Document ID: EPA-HQ-OPP-2012-0010-0003
Agency: epa
Document Type: Supporting & Related Material
Title: 
Posted Date: 2012-04-04T04:00Z

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 developmental study 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.  Long- term 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 Non- Occupational 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 post-
implantation 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 (short- and

intermediate-

term)	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 intermediate- term)	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 intermediate- term)	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

MOE 4

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   HYPERLINK
http://www.epa.gov/pesticides/cumulative/ 
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)	MOE 5

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 post-application 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).

-FCID™), 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
concentrations in 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
(SCI-GROW) model. These models, and their descriptions, are available at
the EPA internet website via the web link,   HYPERLINK
http://www.epa.gov/oppefed1/models/water/ 
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 (95th 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   HYPERLINK
http://www.epa.gov/pesticides/cumulative/ 
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 Non- Occupational 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 post-
implantation 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 (short- and

intermediate-

term)	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 intermediate- term)	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 intermediate- term)	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.

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quinclorac on cranberry or rhubarb.

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