EPA REGISTRATION DIVISION - COMPANY NOTICE OF FILING FOR PESTICIDE 

PETITION

Docket ID Number: EPA-HQ-OPP-2012-0010

EPA Registration Division contact: Sidney Jackson, (703) 305- 7610

Interregional Research Project Number 4 (IR-4)

Pesticide Petition Number: PP-1E7957

21 U.S.C. 346 EPA has received a pesticide petition, PP-1E7957 from IR-4 Project 

Headquarters, Rutgers, The State University of NJ, 500 College Road East, Suite 201 W, 

Princeton, NJ 08540 proposing, pursuant to section 408(d) of the Federal Food, Drug, and 

Cosmetic Act (FFDCA), 21 U.S.C. 346a(d), to amend 40 CFR part 180.463 by establishing a 

tolerance for residues of the herbicide quinclorac, 3,7-dichloro-8-quinolinecarboxylic acid, 

including its metabolites and degradates, in or on the raw agricultural commodity rhubarb at 

0.4 parts per million (ppm) and Berry, low growing, except strawberry, subgroup 13-07H at 

1.1 ppm. EPA has determined that the petition contains data or information regarding the elements 

set forth in section 408(d)(2) of the FFDCA; however, EPA has not fully evaluated the sufficiency 

of the submitted data at this time or whether the data support granting of the petition. Additional 

data may be needed before EPA rules on the petition.

A. Residue Chemistry

1. Plant metabolism. The qualitative nature of the residues in quinclorac in plants is 

well understood. Based on a nature of the residue studies in wheat and supported by similar 

studies in rice and sorghum, the residue of concern from quinclorac use consists only of the 

parent compound. 

2. Analytical method. As per the document “Quinclorac. Human Health Risk 

Assessment for the Proposed Food/Feed Use of the Herbicide (Associated with Section 18 

Registration) on Cranberries in Massachusetts”, docket ID number EPA-HQ-OPP-2009-

0528: Adequate analytical methods, utilizing gas chromatography with electron capture 

detection (GC/ECD), are available to enforce the tolerance expression on plant (BASF 

Method A8902; MRID# 41063537) and animal (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 limit of quantitation (LOQ) for both methods is 0.05 ppm in all matrices.

Furthermore, FDA has reported that quinclorac can be detected by Multiresidue Protocol

B. 

3. Magnitude of residues. Field trials were carried out in order to determine the 

magnitude of residues in rhubarb and cranberry. Four rhubarb field trials were conducted 
in rhubarb growing regions of the United States. Five cranberry field trials were conducted 

in cranberry growing regions of the United States. Cranberry is the representative crop for 

the Berry, low growing, except strawberry, subgroup 13-07H. Field trials were carried out 

using the maximum number of applications, the maximum label rate and shortest pre-harvest 

interval (PHI).

B. Toxicological Profile

As per the document Quinclorac. “Human Health Risk Assessment for the Proposed 

Food/Feed Use of the Herbicide (Associated with Section 18 Registration) on Cranberries in 

Massachusetts”, docket ID number EPA-HQ-OPP-2009-0528: 

Hazard Characterization and Assessment

For detailed information, please refer to the human health risk assessment conducted for 

quinclorac’s use on imported barley (D325790; M.A. Doherty; 13 September 2007). The database

adequately characterizes quinclorac as having low acute oral, dermal and inhalation toxicity. It is

Toxicity Category IV for acute inhalation toxicity, and Toxicity Category III for acute oral toxicity,

acute dermal toxicity, primary dermal irritation, and primary eye irritation. It is a dermal sensitizer.

The database for quinclorac is considered incomplete at this time. ARIA/RD and HED have

determined that a 90-day inhalation toxicity study (OPPTS Guideline 870.3465) is required to

assess potential toxicity from inhalation exposures during spray applications. This is a new 

requirement since the previous Section 3 risk assessment (D238399; M.J. Nelson; 15 December

1998). An oral toxicity endpoint is available for assessment of inhalation risk pending receipt of 

the inhalation study. A waiver request has been submitted by the registrant.

Additionally, recent changes to 40CFR §158 make acute and subchronic neurotoxicity testing

(OPPTS Guideline 870.6200), and immunotoxicity testing (OPPTS Guideline 870.7800) required

for pesticide registration.

The available data for quinclorac do not show the potential for immunotoxic nor neurotoxic

effects. Therefore, an additional 10X database uncertainty factor (UF) has not been warranted. 

The 870.3465 inhalation, 870.6200 neurotoxicity and 870.7800 immunotoxicity studies were also 

a requirement in the document “Quinclorac. Human Health Risk Assessment for the Proposed 

Food/Feed Use of the Herbicide (Associated with Section 18 Registration) on Cranberries in 

Massachusetts”, docket ID number EPA-HQ-OPP-2009-0528. An immunotoxicity study was 

submitted in 2010 (MRID 48346101). The registrant, BASF, plans to conduct acute and 90 day

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

inhalation study. 

The mode of action for mammalian toxicity from quinclorac, an herbicide structurally related to the

pyridinoxy and picolinic acid herbicides, has not been characterized at this time. Following single

or multiple oral doses, quinclorac was well-absorbed and excreted rapidly, but was very poorly

metabolized. In rat metabolism studies, most of an administered dose was excreted unchanged, and

almost all (91-98% by day 5 post-dosing) in the urine. Significant biliary excretion (up to 15%) 
was observed. Tissue retention was low in both sexes, but slightly higher in females. Less than

0.45% of the dose was retained in tissues, with the highest levels in thyroid, bone marrow, and

adrenal glands. Two minor metabolites have been isolated but not identified.

Subchronic or chronic oral exposure to quinclorac caused decreased body weights in all species

tested (rat, dog, mouse). In the dog, kidney, blood and liver were target organs following chronic

exposure. Hydropic degeneration of the kidney, and increased kidney weight were observed at

relatively high doses (about 500 mg/kg/day). Liver weights were also increased, although no 

microscopic findings or clinical changes were seen. Several red blood cell parameters were

decreased. In the rat, quinclorac affected the pancreas in males only following chronic

administration, with an increase in the incidence of pancreatic acinar cell hyperplasia at relatively

high doses (500 mg/kg/day). Subchronic exposure at approximately limit doses (1000 mg/kg/day)

caused increased water intake in both sexes; in males, increased serum glutamic oxaloacetic

transaminase (SGOT), serum glutamic pyruvic transaminase (SGPT), and focal chronic interstitial

nephritis were observed, as well. Interstitial nephritis was also observed in parental females in the

reproductive toxicity study. Although the mouse was the most sensitive species in these studies

(based on the chronic toxicity/ carcinogenicity study), a target organ was not identified in mice;

decreased body weight was the only effect reported at doses exceeding the limit dose.

No toxicity was observed in a 21-day dermal toxicity study in the rabbit, which tested up to the

limit dose. There are no data on the effects of quinclorac via inhalation exposure.

Studies on the effects of quinclorac on development do not show increased susceptibility of 

offspring. In the rabbit, increased rates of early resorption and post-implantation loss, decreased

live fetuses, and reduced fetal body weight were observed at doses that caused significant maternal

toxicity, including mortality. No developmental effects were reported in the rat even at maternally

toxic doses. However, in the rat reproductive toxicity study, offspring effects at maternally toxic

doses included decreased pup weight, delays in pinna unfolding and eye opening, and a possible

marginal reduction in pup viability. There were no effects on reproductive parameters.

Evidence for carcinogenicity of quinclorac is considered equivocal, and insufficient for 

classification. A marginal increase in the incidence of pancreatic acinar adenomas was seen in 

male rats. No tumors were observed in female rats, or in mice. Quinclorac was negative in a 

complete battery of genotoxicity studies.

For all exposure scenarios a UF of 100X was used (10X for intraspecies variation, and

10X for interspecies extrapolation).

An acute dietary reference dose (RfD) of 2.0 mg/kg/day was selected for females age 13 to 49, 

based on the developmental no-observed-adverse-effect level (NOAEL) in rabbits (200 

mg/kg/day) for effects (increased resorption and post-implantation loss, decreased live fetuses and

fetal weight) at 600 mg/kg/day that are presumed to occur following a single exposure. There was 

no appropriate endpoint representing potential toxicity from a single exposure for the general

population, including children and adults.

A chronic dietary RfD of 0.38 mg/kg/day was determined for all populations, including children
and females age 13 to 49, based on the NOAEL in mice (37.5 mg/kg/day) for decreases in body

weight gain observed at 150 mg/kg/day. NOAELs from other species (rat and dog) were 

significantly higher than the mouse.

Assessment of incidental oral exposure of young children to quinclorac is required because there

are residential uses of quinclorac. The point of departure (POD) selected for short- and

intermediate-term exposure (both residential and occupational) was the rabbit maternal toxicity

NOAEL of 70 mg/kg/day. This POD is based on reduced maternal body weight gain and food 

consumption (and increased water consumption) at 200 mg/kg/day. Other studies assessing effects

from dietary exposures of 3 to 6 months duration gave higher NOAELs.

No effects were observed in a 21-day dermal toxicity study in the rabbit at doses up to the limit

dose (1000 mg/kg/day). A dermal assessment is therefore not required because an endpoint has not

been identified.

Inhalation studies are not available for quinclorac. An oral endpoint (the rabbit maternal toxicity

NOAEL of 70 mg/kg/day based on body weight decreases at 200 mg/kg/day) for short- and

intermediate-term exposure was selected, with an assumption of 100% inhalation absorption 

relative to oral absorption. Long-term inhalation endpoints were not selected because long-term 

exposure is not anticipated under current use patterns.

Quinclorac is classified as "Group D, not classifiable as to carcinogenicity in humans" under the

Agency’s 1986 cancer classification guidelines. Available carcinogenicity studies indicate that

there was equivocal evidence of an increase in the incidence of pancreatic acinar cell adenomas in

the male rat, but no treatment-associated increases in tumors were observed in

female rats, or in mice. A quantification of cancer risk is not warranted because the chronic RfD of 

0.38 mg/kg/day is approximately 1200-fold lower than the dose (487 mg/kg/day) that induced the

benign pancreatic tumors. Thus, the chronic RfD will adequately account for all chronic effects

(including the observed adenomas) likely to result from exposure to quinclorac. Additionally, if

quinclorac were evaluated under the current 2005 Guidelines for Carcinogen Risk Assessment, 

quinclorac would be classified as "not likely to be carcinogenic to humans" since only benign

tumors were seen in only one sex, and in one species.

There is no qualitative evidence of increased pre- and/or postnatal susceptibility and, due to the

marginal nature of the effects observed on pup viability in the multigeneration

reproductive toxicity study, no residual uncertainties with regard to prenatal toxicity following in 

utero exposures of rats or rabbits to quinclorac (developmental toxicity studies), and pre- and/or 

postnatal exposure of rats to quinclorac (reproductive toxicity study). Furthermore, the doses 

selected for use in risk assessment from the rabbit developmentalstudy are lower than the NOAEL 

from the multigeneration study, and protective of the pup effects noted therein. Therefore, it is

recommended that the FQPA safety factor (SF) be reduced from 10X to 1X, and that no additional

safety factors beyond the standard 100X are needed.

A summary of the LOCs for risk assessment is listed in Table 1 (below). The toxicological doses 

and hazard endpoints selected for use in dietary and non-occupational human health risk 

assessments are summarized in Table 2 (below), while those for use in occupational human health
risk assessments are summarized in Table 3 (below). The acute toxicity profile and the

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

TABLE 1 Summary of Levels of Concern (LOCs) for Quinclorac Risk Assessment.

Route of Exposure Short-Term

(1-30 Days)

Intermediate-Term

(1-6 Months)

Long-Term

(>6 Months)

Occupational (Worker) Exposure

Dermal 100 100 NA*

Inhalation 100 100 NA

Residential Exposure

Dermal 100 100 NA

Inhalation 100 100 NA

Incidental Oral 100 100 NA

* NA = Not Applicable.

LOCs of 100 are used for all short- and intermediate-term exposure scenarios, based on

10X factors for intra- and interspecies variability, and reduction of the FQPA SF to 1X. Longterm exposure is not anticipated under current use patterns.

FQPA Safety Factor Considerations

ARIA/RD and HED recommend that the FQPA SF be reduced to 1X based on the 

following considerations:

1. The available toxicity data do not show evidence of increased 

susceptibility in offspring,

2. There is no evidence of neurotoxicity from exposure to quinclorac,

3. The toxicology database for quinclorac is sufficiently complete for purposes of

this risk assessment (the Agency is requesting additional data to more appropriately

evaluate risk, per recent changes to 40CFR§158), and

4. Estimates for dietary intake (food + water) are based on conservative 

assumptions, resulting in high-end exposure estimates.

For food, the exposure estimates assume tolerance-level residues, and 100% crop treated (%CT);

for drinking water, modeled values were used. By using these conservative assessments, acute and

chronic exposures and risks will not be underestimated. The residential exposure assessment

utilizes residential SOPs to assess incidental oral ingestion by toddlers. The residential SOPs are

based on reasonable worst-case assumptions, and will not likely underestimate exposure or risk. 

These assessments are unlikely to underestimate the potential exposure to infants and children

resulting from the use of quinclorac. Based on these data, the quinclorac risk assessment team

concluded that no additional SF is needed to account for exposure considerations.
TABLE 2 Summary of Quinclorac Toxicological Doses and Endpoints for Use in Dietary and NonOccupational Human Health Risk Assessments.

Exposure

Scenario

Point of

Departure

Uncertainty and 

FQPA Safety 

Factors

RfD, PAD, LOC 

for Risk 

Assessment

Study and Toxicological Effects

Acute dietary

(general US

population)

Not applicable. An endpoint for acute dietary exposure of the general population was not selected

because there was no available endpoint 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)

NOAEL =

200 

mg/kg/day

UFA = 10X UFH 

= 10X FQPA SF 

= 1X

Acute RfD = 2.0

mg/kg/day

aPAD = 2.0 

mg/kg/day

Developmental study in rabbits.

LOAEL = 600 mg/kg/day, based on 

increased early resorptions and postimplantation loss, decreased live fetuses,

decreased fetal 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

Chronic RfD =

0.38 

mg/kg/day

cPAD = 0.38 

mg/kg/day

Dietary carcinogenicity study in mice.

LOAEL = 150 mg/kg/day, based on 

decreased body weight.

Incidental

oral (shortand

intermediateterm)

NOAEL = 70

mg/kg/day

UFA = 10X UFH 

= 10X FQPA SF 

= 1X

Residential LOC

for MOE = 100

Developmental study in rabbits. 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 at limit dose of 1000 mg/kg/day in a 21-day dermal toxicity study).

Inhalation

(short- and 

intermediateterm)

NOAEL = 70

mg/kg/day

UFA = 10X UFH 

= 10X FQPA SF 

= 1X

Residential LOC

for MOE = 100

(Same as for incidental oral.) Also

supported by subchronic and chronic 

dietary data on mice.

Inhalation absorption rate = 100%.

Inhalation

(long-term)

Not applicable. Long-term inhalation exposure is not anticipated under current use scenarios.

Cancer (oral,

dermal, 

inhalation)

Classification (last assessment was performed under the 1986 Agency Cancer Assessment

Guidelines) was “not classifiable as to carcinogenicity to humans,” based on an equivocal increase 

in pancreatic acinar cell adenomas in the male rat only, and no increases in female rats nor in mice. 

Therefore, cancer risk from exposure to quinclorac is not of concern. ARIA/RD and HED do not 

anticipate that a reevaluation under the 2005 revised guidelines would significantly alter the basic 

conclusions of the existing decision.

Point of Departure (POD) = a data point or estimated point derived from observed dose-response data, which is used

to mark the beginning of extrapolation to determine risk associated with lower environmentally relevant human

exposures.

UF = Uncertainty Factor. UFA = extrapolation from animal to human (interspecies). UFH = potential variation in 

sensitivity among members of the human population (intraspecies). UFDB = database uncertainty factor to account 

for the absence of key data (such as the lack of a critical study). FQPA SF = FQPA Safety Factor. NOAEL = No 

Observed Adverse Effect Level. LOAEL = Lowest Observed Adverse Effect Level. PAD = Population Adjusted 

Dose (a = acute, c = chronic). RfD = Reference Dose. MOE = Margin Of Exposure. LOC = Level Of Concern.
TABLE 3 Summary of Quinclorac Toxicological Doses and Endpoints for Use in Occupational

Human Health Risk Assessments.

Exposure

Scenario

Point of

Departure

Uncertainty

Factors

LOC 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 at limit dose of 1000 mg/kg/day in a 21-day dermal toxicity study).

Inhalation

(short- and 

intermediateterm)

NOAEL = 70

mg/kg/day

UFA = 10X 

UFH = 10X

Occupational LOC

for MOE = 100

Developmental study in rabbits. LOAEL =

200 mg/kg/day, based on decreased

maternal body weight gain and food

consumption (and increased water 

consumption). Also supported by 

subchronic and chronic dietary data on 

mice.

Inhalation absorption rate = 100%.

Cancer (oral,

dermal, 

inhalation)

Classification (last assessment was performed under the 1986 Agency Cancer Assessment

Guidelines) was “not classifiable as to carcinogenicity to humans,” based on an equivocal 

increase in pancreatic acinar cell adenomas in the male rat only, and no increases in female rats 

nor in mice. Therefore, cancer risk from exposure to quinclorac is not of concern. ARIA/RD

and HED do not anticipate that a reevaluation under the 2005 revised guidelines would

significantly alter the basic conclusions of the existing decision.

Point of Departure (POD) = a data point or estimated point derived from observed dose-response data, which is used

to mark the beginning of extrapolation to determine risk associated with lower environmentally relevant human

exposures.

UF = Uncertainty Factor. UFA = extrapolation from animal to human (interspecies).

UFH = potential variation in sensitivity among members of the human population (intraspecies).

NOAEL = No Observed Adverse Effect Level. LOAEL = Lowest Observed Adverse Effect Level.

MOE = Margin Of Exposure. LOC = Level Of Concern.

C. Aggregate Exposure

As per the document “Quinclorac. Human Health Risk Assessment for the Proposed 

Food/Feed Use of the Herbicide (Associated with Section 18 Registration) on Cranberries in 

Massachusetts”, docket ID number EPA-HQ-OPP-2009-0528: 

Aggregate Exposure and Risk

In accordance with the FQPA, ARIA/RD must consider and aggregate pesticide exposures and

risks from three major sources: food, drinking water, and residential exposures. In an aggregate

assessment, exposures from dietary and residential sources are added together, and compared to

quantitative estimates of hazard (such as a NOAEL), or the risks themselves can be aggregated.

When aggregating exposures and risks from various sources, ARIA/RD considers both the route

and duration of exposure.

In estimating aggregate risk, ARIA/RD has combined high-end residue estimates for food and

drinking water with high-end estimates of post-application residential exposure. Use of

these values results in highly conservative, health-protective estimates of aggregate exposure and 

risk. The components of acute and chronic (long-term) aggregate exposure are dietary exposure 

from food and drinking water. Since the dietary exposure estimates incorporate potential

residues in drinking water directly in the assessment, the acute and long-term aggregate exposure 

and risk estimates are equivalent to the acute and chronic dietary estimates, respectively.
Acute Aggregate Risk

Acute aggregate exposure consists of acute exposure to quinclorac residues in food and drinking

water. Acute aggregate risks are, therefore, equivalent to the acute dietary risk estimates

provided in Table 5 (above), and are below ARIA/RD’s and HED’s LOC.

Short- and Intermediate-Term Aggregate Risk

Short- and intermediate-term exposure may occur as a result of quinclorac use in residential

settings. As noted above, the post-application exposure scenarios from the use on turf represent

worst-case estimates of exposure and risk. To evaluate short- and intermediate-term aggregate

risk, ARIA/RD has included the post-application combined MOE (from Table 7,

above) with the MOE derived from chronic dietary exposure estimates (to reflect background

dietary exposure). The behaviors associated with post-application exposures are applicable to 

toddlers, so only those age groups have been assessed for short- and intermediate-term aggregate 

risk. Aggregate MOEs are all greater than 100 (see Table 8, below), and are therefore not of 

concern to ARIA/RD and HED.

TABLE 8 Short- and Intermediate-Term Aggregate Risk Estimates for Exposure of Toddlers to

Quinclorac.

Population

[Years of Age]

Exposure Scenario

LOC for 

Aggregate 

Risk 1

MOE 

(Food + 

Water) 2

MOE 

(Incidental 

Oral) 3

MOE 

(Dermal)

MOE 

(Inhalation)

Aggregate

MOE4

Infants [<1] 100 6,700 5,000 NA

5 NA 2,900

Children [1-2] 100 5,800 5,000 NA NA 2,700

Children [3-5] 100 6,800 5,000 NA NA 2,900

1. See Table 1, above.

2. MOE food = [70 mg/kg/day (short- and intermediate-term NOAEL) ÷ (chronic dietary exposure from Table 6)].

All MOEs have been truncated to 2 significant figures.

3. See Table 7, above.

4. Aggregate MOE = 1 ÷ [(1/MOEfood + water) + (1/MOEincidental oral)].

5. NA = Not Applicable.

Long-Term Aggregate Risk

Long-term residential exposure to quinclorac (longer than 6 months) is not considered likely to

occur with current and proposed use patterns. Ergo, long-term aggregate exposure consists of 

chronic exposure to quinclorac residues in food and drinking water. Long-term aggregate risks are,

therefore, equivalent to the chronic dietary risk estimates provided in Table 6 (above), and are

below ARIA/RD’s and HED’s LOC.

Aggregate Cancer Risk

Quinclorac has been classified as “not classifiable as to carcinogenicity to humans.” 

Therefore, aggregate cancer risk from quinclorac is not of concern.

Cumulative Exposure and Risk

Unlike other pesticides for which EPA has followed a cumulative risk approach based on a

common mechanism of toxicity, EPA has not made a common mechanism of toxicity finding as to

quinclorac and any other substances. Also, quinclorac does not appear to produce a toxic 
metabolite produced by other substances. For the purposes of this tolerance action, therefore, EPA 

has not assumed that quinclorac has a common mechanism of toxicity with other substances. For 

information regarding EPA’s efforts to determine which chemicals have a

common mechanism of toxicity, and to evaluate the cumulative effects of such chemicals, see the 

policy statements released by EPA’s Office of Pesticide Programs (OPP) concerning common 

mechanism determinations, and procedures for cumulating effects from substances found to have a

common mechanism on EPA’s website at http://www.epa.gov/pesticides/cumulative/.

Occupational Exposure and Risk

A Section 18 emergency exemption has been requested by MDAR for the use of

QuinStar 4L (LF; 40% ai) to provide early season protection of cranberries against injury from 

dodder in MA. The product will be applied at the rate of 8 ounces of product per acre (oz/A), 

which equates to 0.24 lb ai/A per application. Up to 2 applications may be made per year, for a 

maximum yearly use rate of 16 oz/A (0.48 lb ai/A). Applications are to be made after the winter 

flood has been withdrawn, and after dodder emergence. Application to cranberry bogs may not be

made via aircraft.

Primary Handlers

Based upon the proposed use pattern, ARIA/RD believes the most highly exposed 

occupational pesticide handlers will be:

1. Mixer/loaders using open-pour loading of liquid formulation,

2. Applicators using open-cab ground-boom sprayers,

3. Applicators using high-pressure hand-wand sprayers, and

4. Persons (chemigators) preparing irrigation systems through which the material

is applied.

An estimate of exposure and risk is not presented for chemigators. ARIA/RD believes that the

estimate of exposure and risk to mixer/loaders using open-pour loading of liquid is adequate to

describe the exposure and risk to chemigators. Chemigators do not “load” or “mix” in the

typical sense of persons supporting ground or aerial applications. Chemigators typically arrange

for “siphon” tubes to lead from minibulk containers of concentrate into the irrigation stream.

Pumping and metering equipment draws the concentrate from the container into the irrigation

system. Thus, it is expected that chemigatorexposure is less than for individuals involved in

“open-pouring” of pesticide from a container into a spray pre-mix tank.

ARIA/RD believes occupational handlers will most likely be exposed to short-term duration

exposures (1 to 30 days). The toxicological endpoints are the same for both short-term duration

and intermediate-term duration exposures. Therefore, the estimates of risk for short- term exposure

are adequate to describe intermediate-term exposures in the event that these might occur. Most

applications are expected to be made by private (grower) applicators.

Private (grower) applicators are permitted to perform all functions; they may mix, load and apply

the material. The HED ExpoSAC standard procedure directs that although the same individual

may perform all those tasks, they shall be assessed separately. By separating the two job

functions, ARIA/RD and HED determine the most appropriate levels of personal protective 

equipment (PPE) for each aspect of the job without requiring an applicator to wear unnecessary
PPE that might be required for a mixer/loader (for example, chemical-resistant gloves may only 

be necessary during the pouring of a liquid formulation).

These exposure scenarios are outlined in the Pesticide Handler Exposure Database (PHED)

Surrogate Exposure Guide (of August 1998). Most exposure scenarios for hand-held equipment

(such as hand wands, backpack sprayers, and push-type granular spreaders) are assessed as a

combined job function. With these types of hand held operations, all handling activities are

assumed to be conducted by the same individual.

No chemical-specific data were available with which to assess potential exposure of pesticide

handlers. The estimates of exposure of pesticide handlers are based upon surrogate study data

available in the PHED (Version 1.1), 1998. The product label directs applicators and other

handlers to wear long-sleeved shirt, long pants, shoes plus socks, and chemical-resistant gloves

(Category A, such as butyl rubber, natural rubber, neoprene rubber, or nitrile rubber of at least 14 

mils thickness).

The toxicological factors used in this assessment are taken from the most recent human health risk 

assessment for quinclorac (D325790; M.A. Doherty; 13 September 2007). No dermal toxicological

endpoints were identified in that risk assessment. Inhalation studies are not available for 

quinclorac. An oral endpoint (the rabbit maternal toxicity NOAEL of 70 mg/kg/day based on body

weight decreases at 200 mg/kg/day) for short- and intermediate-term exposure

was selected, with an assumption of 100% inhalation absorption relative to oral absorption. Since 

the toxic effects were maternal (not fetal effects), a 70-kg body weight is used to calculate 

exposure/dose. As mentioned above, since no inhalation absorption data are available, toxicity via

the inhalation route is considered equivalent to the estimated toxicity via the oral route of 

exposure. 

See Table 9 (below) for a summary of estimated exposures and risks to occupational pesticide

handlers.

TABLE 9 Summary of Inhalation Exposure and Risk Estimates for Exposure of Occupational

Handlers to Quinclorac.

Unit Exposure

1

(mg ai/lb Handled)

Use Rate 2

(lb ai/A)

Units Treated 3

(A/day)

Avg. Daily Exposure 4

(mg ai/kg bw/day)

MOE5

Mixer/Loader (Liquid; Open Pour)

0.0012 0.24 80 0.000326 215,000

Applicator (Ground-Boom; Open Cab)

0.00074 0.24 80 0.0002 350,000

Applicator (High-Pressure Handwand)

0.079 0.24 40 0.0107 6,500

1. Unit exposures are taken from Surrogate Exposure Guide, Estimates of Worker Exposure, from PHED (Version

1.1), of August 1998.

2. Use rate is taken from the MDAR Section 18 request, and product labeling.

3. Units treated are taken from Standard Values for Daily Acres Treated in Agriculture, ExpoSAC SOP Number 9.1, 

revised 5 July 2000. The ExpoSAC SOP indicates that a high-pressure handwand sprayer will likely use

1000 gallons of spray per day. The product label suggests sprays be applied in 10 to 40 GPA. ARIA/RD

assumes an spray volume of 25 GPA. Therefore, [(1000 gallons/day) ÷ (25 GPA)] = 40 A/day.

4. Average daily exposure (ADE) = [(unit exposure) x (use rate) x (units treated)] ÷ (70 kg body weight).

5. MOE = Margin Of Exposure = NOAEL ÷ ADE. NOAEL = 70 mg/kg bw/day.
An MOE of 100 is adequate to protect occupational pesticide handlers from exposures to 

quinclorac. The estimated MOEs are all more than 100; therefore, the proposed use does not 

exceed ARIA/RD’s and HED’s LOC.

Secondary Handlers

It is possible for agricultural workers to have post-application exposure to pesticide residues

during the course of typical agricultural activities. HED, in conjunction with the Agricultural

Re-entry Task Force (ARTF), has identified a number of post-application agricultural activities

that may occur, and which may result in post-application exposures to pesticide residues. HED 

has also identified transfer coefficients (TCs) relative to the various activities, which express 

the amount of foliar contact over time during each of the activities identified.

In this case, since no dermal toxicological POD for quinclorac is identified, an assessment of postapplication exposure is not necessary. Post-application inhalation exposure is believed to be

negligible.

i. Food and Drinking Water. 

As per the document, “Quinclorac. Human Health Risk Assessment for the Proposed 

Food/Feed Use of the Herbicide (Associated with Section 18 Registration) on Cranberries in 

Massachusetts”, docket ID number EPA-HQ-OPP-2009-0528: 

For detailed information, please refer to the dietary exposure assessment memorandum

(D363872; W.T. Drew; 2 June 2009).

Acute and chronic aggregate dietary (food and drinking water) exposure and risk assessments were

conducted using the Dietary Exposure Evaluation Model software with the Food Commodity

Intake Database (DEEM-FCIDTM), Version 2.03, which uses food consumption data from the US 

Department of Agriculture’s Continuing Surveys of Food Intakes by Individuals (CSFII), collected

from 1994 to 1996, and 1998. These analyses were performed to support the Section 18 request

for quinclorac use on cranberries in MA. All registered, pending, and proposed uses of 

quinclorac, as of the date of this memorandum, are included in these assessments.

Permanent tolerances have been established for quinclorac (40CFR §180.463[a]) in livestock and

cereal grain commodities. The ROC, for both tolerance enforcement and risk assessment, is the

parent compound, quinclorac. Both the acute and chronic assessments are highly conservative, and

assume 100%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.

Residues of quinclorac in livestock commodities (such as meat, milk and eggs) are not likely to be

affected by the newly requested use, as there are no significant livestock feed items derived from

cranberries.

The quinclorac drinking water residue used in these dietary risk assessments was provided by

EFED (D363581; Y. Donovan; 5 May 2009), 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

concentration (EDWC) in groundwater is 0.019 ppm for both acute and chronic scenarios. The

acute and chronic surface water EDWCs are 0.077 and 0.070 ppm, respectively. In order to be

more conservative, the acute surface water EDWC of 0.077 ppm was also used in the chronic 

analysis.

Because the proposed use on cranberries involves flooding (for which the PRZM and EXAMS 

models are not currently parameterized), the surface water EDWCs were assessed using a modified

Tier I Provisional Cranberry Model, which is a provisional refinement of the Tier I Rice Model, 

Version 1.0 (8 May 2007). These EDWCs are based on quinclorac concentrationsin tailwater from

cranberry bogs that drain into adjacent surface water bodies. The EDWC in groundwater was 

obtained via exposure modeling which utilized the Screening Concentration in Ground Water (SCIGROW) 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.

Based on these highly conservative assumptions, the acute dietary risk estimate at the 95th 

percentile of exposure is less than 1% of the acute population-adjusted dose (aPAD) for females 

age 13 to 49, the only population subgroup for which an acute endpoint was selected (see Table

5, below).

TABLE 5 Summary of Acute Dietary Exposure and Risk Estimates for Quinclorac.

Population Subgroup

[Years of Age]

DEEM Acute Dietary Analysis (95

th Percentile)

aPAD (mg/kg/day) Exposure Estimate

(mg/kg/day)

% aPAD

General US Population NA* NA NA

All Infants [< 1]

Children [1-2]

Children [3-5]

Children [6-12]

Youths [13-19]

Adults [20-49]

Adults [50+]

Females [13-49] 2.0 0.012602 <1

* NA = Not Applicable. An appropriate acute endpoint was not identified for these population subgroups.

Chronic dietary risk estimates are less than or equal to 3% of the chronic population- adjusted dose 

(cPAD) for all population subgroups (see Table 6, below). Children 1 to 2 years of age are the

most highly-exposed subgroup, utilizing 3% of the cPAD, while the general US population utilizes

2% of the cPAD. Generally, the Agency is concerned when risk estimates exceed 100% of the

PAD; therefore, all acute and chronic dietary risk estimates are below ARIA/RD’s and HED’s 

LOC.
TABLE 6 Summary of Chronic Dietary Exposure and Risk Estimates for Quinclorac.

Population Subgroup* 

[Years of Age]

DEEM Chronic Dietary Analysis

cPAD (mg/kg/day) Exposure Estimate

(mg/kg/day)

% cPAD

General US Population 0.38 0.005596 2

All Infants [<1] 0.010412 3

Children [1-2] 0.012113 3

Children [3-5] 0.010342 3

Children [6-12] 0.006731 2

Youth [13-19] 0.004467 1

Adults [20-49] 0.005145 1

Adults [50+] 0.004419 1

Females [13-49] 0.004504 1

* Values for the population subgroup with the highest risk are in bold type.

Quinclorac has been classified by the Cancer Assessment Review Committee (CARC) as

“not classifiable as to carcinogenicity to humans.” Therefore, cancer risk is not of concern.

D. Cumulative Effects

As per the document Quinclorac. “Human Health Risk Assessment for the Proposed 

Food/Feed Use of the Herbicide (Associated with Section 18 Registration) on Cranberries in 

Massachusetts”, docket ID number EPA-HQ-OPP-2009-0528: 

Cumulative Exposure and Risk

Unlike other pesticides for which EPA has followed a cumulative risk approach

based on a common mechanism of toxicity, EPA has not made a common mechanism of 

toxicity finding as to quinclorac and any other substances. Also, quinclorac does not appear

to produce a toxic metabolite produced by other substances. For the purposes of this

tolerance action, therefore, EPA has not assumed that quinclorac has a common mechanism

of toxicity with other substances. For information regarding EPA’s efforts to determine

which chemicals have a

common mechanism of toxicity, and to evaluate the cumulative effects of such chemicals, see

the policy statements released by EPA’s Office of Pesticide Programs (OPP) concerning

common mechanism determinations, and procedures for cumulating effects from substances

found to have a common mechanism on EPA’s website at

http://www.epa.gov/pesticides/cumulative/.
E. Safety Determination

As per the document “Quinclorac. Human Health Risk Assessment for the Proposed 

Food/Feed Use of the Herbicide (Associated with Section 18 Registration) on Cranberries in 

Massachusetts”, docket ID number EPA-HQ-OPP-2009-0528: 

FQPA Safety Factor Considerations

ARIA/RD and HED recommend that the FQPA SF be reduced to 1X based on the 

following considerations:

1. The available toxicity data do not show evidence of increased 

susceptibility in offspring,

2. There is no evidence of neurotoxicity from exposure to quinclorac,

3. The toxicology database for quinclorac is sufficiently complete for purposes 

of this risk assessment (the Agency is requesting additional data to more

appropriately evaluate risk, per recent changes to 40CFR

§158), and

4. Estimates for dietary intake (food + water) are based on conservative 

assumptions, resulting in high-end exposure estimates.

For food, the exposure estimates assume tolerance-level residues, and 100% crop treated 

(%CT); for drinking water, modeled values were used. By using these conservative

assessments, acute and chronic exposures and risks will not be underestimated. The

residential exposure assessment utilizes residential SOPs to assess incidental oral ingestion by 

toddlers. The residential SOPs are based on reasonable worst-case assumptions, and will not

likely underestimate exposure or risk. These assessments are unlikely to underestimate the

potential exposure to infants and children resulting from the use of quinclorac. Based on 

these data, the quinclorac risk assessment team concluded that no additional SF is needed to

account for exposure considerations.
TABLE 2 Summary of Quinclorac Toxicological Doses and Endpoints for Use in Dietary and NonOccupational Human Health Risk Assessments.

Exposure

Scenario

Point of

Departure

Uncertainty and 

FQPA Safety 

Factors

RfD, PAD, LOC 

for Risk 

Assessment

Study and Toxicological Effects

Acute dietary

(general US

population)

Not applicable. An endpoint for acute dietary exposure of the general population was not

selected

because there was no available endpoint that was appropriate for this scenario (effects

Acute dietary

(females 13-

49)

NOAEL =

200 

mg/kg/day

UFA = 10X UFH 

= 10X FQPA 

SF = 1X

Acute RfD = 2.0

mg/kg/day

aPAD = 2.0 

mg/kg/day

Developmental study in rabbits.

LOAEL = 600 mg/kg/day, based on 

increased early resorptions and postimplantation loss, decreased live

fetuses,

decreased fetal weight. These fetal effects

Chronic

dietary (all 

populations)

NOAEL =

37.5 

mg/kg/day

UFA = 10X UFH 

= 10X FQPA 

SF = 1X

Chronic RfD =

0.38 

mg/kg/day

cPAD = 0.38 

mg/kg/day

Dietary carcinogenicity study in mice.

LOAEL = 150 mg/kg/day, based 

on decreased body weight.

Incidental

oral (shortand

intermediateterm)

NOAEL = 70

mg/kg/day

UFA = 10X UFH 

= 10X FQPA 

SF = 1X

Residential LOC

for MOE = 100

Developmental study in rabbits. 

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 at limit dose of 1000 mg/kg/day in a 21-day dermal toxicity

Inhalation

(short- and 

intermediateterm)

NOAEL = 70

mg/kg/day

UFA = 10X UFH 

= 10X FQPA 

SF = 1X

Residential LOC

for MOE = 100

(Same as for incidental oral.) Also

supported by subchronic and

chronic dietary data on mice.

Inhalation absorption rate = 100%.

Inhalation

(long-term)

Not applicable. Long-term inhalation exposure is not anticipated under current use scenarios.

Cancer (oral,

dermal, 

inhalation)

Classification (last assessment was performed under the 1986 Agency Cancer Assessment

Guidelines) was “not classifiable as to carcinogenicity to humans,” based on an equivocal

increase in pancreatic acinar cell adenomas in the male rat only, and no increases in female 

rats nor in mice. Therefore, cancer risk from exposure to quinclorac is not of concern. 

ARIA/RD and HED do not anticipate that a reevaluation under the 2005 revised guidelines

would significantly alter the basic conclusions of the existing decision.

Point of Departure (POD) = a data point or estimated point derived from observed dose-response data, which is

used

to mark the beginning of extrapolation to determine risk associated with lower environmentally relevant 

human exposures.

UF = Uncertainty Factor. UFA = extrapolation from animal to human (interspecies). UFH = potential 

variation in sensitivity among members of the human population (intraspecies). UFDB = database uncertainty 

factor to account for the absence of key data (such as the lack of a critical study). FQPA SF = FQPA Safety 

Factor. NOAEL = No Observed Adverse Effect Level. LOAEL = Lowest Observed Adverse Effect Level.

PAD = Population Adjusted Dose (a = acute, c = chronic). RfD = Reference Dose. MOE = Margin Of 

Exposure. LOC = Level Of Concern.
TABLE 3 Summary of Quinclorac Toxicological Doses and Endpoints for Use in Occupational

Human Health Risk Assessments.

Exposure

Scenario

Point of

Departure

Uncertainty

Factors

LOC for Risk

Assessment

Study and Toxicological Effects

Dermal

(all durations)

Not applicable. A dermal endpoint was not selected because an appropriate endpoint was

not

Inhalation

(short- and 

intermediateterm)

NOAEL = 70

mg/kg/day

UFA = 10X 

UFH = 10X

Occupational LOC

for MOE = 100

Developmental study in rabbits. 

LOAEL = 200 mg/kg/day, based on 

decreased maternal body weight gain

and food consumption (and increased 

water consumption). Also supported by 

subchronic and chronic dietary data on 

mice.

Inhalation absorption rate = 100%.

Cancer (oral,

dermal, 

inhalation)

Classification (last assessment was performed under the 1986 Agency Cancer Assessment

Guidelines) was “not classifiable as to carcinogenicity to humans,” based on an equivocal 

increase in pancreatic acinar cell adenomas in the male rat only, and no increases in

female rats nor in mice. Therefore, cancer risk from exposure to quinclorac is not of 

concern. ARIA/RD

and HED do not anticipate that a reevaluation under the 2005 revised guidelines would

Point of Departure sign(PiOficDa)n=tly aa data lter tpoheibas nt oric coesnctimluastiedonspoofintthederexiived stingfrdecis om oiobnse. rved dose-response

data, which is used

to mark the beginning of extrapolation to determine risk associated with lower environmentally 

relevant human exposures.

UF = Uncertainty Factor. UFA = extrapolation from animal to human

(interspecies).

UFH = potential variation in sensitivity among members of the human

population (intraspecies).

NOAEL = No Observed Adverse Effect Level. LOAEL = Lowest Observed Adverse

Effect Level.

MOE = Margin Of Exposure. LOC = Level

Of Concern.

F. International Tolerances

There is a time limited US tolerance for residues of quinclorac on cranberry

at 15.0 ppm that expires on December 31, 2012. There are no CODEX or Mexican 

maximum residue limits established for quinclorac on cranberry or rhubarb.