el i n es woul d s i gni f i c antl y a lt er th e bas i c co nc lu s i ons o f t h e ex i s tin g dec is i o n . Po i nt o f Dep art

ure ( P O D ) = a data po int or e s t i mat ed po i nt der ived f r om o b se rv e d d o se - r es p onse data, whi c h is us e d to mark th e b e gi nni n g of extr apolati o n to d e termi n e risk a s sociated with l o w e r env iro nme ntally rele v ant human e xp o s ur es. UF = Unc e rta inty Factor. U F A = e xtrap o lati o n fr o m ani ma l to human (interspecie s ). UF H = p o te ntial v ariation in se n siti v ity amon g me m b ers o f th e human po pulation (i ntras p ecies). N O AE L = No Obs erv ed Adv erse E ffect Le v el. L OAE L = L o we st O b s e rv ed A dv e rse E f f ect Level. M OE = M arg in Of Expo s ure. L OC = L e vel Of C o ncern. 

### C. Aggregate Exposure **As per the document “**  **Quinclorac. Human Health Risk Assessment for the Proposed Food/Feed Use of the Herbicide (Associated with Section 18 Registration) on Cranberries in**  **Massachusett s**  **” , docket ID number EPA**  **- HQ**  **- OPP**  **- 2009**  **- 0528:**  **Aggregate Exposure and Risk** In acc o rdan ce with th e F Q PA, AR IA/RD m ust consider and aggregate p esticide exposures and risks from three m ajor sources: food, drinking water, and residential exposures. In an aggregate assess m ent, exposures from die t ary and residential sources are added together, and co m pared to quantitative esti m ates of hazard (such as a N OAEL), or the risks the m selves can be aggregated. Wh e n aggregating exposures and risks from various sources, ARIA/RD considers both the route and duration of exposure. In esti m ating aggregate risk, ARIA/RD has combined high

- end residue esti m ates for food and drinking water with high

- end esti m ates of post

- application resident ial exposure. Use of these values results in highly conservative, h ealth

- protective esti m ates of aggregate exposure and risk. The components of acute and chronic (lon g - ter m) aggregate exposure are dietary exposure from food and drinking water. Since the di etary exposure esti m ates incorporate pote ntial residues in drinking water directl y in the assessment, the acute and long

- term aggregate exposure and risk esti m ates are e quivale nt to the acute and chronic di etary esti m ates, respecti v el y.

### Acute Aggregate Risk

Acute aggregate exposure consists of a cute exposure to quinclorac residues in food and drinking water. Acute a g gregate risks are, th e r efore, equivalent to th e ac ute dietary ri s k esti m ates provided in Table 5 (above), and are below ARIA/RD’s and HED’s LOC. **Short -**  **and Intermediate -**  **Term Aggregat e Risk**  Short

- and inter

m ediate

- term exposure m ay occur as a result of quinclorac use in residential settings. As noted above, the post - a pplication exposure scenari o s from the use on turf represent w orst - case esti m ates of exposure and ri s k. To evaluate sho rt - and inter m ediate

- term aggregate risk, ARIA/RD has included the po s t - application co m bined MOE (from Table 7, above) with the MOE derived from chronic di etary exposure esti m ates (to reflect background dietary exposure). The behaviors as s ociated with pos t - ap p lication exposures are applicable to toddlers, so only those age groups have been assessed for short

- and inter m ediate

- term aggregate risk. Aggregate MOEs are all greater than 100 (see Table 8, below), and are therefore not of concern to ARIA/RD and HED. **TABLE 8 Sho**  **r t**  **- and Interm**  **ediat e**  **- T**  **e rm Aggregate**  **Risk Esti ma**  **tes for E**  **x posure of Toddlers to**  **Qu i**  **nc l**  **o r**  **ac. Popu**  **l at**  **i o**  **n [Y**  **e a**  **rs o**  **f A**  **g e]**  **Exposure Sc**  **e nario** 

**LOC f**  **o r**  **A g**  **gr e**  **g a**  **te Risk**  **1 MOE** 

**(F o**  **o d**  **+ Water)**  **2 MOE** 

**(Incident a**  **l Oral)**  **3 MOE** 

**(Der m**  **al) MOE** 

**(In h**  **al a**  **t io**  **n )**  **A g**  **gr e**  **g a**  **te**

**MOE 4**  I n fants [ < 1] 1 0 0 6 , 7 0 0 5 , 0 0 0 N A **5** NA 2 , 9 0 0 C h il dr e n [ 1
- 2] 1 0 0 5 , 8 0 0 5 , 0 0 0 NA NA 2 , 7 0 0 C h il dr e n [ 3
- 5] 1 0 0 6 , 8 0 0 5 , 0 0 0 NA NA 2 , 9 0 0 1. See T ab l e 1, a

b ov e . 2. M O E f oo d = [ 7 0 mg/kg/day ( s h o rt - an d i ntermediate

- te r m N OAE L) ÷ ( c hro nic dietary e xp o s ure f rom Table 6) ]
. All MOEs h ave b een trun cated to 2 sign ificant f i gures. 3. See T ab l e 7, a

b ov e . 4. Aggr e g ate MOE = 1 ÷ [(1/MOE f ood + water) + (1/M OE incidental oral ) ]
. 5
. NA = N o t A

pp licab le. 

### Long **- Term**  **Aggregate Risk**  Long
- term residential exposure t o quinclorac (longer than 6 m onths) is not considered likel y to occur with current and proposed use patterns. Ergo, long

- term aggregate exposure consists of chronic exposure to quinclorac r e sidues in food and drinking water. Long
- term aggregate risks are, therefore, e quivalent to the chronic dietary ri sk esti m ates provided in Table 6 (above), and are below ARIA/RD’s and HED’s LOC. **Aggregate Cancer Risk** Quinclorac has been classified as “not classifiable as to carcinogenicity to hum ans.” Therefore, aggregat e can cer risk from quinclorac is not of concern. **Cumulative Exposure and Risk** Unlike other pesticides f

or which EPA has followed a cum u l ative risk approach based on a common m echani s m of toxicity , EPA has not m ade a common m echanism of toxicity finding as to quinclorac and an y other substances. Al s o, quinclorac does not app e ar to produce a toxic

### m etabolite p roduced by other sub s tances. For th e purposes o f this toleran ce action, th erefore, EPA has not assum ed that quinclorac has a co mm on m echanism of toxici ty with other substances. For infor m ation regarding EPA’s efforts to d eter mine which che micals have a common m e chanism of t oxicity , and to evalu ate the cum ulative effects of such che micals, see the policy s t ate m ents relea s ed by EPA’s Office of Pesticide P rogram s (OPP) concerning common m echani s m deter

minations, and procedures for c um ulating e f fects from s ubstances found to have a common m echanism on EPA’s website at http://www.epa.gov/pes t icides/cum ul ative/

. **Occupational Exposure and Risk** A Section 18 e m ergency exe m ption has been requested by MDAR for the use of QuinStar 4L (LF; 40% ai) to provide early season protection of cranberries against injury from dodder in MA. The product will be applied at the rate of 8 ounces of product per acre (oz/A), which equates to 0.24 lb ai/A per application. U p to 2 applications m ay be m ade per ye ar, for a m ax i m um yearl y use rate of 16 oz/A (0.48 lb ai/A). Applications are to be m ade aft e r the winter flood has been withdrawn, and after dodder e m erge n ce. Application to cranberry bogs m ay not be m ade via aircraft. **Primary H** 

**a ndlers**  Based upon the proposed use pattern, AR IA/RD believes the most highly exposed occupational pesticide handlers will be: 1. Mixer/loaders using open - pour loa ding of liquid fo rm ulation, 2. Applicators using open - cab ground

- boom sprayers, 3. Applicators using high

- pressure hand

- wand sprayers, and 4. P ersons (che mi gators) preparing irrigation sy ste m s through which the m aterial is applied. An esti m ate of exposure and risk is not presented for che migators. ARIA/RD believes that the esti m ate of exposure and risk to mi xer/loaders using open - pour loading of liquid is adequate to describe the exposur e and risk to che migators. Che migators do not “load” or “ mix” in the ty pical sense of persons supporting ground or aerial applications. C he migators ty picall y arrange for “siphon” tubes to lead from mi nibulk containers of concentrate into the irrigation stream . Pumping and m etering equip m ent draws the concentrate from th e container into the irrigation sy ste m . Thus, it is expected that che mi gatorexposure is less than for individuals involved in “open
- pouring” of pesticide from a c ontainer i nto a spray pre - mi x tank. ARIA/RD believes occupational handler s w i ll m ost likely be exposed to short

- term duration exposures (1 to 30 day s). T he toxicol o gical endpoints are the sam e for both short

- term duration and inter m ediate

- term duration exposures. Therefore, the esti m ates of risk for short

- term exposure are a dequate to describe inter m edi a te - term exposures in the event that these mi ght occur. Mo s t applicatio n s are expected to be m ade by private (grower) applicators. Private (gro wer) applic at ors ar e p er mitted to pe rf

orm all f unction s ; they m ay mi x, load and app ly the m aterial. The HED ExpoSAC standard procedure di rects that although the sam e individual may perform a ll those t a s k s, they shall be assessed separately

. By separating the two job f unctio n s, ARIA/RD and HED deter mine the m o st a

pp rop ri at e l e v e l s of pers onal protective equip m ent (PPE) for each aspect of the job with out requ iring an applicat o r to wear unnecessary

### PPE that mi ght be required for a mi xer/loader (for exam ple, che mical

- resistant gloves m ay onl y be neces s ary during th e p ouring of a liquid for m ul atio n). These exposure scenari o s are outlined in the Pesticide Handler Exposure Database (PHED) Su rrogate Exposure Guide (of August 1998). Most exposure scenarios for hand

- held equip m ent (such as hand wands, backpack spr aye rs, and push

- ty pe granu lar s p re ader s ) are assessed as a co m bined job fun c tion. W ith these ty pes of hand held operations, all handling activities are assum ed to be conducted by the sam e individual. No ch e mical

- specific data were available with which to assess potential exposure of pesti cide handlers. The esti m ates of exposure of pesticide handlers are based upon surrogate study data available in the PHED (V ersion 1.1 ) , 1998. The product label directs applicators and other handlers to wear long

- sleeved shirt, long pants, shoes plus sock s, and che mical

- resistant gloves (Category A, such as butyl rubber, natural rubber, neoprene rubber, or nitrile rubber of at lea s t 14 mils thickn e ss). The toxic o l o gical factors used in th is assess m ent are taken fro m the m ost recent hum an health risk asses s m ent for qu i nclorac (D325790; M.A. Doherty ; 13 September 2007). No derm al toxicological endpoints were ide ntified in that risk assess m ent. Inhalation studies are not available for quinclorac. An oral endpoint (the rabbit m aternal toxicity N OAEL of 70 m g/kg/day based on body weight decreases at 200 mg/kg/day) for short

- and inter m e diate

- term e xposure was selected, with an assum ption of 100% inh a lation absorption relative to oral absorption. Since the toxic effects were m ater n al (not fetal effects), a 70
- kg body weight is used to calculate exposure/dose. As m ent ioned above, since no inhalation absorption data are available, toxicity via the inhalation route is considered equivalent to the e s ti m ated toxicity via the oral route of exposure. See Table 9 (belo w) for a summ ary of esti m ated exposures and risks to occupational pesticide handlers. **TABLE 9 Summ**  **a ry of Inh**  **a l**  **a t**  **i o**  **n E**  **x p**  **o sure**  **a n**  **d Risk**  **Estim a**  **tes for E x**  **p o**  **sure of Occup**  **a t**  **i o**  **n a**  **l Handlers to**  **Quinclora c**  **. Unit**  **E x**  **p o**  **su r**  **e 1**  **(m g**  **a i/lb H**  **a ndled)**  **Use R**  **a te**  **2 (lb**  **ai/A) U**  **nits Treated**  **3**

**(A/ d**  **a y**  **) Av**  **g .**  **D a**  **ily E**  **x p**  **o sure**  **4**

**(m g**  **a i/k** **g bw** **/ d**  **a y**  **) MOE**  **5 Mixer/L**  **o ader**  **(Liqui d**  **; O**  **p e**  **n P**  **o ur)**  0
. 0 01 2 0
. 24 80 0
. 0 00 3 2 6 2 1 5 ,0 00 **Applicator ( G**  **rou n**  **d -**  **B oo**  **m ;**  **Open Cab)**  0
. 0 00 74 0
. 24 80 0
. 0 00 2 3 5 0 ,0 00 **Applicat o**  **r (Hi g**  **h -**  **Pressure H**  **a ndw**  **a nd)**  0
. 0 7 9 0
. 24 40 0
. 0 10 7 6 , 5 0 0 1. Unit e xp o sures ar e take n f r om Su rroga te Exp o sure Gu id e, E s timates of Worker Expo s u re , f r o m PH E D (Version 1

. 1 ) , o f Au gu st 1 9 9 8
. 2 . Use rate is taken fr o m th e MDAR Section 1 8 requ est, an d pr o du ct labeli ng . 3 . Units treated are take n from Stan d a r d Valu es f

o r D a ily Acres Tre a ted in A gric u ltu re, Exp oS AC SOP N

u m b er 9.1 , re v i sed 5 July 2 00 0
. T h e Exp o SAC SOP in d i cates that a hi gh

- press ur e h an dw an d sprayer will li kely use 1 00 0 gall o n s o f s p ray per day . T h e p ro duct l abel s ug g ests s p ray s be applie d in 1 0 to 40 GPA. ARI A/RD assumes an s p r ay

vo lume of 2 5 G P A. T h er e f o r e, [ (1 0 0 0 g a llons/ d ay) ÷ (2 5 GP A)] = 4 0 A/day . 4. Av e rage da i ly

exp o s ure (ADE) = [ ( unit e xp o s ur e ) x ( us e rate) x ( units treated)] ÷ (70 kg bo dy we i g ht)

. 5. M OE = Marg in Of E xp o s ure = N O AEL ÷ ADE. NOAEL = 70 mg/kg bw/day.

### An MOE of 100 is adequate to protect oc c upational pesticide handle r s from exposures to

quinclorac. The esti m ated MOEs are all m ore than 100; therefore, th e proposed use does not exceed ARIA/RD’s and HED’s LOC. **Second ary Handlers**  It is possible for agricultural workers to have post - application exposure to pesticide residues during the course of typic a l agric u ltural acti v ities. H ED, in conj unction with the Agricultura l Re
- entry T a sk Force ( ARTF), has identified a number of post

- application agricultural acti v ities that m ay occur, and which m ay result in post - application exposures to pesticide residues. HED has also id e nti f

ied tran sf er coe ff ici e nts (TCs) r elative to the various activities, which express the am ount of foliar contact over time during each of the activities identified. In this case, since no derm al toxicol o gical POD for quinclora c is i d enti f i e d, an assess m ent of post

application e xposure is not necessary . Post
- a pplication inhal ation exposure is believed to be negligible. i. Food and Drinking W

ater
. **As p er the document**  **, “**  **Quinclorac. Human Health Risk Assessment for the Proposed Food/Feed Use of the Herbicide (Associated with Section 18 Registration) on Cranberries in**  **Massachusetts ”**  **, docket ID number EPA -**  **HQ -**  **OPP -**  **2009 -**  **0528:** For detailed infor

m ation, please refer to the dietary exposure assess m ent me m orandum (D363872; W.T. Drew; 2 June 2009). Acute and chronic aggregate dietary ( f ood and drinking water) exposure and risk assess m ents were conducted using the D ietary E xposure Evaluation Model software with the Food Commodity Intake Database (DEE M
- FCIDTM), Version 2.03, which uses food consumption data from the US Departm ent of Agriculture’s Continuing Survey s of Food Intakes by Individu als (CSFII), collected fro m 1994 to 1996, and 1998. These anal ys es were perfor m ed to support the Section 18 reque st for quinclorac use on cranberri es in MA. All registered, pending, and proposed uses of quinclorac, as of the date of this m e m or andum , are included in these a s ses s m ents. Per m anent tolerances have been established for qui n clorac (40CFR §180.463[a]) in l ive s tock an d cere a l grai n commodities. The ROC, f or both toleran ce en f

orce m ent and risk assess m ent, is the parent co m

pound, quinclorac. Both the acute and chronic assess m e nts are highl y conservative, and assum e 100%CT, along with tolerance

- lev e l residues f or a ll agricultural commodities. Default proces s i ng factors from DEEM 7.81 were used (for dried beef, and cranb e rry j u ice) in the analy ses. R e sidues of quinclora c in livestock co mm odities (s u ch as m eat, milk and eggs) are not likely to be affected by

the n ewl y requested use, as there are no significant livestock feed ite m s derived from cranberries. The quinclorac drinking water residue used in these dietary risk assess m ents was provided by EFED (D363581; Y. Donovan; 5 May 2009), and incorporated directl y i nto the dietary assess m ents. W ater residues were inc o rporated in DEEM
- FCID via entry into the food categ o ries

### “water, direct, all so urce s ” and “water, indirect, all sources.” T he esti m ated drinking water

concentration (E D W C) in groundwater is 0 .019 ppm for both acute and chronic scenarios. The acute an d chronic s urface water EDWCs are 0.077 and 0.070 pp m , respectively

. In order to be m ore conservative, the acute surface water E D WC of 0.077 ppm was also used in the chronic anal ys is. Because the proposed use on cranberries involves flooding (for which the PRZM and EXAMS models are not curre ntly param eterize d), the surface water EDWCs were as s essed using a m odified Tier I Provisional Cranberry Model , which is a provisional refine m ent of the Tier I Rice Model, Version 1.0 (8 May

2007). These E D WCs are b a sed on quinclorac concentrations in tailwater from cranberry bogs that drain into adjacent surface water bodies. The EDWC in groundwater was obtained via exposure m odeling whi ch utilized the Screening Concentrat ion in Ground W ater (SCI

GRO W) m odel. These m odels, and their descriptions, are available at the EPA intern e t website via the web li nk, http://www.epa.gov/oppefed1/m o dels/water /

. No surface or ground water m onitoring data were available f

or quinclorac. Based on these highl y conservative assum ption s , the ac ute dietary risk esti m ate at the 95 th 

### percentile of exposure is less th an 1% of the acute population

- a d justed dose (aPAD) for f

e m ales age 13 to 49, the only population subgroup for whi c h an acute endpoint was selected (see Table 5, below). **TABLE 5 Summ**  **a ry of**  **Acute Diet a**  **r y E**  **x p**  **o sure**  **and Risk Estim ates**  **f o**  **r Quinc l**  **o r**  **a c**  **. Popu**  **l at**  **i o**  **n S**  **u bg**  **r o**  **up [Y**  **e a**  **rs o**  **f A**  **g e]**  **DEEM Ac**  **u t**  **e Die**  **t ary**  **A na**  **l y**  **sis (**  **9 5**  **th Perc**  **e ntile)**  **a P**  **A D**  **( m**  **g /**  **k g** **/d a**  **y) Exposure E**  **s t**  **i mate**  **(m g** **/k g** **/d a**  **y )**  **% aPAD**  Gen e ral US P o pulati o n NA * NA NA All I n f ants [< 1] Childr e n [ 1
- 2] Childr e n [ 3
- 5] Childr e n [ 6
- 12 ] Y o uth s [1 3
- 1 9] A dult s [2 0
- 4 9 ] A dult s [5 0 +] **Fem a**  **les [**  **13 -**  **4 9**  **] 2**  **. 0**  **0 .**  **0 12**  **6 0**  **2 <1**  ***** NA = N o t A

pp licab le. An ap pr o p ri ate a c ute e ndpo int was n o t i d e ntifi e d f o r th e se p op ulation s ub gro up s . 

### Chronic dietary risk esti m ates are less than or equal to 3% of the chronic population

- adjusted dose (cPAD) for all population subgroups ( s ee Table 6, b elow). Children 1 to 2 years of age are the most highly

- exposed subgroup, utili z ing 3% of the cPAD, while the general US population utilizes 2% of the cPAD. Generally , the Agency is concerned when risk esti m ates exceed 10 0 % of the PAD; therefore, all acut e an d chronic di etary risk esti m ates are b elow ARIA/RD’s and HED’s LOC.**TABLE 6 Summ**  **a ry of**  **Chr o**  **nic Dietary**  **E x**  **p o**  **sure and**  **Risk Estim a**  **tes f o**  **r Quincl**  **o r**  **a c.**  **Popu l**  **at i**  **o n**  **S u**  **bg r**  **o u**  **p** ***** **[Y e**  **a rs**  **o f**  **A g**  **e] D**  **EE M Ch**  **r o**  **ni c**  **D i**  **e t**  **ary An**  **a l** **ys i**  **s cPAD (m**  **g/kg /**  **day) Exposure E**  **s t**  **i mate**  **(m g** **/k g** **/d a**  **y )**  **% cPAD**  Gen e ral US P opul atio n 0
. 38 0
. 0 05 5 9 6 2 A l l I n f ant s [ < 1] 0
. 0 10 4 12 3 **Ch ildre**  **n [**  **1 -**  **2 ]**  **0 .**  **0 12**  **1 13**  **3** C h il dr e n [ 3
- 5] 0
. 0 10 3 4 2 3 C h il dr e n [ 6
- 12] 0
. 0 06 7 31 2 Y o uth [1 3
- 19] 0
. 0 04 4 6 7 1 A dults [2 0
- 4 9] 0
. 0 05 1 4 5 1 A dults [5 0+] 0
. 0 04 4 1 9 1 Fe ma les [13

- 49] 0
. 0 04 5 04 1 ***** Valu es f

o r the p o p ulation sub gr o up with t h e h ig h est risk are in **b o**  **l d**  ty p e . 

### Quinclorac has been classified by the C ancer A s sess m ent Review Committee (CARC) as “not classifiable as to carcinogenicity to hum an s .” Therefore, can cer risk is not of concern. D. Cumulative Effects **As per the document Quinclorac. “**  **Human Health Risk Assessment for the Proposed Food/Feed Use of the Herbicide (Associated with Section 18 Registration) on Cranberries in**  **Massachusetts ”**  **, docket ID number E PA**  **- HQ**  **- OPP**  **- 2009**  **- 0528:**  **Cumulative Exposure and Risk Unlike**  **other pesticides**  **f or which**  **EPA has followed a**  **cu m**  **u l**  **ative risk approach**  **based on a**  **common m**  **echani s**  **m of toxicity,**  **EPA has not m**  **ade a**  **common m**  **echanism of**  **toxicity finding**  **as to quinclorac**  **and any**  **oth er**  **substances. Al**  **s o, quinclorac**  **does not app**  **e ar**  **to produce**  **a toxic**  **m etabolite**  **p roduced**  **by other sub**  **s tances.**  **For t h**  **e purposes**  **o f**  **this tolera**  **n ce**  **action, t**  **h eref** 

**ore, EPA has not assu**  **m ed**  **that quinclorac**  **has a co**  **m m**  **on m**  **echanism of toxicity**  **with other substances.**  **Fo r infor**  **m ation**  **regarding EPA’s efforts**  **to d**  **eter m**  **ine which**  **che m** **icals have**  **a common**  **m e**  **chanism of**  **t oxicity,**  **and to**  **eval u**  **ate the**  **cu m**  **ulative effects**  **of such che m** **icals, see**  **the policy s**  **t ate**  **m ents**  **relea s**  **ed by EPA’s Office**  **of Pesticide Progra**  **m s**  **(OPP) concerning c**  **ommon m**  **echani s**  **m deter**  **m inations,**  **and procedures**  **for c u**  **m ulating**  **e f**  **fects from**  **s ubstances**  **found to have a**  **common m**  **echanism on EPA’s website**  **at http://www.epa.gov/pes**  **t icides/cu**  **m ulative** **/ .** 

### E. Safety Determination

**As per the document “**  **Quinclorac. Human Health Risk Assessment for the Proposed Food/Feed Use of the Herbicide (Associated with Section 18 Registration) on Cranberries in**  **Massachusetts ”**  **, docket ID number EPA -**  **HQ -**  **OPP -**  **2009 -**  **0528: FQ**  **PA Safety Factor C**  **onsiderations ARIA/RD**  **a nd**  **HED recom m**  **end that**  **the FQPA SF be**  **reduced to**  **1X based on the**  **f ollowing**  **c o**  **nsider a**  **tio n**  **s: 1.**  **T he**  **available toxicity**  **data do not**  **s h**  **ow evidence of increased**  **susceptibility in**  **offspring, 2.**  **T here**  **is no evidence**  **of neurotoxicity from**  **exposure to**  **quinclorac, 3.**  **T he**  **to x**  **i col**  **o gy**  **databa s**  **e f**  **or quinclo r**  **ac is**  **su ff** 

**i ci**  **e ntly**  **co m** **plete f** 

**or purposes of**  **this r**  **isk a**  **s s**  **e ss**  **m ent**  **(the Agency**  **is r**  **e questing**  **ad d**  **itio n**  **al data to**  **m ore**  **appropriately evaluate**  **risk, per recent**  **changes to**  **40CFR §158), and**  **4. E**  **sti m**  **ates for dietary**  **intake (food**  **+ water)**  **are based**  **on conservative assu**  **m ptions,**  **resulting in**  **high -**  **end exposure**  **esti m**  **ates. For food, the**  **exposure esti**  **m ates**  **assu m**  **e tolerance**  **- level**  **residues, a**  **nd 100% crop**  **treated (%CT);**  **for drinking water,**  **m odeled**  **values were**  **used. By using**  **these conservative**  **assess m**  **ents, acute and**  **c h**  **ronic expo**  **s ures and**  **ris k**  **s will not**  **be underestimated.**  **The residential**  **ex p**  **osure assess m**  **ent utilizes**  **residential SOPs to**  **assess incidental**  **oral ingestion**  **by toddlers.**  **The residential**  **S O**  **Ps are based**  **on reasonable worst**  **- case**  **assu m** **ptions, and**  **will not**  **likely underesti m**  **ate exposure**  **or risk. These assess**  **m e**  **nts are**  **unlikely to**  **underesti m**  **ate the**  **potential exposure to**  **infants and**  **children resulting**  **from the**  **use of quinclorac. Based**  **on these**  **data, the quinclo**  **rac risk assess**  **m ent**  **team concluded**  **that no additional**  **SF is needed**  **to account**  **for exposure**  **considerations. TABLE 2**  **Summ a**  **ry of Quincl**  **o r**  **a c**  **T ox**  **i c**  **o lo**  **g i**  **c a**  **l D**  **o ses**  **a n**  **d Endp o**  **i nts f**  **o r Use in Diet**  **a r** **y a**  **n d N**  **o n**  **** **Occu p**  **a t**  **i o**  **n al**  **Hu m**  **a n**  **Health Risk Asses**  **s ments.**  **Exposure S**  **cenar i**  **o Point of** 

**Departure Unce**  **r tai**  **n ty**  **a nd** 

**FQPA S**  **a f** 

**e ty**  **Factors R** **f**

**D, P**  **A D,**  **LOC for**  **Risk Assessm**  **e nt**  **Stu d**  **y a**  **n d**  **T o**  **x i**  **co lo**  **g i**  **cal E**  **f f**  **ects**
**Acute dietary**  **(g e**  **n eral**  **US p**  **op u**  **lati o**  **n) Not**  **ap p**  **li cable.**  **A n**  **en d**  **p o**  **i nt**  **f o**  **r acute dietary expo**  **s u**  **re of**  **t h**  **e ge**  **n e**  **ral p**  **op u**  **lati o**  **n was n o**  **t selected**  **because th e**  **r e**  **was no**  **a v**  **ailable endpoint**  **t h**  **a t was**  **a p**  **propr i**  **ate for this**  **sc e**  **n ar**  **i o**  **( e**  **ffects Acute**  **dietary (fe**  **m ales**  **13 -**  **4 9**  **) N**  **O AEL**  **=**

**2 0**  **0 m**  **g /**  **kg /**  **day UF**  **A =**  **10X UF H** 

**= 10**  **X FQ P**  **A SF =**  **1X Acute**  **R fD =**  **2 .0** 

**m g** **/ kg** **/ day**  **aP A** **D =**  **2 .**  **0 m**  **g /**  **kg /**  **day De**  **v e**  **l op**  **m e**  **n tal stu**  **d y in rab**  **b its.** 

**LO A**  **EL =**  **60 0**  **m g** **/k g/da**  **y ,**  **b a**  **s ed on**  **increas e**  **d e**  **a rly re**  **s o**  **rptions an**  **d pos**  **t****** **i m** **p la**  **n tati**  **o n**  **loss, d**  **ecreased l**  **i v**  **e fet**  **u ses,**  **decreas e**  **d fetal weight. T**  **h ese**  **fetal effects C**  **h r**  **onic dietary (all**  **p op**  **u lati**  **on s**  **) N**  **O AEL**  **=**

**3 7**  **.5 m**  **g /**  **kg /**  **day UF**  **A =**  **10X UF H** 

**= 10X FQ**  **P A**  **SF = 1X**  **C h**  **r onic**  **R fD =** 

**0 .**  **38 m**  **g /**  **kg /**  **day cPAD =**  **0.38 m**  **g /**  **kg /**  **day Dietary**  **carc i**  **nog e**  **nicity study**  **in m** **i ce.** 

**LO A**  **EL =**  **15 0**  **m g** **/k g/da**  **y ,**  **b a**  **s ed**  **on decreas**  **e d body weight.** 

**Inc i**  **den t**  **al oral (**  **s h**  **o rt**  **** **and i**  **n ter**  **m e**  **d iate**  **** **ter m** **) N**  **O AEL**  **= 70** 

**m g** **/ kg** **/ day**  **UF A**  **= 10X UF**  **H**

**= 10X FQ**  **P A**  **SF = 1X**  **Resi d**  **e n**  **tial LOC**

**f o**  **r MO**  **E =**  **10 0**  **De v**  **e l**  **op m**  **e n**  **tal stu d**  **y in rab b**  **its.**

**LO A**  **EL =**  **20 0**  **m g** **/k g/da**  **y ,**  **b a**  **s ed on**  **decreas e**  **d m**  **aternal body**  **weight ga i**  **n a**  **n d f**  **oo d**  **c on**  **s u**  **m p**  **ti on (**  **a nd**  **i n**  **cr ea**  **sed wa**  **t er**  **co n**  **s u**  **m p**  **ti on**  **) .**  **Der m**  **al (all d**  **u rati**  **o ns)**  **Not ap**  **plicable. A d e**  **r m**  **al en d**  **po i**  **nt w a**  **s not s**  **e l**  **ected bec**  **a u**  **s e an**  **ap propria**  **t e endpoint**  **was not** 

**avai l**  **ab l**  **e (n**  **o d**  **er m**  **al t**  **ox i**  **ci t** **y at**  **l i**  **m i**  **t dose o**  **f 1**  **0 0**  **0 m** **g /**  **kg /**  **d ay**  **i n**  **a 2**  **1 -**  **d ay**  **der m**  **al t**  **ox i**  **ci t** **y In**  **h alati**  **o n**  **(s h**  **o r**  **t -**  **a n**  **d i**  **n ter**  **m e**  **d iate**  **** **ter m** **) N**  **O AEL**  **= 70** 

**m g** **/ kg** **/ day**  **UF A**  **= 10X UF**  **H**

**= 10X FQ**  **P A**  **SF = 1X**  **Resi d**  **e n**  **tial LOC**

**f o**  **r MO**  **E =**  **10 0**  **(Sa m**  **e as for incidental oral.) Also** 

**s u**  **pp o**  **r te**  **d b**  **y s**  **ub ch**  **r o**  **n i**  **c a**  **n d**  **c h**  **ro n**  **ic dietary data**  **on m ice.**  **In h**  **alati o**  **n abso r**  **p tion rate =**  **1 0**  **0%. In**  **h alati**  **o n**  **(l o**  **n g**  **- ter**  **m )**  **N o**  **t ap p**  **lica b**  **le. L o**  **n g**  **- term**  **i nh**  **alati o**  **n exp o**  **s u**  **re is n o**  **t a n**  **tici p**  **ated u**  **n d**  **e r**  **c u**  **rrent use**  **scenarios. Cancer**  **(oral, der**  **m a**  **l ,**  **i nh**  **alatio n**  **) C**  **lass i**  **fication (**  **last assess m**  **ent was**  **p e**  **r f**  **or m**  **ed u**  **n d**  **e r**  **t h**  **e 19**  **8 6 A** **g e** **n cy Cancer Assessm**  **e n**  **t G** **u i**  **d eli**  **n e** **s ) w**  **a s “not classifi**  **a b**  **le as t**  **o ca**  **r ci**  **n og**  **e nicity to h**  **um ans,”**  **based o**  **n a**  **n e**  **qu i** **vocal i**  **n crease in**  **p a**  **n c**  **reatic aci n**  **ar cell a d**  **en o**  **m as in**  **t h**  **e m**  **a le rat o**  **n ly, a**  **n d no**  **i n**  **creases in fe m**  **ale rats**  **no r in**  **m ice. Ther**  **ef ore, c**  **a ncer ri**  **s k from**  **exp o**  **s u**  **re to**  **q u**  **i n**  **cl o**  **r ac**  **is not**  **o f**  **c onc**  **e r**  **n .**  **A R**  **IA/RD a n**  **d H E**  **D do**  **n o**  **t a n**  **tici p**  **ate t h**  **at a ree**  **v al**  **u ation**  **u n**  **d e**  **r t h**  **e 20 0**  **5 re v**  **i sed g**  **u i**  **d e**  **l i**  **n es**  **wo u**  **l d sig**  **n ifica**  **n tly alter**  **t h**  **e b**  **a sic conc**  **l u**  **s io**  **n s**  **o f**  **t h**  **e ex**  **i s**  **tin g**  **d e**  **c i**  **s i**  **on. Po**  **i n**  **t o**  **f Dep art**  **ure ( P**  **O D**  **) =**  **a data**  **po i**  **nt or**  **e s**  **t i**  **m a**  **t ed**  **po i**  **nt der**  **i ved**  **f r**  **om o**  **b se**  **r v**  **e d d**  **o se**  **- r**  **es p**  **onse data,**  **whi c**  **h is**  **us e**  **d to**  **m ark**  **t h**  **e b e**  **gi n**  **n i**  **n g of ext**  **r apolati**  **o n**  **t o d**  **e ter**  **m i**  **n e risk a**  **s sociated**  **with l**  **o w**  **e r en**  **v iro**  **n m**  **e n**  **tally rele v**  **ant hu**  **m an**  **e xp**  **o s**  **u r**  **es. UF =**  **Unc e**  **rtainty Factor. U F**  **A = e**  **x trap**  **o lati**  **o n fr**  **o m**  **a n**  **i m**  **a l**  **to hu m**  **an (in t**  **erspecie s**  **). U F**  **H = p**  **o t**  **e n**  **tial variati**  **o n**  **i n se**  **n siti** **v ity a**  **m o**  **n g**  **m e**  **m b**  **ers o**  **f t h**  **e hu**  **m an**  **po pu**  **lation (i n**  **tras p**  **ecies). U**  **F DB**  **= d**  **ata b**  **a se**  **un c**  **ertai n**  **ty factor**  **to accou**  **n t for the**  **absence of**  **key data (**  **s uch as**  **t h**  **e lack of a c**  **ritical st**  **ud y** **) .**  **F Q**  **PA S**  **F = F**  **Q P**  **A Safety Factor.**  **NOA E**  **L = No Obs**  **e rved Advers**  **e E**  **ffect Level.**  **L OA**  **E L =**  **Lowest Obs e**  **r v**  **ed Ad v**  **e rse Effect Le**  **v el.**  **PAD = Pop**  **u lati**  **o n A**  **d**

**j u**  **sted Dose (a**  **= a c**  **ute, c = ch**  **ronic). RfD = R**  **e fer**  **e nce**  **Dose. MOE = Margin Of**  **Exposure. LO**  **C = Level Of**  **Conc e**  **rn. TABLE 3**  **Summ a**  **ry of Quincl**  **o r**  **a c**  **T ox**  **i c**  **o lo**  **g i**  **c a**  **l D**  **o ses**  **a n**  **d Endp o**  **i nts f**  **o r Use in Occupation**  **a l**  **Hu m**  **a n**  **Health Risk Asses**  **s me**  **nts. Exposure**  **Scenar i**  **o Point of** 

**Departure Unce**  **r tai**  **n ty** 

**Factors LOC**  **for Ri**  **s k** 

**Assessm e**  **nt Stu**  **d y**  **a n**  **d T**  **o x**  **i co**  **lo g**  **i cal**  **E f**  **f ects**  **Der m**  **al (all d**  **u ratio**  **n s**  **) Not**  **ap plicable. A d**  **e r**  **m al en**  **d po**  **i nt w**  **a s not**  **s e**  **l ected**  **bec a**  **u s**  **e an**  **ap propria**  **t e endpoint**  **was**

**not I**  **n hala**  **ti on**  **(s h**  **o r**  **t -**  **a n**  **d i**  **n ter**  **m e**  **d iate**  **** **ter m** **) N**  **O AEL**  **= 70** 

**m g** **/ kg** **/ day**  **UF A**  **= 10X** 

**UF H**  **= 10X**  **Occu p**  **atio n**  **al LOC** 

**f o**  **r MO**  **E =**  **10 0**  **De v**  **e l**  **op m**  **e n**  **tal stu d**  **y in rab b**  **its.**

**LO A**  **EL =**  **20 0**  **m g** **/k g/da**  **y ,**  **b a**  **s ed on**  **decreas e**  **d m**  **aternal body**  **weight ga i**  **n a**  **n d f**  **oo d**  **c on**  **s u**  **m p**  **ti on (**  **a nd**  **i n**  **cr ea**  **sed wa**  **t er co**  **n su**  **m p**  **ti on**  **) . A**  **l so**  **s u**  **pp o**  **r te**  **d by s**  **u bchro**  **n ic a**  **n d chr**  **o n**  **ic d**  **ietary d**  **ata on mi**  **ce. In**  **h alati**  **o n absor**  **p tion rate =**  **1 0**  **0%. Cancer**  **(o ral,**  **der m**  **a l**  **, i**  **nh alatio**  **n )**  **C lass**  **i fication**  **( last assess**  **m ent**  **was p**  **e r**  **f or**  **m ed**  **u n**  **d e**  **r t**  **h e**  **19 8**  **6 A g** **e n**  **cy Cancer Assessm e** **n t**  **G u**  **i d**  **eli n**  **e s** **) w a**  **s “**  **n ot c**  **l ass**  **i f** 

**ia b**  **l e as**  **t o**  **ca r**  **c in**  **og e**  **n i**  **c it** **y t**  **o h um**  **ans,” based**  **o n**  **a n**  **e qu**  **i vocal**  **increase i**  **n p a**  **ncreatic acinar**  **c ell adeno**  **m as in the**  **m ale**  **rat on**  **ly, and n**  **o increases i**  **n fe**  **m ale rats n**  **o r**  **i n**  **m ice.**  **Ther e**  **f o**  **re, canc e**  **r ri**  **s k f** 

**r om**  **ex p**  **o s**  **u re**  **t o qu**  **i ncl**  **o rac**  **is n**  **o t**  **of c**  **onc er**  **n. A R** 

**I A** **/RD a**  **n d HED do n**  **o t a**  **n tici**  **p ate**  **t h**  **at a re**  **e v**  **aluat io**  **n u**  **n d**  **e r**  **t h**  **e 20**  **0 5 r**  **e v** **i sed**  **g u**  **i d**  **el i**  **n es**  **w ou**  **l d**  **s i**  **gn i**  **f i**  **c a**  **n tl** **y a lt**  **er t**  **h e**  **bas i**  **c co**  **nc l**  **u s**  **i ons**  **o f**  **t h**  **e ex**  **i s**  **tin g**  **decis i**  **o n**  **. Po**  **i n**  **t o**  **f Dep**  **art ure**  **( P**  **O D**  **) =**  **a data**  **po i**  **nt or**  **e s**  **t i**  **m a**  **t ed**  **po i**  **nt der**  **i ved**  **f r**  **om o**  **b se**  **r v**  **e d**  **d o**  **se -**  **r es**  **p onse**  **data, whi**  **c h**  **is us**  **e d**  **to m**  **ark t**  **h e b**  **e gi**  **n n**  **i n**  **g of ext r**  **apolati o**  **n t**  **o d e**  **ter m** **i n**  **e risk a s**  **sociated with**  **l o**  **w e**  **r en v**  **iro n**  **m e**  **n tally**  **rele v**  **ant hu m**  **an e**  **xp o**  **s u**  **r es.**  **UF = Unc**  **e rtainty Factor. U**  **F A**  **= e x**  **trap o**  **lati o**  **n fr o**  **m a**  **n i**  **m a**  **l to**  **hu m**  **an (in**  **t erspecie**  **s ).**  **UF H**  **= p**  **o te**  **n tial**  **v ariation**  **in se**  **n siti** **v ity**  **a m**  **on g**  **m e**  **m b**  **ers o**  **f t**  **h e**  **hu m**  **an po**  **pu lation (i**  **n tras**  **p ecies).**  **N O**  **AEL =**  **No Obs**  **er v**  **ed Adv**  **erse E**  **ffect Le**  **v el.**  **L OA**  **E L**  **= L**  **o west**  **O b**  **s e**  **r v**  **ed A**  **d v**  **e rse**  **E f**  **f ect**  **Level. MOE**  **= M**  **a rg**  **i n**  **Of Expo**  **s u**  **re. L**  **OC = L**  **e vel**  **Of C**  **o ncern.**  

### F. International Tolerances **There is a time limited**  **US tolerance for residues of quinclorac**  **on cranberry at 15.0 ppm that expires on December 31, 2012.**  **There are no CODEX or Mexican**  **maximum residue limits established for q uinclorac on cranberry or rhubarb**  **.**