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

MEMORANDUM

Date:		November 6, 2012

SUBJECT:	Quinclorac:  Risk Assessment In Support of Registration Review and for New Proposed Use on Rhubarb and Berry, low growing, except Strawberry, Subgroup 13-07H.

PC Code:  128974, 028974
DP Barcode:  D404794, D404808
Decision No.:  459055, 468877
Registration No.:  NA
Petition No.:  1E7957
Regulatory Action:  Section 3 Registration and Registration Review
Risk Assessment Type:  Single Chemical/ Aggregate
Case No.:  7222
TXR No.:  NA
CAS No.:  84087-01-4, 84087-48-9
MRID No.:  NA
40 CFR:  180.463

FROM:	Jessica Kidwell, Risk Assessor
		Abdallah Khasawinah, Ph.D., Toxicologist
		Susan Hummel/Gary Otakie, Chemists
		Bonnie Cropp-Kohlligian, Dietary Exposure Assessor
		Ivan Nieves, ORE Assessor
		Risk Assessment Branch IV, Health Effects Division (7509P)

THROUGH:	Elissa Reaves, Ph.D., Branch Chief
		Risk Assessment Branch IV
		Health Effects Division (7509P)

TO:		Wilhelmena Livingston, RM60
		Risk Management and Implementation Branch 4
      Pesticide Re-Evaluation Division (7508P)

		Erik Kraft and Kable Davis, PM25
	        	Herbicide Branch, Registration Division (7505P)

            Barbara Madden, PM5
            RIMUERB, Registration Division (7505P)

This document provides the Health Effect Division's (HED's) risk assessment on quinclorac conducted in support of registration review of currently registered uses including the use of quinclorac dimethyl amine, as well as the Albaugh Inc. and the Interregional Research Project No. 4 (IR4) request for proposed uses of the product QUINCLORAC 4L AG Herbicide (EPA Reg. No. 42750-169).  Registration is proposed for QUINCLORAC 4L AG Herbicide with the active ingredient quinclorac on rhubarb and berry, low growing, except strawberry, subgroup 13-07H.

Table of Contents

1.0.	Executive Summary	5
2.0.	HED Recommendations	8
2.1.	Data Deficiencies	9
2.2.	Tolerance Considerations	9
2.2.1.	Enforcement Analytical Method	9
2.2.2.	Recommended Tolerances	9
2.2.3.	Revisions to Petitioned-For Tolerances	12
2.2.4.	International Harmonization	13
2.3.	Label Recommendations	13
2.3.1.	Recommendations from Residue Chemistry Reviews	13
2.3.2.	Recommendations from Occupational Assessment	13
2.3.3.	Recommendations from Residential Assessment	13
3.0.	Introduction	13
3.1.	Chemical Identity	13
3.2.	Physical/Chemical Characteristics	14
3.3.	Pesticide Use Pattern	15
3.4.	Anticipated Exposure Pathways	21
3.5.	Consideration of Environmental Justice	21
4.0.	Hazard Characterization and Dose-Response Assessment	22
4.1.	Toxicology Studies Available for Analysis	22
4.2.1.	Dermal Absorption	23
4.4.	Safety Factor for Infants and Children (FQPA Safety Factor)	24
4.4.1.	Completeness of the Toxicology Database	24
4.5.	Toxicity Endpoint and Point of Departure Selections	25
4.5.1.	Dose-Response Assessment	25
4.5.2.	Recommendation for Combining Routes of Exposures for Risk Assessment	26
4.5.3.	Cancer Classification and Risk Assessment Recommendation	26
4.5.4.	Summary of Points of Departure and Toxicity Endpoints Used in Human Risk Assessment	26
4.6.	Incident Reports	29
5.0.	Dietary Exposure and Risk Assessment	31
5.1.	Metabolite/Degradate Residue Profile	31
5.1.1.	Summary of Plant and Animal Metabolism Studies	31
5.1.2.	Summary of Environmental Degradation	33
5.1.3.	Comparison of Metabolic Pathways	34
5.1.4.	Residues of Concern Summary and Rationale	34
5.2.	Food Residue Profile	34
5.3.	Water Residue Profile	37
5.4.	Dietary Risk Assessment	40
5.4.1.	Description of Residue Data Used in Dietary Assessment	40
5.4.2.	Percent Crop Treated Used in Dietary Assessment	41
5.4.3.	Acute Dietary Risk Assessment	41
5.4.4.	Chronic Dietary Risk Assessment	41
5.4.5.	Cancer Dietary Risk Assessment	42
5.4.6.	Summary Table	42
6.0.	Residential (Non-Occupational) Exposure/Risk Characterization	43
6.1.	Residential Handler Exposure	43
6.2.	Residential Post-Application Exposure	45
6.2.3. Residential (Non-occupational) post-application inhalation	45
6.2.4. Residential (Non-Occupational) Post-Application Dermal and Incidental Oral	45
6.3.	Combined Residential Risk Estimates (Multiple Exposure Scenarios)	46
6.4.	Residential Risk Estimates for Use in Aggregate Assessment	46
6.5.	Residential Bystander Post-application Inhalation Exposure	47
6.6.	Spray Drift	47
7.0.	Aggregate Exposure/Risk Characterization	48
7.1.    Acute Aggregate Risk	48
7.2.    Short-Term Aggregate Risk	48
7.3.    Intermediate-Term Aggregate Risk	49
7.4.    Chronic Aggregate Risk	49
7.5.    Cancer Aggregate Risk	50
7.6.    Cumulative Exposure/Risk Characterization	50
8.0.	Occupational Exposure/Risk Characterization	50
8.1.    Short-/Intermediate-/Long-Term/Cancer (if needed) Handler Risk	50
8.2.   Short-/Intermediate-/Long-Term/Cancer (if needed) Post-Application Risk	57
8.2.1.    Dermal Post-application Risk	57
8.2.2.   Inhalation Post-application Risk	57
9.0.	References	58
Appendix A.  Toxicology Profile and Executive Summaries	60
A.1	Toxicology Data Requirements	60
A.2	Toxicity Profiles	61
A.3	Hazard Identification and Endpoint Selection	65
A.4	Executive Summaries	69
Appendix B.  Review of Human Research	78
Appendix C: International Residue Limits	79

 Executive Summary

Quinclorac is an herbicide for the selective post-emergent control of various annual grasses and broadleaf weeds. It is adsorbed via the root system and partially through the foliage and acts as an inhibitor of cell wall synthesis.  Quinclorac is currently formulated into a variety of product formulations including; dry flowable, wettable powder, ready-to-use, granular, emulsifiable concentrate, flowable concentrate, and liquid formulations. Two new agricultural uses of quinclorac have been proposed for the dry flowable formulation of the end-use product QUINCLORAC 4L AG Herbicide (EPA Reg. No. 42750-169), a 3.8 lb a.i./gallon liquid formulation.  The new uses include the following crops; low growing berries, except strawberries, subgroup 13-07H, and rhubarb.  The maximum single application rates for the proposed uses are 0.25 and 0.37 lb ai/A for low growing berries, except strawberries, subgroup 13-07H, and rhubarb, respectively.  QUINCLORAC 4L AG Herbicide may be applied as a foliar spray using ground equipment only.

The variety of end-use products containing quinclorac is currently registered on rice, sorghum, and wheat. In addition to agricultural crops, quinclorac is also registered for: agricultural fallow/idleland/conservation reserves; nonagricultural uncultivated areas/soils; grass forage/fodder/hay; grasses grown for seed; pastures and rangelands; agricultural and nonagricultural rights of way/fencerows/hedgerows; agricultural uncultivated areas; utility poles/rights of way; airports/landing fields; ornamental sod farms; commercial/industrial lawns.  Additionally, quinclorac is registered for use by commercial applicators and homeowners on lawns, parks, in and around ornamentals, and golf courses.

A new physical form of quinclorac (EPA Reg. No. 7969-272) has recently been registered: Drive XLR-8 (Reg. No 7969-272), Paramount L Herbicide (Reg. No. 7969-315), Facet L Herbicide (EPA Reg. No. 7969-316), and Quinclorac 1.5 DMA (Reg. No 42750-224).  These products are DMA (dimethylamine) salt forms of quinclorac.  These products were not proposed for the new uses of quinclorac, proposed in the current petition, but are registered for use on rice and ornamental turf.

Hazard

Quinclorac toxicity in experimental animals is observed mostly at doses above 150 mg/kg/day following subchronic and chronic exposures.  Subchronic exposure to quinclorac caused decreased body weight gains, increased water intake, increased liver enzymes and focal chronic interstitial nephritis (rats).  Chronic toxic effects include body weight decrement, increase in kidney and liver weights, and hydropic degeneration of the kidneys (dogs).  At high doses, chronic toxicity also includes increased incidences of pancreatic acinar cell hyperplasia and adenomas.  Neurotoxic effects were not observed in any of the acute, subchronic and chronic studies with quinclorac.  There was no increased qualitative or quantitative fetal or offspring susceptibility in the prenatal developmental studies in rats or rabbits or postnatal reproduction study in rats.

There are no mutagenicity concerns.  Quinclorac was classified in 1992 by the HED Cancer Peer Review committee (CPRC) as a group D carcinogen - not classifiable as to human carcinogenicity- based on recommendation by the EPA Scientific Advisory Panel.  Based on the classification, a quantification of cancer risk is not warranted because the chronic RfD will adequately account for all chronic effects, including carcinogenicity, that may result from exposure to quinclorac.

Quinclorac (technical grade material) has a low order of acute toxicity as demonstrated by Toxicity Category III by the oral, dermal, and inhalation routes. The chemical is a mild eye irritant, is not a skin irritant, but was positive for dermal sensitization.

Endpoints and Uncertainty Factors for Risk Assessment

HED reviewed the toxicity database for quinclorac as well as the most recent risk assessment (D359759, Y. Donovan et al, 8/5/2009) and concluded that no changes in the points of departure (PODs) or FQPA SF (1x) are warranted. Since the last risk assessment the immunotoxicity study in mice was submitted and reviewed. The results of this study did not impact the overall risk assessment.  Since the last risk assessment, the HED Hazard and Science Policy Council (HASPOC) waived the requirement for a neurotoxicity battery (acute and subchronic neurotoxicity studies) and a DNT study.

Chemistry

Permanent tolerances have been established for residues of quinclorac per se in/on barley, rice, sorghum and wheat at levels ranging from 0.1 ppm in wheat straw to 1200 ppm in aspirated grain fractions [40 CFR §180.463(a)].  Permanent tolerances have also been established for residues of quinclorac, per se, in/on livestock commodities at levels ranging from 0.05 to 1.5 ppm.  In addition, there is a tolerance for quinclorac residues on cranberry in §180.463(b), as a result of a Section 18 emergency exemption at 15 ppm.

The Inter Regional Project No. 4 (IR-4) has submitted a request for tolerances and registration of quinclorac on low growing berries, except strawberries, subgroup 13-07H, and rhubarb.  Tolerances were proposed for residues of quinclorac in low growing berries, except strawberries, subgroup 13-07H, at 1.1 ppm, and rhubarb at 0.4 ppm.

The qualitative nature of quinclorac residues in plants was considered adequately understood for the currently registered crops, based upon the metabolism studies on rice, sorghum, and wheat.  Further metabolism data may be needed if uses are further expanded.  The qualitative nature of quinclorac residues in livestock is also understood based upon the adequate goat and poultry metabolism studies.  The Agency had concluded that parent is the only residue of concern in both plant and livestock commodities for purposes of the tolerance expression and risk assessment.

An adequate enforcement method is available for enforcing quinclorac tolerances on plants and livestock, a GC/ECD method that uses methylation with diazomethane.  There is available FDA multi-residue method (MRM) testing data that indicate that quinclorac is completely recovered using Protocol B.

Adequate cattle and poultry feeding studies are available and support the use of quinclorac.

Adequate rotational crop studies are available and support the use of quinclorac.

Dietary (food+water) Exposure and Risk

The Environmental Fate and Effects Division (EFED) completed a drinking water assessment in support of human health risk assessment. The current assessment is performed according to current EFED guidance and up-to-date models including the Tier II surface water model (PRZM/EXAMS) for all uses of quinclorac, except cranberries and rice. Screening-level Tier I modeling was used to estimate surface water concentrations for use on cranberry (provisional cranberry model) and rice (Tier I rice model) because the current Tier II model is not parameterized for those uses.  The Tier I SCI-GROW model was used to estimate groundwater concentrations for all uses.  Surface water EDWCs (acute = 511 ug/L and chronic = 511 ug/L) resulting from use on rice supersede previously recommended EDWCs.  The recommended groundwater EDWC has not changed (29 ug/L for acute and chronic exposure).

Both the acute and chronic dietary assessments are highly conservative, and assume 100% crop treated (%CT), along with tolerance-level residues for all agricultural commodities.  Default processing factors from DEEM 7.81 were used (for dried beef and cranberry juice) in the analyses. The acute (food + water) dietary risk estimate at the 95[th] percentile of exposure is 1.6% of the acute population adjusted dose (aPAD) for females age 13 to 49.  This is the only population subgroup for which an acute endpoint was selected.  The chronic (food + water) dietary risk estimates are less than or equal to 8.9% of the chronic population adjusted dose (cPAD) for all population subgroups.  All Infants < 1 year of age is the most highly-exposed subgroup, utilizing 8.9% of the cPAD, while the general US population utilizes 3.6% of the cPAD.

Occupational Exposure/Risk

The occupational handler assessment was completed assuming the maximum label application rate from the list of end-use products for each crop.  The labels allow for application via aerial, groundboom, chemigation, backpack, manually-pressurized handwand, mechanically-pressurized handgun, trigger-spray bottle, belly grinder, rotary spreader, and tractor-drawn spreader equipment. Based on the activity use pattern, the duration of exposure is expected to be short- term (ST; 1 to 30 days) and intermediate-term (IT; 1 to 6 months) for occupational scenarios; long-term exposures (greater than 6 months) are not anticipated based on the proposed use pattern.  No dermal endpoint was selected therefore only inhalation exposure was quantified.  For the inhalation route of exposure, the same points of departure were chosen for short- and intermediate-term exposures; therefore, risk estimates are the same for all durations of exposure.  An estimated short- and intermediate-term inhalation NOAEL of 70 mg/kg/day for quinclorac was selected from a developmental rabbit toxicity study.  Therefore, for risk characterization purposes, since no inhalation absorption data are available, toxicity by the inhalation route is considered to be equivalent to the estimated toxicity by the oral route of exposure. The proposed label requires long-sleeved shirt, long pants, shoes plus socks, and chemical-resistant gloves as personal protective equipment (PPE) for all applicators and other handlers.  All risk estimates of the proposed uses for occupational handlers are above the target MOE of 100. Occupational handler risk estimates resulted in inhalation MOEs ranging from 4800-940,000 for proposed new uses and 1000-1,100,000 for registered uses. The occupational handler inhalation risk estimates above 100 do not exceed HED's level of concern.

Based on the Agency's current practices, a quantitative non-cancer occupational post-application inhalation exposure assessment was not performed for quinclorac at this time; handler inhalation exposure estimates are considered to be protective of occupational post-application inhalation exposure scenarios.  If new policies or procedures are put into place, the Agency may revisit the need for a quantitative occupational post-application inhalation exposure assessment for quinclorac.

There is potential for dermal exposure during occupational post-application activities, such as crop maintenance activities, scouting, irrigation, and harvesting.  However, since no dermal (short- or intermediate-term) toxicological endpoints were identified, an assessment of post-application exposure and risk cannot be quantified.

Residential Exposure/Risk

There are no proposed residential uses at this time; however, there are existing uses for quinclorac on residential, non-residential turf (i.e., athletic fields, cemeteries, parks, etc.) and sod farms to control several broadleaf and grass weeds that have been reassessed in this document to reflect updates to HED's 2012 Residential SOPs, along with policy changes for body weight assumptions.  Since individuals can potentially be exposed to treated turf, a residential post-application assessment was previously conducted (T. Moriarty; 08/13/2008; D342993).  The revision of residential exposures will impact the human health aggregate risk assessment for quinclorac.  Post-application exposure and risk estimates resulted in inhalation MOEs ranging from 3600-250,000,000. These MOEs were greater than the LOC of 100, and, therefore, were not of concern.

Aggregate

In general, aggregate exposures are calculated by summing dietary (food and drinking water) and residential exposures (residential or other non-occupational exposures).  HED reviewed all residential sources of exposure to determine which residential exposure scenarios would be appropriate to combine with dietary exposure for an aggregate risk assessment.  The only applicable exposure pathways are inhalation (for adult handlers) and incidental oral (for post-application exposure to children). The short-term aggregate MOEs for the adult handlers and the children were 2100 and 1600, respectively, which are above the LOC of 100 and, therefore, not of concern. An intermediate-term adverse effect was identified; however, quinclorac is not registered for any use patterns that would result in intermediate-term residential exposure. Therefore, an intermediate-term aggregate risk assessment was not performed nor required. Additionally, aggregate acute and chronic (food and water) exposures were <=100% the cPAD for all population subgroups as a result of all registered/proposed uses.  Thus, acute and chronic aggregate exposure to quinclorac is not of concern.

 HED Recommendations

HED is recommending in favor of registration of quinclorac on the requested crops and establishment of tolerances as summarized in Table 2.2.3. HED has evaluated current uses of quinclorac and its dimethylamine salt. Tolerance changes are recommended due to recalculation of the dietary burden and for harmonization.

      0.1.  Data Deficiencies

Toxicology: None

Residue Chemistry:

::Data on catfish and crayfish are required, or the label must prohibit use of treated water from rice and cranberry fields for aquaculture (See Section 2.3). For registration review, data are required or the PM must ensure that all quinclorac labels with uses on rice and cranberry contain such a restriction.

::Further expansion of the use of quinclorac to other commodities grown on larger acreages than rhubarb and cranberry will trigger a requirement of additional metabolism data.

::For the current petition, Albaugh must supply the Pesticide Repository with analytical standards for quinclorac and the quinclorac methyl ester which is used in the current enforcement method.

::For registration review, an analytical standard for the quinclorac DMA salt must be submitted to the EPA National Pesticide Standards Repository.

ORE:  None.

      0.2.  Tolerance Considerations

            0.2.1. Enforcement Analytical Method

Adequate analytical methods (GC/ECD) are available for enforcing quinclorac tolerances on plant (BASF Method A8902; MRID# 41063537) and livestock (BASF Method 268/1; MRID# 41063536) commodities.  Both methods have undergone successful agency method validation trials and have been submitted to FDA for publication in PAM II as the tolerance enforcement methods.  The LOQ of both methods is 0.05 ppm for all matrices.

In BASF Method 268/1, used for both plant and animal matrices, samples are extracted with acetone and dichloromethane and redissolved in acetone/hexane. An aliquot is subjected to GC chromatography using a DB-5 column and electron capture detection.  Methylated standard is used for quantitation.  The LOD was reportedly 0.05 ppm, but this was also the lowest level validated.

Quinclorac is detected by FDA Multiresidue Protocol B, but not the other FDA Multiresidue Method (MRM) Protocols.

            0.2.2. Recommended Tolerances

The current tolerance expression for quinclorac is:

"Tolerances are established for residues of the herbicide quinclorac, including its metabolites and degradates, in or on the commodities in the table in this paragraph. Compliance with the tolerance levels specified in this paragraph is to be determined by measuring only quinclorac, 3,7-dichloro-8-quinolinecarboxylic acid, in or on the commodity."

The tolerance expression is in accord with our current guidance on tolerance expressions.

Current Petition: Tolerance recommendations for the current petition (IE7957) on low growing berries, except strawberries, subgroup 13-07H, and rhubarb are in the first two lines of Table 2.2.2.

Tolerance Consideration for Registration Review: Permanent tolerances have been established for residues of quinclorac in/on small cereal grain commodities at levels ranging from 0.1 ppm in wheat straw to 15 ppm in rice bran [40 CFR §180.463(a)], and for grass forage at 150 ppm and grass hay at 130 ppm.  There is also a 1200 ppm tolerance for AGF; however, recently reviewed data indicate that a tolerance on AGF is not necessary (DP# 344496, G. Otakie, 9/25/08).  Permanent tolerances have also been established for residues of quinclorac per se in/on livestock commodities at levels ranging from 0.05 to 1.5 ppm.

Based on the recalculated dietary burdens for livestock and the data from the available cattle and poultry feeding studies, the current tolerances for livestock commodities are adequate, with the exceptions of the tolerances on poultry meat byproducts and hog fat and meat byproducts.  Based on the recalculated Maximum Dietary Burdens (MDBs) for swine (6.0 ppm) and poultry (5.4 ppm) and the data from the poultry and cattle feeding studies, the existing tolerances for poultry meat byproducts and hog fat and meat byproducts are too high as quinclorac residues in these commodities are expected to be <0.05 ppm at 1x the MDB.  Therefore, the tolerances for these livestock commodities should be lowered to 0.05 ppm.  Lowering the tolerances on these commodities will also harmonize the U.S. tolerances with the existing Canadian MRLs for poultry meat byproducts and hog fat and meat byproducts.

In addition, HED notes that the Agency no longer considers rice straw to be a significant livestock feedstuff (OPPTS 860.1000, Table I, ChemSAC memo 6/30/08).  Therefore, the current tolerance for residues of quinclorac on rice straw may be revoked.

The use of the DMA salt of quinclorac will not affect the established tolerances for quinclorac on rice, grain sorghum, and wheat.

Table 2.2.2 	Tolerance Summary for Quinclorac.  § 180.463
Commodity
                       Current/Proposed Tolerance (ppm)
                          Recommended Tolerance (ppm)
Comments; Correct Commodity Definition
Berry, low growing, except strawberry, subgroup 13-07H
                                      1.1
                                      1.5
Revised level based on OECD tolerance calculation procedures.  At the time of publication of this tolerance, the tolerance for residues quinclorac on cranberry in § 180.463(b) should be revoked.
Rhubarb
                                      0.4
                                      0.5
Revised level based on OECD tolerance calculation procedures.
     Currently Established Tolerances Reevaluated for Registration Review
Barley, grain
                                      2.0
                                      2.0
The tolerance needs a footnote to indicate that there are no U. S. Registrations.
Cattle, fat
                                      0.7
                                      0.7

Cattle, meat byproducts
                                      1.5
                                      1.5

Cattle, meat
                                     0.05
                                     0.05

Egg
                                     0.05
                                     0.05

Goat, fat
                                      0.7
                                      0.7

Goat, meat byproducts
                                      1.5
                                      1.5

Goat, meat
                                     0.05
                                     0.05

Grain, aspirated fractions
                                     1200
                                    revoke
Data submitted demonstrate that the tolerance is not needed. Current tolerance was based on a theoretical calculation.
Grass, forage
                                      150
                                      150

Grass, hay
                                      130
                                      130

Hog, fat
                                      0.7
                                     0.05
Based on the residue data from the cattle feeding and the calculated MDB of 6.0 ppm for swine, the tolerances can be lowered to the method LOQ (0.05 ppm).  This level is harmonized with Canada.
Hog, meat byproducts
                                      1.5
                                     0.05
Based on the residue data from the cattle feeding and the calculated MDB of 6.0 ppm for swine, the tolerances can be lowered to the method LOQ (0.05 ppm).  This level is harmonized with Canada.
Hog, meat
                                     0.05
                                     0.05

Horse, fat
                                      0.7
                                      0.7

Horse, meat byproducts
                                      1.5
                                      1.5

Horse, meat
                                     0.05
                                     0.05

Milk
                                     0.05
                                     0.05

Poultry, fat
                                     0.05
                                     0.05

Poultry, meat byproducts
                                      0.1
                                     0.05
Based on the residue data from the poultry feeding and the calculated MDB of 5.4 ppm for poultry, the tolerance can be lowered to the method LOQ (0.05 ppm).   This level is harmonized with Canada.
Poultry, meat
                                     0.05
                                     0.05

Rice, bran
                                     15.0
                                     15.0

Rice, grain
                                      5.0
                                      5.0

Rice, straw
                                     12.0
                                    Revoke
Rice straw is no longer a regulated livestock feedstuff.
Sheep, fat
                                      0.7
                                      0.7

Sheep, meat byproducts
                                      1.5
                                      1.5

Sheep, meat
                                     0.05
                                     0.05

Sorghum, grain, forage
                                      3.0
                                      3.0

Sorghum, grain, grain
                                      6.0
                                      6.0

Sorghum, grain, stover
                                      1.0
                                      1.0

Wheat, forage
                                      1.0
                                      1.0

Wheat, germ
                                     0.75
                                     0.75

Wheat, grain
                                      0.5
                                      0.5

Wheat, hay
                                      0.5
                                      0.5

Wheat, straw
                                      0.1
                                      0.1

            0.2.3. Revisions to Petitioned-For Tolerances and Existing Tolerances

Current Petition: Revisions are recommended to petitioned-for tolerances due to the use of the OECD tolerance calculation procedures.  The recommended changes are documented in Table 2.2.2.

Tolerance Revisions for Registration Review: Revisions to current tolerances for registration review are documented in Table 2.2.2.  Some tolerances are being removed because the commodity is no longer regulated.  The tolerance for Grain, Aspirated Fractions is being removed because it it not necessary.  Tolerances on meat, poultry, milk, and eggs are being revised based on a recalculation of the dietary burden, and to harmonize internationally.

            0.2.4. International Harmonization

CODEX has not established any established maximum residue limits (MRLs) for quinclorac.  Canada has established maximum residue limits (MRLs) for quinclorac on selected agricultural commodities but not the commodities in the current petition. Recommendations for harmonization are in Table 2.2.2 for Registration Review.

      0.3. Label Recommendations

            0.3.1. Recommendations from Residue Chemistry Reviews

      ::Cranberry is an aquatic crop, and as such, a label restriction is needed regarding the use of treated rice and cranberry fields for aquaculture.  Alternatively, the petitioner may determine residues in catfish and crayfish raised in treated fields and propose tolerances for these commodities, if necessary.  The label provided for Quinclorac/QuinStar 4-L does not contain any restriction against aquaculture.

      ::For Registration Review, the PM must ensure that all labels for quinclorac on rice and cranberry contain a label restriction restricting the use of treated rice and cranberry fields for aquaculture.

            0.3.2. Recommendations from Occupational Assessment

The proposed label requires long-sleeved shirt, long pants, shoes plus socks, and chemical-resistant gloves as personal protective equipment (PPE) for all applicators and other handlers. The 12 hour REI which is currently on the label is adequate for the new crop uses with the product QUINCLORAC 4L AG Herbicide.

            0.3.3. Recommendations from Residential Assessment
None.

 Introduction

      0.4.  Chemical Identity

Quinclorac is a herbicide for the selective post-emergent control of various annual grasses and broadleaf weeds.  Quinclorac is adsorbed via the root system and partially through the foliage and acts as an inhibitor of cell wall synthesis.  The nomenclature of quinclorac and quinclorac DMA salt are summarized in Table 3.1.

Table 3.1.	Quinclorac and Quinclorac (DMA salt)  Nomenclature.
Compound

Common name
Quinclorac,
Company experimental name
BAS 514 34H
IUPAC name
3,7-dichloroquinoline-8-carboxylic acid
CAS name
3,7-dichloro-8-quinolinecarboxylic acid
CAS registry number
84087-01-4
Molecular weight
242.1
End-use product (EP)
Drive(R) 75 DF

Compound

Common name
Quinclorac, DMA salt
Company experimental name
BAS 514 51H
IUPAC name
3,7-dichloroquinoline-8-carboxylic acid, DMA salt
CAS name
3,7-dichloro-8-quinolinecarboxylic acid, DMA salt
CAS registry number
84087-48-9
Molecular weight
287.2
End-use product (EP)
Drive(R)XLR8 Herbicide, EPA Reg. No. 7969-272; Paramount(R) L Herbicide, EPA Reg. No. 7969-GRA; Facet L Herbicide, EPA Reg. No. 7969-GRL

      0.5.  Physical/Chemical Characteristics

The physicochemical properties of the technical grade quinclorac are summarized in Table 3.2.1.
Only several physicochemical properties of the DMA salt of quinclorac are available (Table 3.2.2). The physical and chemical properties of quinclorac indicate that it is unlikely to volatilize and has low potential to accumulate in fatty tissues.

In addition, the registrant has submitted a comparative study of the dissociation behavior of quinclorac and its dimethylamine salt (MRID 48051902, "Comparative study of the Dissociation Behavior of Quinclorac Acid and its Dimethylamine Salt").  The UV/Vis spectra of quinclorac TGAI and the UV/Vis spectra and dissociation constant of quinclorac DMA were presented.  The results of the study show that in aqueous solutions, the chemical form of the quinclorac dimethylamine salt is the same as that of the quinclorac acid form.

Table 3.2.1		Physicochemical Properties of the Technical Grade Quinclorac.
Parameter
Value
Reference
Melting point/range
~269°C
D342446, M. Doherty, 9/11/07
pH
3.4-3.5
RCB 3283 S. Hummel, 2/26/88
Density
~560 g/L
D342446, M. Doherty, 9/11/07
Water solubility (20°C)
0.0064 g/100 mL

Solvent solubility (g/100 mL at 20°C to 25°C)
ethanol	0.2 	toluene	<0.1
Lutrol(R)	<0.1	acetone	0.2
olive oil	<0.1	n-octanol	<0.1
acetonitrile	<0.1	1,2-propandiol	<0.1
ethyl acetate	0.1	dichloromethane	<0.1
ethyl ether	0.1	n-hexane	<0.1

Vapor pressure (20°C)
<1.0x10-7 mbar (<0.75x10-7 Torr)

Dissociation constant, pKa
4.34 at 20°C
4.35 at 25°C

Octanol/water partition coefficient, log POW (20°C)
1.76 at pH 4
-0.74 at pH 7
 3.74 at pH 10

UV/visible absorption spectrum
314 nm, 300 nm, 278 nm (95% ethanol)
MRID 48051092

Table 3.2.2		Physicochemical Properties of the Quinclorac, DMA Salt.
Parameter
Value
Reference
Melting point/range
NA

pH
NA

Density
NA

Water solubility (20°C)
NA

Solvent solubility (g/100 mL at 20°C to 25°C)
NA

Vapor pressure (20°C)
NA

Dissociation constant, pKa
4.33 +- 0.15  (Temperature not reported)
MRID 48051092
Octanol/water partition coefficient, log POW (20°C)
NA

UV/visible absorption spectrum
314 nm, 300 nm, 278 nm (95% ethanol)
MRID 48051092

      0.6.  Pesticide Use Pattern

Proposed new uses.  IR-4 is proposing use of the Quinclorac 4-L AG (Reg. No. 42750-169), registered to Albaugh, Inc., containing 3.8 lb quinclorac/gallon, in connection with the current petition.

Table 3.3.1.  Summary of Directions for Proposed Use of Quinclorac on Low Growing Berries (Crop Sub- Group 13-07H), Except Strawberries, and Rhubarb.
                       Applic. Timing, Type, and Equip.
                     Formulation [EPA Reg. No. 42750-169]
                         Max. Single Application Rate
                                   (lb ai/A)
                          Max. No. Applic. per Season
                   Max. Seasonal Application Rate (lb ai/A)
                                  PHI (days)
                        Use Directions and Limitations
Low Growing Berries (Crop Sub- Group 13-07H), Except Strawberries
Foliar; Ground.
QUINCLORAC 4L AG Herbicide 40% ai, Dry Flowable
(3.8 lb ai/gal)
                          0.25 lb ai/A (8.4 fl oz/A)
                                       2
                                 0.50 lb ai/A
                                (16.8 fl oz/A)
                                      60
Re-treatment Interval = 30 days.
Ground application (foliar) only.
Do not apply by air.
Do not apply to irrigation ditches.
Crop oil concentrate permitted.
Rhubarb
Foliar; Ground.
QUINCLORAC 4L AG Herbicide 40% ai, Dry Flowable
(3.8 lb ai/gal)
                          0.37 lb ai/A (12.6 fl oz/A)
                                       2
                                 0.74 lb ai/A
                                (25.2 fl oz/A)
                                      30
Re-treatment Interval = 30 days.
Ground application (foliar) only.
Do not apply by air.
Do not apply to irrigation ditches.
Crop oil concentrate permitted.
Maximum Single Application Rate for Low Growing Berries (Crop Sub- Group 13-07H), Except Strawberries (lb ai/A) = (8.4 fl oz/A) (3.8 lb ai/gal)(1 gal/128 fl oz) = 0.25 lb ai/A.  Maximum Single Application Rate for Rhubarb (lb ai/A) = (12.6 fl.oz/A)(1 gal/1 128 fl.oz) (3.8 lb ai/gal) = 0.37 lb ai/A.

Existing Uses.  Existing uses of quinclorac include use on rice, grain sorghum, wheat, pasture and rangeland grasses, and use on barley in Canada for import into the US.  The dimethylamine salt of quinclorac has recently been registered for use on rice, grain sorghum, and wheat.

Table 3.3.3 provides use sites and maximum application rates for the existing uses for quinclorac.  Please refer to Section 2.3 for recommended modifications to the proposed label.
Table 3.3.2. Summary of Quinclorac Registered Uses Assessed Under Registration Review
                                   Commodity
                                 Form-ulation
                                 Product Name
                                (EPA Reg. No.)
                             Application Equipment
                             Max. Single App Rate
                                   (lb ai/A)
                                      PHI
                                    (days)
                                     Rice
                                      DF
279-3366; 34704-920; 42750-88; 66222-160; 7969-222; 7969-313; 80289-14
Aerial; Groundboom
                                     0.503
                                      309

                                       L
42750-169; 71085-26; AR080007; AR120003

                                     0.47

                                      WSP
7969-93

                                      0.5

                               Sorghum and Wheat
                                      DF
7969-152; 7969-113; 66222-160; 42750-131

                                     0.375

                                       L
42750-169; 42750-171

                                     0.35

Agricultural fallow/idleland/conservation reserves; Nonagricultural uncultivated areas/soils; Grass forage/fodder/hay; Grasses grown for seed; Pastures and Rangelands
                                      DF
7969-113; 42750-131; 7969-152
Aerial; Groundboom
                                     0.75
                                      40

                                       L
42750-169; 42750-171

                                     0.75

Agricultural and nonagricultural rights of way/fencerows/hedgerows; Agricultural uncultivated areas; Utility poles/rights of way
                                      DF
42750-131; 83070-9; 7969-130; 7969-113; 66222-160; 42750-131; 228-592
Backpack; Mechanically-pressurized Handgun
                                     0.75
                              (0.15 lb ai/gal)[*]
                                     7-309

                                       L
7969-267; 70506-282; 42750-220; 42750-172; 42750-171; 42750-169; 228-705; 228-595; 228-531; 228-423; 2217-946; 2217-919; 2217-901; 2217-888; 2217-886; 42750-169; 42750-171

                                     1.48
                              (0.296 lb ai/gal) *

                                       G
2217-927; 2217-964
Rotary Spreader
                                     0.68

Airports/landing fields
                                      DF
228-592; 7969-130
Backpack; Manually-pressurized Handwand; Mechanically-pressurized Handgun
                                     0.75
                              (0.15 lb ai/gal)[*]
                                     NS[3]

                                       L
228-531; 228-705; 42750-172; 42750-220; 70506-282; 7969-267

                                     0.75
                              (0.15 lb ai/gal)[*]

Commercial/industrial lawns
                                      DF
228-592; 279-3355; 66222-160; 7969-130; 83070-9
Backpack; Manually-pressurized Handwand; Mechanically-pressurized Handgun
                                      1.4
                              (0.28 lb ai/gal)[*]
                                      NS

                                       L
7969-267; 70506-282; 42750-220; 42750-172; 228-705; 228-595; 228-531; 228-423; 2217-946; 2217-919; 2217-901; 2217-888; 2217-886

                                     0.78
                             (0.156 lb ai/gal)[*]

                                       G
2217-927; 2217-964
Belly grinder; Rotary spreader
                                     0.68

                                      RTU
228-594
Trigger-spray bottle
                                     0.76
                           (0.0172 lb ai/bottle)[*]

Ornamental lawns and turf
                                      DF
83070-9; 7969-130; 66222-160; 42750-90; 228-592
Backpack; Manually-pressurized Handwand; Mechanically-pressurized Handgun
                                     0.75
                              (0.15 lb ai/gal)[*]
                                      NS

                                       L
7969-267; 70506-282; 42750-172; 239-2713; 228-705; 228-704; 228-595; 228-423; 2217-946; 2217-919; 2217-901; 2217-888; 2217-886

                                     0.78
                             (0.156 lb ai/gal)[*]

                                       G
2217-927; 2217-964; 538-296
Hand dispersal; Belly grinder; Cup; Rotary spreader; Spoon
                                     0.68

                                      RTU
228-594; 228-703
Trigger-spray bottle
                                     0.76
                           (0.0172 lb ai/bottle)[*]

Recreation area and residential lawns
                                      DF
83070-9; 7969-130; 66222-160; 279-3355; 228-592
Backpack; Manually-pressurized Handwand; Mechanically-pressurized Handgun
                                      1.4
                              (0.28 lb ai/gal)[*]
                                      NS

                                       L
7969-267; 72155-86; 70506-282; 42750-220; 42750-172; 228-705; 228-704; 228-595; 228-531; 228-423; 2217-954; 2217-946; 2217-945; 2217-939; 2217-938; 2217-919; 2217-901; 2217-896; 2217-894; 2217-888; 2217-886; 2217-885;

                                     0.78
                             (0.156 lb ai/gal)[*]

                                       G
2217-927; 2217-963; 2217-964
Belly grinder; Rotary spreader
                                     0.68

                                      RTU
2217-887; 2217-917; 2217-918; 2217-953; 228-594; 228-703; 239-2689
Trigger-spray bottle
                                     0.76
                           (0.0172 lb ai/bottle)[*]

Ornamental sod farms (turf)
                                      DF
83070-9; 7969-130; 66222-160; 42750-90; 279-3355; 228-592
Aerial; Groundboom; Chemigation
                                      1.4
                                      90

                                       L
70506-282; 42750-220; 42750-172; 228-705; 228-595; 228-531; 228-423; 2217-946; 2217-919; 2217-901; 2217-888; 2217-886

                                     0.78

                                      RTU
228-594
Trigger-spray bottle
                                     0.76

Golf course turf
                                      DF
42750-90; 228-592; 279-3355; 83070-9; 7969-130; 66222-160;
Groundboom; Mechanically-pressurized Handgun
                                      1.4
                                      NS

                                       L
2217-886; 2217-888; 2217-901; 2217-919; 2217-946; 228-423; 228-531; 228-595; 228-705; 42750-172; 42750-220; 70506-282; 7969-267

                                     0.78

                                       G
2217-964; 2217-927
Tractor-drawn Spreader; Rotary spreader
                                     0.68

                                      RTU
228-594
Trigger-spray bottle
                                     0.76

 Anticipated Exposure Pathways

The Registration Division has requested an assessment of human health risk to support the proposed new uses of quinclorac. The Pesticide Re-Evaluation Division also has requested an assessment for registration review.  The variety of end-use products containing quinclorac currently registered is as follows; rice, sorghum, and wheat.  In addition to agricultural crops, quinclorac is also registered for: agricultural fallow/idleland/conservation reserves; nonagricultural uncultivated areas/soils; grass forage/fodder/hay; grasses grown for seed; pastures and rangelands; agricultural and nonagricultural rights of way/fencerows/hedgerows; agricultural uncultivated areas; utility poles/rights of way; airports/landing fields; ornamental sod farms; commercial/industrial lawns.  Additionally, quinclorac is registered for use by commercial applicators and homeowners on lawns, parks, in and around ornamentals, and golf courses. The new uses include the following crops; low growing berries, except strawberries, subgroup 13-07H, and rhubarb.

Humans may be exposed to quinclorac in food and drinking water, since quinclorac may be applied directly to growing crops and application may result in quinclorac reaching surface and ground water sources of drinking water.  In the occupational and residential settings, inhalation exposure is expected to be of short- and intermediate term durations based on the activity use pattern. Long-term exposures (greater than 6 months) are not anticipated based on the proposed use pattern. No dermal endpoint was selected, therefore, only inhalation exposure was quantified.  Incidental oral residential exposures (short-term only) are also expected.

Risk assessments have been previously prepared for the existing uses of quinclorac. This risk assessment considers all of the aforementioned exposure pathways based on the proposed new uses of quinclorac, but also considers the existing uses as well, particularly for the dietary exposure assessment.

      0.7.  Consideration of Environmental Justice

Potential areas of environmental justice concerns, to the extent possible, were considered in this human health risk assessment, in accordance with U.S. Executive Order 12898, "Federal Actions to Address Environmental Justice in Minority Populations and Low-Income Populations," (http://www.eh.doe.gov/oepa/guidance/justice/eo12898.pdf.  As a part of every pesticide risk assessment, OPP considers a large variety of consumer subgroups according to well-established procedures.  In line with OPP policy, HED estimates risks to population subgroups from pesticide exposures that are based on patterns of that subgroup's food and water consumption, and activities in and around the home that involve pesticide use in a residential setting.  Extensive data on food consumption patterns are compiled by the USDA under the Continuing Survey of Food Intake by Individuals (CSFII) and are used in pesticide risk assessments for all registered food uses of a pesticide.  These data are analyzed and categorized by subgroups based on age, season of the year, ethnic group, and region of the country.  Additionally, OPP is able to assess dietary exposure to smaller, specialized subgroups and exposure assessments are performed when conditions or circumstances warrant.  Whenever appropriate, non-dietary exposures based on home use of pesticide products and associated risks for adult applicators and for toddlers, youths, and adults entering or playing on treated areas post-application are evaluated.  Further considerations are currently in development as OPP has committed resources and expertise to the development of specialized software and models that consider exposure to bystanders and farm workers as well as lifestyle and traditional dietary patterns among specific subgroups.

 Hazard Characterization and Dose-Response Assessment

HED reviewed the toxicity database for quinclorac as well as the most recent risk assessment which was conducted in association with the new use on pasture/rangeland (D359759, Y. Donovan et al, 8/5/2009) and concluded that no changes in the points of departure (PODs) or FQPA SF (1x) are warranted. Since the last risk assessment the immunotoxicity study in mice was submitted and reviewed (TXR 0052889). The results of this study did not impact the overall risk assessment.

      0.8.  Toxicology Studies Available for Analysis

The toxicology database for quinclorac is adequate for evaluating and characterizing its toxicity and selecting endpoints for purposes of risk assessment. Studies considered for this assessment include acute lethality (oral, dermal and inhalation routes), primary eye and dermal irritation, dermal sensitization, subchronic oral toxicity (rat and mouse), rat 21-day dermal toxicity, dog chronic toxicity, rat combined chronic toxicity/carcinogenicity, mouse carcinogenicity, developmental toxicity (rat and rabbit), rat two-generation reproductive toxicity, genotoxicity, rat metabolism, and mouse immunotoxicity.  Since the last risk assessment, the HED HASPOC
waived the requirement for a neurotoxicity battery (acute and subchronic) and a DNT study based on a WOE approach that considered (1) lack of neurotoxic effects in the available acute, subchronic, chronic, developmental, and reproduction studies; (2) the selected endpoints are considered to be protective of neurotoxic effects; (3) dietary exposure to quinclorac is low; and (4) residential and occupational MOEs are high (HASPOC TXR 0056385).  The requirement of a 28-day inhalation toxicity study was also waived previously based on low volatility, low acute inhalation toxicity and large extrapolated inhalation MOE (D376603, 23 September 2010).

      0.9.  Absorption, Distribution, Metabolism, & Elimination (ADME)

The metabolism of quinclorac ((2,3,4-[14]C)3,7-dichloro-8- quinolinecarboxylic acid) following oral administration was studied extensively in male and female CD rats. The compound was rapidly absorbed and eliminated in the urine following administration of single oral doses of ([14]C) quinclorac at 15 or 600 mg/kg or after daily exposures of unlabeled compound at 15 mg/kg for 14 days followed by a single 15 mg/kg oral dose of labeled compound. Elimination in the urine 5 days after dosing accounted for 91 to 98 % of the dose with only 1 to 4 % eliminated in the feces. No radioactivity was detected in expired air. Biliary excretion was significant (11.5 to 14.5 % of the dose) in animals receiving 600 mg/kg. However, most of this radioactivity was reabsorbed from the intestines and eliminated in the urine. Most of the radioactivity in the bile is associated with the glucuronide conjugate of quinclorac. The conjugate is apparently hydrolyzed in the intestines and reabsorbed. Almost all the radioactivity in the urine is unchanged quinclorac. Radioactive tissue residue levels 5 days after dosing were dose-dependent. Results from these and whole-body autoradiography and time-course studies indicate that relatively higher radioactivity levels were detected in the adrenal glands, bone marrow, thyroid, squamous epithelium of the non-fundic stomach, and ovaries compared to the other body organs/tissues. In 7-day time-course studies (oral gavage at 15 mg/kg/day or dietary at about 1,000 mg/kg/day) maximum [14]C residue levels were detected 30 minutes after the final dose; thereafter, residue levels decreased with time. Mean [14]C residues in plasma were also detected at 30 minutes in animals receiving single oral doses of 15, 100, or 600 mg/kg or 15 mg/kg/day for 7 days. Elimination was biphasic with half-lives of 3 to 4 hours for the rapid phase at the low doses and a half-life of about 13 hours at 600 mg/kg. Peak plasma levels of radioactivity in animals receiving higher doses (1200 mg/kg or 600 mg/kg/day for 7 days) were noted for 7 to 48 hours post dosing; saturation kinetics were also noted at these higher doses.

            0.9.1. Dermal Absorption

Dermal penetration studies on quinclorac are not available. There was no dermal toxicity seen at the limit dose of 1000 mg/kg/day in a 21-day dermal toxicity study in rabbits.

      0.10. Toxicological Effects

Quinclorac toxicity in experimental animals is observed mostly at doses above 150 mg/kg/day following subchronic and chronic exposures.  Subchronic toxicity includes decreased body weight gains, increased water intake, increased liver enzymes (SGOT, SGPT) and focal chronic interstitial nephritis (rats).  Chronic toxic effects include body weight decrement, increase in kidney and liver weights, and hydropic degeneration of the kidneys (dogs).  At high doses, chronic toxicity also includes increased incidences of pancreatic acinar cell hyperplasia and adenomas (rats).  Neurotoxic effects were not observed in any of the acute, subchronic and chronic studies with quinclorac.

There was no increased qualitative or quantitative fetal or offspring susceptibility in the prenatal developmental or postnatal reproduction studies.  Developmental toxicity in the rabbit consisted of increased resorptions, post-implantation loss, decreased number of live fetuses, and reduced fetal body weight. These effects occurred at much higher doses than the maternal effects of decreased food consumption and increased water consumption and decreased body weight gain.  In the rat no developmental toxicity was observed at the highest dose tested (438 mg/kg/day).  In the 2-generation reproduction study, parental toxicity and offspring toxicity occurred at the same dose.  Parental toxicity consisted of reduced body weight in both sexes during premating and lactation periods.  Offspring toxicity consisted of decreased pup weight, developmental delays and possible marginal effect on pup viability.  No reproductive toxicity occurred at the highest dose tested (480 mg/kg/day).

There are no mutagenicity concerns.  Quinclorac is not mutagenic in bacterial assays and does not cause unscheduled DNA damage in primary rat hepatocytes.  There is also no evidence of a genotoxic response in whole animal test systems (in vivo mouse bone marrow micronucleus assay). Quinclorac was negative in a mammalian cell in vitro cytogenetic chromosomal aberration assay in Chinese hamster ovary cells (CHO).

Quinclorac was classified in 1992 by the HED Cancer Peer Review committee (CPRC) as a group D carcinogen - not classifiable as to human carcinogenicity- based on recommendation by the EPA Scientific Advisory Panel (TXR# 0010416).  This classification was based on equivocal increase in the incidence of one type of benign tumor (pancreatic acinar cell adenomas) in only one sex and one species of animals (male Wistar rats).  Based on this classification, a quantification of cancer risk is not warranted because the chronic RfD will adequately account for all chronic effects, including carcinogenicity, likely to result from exposure to quinclorac.

Quinclorac (technical grade material) has a low order of acute toxicity as demonstrated by Toxicity Category III by the oral, dermal, and inhalation routes. The chemical is a mild eye irritant, is not a skin irritant, but was positive for dermal sensitization.

The complete toxicity profile for quinclorac is provided in Appendix A.

      0.11.  Safety Factor for Infants and Children (FQPA Safety Factor)

The FQPA Safety Factor Committee recommended in 1998 that the 10x factor for the protection of infants and children (as required by FQPA) be removed (TXR 0012902).  The removal of the 10x factor is based on 1) completeness of the data base; 2) there is no indication of increased susceptibility of rats or rabbit fetuses to in utero and/or postnatal exposure in the developmental and reproductive toxicity data; 3) unrefined (Tier 1) dietary exposure estimates are protective since they exaggerate the dietary exposure estimates; and 4) modeling data are used for ground and surface source drinking water exposure assessments resulting in conservative upper-bound concentrations.

            0.11.1. Completeness of the Toxicology Database

The toxicology database for quinclorac is complete and the risk assessment team has concluded that the FQPA safety factor can be reduced to 1x.  The following acceptable studies are available for FQPA consideration:  (1) Developmental toxicity studies in rats and rabbits; and (2) Two-generation reproduction study in rats.  Acute and subchronic neurotoxicity studies have been waived per HASPOC (TXR# 0056385).

            0.11.2. Evidence of Neurotoxicity

There are no acute, subchronic or chronic neurotoxicity studies on quinclorac available from the registrant or from the published literature.  Neurotoxic effects were not observed in any of the acute, subchronic and chronic studies with quinclorac.  Because of the lack of evidence of neurotoxic effects, HIARC (TXR# 0012717) determined in 1998 that no acute, subchronic, or developmental neurotoxicity studies are required for quinclorac. This was confirmed by HASPOC in 2012 (TXR# 0056385).

            0.11.3. Evidence of Sensitivity/Susceptibility in the Developing or Young Animal

The toxicology database for quinclorac is adequate for the FQPA assessment.  Developmental toxicity studies in rats and rabbits and the reproduction studies in rats provided no indication of increased qualitative or quantitative susceptibility.

            0.11.4. Residual Uncertainty in the Exposure Database

There are no residual uncertainties with regard to dietary and residential/occupational exposure.
The dietary exposure assessments are based on tolerance level residues and 100% crop treated information. Modeled values were used for drinking water estimates. Occupational and residential exposure assessments are based on reasonable worst-case assumptions and will not likely underestimate potential exposure or risk. Based on these data, the quinclorac risk assessment team concluded that no additional safety factor is needed to account for exposure considerations.

      0.12.  Toxicity Endpoint and Point of Departure Selections

            0.12.1. Dose-Response Assessment

Toxicity endpoints and points of departure (PODs) for dietary and occupational exposure scenarios are summarized below.  A detailed description of the studies used as a basis for the selected endpoints are presented in Appendix A.

An appropriate endpoint attributable to a single exposure to assess dietary exposure for the general populations including infants and children was not available from the oral toxicity studies including the rat and rabbit developmental toxicity studies.

An acute dietary POD of 200 mg/kg (NOAEL) for the sub-population females 13-49 years old was selected from a rabbit developmental toxicity study based on increased rate of resorptions and post-implantation loss, a decrease in the number of live fetuses, and reduced fetal body weight seen at 600 mg/kg/day.  A UF 100x (10x for intraspecies variation, 10x for interspecies extrapolation and a 1x FQPA safety factor) was applied to the dose to obtain an acute reference dose/population adjusted dose (aRfD/aPAD) of 2.0 mg/kg.

A chronic dietary POD of 37.5 mg/kg/day (NOAEL) was selected for the general population from a carcinogenicity study in mice based on effects on body weight.  A UF 100x (10x for intraspecies variation, 10x for interspecies extrapolation and a 1x FQPA factor) was applied to the dose to obtain a chronic reference dose/population adjusted dose (cRfD/cPAD) of 0.38 mg/kg/day.

A POD of 70 mg/kg/day (NOAEL) for assessing incidental oral short-term (1-30 days) as well as short- and intermediate term inhalation exposure scenarios was selected from the developmental toxicity study in rabbits based on decreased maternal body weight gain and food consumption (and increased water consumption) at 200 mg/kg/day. This is supported by subchronic and chronic dietary data on mice.  The LOC for MOE of 100 is applied for this exposure scenario. This includes 10X for interspecies extrapolation, 10X for intraspecies variation and a 1x FQPA SF.

A dermal endpoint was not selected because an appropriate endpoint was not available (i.e. no dermal toxicity was seen at limit dose of 1000 mg/kg/day in a 21-day dermal toxicity study). In addition, there were no susceptibility concerns.

Long-term inhalation exposure is not anticipated based on the current use pattern for quinclorac. Therefore, long-term PODs have not been established.

            0.12.2. Recommendation for Combining Routes of Exposures for Risk Assessment

Under FQPA, when there are potential residential exposures to the pesticide, aggregate risk assessment must consider exposures from three major sources: oral, dermal and inhalation exposures.  These combined residential exposures must then be aggregated with dietary exposure (food and drinking water) to determine aggregate risk. Dermal exposures were not quantified due to a lack of a dermal toxicological endpoint. Because the inhalation and incidental oral endpoints are based on the same endpoint from the same study, the developmental rabbit, exposures from these routes may be combined.

            0.12.3. Cancer Classification and Risk Assessment Recommendation

Quinclorac was classified in 1992 by the HED Cancer Peer Review committee (CPRC) as a group D carcinogen - not classifiable as to human carcinogenicity- based on recommendation by the EPA Scientific Advisory Panel (TXR# 0010416).  This classification was based on equivocal increase in the incidence of one type of benign tumor (pancreatic acinar cell adenomas) in only one sex and one species of animals (male Wistar rats).  Based on this classification, a quantification of cancer risk is not warranted because the chronic RfD will adequately account for all chronic effects, including carcinogenicity, that may  result from exposure to quinclorac. There was no evidence of carcinogenicity in mice or female rats.

            0.12.4. Summary of Points of Departure and Toxicity Endpoints Used in Human Risk Assessment

Toxicological doses and endpoints for dietary and non-occupational human health risk assessments for quinclorac are presented below in Table <IP_ADDRESS>.

Table <IP_ADDRESS>.  Summary of Toxicological Doses and Endpoints for Quinclorac for Use in Dietary and Non-Occupational Human Health Risk Assessments.
Exposure/
Scenario
Point of Departure
Uncertainty/FQPA Safety Factors
RfD, PAD, Level of Concern for Risk Assessment
Study and Toxicological Effects

Acute Dietary (General Population, including Infants and Children)
Not applicable.  An endpoint for acute dietary exposure to the general population was not selected because there was no available endpoint attributable to a single dose that was appropriate for this scenario (effects observed in the available studies are presumed to require more than one exposure).

Acute Dietary
(Females 13-49 years of age)
NOAEL (developmental) = 200 mg/kg/day
UFA= 10x
UFH=10x
FQPA SF= 1x

aRfD =  2.0 mg/kg/day

aPAD = 2.0 mg/kg/day
Developmental toxicity study in rabbits (MRID# 41063525 and 41680501) Developmental toxicity LOAEL =  600 mg/kg/day based on increased early resorptions and postimplantation loss, decreased live fetuses, decreased fetal body weight.  These fetal effects are presumed to occur after a single dose.
Chronic Dietary (All Populations)
NOAEL= 37.5 mg/kg/day
UFA= 10x
UFH=10x
FQPA SF= 1x

cRfD = 0.38
mg/kg/day

cPAD = 0.38 mg/kg/day
Carcinogenicity study in mice
(MRID # 41063523)
LOAEL = 150 mg/kg/day based on decreased body weight.
Incidental Oral Short-Term (1-30 days)
NOAEL= 70 mg/kg/day
UFA= 10x
UFH=10x
FQPA SF= 1x
Residential LOC for MOE = 100
Developmental toxicity study in rabbits. (MRID# 41063525 and 41680501)
Maternal toxicity LOAEL = 200 mg/kg/day based on decreased maternal body weight gain and food consumption, and increased water consumption.
Dermal (all durations)
Not applicable.  A dermal endpoint was not selected because an appropriate endpoint was not available (no dermal toxicity was seen at the limit dose of 1000 mg/kg/day in a 21-day dermal toxicity study).
Inhalation Short-Term (1-30 days) and Intermediate-Term (1-6 months)
NOAEL= 70 mg/kg/day
[Inhalation absorption rate = 100% relative to oral absorption]
UFA= 10x
UFH= 10x
FQPA SF= 1x
Residential LOC for MOE = 100
Developmental toxicity study in rabbits. (MRID# 41063525 and 41680501)
Maternal toxicity LOAEL = 200 mg/kg/day based on decreased maternal body weight gain and food consumption, and increased water consumption.

Inhalation Long-Term (>6 months)
Not applicable.  Long-term inhalation exposure is not anticipated under current use scenarios.
Cancer (oral, dermal, inhalation)
Quinclorac was classified in 1992 by the HED Cancer Peer Review committee (CPRC) as a group D carcinogen - not classifiable as to human carcinogenicity- based on recommendation by the EPA Scientific Advisory Panel (TXR# 0010416).  This classification was based on equivocal increase in the incidence of one type of benign tumor (pancreatic acinar cell adenomas) in only one sex and one species of animals (male Wistar rats).  A quantification of cancer risk is not warranted because the chronic RfD will adequately account for all chronic effects, including carcinogenicity, that may  result from exposure to quinclorac. There was no evidence of carcinogenicity in mice or female rats.
Point of Departure (POD) = A data point or an estimated point that is derived from observed dose-response data and  used to mark the beginning of extrapolation to determine risk associated with lower environmentally relevant human exposures.  NOAEL = no observed adverse effect level.  LOAEL = lowest observed adverse effect level.  UF = uncertainty factor.  UFA = extrapolation from animal to human (interspecies).  UFH = potential variation in sensitivity among members of the human population (intraspecies).  UFL = use of a LOAEL to extrapolate a NOAEL.  UFS = use of a short-term study for long-term risk assessment.  UFDB = to account for the absence of key date (i.e., lack of a critical study).  FQPA SF = FQPA Safety Factor.  PAD = population adjusted dose (a = acute, c = chronic).  RfD = reference dose.  MOE = margin of exposure.  LOC = level of concern.  N/A = not applicable.

Table <IP_ADDRESS> Summary of Toxicological Doses and Endpoints for Quinclorac for Use in Occupational Human Health Risk Assessments
                              Exposure/ Scenario
                              Point of Departure
                              Uncertainty Factors
                     Level of Concern for Risk Assessment
                        Study and Toxicological Effects
Dermal (all durations)
Not applicable.  A dermal endpoint was not selected because an appropriate endpoint was not available (no dermal toxicity was seen at the limit dose of 1000 mg/kg/day in a 21-day dermal toxicity study).
Inhalation Short-Term (1-30 days) and Intermediate-Term (1-6 months)
NOAEL=70 mg/kg/day
[Inhalation absorption rate = 100% relative to oral absorption]
UFA= 10x
UFH= 10x
FQPA SF= 1x
Residential LOC for MOE = 100
Developmental toxicity study in rabbits. (MRID# 41063525 and 41680501)
Maternal toxicity LOAEL = 200 mg/kg/day based on decreased maternal body weight gain and food consumption, and increased water consumption.
Cancer (oral, dermal, inhalation)
Quinclorac was classified in 1992 by the HED Cancer Peer Review committee (CPRC) as a group D carcinogen - not classifiable as to human carcinogenicity- based on recommendation by the EPA Scientific Advisory Panel (TXR# 0010416).  This classification was based on equivocal increase in the incidence of one type of benign tumor (pancreatic acinar cell adenomas) in only one sex and one species of animals (male Wistar rats).  A quantification of cancer risk is not warranted because the chronic RfD will adequately account for all chronic effects, including carcinogenicity, that may result from exposure to quinclorac. There was no evidence of carcinogenicity in mice or female rats.
Point of Departure (POD) = A data point or an estimated point that is derived from observed dose-response data and  used to mark the beginning of extrapolation to determine risk associated with lower environmentally relevant human exposures.  NOAEL = no observed adverse effect level.  LOAEL = lowest observed adverse effect level.  UF = uncertainty factor.  UFA = extrapolation from animal to human (interspecies).  UFH = potential variation in sensitivity among members of the human population (intraspecies).  UFL = use of a LOAEL to extrapolate a NOAEL.  UFS = use of a short-term study for long-term risk assessment.  UFDB = to account for the absence of key data (i.e., lack of a critical study).  MOE = margin of exposure.  LOC = level of concern.  N/A = not applicable.

      0.13.  Incident Reports

Quinclorac incidents were previously analyzed in 2007 (M. Hawkins, 08/30/2007, D343370).  In the previous review, two incidents were identified in IDS from 1999 to 2007; a total of five quinclorac cases were identified in the PCC data base 1993 to 2005; and there were no incidents identified in National Institute of Occupational Safety and Health Sentinel Event Notification System for Occupational Risks (NIOSH SENSOR) data from 1998 to 2003.  The document concluded that "No mitigation actions are necessary for quinclorac at this time."  Updated incident analysis of the Main and Aggregate Incident Data System (IDS) from January 1, 2007, to August 14, 2012, shows an increase in the number of incidents since the previous incident review performed in 2007.  This is most likely due to the fact that, prior to 2007, all quinclorac products used to treat residential turf could be applied only by a certified applicator. This was a self-imposed restriction by the registrant.  In 2007, the registrant requested this restriction be removed. Since the restriction was removed in 2007, there have been approximately 19 quinclorac products intended for use on residential turf registered that may be applied by the homeowner.  Obtaining additional information on current usage data for quinclorac would improve future assessments.  The updated analysis of NIOSH SENSOR from 1998 to 2008, is not current enough to represent the more recent residential registrations but is consistent with the previous 2007 review.  It should be noted the SENSOR dataset through 2009 is forthcoming (NIOSH plans to provide the updated dataset within the 2012 calendar year) and will be analyzed for additional quinclorac cases.

Overall, only a moderate number of incidents have been reported involving quinclorac.  The vast majority of these incidents were of low severity, although, there were a few high severity outcomes reported in the IDS database.  While incident information can be an important source of feedback to the Agency, reports of adverse health effects allegedly due to a specific pesticide exposure (i.e., an "incident") are largely self-reported and therefore, generally speaking, neither exposure to a pesticide or reported symptom (or the connection between the two) is validated or otherwise confirmed.  Typically, causation cannot be determined based on incident data.  The Agency will continue to monitor the incident information and if a concern is triggered, additional analysis will be performed (Memo, S. Recore, 9/25/2012, D405512).

 Dietary Exposure and Risk Assessment

      0.14.  Metabolite/Degradate Residue Profile

            0.14.1. Summary of Plant and Animal Metabolism Studies

The qualitative nature of quinclorac residues in plants was considered adequately understood for the currently registered uses, based upon the metabolism studies on rice, grain sorghum, and wheat.  In each of these studies, the major [14]C-residue in/on various matrices was identified as parent compound.  Based on the metabolite profiles observed in these studies, quinclorac undergoes hydroxylation of the quinoline ring of the parent, followed by conjugation with glucose and other biologically available compounds at the hydroxylated site.   Some radioactive residues are incorporated into the high molecular weight natural products.  Based on the above studies, HED concluded that parent is the only residue of concern in plant commodities for purposes of the tolerance expression and risk assessment.  However, all three metabolism studies are on grain commodities.  A 4[th] metabolism study, on canola, is available but has not been reviewed.

Metabolism in Rice:  (MRID 41063534).  The metabolism of 14C-ring labeled quinclorac in rice plants was studied under growth chamber and field conditions.  Growth chamber plants were treated at 1.4 lb.ai/A 14C-BAS 514H, an exaggerated dosage rate, at the four leaf stage of plant development. Growth-chamber rice plant samples were harvested for analysis at PHI=97 days. Field plants were treated at 0.75 lb/A 14C-BAS 514H, at the 3-5 leaf stage. The treatment level of field plants simulates the expected herbicide use rate. Field rice plants were harvested at PHI= 28 and 118 days.  Greater than 84% of the TRR in rice grain or straw was identified as the parent compound, quinclorac.

Metabolism in Sorghum:  (MRID #44322211).  Preemergence and post emergence applications of radiolabeled quinclorac were made to a confined sorghum plot.  The soil was a loamy sand soil with low organic matter.  Treatment levels were 0.47 lb ai/A preemergence (0 DAT) and 0.45 lb a.i./A postemergence (25 DAT) for a total of 0.92 lb ai/A.  Crop samples were collected and analyzed at various stages of maturity, including forage samples collected at twenty-five days after the postemergence treatment, and mature stover and grain collected at the final harvest (120 DAT).

Table 5.1.  Distribution and Identification of Residues from Sorghum RACs Treated at 0.92 lb a.i./A.

RAC
Radioactive Residues

Identified
Unidentified
Residuum

quinclorac
quinclorac methyl ester
Soluble polars
Organosoluble

ppm
%TRR
ppm
%TRR
ppm
%TRR
ppm
%TTR
ppm
%TRR
ppm
forage
4.01
73.4
2.94
3.6
0.145
18.7
0.750
4.7
0.188
<1
<0.01
fodder
0.87
21.5
0.186
5.9
0.051
52.4
0.455
19.4
0.169
<1
<0.01
grain
0.83
73.5
0.610
1.7
0.014
5.5
0.044
6.6
0.055
<1
<0.01

The radioactive residues of quinclorac found in sorghum following typical agricultural practices consist predominantly of parent compound.  A minor metabolite, the methyl ester of quinclorac, is found in all tissues, but always at less than 10% TRR.   A lower percentage of the residue in sorghum fodder was found to be quinclorac, but the majority of the residue was soluble polar compounds.  The current analytical methodology (BASF Method No. A8902) employs a similar acetone extraction step as used in the above extractions.  Therefore, the accountability of the residues is high.

Metabolism in Wheat:   (MRID #44322207).   The test substance used in this study was quinclorac (labeled at the 3 position) at two application rates (0.112 lb ai/A (0.45X the proposed  rate) and 0.446 lb ai/A (1.8X the proposed rate)).  Only the higher application rate is presented in the table below.  Plants were grown in greenhouse conditions and sprayed 22 days after planting, when they were in the 3 to 5 leaf stage.  Forage samples were collected at a 37-day PHI, straw and grain at a PHI of 92 days.

Table 5.2.  Distribution and Identification of Residues from Wheat RACs Treated at 0.446 lb ai/A Quinclorac.

RAC
Radioactive Residues

ppm
Identified
Unidentified
Unextracted Marc

quinclorac
quinclorac methyl ester
aqueous acetone soluble
hydrolyzable
non-hydrolyzable

%TRR
ppm
%TRR
ppm
%TRR
ppm
%TRR
ppm
%TRR
ppm
forage
13.1
45.1
5.9
6.4
0.84
38.4
5.1
10.3
0.34
1.9
0.06
straw
8.2
22.4
1.8
12.6
1.0
45.1
3.7
12.4
0.23
3.3
0.06
grain
3.9
68
2.7
3.7
0.15
17.2
0.68
3.3
0.04
0.3
<0.01

The primary path by which plants metabolize quinclorac is through the hydroxylation of the quinoline ring of the parent, followed by the conjugation of glucose and other biologically available compounds at the hydroxylated site.  Ultimately, some radioactive residues are incorporated into the high molecular weight natural products.

The petitioner, IR-4, requests a waiver from the requirement of another metabolism study based on the following.  In the studies to date it has been shown that in plants the primary path by which quinclorac is metabolized is through hydroxylation of the quinolone ring of the parent, followed by the conjugation of glucose and other biologically available compounds at the hydroxylated site.    These results were similar for all quinclorac metabolism studies submitted to date.

Rhubarb and cranberry are very low acreage crops.  Cranberry is commercially grown on just over 40,000 acres, and Rhubarb is commercially grown on approximately 2,000 acres in the US (based on 2002 census of Agriculture).

In addition, other related quinoline compounds, such as quinoxyfen have shown similar metabolism results in that the parent is the primary residue component (D276835, 3/26/2003, G. Kramer) when conducted on a wide variety of plant matrices (cucumber, grape, sugarbeet, and tomato).  In these studies, quinoxyfen was the primary residue component and other remaining compounds were incorporated into natural plant constituents.  In cucumber and tomato, unchanged quinoxyfen remained largely on the surface of treated plants.  The presence of multiple unidentified polar residues suggests that metabolism of quinoxyfen does occur to some extent to form more polar soluble components with the incorporation into insoluble material.

Conclusions.  While the metabolism of quinclorac is adequately understood with regard to the currently registered uses, there are no plant metabolism data for quinclorac on commodities similar to cranberry.  These data are not being required at this time.  However, any further expansion of the use of quinclorac to other commodities grown on larger acreages than rhubarb and cranberry, will trigger a requirement of additional metabolism data.

The methyl ester of quinclorac was reported in some grain commodities at <15% of the TRR.  The methyl ester is measured by the enforcement method, which includes a methylation step.

 860.1300 Nature of the Residue - Livestock
D241204, J. Stokes, 11/6/1998
D325790, M. Doherty, 9/13/2007

The qualitative nature of quinclorac residues in livestock is understood based upon the adequate goat and poultry metabolism studies (MRIDs 41076104 and 41063535, respectively).  In both studies, quinclorac was the principal residue identified in each commodity.  HED concluded that parent is the only residue of concern for risk assessment and tolerance expression for livestock.  However, the enforcement method includes a methylation step and determines the methyl ester of quinclorac.

In a rat metabolism study (MRID 41063533), quinclorac was the primary metabolite reported.  Elimination was primarily in the urine (91-98%) with small amounts in the feces (1-4%) eliminated by day 5 after dosing.

Conclusions.  No further livestock metabolism data are required at the present time.

            0.14.2. Summary of Environmental Degradation

M. Lowit, N. Andrews, D397720, 8/9/12; M. Lowit, N. Andrews, D405093, 9/14/12

Vapor pressure (7.5 x 10[-8] mm Hg at 20[o] C) and Henry's Law Constant (1.22 to 24.3 x 10[-15] atm.m[3] mol[-1]) indicate a low possibility of volatilization from soil and water.  Laboratory data indicate that quinclorac is stable to hydrolysis, photolysis in sterile water, aerobic soil metabolism, and aquatic metabolism (aerobic and anaerobic).  Conversely, quinclorac undergoes rapid photolysis in non-sterile rice paddy, natural river waters, and solutions containing activated sewage sludge (half-lives of 5-10 days).  Photolysis on soil surface is also a route of dissipation with a mean half life of 141 days.  Based on available laboratory studies, two major (BH 514-1 and BH 514 2-OH; >10% applied) and one minor (BH 514-HMe-ester; <10% applied) metabolites of quinclorac were identified.  The adsorption coefficients for quinclorac and its degradation products suggest that leaching could be a route of dissipation.  Field studies indicate that quinclorac is moderately persistent to persistent (18-176 day half-lives) in terrestrial environments. The octanol/water partition coefficient (KOW) of 0.266 also suggests that quinclorac has a low potential to bioaccumulate.  A detailed assessment of the environmental fate of quinclorac can be found in the new chemical risk assessment (DP 250179+).

            0.14.3. Comparison of Metabolic Pathways

Quinclorac was the predominant metabolite in all 3 plant metabolism studies (all in grains), and in the livestock metabolism study and the rat metabolism study.  Small amounts of a methyl ester in plants was reported.

The primary path by which plants metabolize quinclorac is through the hydroxylation of the quinoline ring of the parent, followed by the conjugation of glucose and other biologically available compounds at the hydroxylated site.  Ultimately, some radioactive residues are incorporated into the high molecular weight natural products. The forage, fodder, and straw reported a number of aqueous metabolites, which would be polar metabolites, such as hydroxylated metabolites or conjugates.

The qualitative nature of quinclorac residues in livestock is understood based upon adequate goat and poultry metabolism studies (MRIDs 41076104 and 41063535, respectively).  Quinclorac was the principal residue identified in each commodity.

In a rat metabolism study (MRID 41063533), quinclorac was the primary metabolite reported.  Elimination was primarily in the urine (91-98%) with small amounts in the feces (1-4%) eliminated by day 5 after dosing.

            0.14.4. Residues of Concern Summary and Rationale

Quinclorac was not reviewed by ROCKs or its predecessor. Previous risk assessment teams determined that quinclorac was the residue of concern since it was the predominant metabolite.

Table 5.1.4  Summary of Metabolites and Degradates to be included in the Risk Assessment and Tolerance Expression
Matrix
Residues included in Risk Assessment
Residues included in Tolerance Expression
Plants
Primary Crop
Quinclorac
Quinclorac

Rotational Crop
Quinclorac
Quinclorac
Livestock
Ruminant
Quinclorac
Quinclorac

Poultry
Quinclorac
Quinclorac
Drinking Water
Quinclorac
Not Applicable

      0.15.  Food Residue Profile

D397719, D404569, D404912, S. Hummel, G. Otakie, 9/6/12

Residue Analytical Methods: An adequate GC/ECD method is available for enforcing the proposed tolerances, and the field trial data were collected using an LC/MS/MS method adequate for determining quinclorac, per se.  If LC/MS/MS is to be used, a method is needed for the methyl ester of quinclorac and any other metabolites found in the required metabolism study.

Multiresidue Methods: Adequate data are available evaluating quinclorac through the FDA Multi-Residue Methods Test guidelines, and quinclorac is detected by Protocol B.  Quinclorac is not detected by the other FDA MRM protocols.

Storage Stability: The available storage stability data are adequate and support the storage conditions and durations incurred in the existing field trials, for currently registered uses.  The IR-4 concurrent storage stability data for rhubarb and cranberry are adequate for residues of quinclorac, demonstrating stability for the time and conditions the samples were stored.  Storage stabilty data are needed for residues of the methyl ester of quinclorac and other residues of concern found in the required metabolism study.

Water, Fish, and Irrigated Crops: For existing use on rice and the proposed use on cranberry, a label restriction is needed regarding the use of treated rice and cranberry fields for aquaculture.  Alternatively, the petitioner can determine residues in catfish and crayfish raised in treated fields and propose tolerances for these commodities if necessary.  The label provided for Quinclorac/QuinStar 4-L does not contain any restriction against aquaculture.

Conclusions.  Data on catfish and crayfish are required, or the label must prohibit use of treated water from rice and cranberry fields for aquaculture. For registration review, the PM must ensure that all quinclorac labels with uses on rice and cranberry contain such a restriction.

Meat, Milk, Poultry, and Eggs: Adequate cattle and poultry feeding studies are available. The uses proposed in this petition do not involve livestock feeds, and will not affect the existing tolerances on meat, milk, poultry and eggs.

For registration review, we are recommending that the tolerance on Grain, aspirated fractions be revoked, since data have been received demonstrating that the tolerance is not needed, as residues on aspirated grain fractions (AGF) are no higher than the tolerances on the grains. AGF were the highest contributor to the livestock dietary burden, but tolerances have since been established for grass commodities, which is now the highest contributor to the livestock dietary burden.

Conclusions. Tolerances in livestock commodities will be changed in connection with Registration Review.  Residues are expected to be found in meat byproducts and fat but not in milk and eggs.  The dietary burden for hogs and poultry is low enough that no quantifiable residues are expected in hog and poultry commodities.

Crop Field Trials:

Cranberry (for Low Growing Berries except strawberry, subgroup 13-07.  Five cranberry field trials were conducted in the United States during the 2009 growing season, in North American Free Trade Agreement (NAFTA) Growing Zones 1 (MA; 2 trials), 5 (WI; 2 trial), and 12 (OR; 1 trial).  The two MA trials (MA01 and MA03) and the two WI trials (WI01 and WI02) were each conducted using the same Field Research Director (FRD).   Careful examination of the field trial records indicates that the only difference between each pair of trials was the use of different varieties of cranberry, and distance between MA trials of > 20 miles, and different soil characteristics for the MA trials.  HED has concluded that there are insufficient distinguishing characteristics to classify the WI pair as separate trials; however, the trials were conducted prior to development of the guidance on field trial differentiation.

Following two foliar broadcast applications of the 3.8 lb ai/gal SC formulation of quinclorac at 0.484-0.528 lb ai/A, residues of quinclorac (and per trial averages) in/on cranberry harvested at a 57- to 62-day PHI were 0.15-0.68 (0.16-0.67) ppm.  Applications were made at a 28- to 32-day retreatment interval (RTI) using ground equipment in spray volumes of 29.7-35.3 gal/A.  A crop oil concentrate (COC) was added to the spray mixture for each of the applications at 2 pints/A.

Rhubarb.  Four field trials were conducted in the United States during the 2009 growing season in the North American Free Trade Agreement (NAFTA) Growing Zones 5 (MI; 1 trial) and 12 (OR; 3 trials).  The two rhubarb trials in Canby, OR (OR11 and OR12) and the trial in Hillsboro, OR (OR10) were conducted by the same Field Research Director (FRD).  Careful examination of the field trial records indicates there are sufficient distinguishing characteristics to classify the Hillsboro, OR trial as a separate trial from the Canby, OR trials, based on location (>20 miles apart) and spray volume (>25% higher at the Hillsboro site).  There are insufficient distinguishing characteristics to classify the two Canby, OR trials as separate trials; therefore, the Canby, OR trials constitute a single trial with replicate samples for purposes of 860.1500 data requirements.  The adjustment in trial numbers results in a total of three field trials, with one trial in Zone 5 and two trials in Zone 12.

Following two foliar broadcast applications of the 3.8 lb ai/gal SC formulation of quinclorac at 0.736-0.798 lb ai/A, residues (and per trial averages) of quinclorac in/on rhubarb harvested at a 29- to 33-day PHI were 0.05-0.231 (0.082-0.205) ppm.  The method LOQ was 0.05 ppm.  Applications were made at a 28- to 31-day retreatment interval (RTI) using ground equipment in spray volumes of 19.9-36.7 gal/A.  A crop oil concentrate (COC) was added to the spray mixture for each of the applications at a rate of 1-2 pints/A.

Conclusions.  Field trial data are adequate to determine residues of quinclorac, per se.  Samples must be reanalyzed for the methyl ester of quinclorac and any other residue of concern found in the metabolism study.

IR-4 should note the current guidance for differentiating field trial sites.

Existing Uses of Remaining Crops:

Existing uses of Quinclorac include use on rice, wheat, soybeans, barley (import), grass forage and hay.  Field trial data are adequate to support the existing uses of quinclorac on rice, grain sorghum, barley (imported), and pasture and range grasses. In decline studies, residues generally degraded substantially within 14 days.

The established tolerance on aspirated grain fractions should be revoked as it is not needed.  The tolerance on rice straw may be revoked, as rice straw is no longer considered a livestock feedstuff.

Processed Food and Feed

There are no processed commodities in connection with the current petition.

For registration review, processing studies submitted to support existing tolerances are adequate.   Processing studies were submitted for Rice (MRID 41063543), Sorghum (MRID#44322213), and Wheat (MRID#44322209).  Residues of quinclorac concentrate in hulls and in some grain milled products. Available processing data are adequate to support the currently registered uses of quinclorac.

Confined and Field Accumulation in Rotational Crops

Adequate rotational crop studies are available to support the use of quinclorac.  No residues greater than the limit of detection of 0.05 ppm quinclorac were found in mustard leaves and turnip leaves and roots when planted 120 and/or 270 days after a quinclorac application to rice.  (The analytical method was validated down to 0.05 ppm, so 0.05 ppm may be called the limit of quantitation (LOQ) or the lower limit of method validation (LLMV). Quantifiable residues of concern are not expected at rotational crop intervals of 120 days or longer.

      0.16.  Water Residue Profile

M. Lowit, N. Andrews, D397720, 8/9/12; M. Lowit, N. Andrews, D405093, 9/14/12

The current assessment is performed according to current EFED guidance and up-to-date models including the Tier II surface water model (PRZM/EXAMS) for all uses of quinclorac except cranberries and rice. Screening-level Tier I modeling was used to estimate surface water concentrations for use on cranberry (provisional cranberry model) and rice (Tier I rice model) because the current Tier II model is not parameterized for those uses.  The Tier I SCI-GROW model was used to estimate groundwater concentrations for all uses.

 As in past assessments, this assessment does not consider quinclorac major degradation products BH 514-1 and BH 514 2-OH. Although these degradates were detected in the laboratory studies, they seem to be intermediate degradates (DP 344485), and were not found in field dissipation studies at any significant levels. Furthermore, since quinclorac is persistent and mobile, it is expected to be the predominant residue in ground and surface waters.

Surface water EDWCs (acute = 511 ug/L and chronic = 511 ug/L) resulting from use on rice supersede previously recommended EDWCs.  The recommended groundwater EDWC has not changed (29 ug/L for acute and chronic exposure).

Table 5.3a.  Estimated Drinking Water Concentrations (EDWCs) of Quinclorac in Surface Water Sources.

                                      Use
                                   Scenario
Estimated Drinking Water Concentrations from Surface Water Sources (ug/L)[1,2,3]

                              1-in-10 year acute
                             1-in-10 year chronic
                                 30-year mean
Turf grasses
(1.4 lb ai/A x 1)

(0.76 lb ai/A x 2)

FL turf [4]
41.3
28.5
16.8

PA turf [4,5]
58.3
37.8
20.0

FL turf [4]
43.1
32.8
16.3

PA turf [4,5]
74.1
62.0
23.7
Sorghum
(0.375 lb ai/A x 2)

(0.245 lb ai/A x 3)

KS sorghum (postplant)[6]
26.3
10.5
6.9

KS sorghum (postplant/fall)[7]
20.5
10.2
6.3

KS sorghum (preplant)
23.6
9.5
6.4
Wheat
ND wheat (preplant spring)
38.7
26.9
16.5

ND wheat (preplant winter)
46.6
28.6
19.3
Rangeland / Pasture
FL turf[4]
29.3
21.2
14.6

PA turf[4,5]
36.6
25.3
16.0

CArangelandhayRLF_v2[4]
54.0
36.9
20.5
Rights of way /Fencerow /Hedgerows
1.5 lb ai/A x 1
0.76 lb ai/A x 2
CArightofwayRLF_v2[4]
24.7
14.9
8.2

CArightofwayRLF_v2[4]
27.7
14.3
8.4
Grass grown for seed[4,5]
ORgrassseed[4,5]
25.4
15.8
11.0
Fallow land
FL turf[4]
27.1
19.6
13.7

PA turf[4,5]
31.5
21.1
13.6

CArangelandhayRLF_v2[4]
39.3
27.2
16.4
Grass forage /Fodder /Hay
FL turf[4]
26.4
18.5
14.4

PA turf[4,5]
27.1
21.4
14.9

CArangelandhayRLF_v2[4]
46.8
31.7
20.6
Low growing berry (except cranberry and strawberry)
ORberriesOP
3.4
2.0
1.3
Rhubarb
CA cole crop RLF_v2
33.8
18.0
11.4

CA lettuce
27.9
18.8
12.9
Cranberry

Provisional Cranberry Model[8]
161.9
147.2
--
Rice
Tier I Rice Model[9]
511.1
511.1
--
Aquatic Weeds[10]
Labeled concentration
500.0
500.0
--
1 PCA = 1  (www.epa.gov/oppefed1/models/water ) because this is a national drinking water assessment and quinclorac is registered for non-agricultural, non-turf uses.
[2] BOLD indicates highest EDWC
[3] EDWCs based on aerial applications are presented for uses that permit aerial and ground applications at the same application rate.
[4] Highest value of twelve estimates (first application on the first day of each month) because there are no restrictions on when pesticide may be applied.
[5] Although permitted, it was assumed that winter applications would be unlikely (December, January, February).
[6] Two applications between preemergence and postemergence (up to 12 inches)
[7] One application between preemergence and postemergence (up to 12 inches) and one application in the fall prior to the first killing frost
[8]Based on a one-year simulation; 1 in 10 year calculation is not applicable.
[9] Based on a single, screening level concentration; 1 in10 year calculation is not applicable.
[10] Registered as an experimental use permit.

Table 5.3b.  Estimated Drinking Water Concentrations (EDWCs) of Quinclorac in Ground Water Sources

                                      Use
                               Application Rate
 Estimated Drinking Water Concentrations from Ground Water Sources (ug/L)[1]

                                     Acute
                                    Chronic
Turf grasses
1.4 lb ai/A x 1
                                      27
                                      27

0.76 lb ai/A x 2
                                      29
                                      29
Sorghum
0.375 lb ai/A x 2 and 0.245 lb ai/A x 3
                                      14
                                      14
Wheat
0.245 lb ai/A x 3
                                      14
                                      14
Rangeland / Pasture
0.75 lb ai/A x 1
                                      14
                                      14
Rights of way/Fencerow/Hedgerows
1.5 lb ai/A x 1
                                      29
                                      29

0.76 lb ai/A x 2
                                      29
                                      29
Grass grown for seed
0.375 lb ai/A x 2
                                      14
                                      14
Fallow land
0.75 lb ai/A x 1
                                      14
                                      14
Grass forage /Fodder /Hay
0.375 lb ai/A x 2
                                      14
                                      14
Low growing berry (except cranberry and strawberry)
0.25 lb ai/A x 2
                                      10
                                      10
Rhubarb
0.375 lb ai/A x 2
                                      14
                                      14
Rice[2]
--
                                      --
                                      --
Cranberry[2]
--
                                      --
                                      --
Aquatic Weeds[2]
--
                                      --
                                      --
1 BOLD indicates highest EDWC
[2] Groundwater concentrations are not estimated for aquatic uses.

      2.1.  Dietary Risk Assessment

            2.1.1. Description of Residue Data Used in Dietary Assessment

Acute and chronic aggregate dietary (food and drinking water) exposure and risk assessments were conducted using the Dietary Exposure Evaluation Model DEEM-FCID, Version 3.16 which uses food consumption data from the U.S. Department of Agriculture's National Health and Nutrition Examination Survey, What We Eat in America, (NHANES/WWEIA).  This dietary survey was conducted from 2003 to 2008.  These analyses were performed to support the Section 3 request for quinclorac uses on rhubarb and low growing berry, except strawberry, subgroup 13-07H and to support Registration Review for quinclorac and the dimethylamine (DMA) salt of quinclorac.  All registered, pending and proposed uses of quinclorac and the DMA salt of quinclorac, as of the date of this memorandum, are included in these assessments.

Tolerances have been established for quinclorac (40CFR §180.463[a]) in livestock and cereal grain commodities.  HED has determined that the use of the DMA salt of quinclorac on cereal grains will not affect the established tolerances for quinclorac on rice, grain sorghum, and wheat.
The residue of concern (ROC), for both tolerance enforcement and risk assessment, is the parent compound, quinclorac.

The quinclorac drinking water estimates used in these dietary risk assessments were provided by EFED (DP# 397720, M. Lowit/N. Andrews, 8/9/12 and DP# 405093, M. Lowit/N.Andrews, 9/14/12), and incorporated directly into the dietary assessments.  Water residues were incorporated in DEEM-FCID via entry into the food categories "water, direct, all sources" and "water, indirect, all sources."  The estimated drinking water concentrations (EDWCs) from existing and proposed uses of quinclorac for both acute and chronic scenarios in ground and surface water are 0.029 ppm and 0.511 ppm, respectively.

Rice (labeled for a single application of 0.5 lb ai/A) was identified as the use resulting in the highest EDWCs for surface water.  Because the use on rice involves flooding (for which the current Tier II model is not parameterized), the surface water EDWCs were assessed using a Tier I Rice Model, Version 1.0 (May 8, 2007).  Turf grass was identified as the use resulting in the highest EDWCs for ground water.  The EDWC in ground water was assessed using the Tier I Screening Concentration in Ground Water (SCI-GROW, Version 2.3) model.  These models, and their descriptions, are available at the EPA internet website via the web link, http://www.epa.gov/oppefed1/models/water/.  No surface or ground water monitoring data were available for quinclorac.

            2.1.2. Percent Crop Treated Used in Dietary Assessment

The acute and chronic assessments are based on the assumption that 100% of all commodities with tolerances will be treated.

            2.1.3. Acute Dietary Risk Assessment

The acute dietary assessment is highly conservative, and assumes 100% crop treated (%CT), along with tolerance-level residues for all agricultural commodities.  Default processing factors from DEEM 7.81 were used (for dried beef and cranberry juice) in the analyses.  Tier I modeling was used to estimate drinking water concentrations.

The acute (food + water) dietary risk estimate at the 95[th] percentile of exposure is 1.6% of the acute population adjusted dose (aPAD) for females age 13 to 49.  This is the only population subgroup for which an acute endpoint was selected.

Generally, the Agency is concerned when risk estimates exceed 100% of the PAD.  The acute dietary risk estimate for quinclorac is below HED's level of concern.

            2.1.4. Chronic Dietary Risk Assessment

The chronic dietary assessment is highly conservative, and assumes 100% crop treated (%CT), along with tolerance-level residues for all agricultural commodities.  Default processing factors from DEEM 7.81 were used (for dried beef and cranberry juice) in the analyses.  Tier I modeling was used to estimate drinking water concentrations.

The chronic (food + water) dietary risk estimates are less than or equal to 8.9% of the chronic population adjusted dose (cPAD) for all population subgroups.  All Infants < 1 year of age is the most highly-exposed subgroup, utilizing 8.9% of the cPAD, while the general US population utilizes 3.6% of the cPAD.

Generally, the Agency is concerned when risk estimates exceed 100% of the PAD.  All chronic dietary risk estimates for quinclorac are below HED's level of concern.

            2.1.5. Cancer Dietary Risk Assessment

Quinclorac was classified in 1992 by the HED Cancer Peer Review committee (CPRC) as a group D carcinogen - not classifiable as to human carcinogenicity- based on recommendation by the EPA Scientific Advisory Panel (TXR# 0010416).  This classification was based on equivocal increase in the incidence of one type of benign tumor (pancreatic acinar cell adenomas) in only one sex and one species of animals (male Wistar rats).   Based on this quantification, a quantification of cancer risk is not warranted because the chronic RfD will adequately account for all chronic effects, including carcinogenicity, that may result from exposure to quinclorac.

            2.1.6. Summary Table

 Table 5.4.6.  Summary of Dietary (Food and Drinking Water) Exposure and Risk for Quinclorac
                              Population Subgroup
                                 Acute Dietary
                               (95th Percentile)
                                Chronic Dietary
                                     Cancer

                          Dietary Exposure (mg/kg/day)
                                    % aPAD*
                                Dietary Exposure
                                  (mg/kg/day)
                                    % cPAD*
                                Dietary Exposure
                                  (mg/kg/day)
                                      Risk
 General U.S. Population
                                      N/A
                                      N/A
                                   0.013728
                                      3.6
                                      N/A
                                      N/A
 All Infants (< 1 year old)

                                   0.033999
                                      8.9

 Children 1-2 years old

                                   0.023500
                                      6.2

 Children 3-5 years old

                                   0.019280
                                      5.1

 Children 6-12 years old

                                   0.013431
                                      3.5

 Youth 13-19 years old

                                   0.010195
                                      2.7

 Adults 20-49 years old

                                   0.013614
                                      3.6

 Adults 50+ years old

                                   0.012525
                                      3.3

 Females 13-49 years old
                                   0.032108
                                      1.6
                                   0.012893
                                      3.4

 Residential (Non-Occupational) Exposure/Risk Characterization

Ivan Nieves, D404915, D404797, 9/18/12

Although this document addresses proposed new agricultural uses which do not involve applications by homeowners or commercial applicators in residential settings, HED has recently updated the residential exposure standard operating procedures (SOPs) and body weights to be used in all human health assessments as well as the incorporation of new chemical specific toxicological information.  As a result of the updated policies and parameters, all of the existing residential (non-occupational) use patterns have been reassessed in this document because these scenarios will impact the quinclorac aggregate assessment.

Although, quinclorac products do not appear to be specifically marketed towards residential handler use (i.e., homeowners); a residential handler assessment was performed to be protective of any such use.  Quinclorac is currently registered for use on turfgrass (lawns, sod, turf areas) including but not limited to grounds or lawns around residential and commercial establishments, multifamily dwellings, military and other institutions, parks, airports, roadsides, schools, picnic grounds, athletic fields, houses of worship, cemeteries, golf courses, prairie grass areas, and sod farms.  Quinclorac may also be used in and around established landscape ornamentals and ornamental gardens.  The quinclorac products used in residential settings can be formulated as granular, liquid, and dry flowable formulations.

      60.1.  Residential Handler Exposure

Based on the anticipated use patterns and current labeling, types of equipment and techniques that can potentially be used, residential handler exposure is expected from the existing uses.  The quantitative exposure/risk assessment developed for residential handlers is based on the following scenarios:

   1. Loading/Applying granules for belly grinder,
   2. Loading/Applying granules for push type rotary spreader,
   3. Loading/Applying granules for a spoon;
   4. Loading/Applying granules for a cup and shaker can;
   5. Applying granules by hand;
   6. Mixing/loading/applying liquid and dry flowable formulations via manually-pressurized handwand, a hose-end sprayer, a backpack, and a sprinkler can;
   7. Mixing/loading/applying ready-to-use formulation via a trigger sprayer, and a hose-end sprayer.

For residential handlers, HED presents exposure estimates for individuals wearing shorts, short-sleeved shirts, shoes plus socks.  Pesticide application area assumed to be performed by adults only, however the assessment does group 16 year olds with adults.

Table 6.1 lists the exposures and risk estimates for the residential handler scenarios. The updated exposure scenarios result in risk estimates that do not exceed HED's level of concern (MOEs >= 100).

Table 6.1. Quinclorac Residential (Non-Occupational) Handler Estimated Risks
                                  Formulation
                         Application Equipment/Method
                              Application Rate[1]
                                     Units
                     Area Treated or Amount Handled Daily
                                Units (per day)
                    Inhalation Unit Exposure (mg/lb ai)[2]
                          Inhalation Exposure (mg/day)
                    Inhalation Absorbed Dose[3] (mg/kg/day)
                               Inhalation MOE[4]
                                    Granule
Push-type spreader
                                     0.68
                                  lb ai/acre
                                      0.5
                                     acres
                                    0.0026
                                    0.00088
                                   0.000011
                                   6,300,000

Belly grinder
                                   0.0000172
                                  lb ai/ft[2]
                                     1200
                                     ft[2]
                                     0.039
                                    0.0008
                                    0.00001
                                   7,000,000

Spoon

                                      100
                                     ft[2]
                                     0.087
                                    0.00015
                                   0.0000019
                                  37,000,000

Cup; Shaker can

                                     0.013
                                   0.000022
                                  0.00000028
                                  250,000,000

Hand dispersal

                                     0.38
                                    0.00065
                                   0.0000082
                                   8,600,000
                              Liquid concentrate
Hose-end Sprayer
                                     0.78
                                  lb ai/acre
                                      0.5
                                     acres
                                     0.022
                                    0.0086
                                    0.00011
                                    650,000

Manually-pressurized handwand
                                     0.16
                                 lb ai/gallon
                                       5
                                    gallons
                                     0.018
                                     0.014
                                    0.00018
                                    390,000

Backpack

                                     0.14
                                     0.11
                                    0.0014
                                    50,000

Sprinkler can
                                   0.0000172
                                  lb ai/ft[2]
                                     1000
                                     ft[2]
                                     0.022
                                    0.00038
                                   0.0000047
                                  15,000,000

Trigger-sprayer
(Ready-to-Use)
                                    0.0172
                                 lb ai/bottle
                                       1
                                    bottle
                                     0.061
                                     0.001
                                   0.000013
                                   5,300,000

Hose-end Sprayer
(Ready-to-Use)
                                     0.76
                                  lb ai/acre
                                      0.5
                                     acres
                                     0.034
                                     0.013
                                    0.00016
                                    430,000
                   Water-dispersible Granule / Dry Flowable
Manually-pressurized handwand
                                     0.28
                                 lb ai/gallon
                                       5
                                    gallons
                                      1.1
                                      1.5
                                     0.019
                                     3,600

Hose-end Sprayer
                                      1.4
                                  lb ai/acre
                                      0.5
                                     acres
                                     0.022
                                     0.015
                                    0.00019
                                    360,000

Backpack
                                     0.28
                                 lb ai/gallon
                                       5
                                    gallons
                                      1.1
                                      1.5
                                     0.019
                                     3,600

Sprinkler can
                                   0.0000172
                                  lb ai/ft[2]
                                     1000
                                     ft[2]
                                     0.022
                                    0.00038
                                   0.0000047
                                  15,000,000
   1. Max application rate based on various labels containing non-occupational use sites registered for quinclorac
   2. Based on Standard Operating Procedures for Residential Pesticide Exposure Assessment http://www.epa.gov/pesticides/science/EPA-OPP-HED_Residential%20SOPS_Feb2012.pdf :
   3. Inhalation Dose (mg/kg/day) = daily unit exposure (mg/ - lb ai) * application rate (lb ai/acre) * amount handled (acres) * inhalation absorption (100%) /  - body weight (79.5 kg);
   4. Inhalation MOE = PoD (NOAEL of 70 mg/kg/day) / Daily inhalation dose (mg/kg/day). Level of concern = 100.

      4.1.  Residential Post-Application Exposure

There are no proposed residential uses at this time; however, there are existing registered residential uses on lawns and turf for liquid and granular formulations that have been reassessed as part of Registration Review.  A summary of the exposure and risk is provided below for use in performing an aggregate exposure assessment.

            4.1.1. Residential (Non-occupational) post-application inhalation

Based on the Agency's current practices, a quantitative residential post-application inhalation exposure assessment was not performed for quinclorac at this time primarily because quinclorac's vapor pressure (2.7 x 10-7 mm Hg @ 25.0°C) and Henry's Law Constant (3.72 X 10[-2] Pa m[3]/mol-1) indicate that the compound is relatively non-volatile under field conditions.    The Agency sought expert advice and input on issues related to volatilization of pesticides from its Federal Insecticide, Fungicide, and Rodenticide Act Scientific Advisory Panel (SAP) in December 2009.  The Agency received the SAP's final report on March 2, 2010 (http://www.epa.gov/scipoly/SAP/meetings/2009/120109meeting.html).  The Agency is in the process of evaluating the SAP report and may, as appropriate, develop policies and procedures to identify the need for and, subsequently, the way to incorporate post-application inhalation exposure into the Agency's risk assessments.  If new policies or procedures are put into place, the Agency may revisit the need for a quantitative post-application inhalation exposure assessment for quinclorac.

            4.1.2. Residential (Non-Occupational) Post-Application Dermal and Incidental Oral

Post-application short-term dermal and incidental oral exposure is expected from quinclorac treated turf in residential settings (i.e., lawns).  Dermal exposures were not quantified due to a lack of a dermal toxicological endpoint.  Incidental oral exposure risk estimates were calculated for hand-to-mouth, object-to-mouth, and soil ingestion exposures for 1 to <2 year old children playing in the treated turf.  Even though there is a granular product, an assessment for episodic granular ingestion was not done since there is no applicable endpoint (i.e., no acute dietary point of departure for children).

Table 6.2.  Short-Term Oral Non-dietary Ingestion Residential Post-application Exposure and Risk Estimates for Quinclorac Resulting from Application to Turf
                                   Lifestage
                      Post-application Exposure Scenario
                             Application Rate [a]
                                   (lb ai/A)
                                    TTR[b]
                                  (ug/cm[2])
                       Oral Dose [c, d], [e] (mg/kg/day)
                                 Oral MOEs[f]
                                    Liquids
                            Child 1 < 2 year old
                                     Oral
                                 Hand-to-Mouth
                                      1.4
                                     0.16
                                     0.021
                                     3,300

                                Object-to-Mouth

                                    0.00065
                                    110,000

                                Soil Ingestion

                                    4.7E-05
                                   1,500,000
                                   Granular
                            Child 1 < 2 year old
                                    Oral
                                 Hand-to-Mouth
                                     0.68
                                     0.015
                                    0.0010
                                    68,000

                                Object-to-Mouth

                                   0.000063
                                   1,100,000

                                Soil Ingestion

                                    2.3E-05
                                   3,000,000
   a.    Application rates = maximum application rates from latest LUIS report current as of 7/19/2012.
   b.    Turf Transferable Residue (TTR) (Not Chemical Specific) = AR*FAR ((1-FD)[t])* 4.5x108 [ug/lb]*2.5[-8] [acre/cm[2]]
   c.    Hand-to-Mouth Dose (mg/kg/day) = E = [HR * (FM * SAH) * (ET * N_Replen) * (1- (1- SE)[(][Freq_Replen][/N-Replens)])]
   d.    Object-to-Mouth Dose (mg/kg/day) = E = [OR* CF1 * SAMO * (ET * N_Replen) * (1- (1- SEO)[(][Freq_Replen][/][N_Replen][)])]
   e.    Soil Ingestion Dose (mg/kg/day) = E = SRt * SIgR * CF1
   f.    Oral MOE = NOAEL (70 mg/kg/day) / Oral Dose (mg/kg/day)

      6.1.  Combined Residential Risk Estimates (Multiple Exposure Scenarios)

HED combines risk values resulting from separate exposure pathways when it is likely they can occur simultaneously based on the use pattern, the behavior associated with the exposed population, and the hazard associated with the points of departure.  HED reviewed all residential sources of exposure to determine which residential exposure scenarios would be appropriate to combine with dietary exposure for an aggregate risk assessment.  The only applicable exposure pathways are inhalation (for adult handlers) and incidental oral (for post-application exposure to children).  For children, the incidental oral scenarios (i.e., hand-to-mouth, object-to-mouth, and soil ingestion) should be considered inter-related and it is likely that they occur interspersed amongst each other across time.  Combining these scenarios together would be overly-conservative because of the conservative nature of each individual assessment.

      6.2.  Residential Risk Estimates for Use in Aggregate Assessment

Table 6.4 reflects the residential risk estimates that are recommended for use in the aggregate assessment for quinclorac.
   * The recommended residential exposure for use in the adult aggregate assessment reflects inhalation exposure from residential handlers mixing/loading/applying water-dispersable granule/dry flowable formulations with a manually-pressurized handwand and/or backpack equipment.
   * The recommended residential exposure for use in the children 1<2 years old aggregate assessment reflects hand-to-mouth exposures from post-application exposure to treated turf.

Table 6.4.  Residential Risk Estimates for Use in the Quinclorac Aggregate Assessment
                         Lifestage / Exposure Scenario
                                     Dose
                                      MOE
Adults  -  Residential Handler M/L/A, Water-dispersible Granule/Dry Flowable, Manually-Pressurized Handwand and/or Backpack
                                     0.019
                                     3,600
Children 1 < 2 Years Old - Turf (Liquids), Hand-to-Mouth
                                     0.021
                                     3,300

      6.3.  Residential Bystander Post-application Inhalation Exposure

Based on the Agency's current practices, a quantitative post-application inhalation exposure assessment was not performed for quinclorac at this time primarily because of the low acute inhalation toxicity (Toxicity Category III and IV), low vapor pressure 2.7 x 10-7 mm Hg @ 25.0°C, and the low proposed use rates.  However, volatilization of pesticides may be a source of post-application inhalation exposure to individuals nearby pesticide applications.  The Agency sought expert advice and input on issues related to volatilization of pesticides from its Federal Insecticide, Fungicide, and Rodenticide Act Scientific Advisory Panel (SAP) in December 2009, and received the SAP's final report on March 2, 2010.  The Agency is in the process of evaluating the SAP report and may, as appropriate, develop policies and procedures to identify the need for and, subsequently, the way to incorporate post-application inhalation exposure into the Agency's risk assessments.  If new policies or procedures are developed, the Agency may revisit the need for a quantitative post-application inhalation exposure assessment for quinclorac.

      6.4.  Spray Drift

Spray drift is always a potential source of exposure to residents nearby to spraying operations.  This is particularly the case with aerial application (a method proposed to be employed for quinclorac), but, to a lesser extent, could also be a potential source of exposure from the ground application method also employed for quinclorac.  The Agency has been working with the Spray Drift Task Force, EPA Regional Offices and State Lead Agencies for pesticide regulation and other parties to develop the best spray drift management practices.  On a chemical by chemical basis, the Agency is now requiring interim mitigation measures for aerial applications that must be placed on product labels/labeling.  The Agency has completed its evaluation of the new database submitted by the Spray Drift Task Force, a membership of U.S. pesticide registrants, and is developing a policy on how to appropriately apply the data and the AgDRIFT computer model to its risk assessments for pesticides applied by air, orchard airblast and ground hydraulic methods.  After the policy is in place, the Agency may impose further refinements in spray drift management practices to reduce off-target drift with specific products with significant risks associated with drift.

Although a quantitative residential post-application inhalation exposure assessment was not performed as a result of pesticide drift from neighboring treated agricultural fields, an inhalation exposure assessment was performed for flaggers.  This exposure scenario is representative of a worse case inhalation (drift) exposure and may be considered protective of most outdoor agricultural and commercial post-application inhalation exposure scenarios.

 Aggregate Exposure/Risk Characterization

In accordance with the FQPA, HED must consider and aggregate (add) pesticide exposures and risks from three major sources: food, drinking water, and residential exposures.  In an aggregate assessment, exposures from relevant sources are added together and compared to quantitative estimates of hazard (e.g., a NOAEL or PAD), or the risks themselves can be aggregated.  When aggregating exposures and risks from various sources, HED considers both the route and duration of exposure.

      6.5.  Acute Aggregate Risk

In examining acute aggregate risk, HED has assumed that the only pathway of exposure relevant to the acute time frame is dietary exposure. Therefore, the acute aggregate risk is comprised on exposures to quinclorac residues in food and drinking water and is equivalent to the acute dietary risk estimates summarized in Table 5.4.6 in Section 5.4.3. The acute dietary risk estimates are well below HED's level of concern for Females 13-49 years old.

      6.6.  Short-Term Aggregate Risk

In examining short-term aggregate risk, HED reviewed all residential sources of exposure to determine which residential exposure scenarios would be appropriate to combine with dietary exposure for an aggregate risk assessment.  The only applicable exposure pathways are inhalation (for adult handlers) and incidental oral (for post-application exposure to children).  For children, the incidental oral scenarios (i.e., hand-to-mouth, object-to-mouth, and soil ingestion) should be considered inter-related and it is likely that they occur interspersed amongst each other across time.  Combining these scenarios together would be overly-conservative because of the conservative nature of each individual assessment.   The recommended residential exposure for use in the adult aggregate assessment reflects inhalation exposure from residential handlers mixing/loading/applying water-dispersable granule/dry flowable formulations with a manually-pressurized handwand and/or backpack equipment. The recommended residential exposure for use in the children 1<2 years old aggregate assessment reflects hand-to-mouth exposures from post-application exposure to treated turf.

The Aggregate MOEs are above the LOC of 100 and are not of concern (Table 7.2).

Table 7.2  Short-Term Aggregate Risk Calculations
                                  Population
                              Short-Term Scenario

                                NOAEL mg/kg/day
                                    LOC[1]
                      Max Allowable Exposure[2] mg/kg/day
                   Average Food and Water Exposure mg/kg/day
                       Residential Exposure mg/kg/day[3]
                          Total Exposure mg/kg/day[4]
                Aggregate MOE (food, water, and residential)[5]
Adults  -  Residential Handler M/L/A, Water-dispersible Granule/Dry Flowable, Manually-Pressurized Handwand and/or Backpack[1]
                                      70
                                      100
                                     0.70