Document ID: EPA-HQ-OPP-2008-0937-0002
Agency: epa
Document Type: Supporting & Related Material
Title: 
Posted Date: 2009-04-08T04:00Z

<EPA REGISTRATION DIVISION COMPANY NOTICE OF FILING FOR PESTICIDE
PETITIONS PUBLISHED IN THE FEDERAL REGISTER  >

<EPA Registration Division contact: Hope Johnson (PM Team 25)
703-305-5410>

<BASF Corporation>

<8F7442>

<	EPA has received a pesticide petition 8F7442 from BASF Corporation, 26
Davis Drive, P.O. Box 13528, Research Triangle Park, North Carolina
27709-3528 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 by establishing tolerances for residues of Quinclorac,
3,7-dichloro-8-quinolinecarboxylic acid in or on the raw agricultural
commodity grass, forage at 105 parts per million (ppm) and grass, hay at
70 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 supports 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 rice, sorghum, wheat and canola, the residue of
concern from quinclorac use consists only of the parent compound.

>

<	2. Analytical method. An adequate analytical method for enforcement of
the tolerances exists. The analytical method used for quantitative
determinations was designed to measure quinclorac residues present as
the parent compound.>

<	3. Magnitude of residues. Magnitude of the Residue -Raw Agricultural
Commodities:  Thirteen pasture and rangeland field trials were conducted
using rates and timing intervals to represent the use patterns,
conditions and areas of use for this product in grass growing regions of
the United States. Five test sites included bermuda grass, four test
sites included bluegrass, and four test sites included bromegrass. These
studies should be adequate to establish grass, forage and grass, hay
tolerances at the proposed 105 and 70 ppm levels, respectively.   The
tolerances proposed reflect the maximum residue determined from these
trials.   No additional data were needed in support of residues in meat,
milk, poultry and eggs. 

>

<B. Toxicological Profile>

<	1. Acute toxicity.  Based on available acute toxicity data quinclorac
does not pose any acute toxicity risks. Several acute toxicology studies
place technical-grade quinclorac in Toxicity Category III for acute
oral, acute dermal, acute inhalation toxicity, and for eye irritation.
Technical-grade quinclorac is in category IV for primary dermal
irritation and has tested negative for skin sensitization.>

<	2. Genotoxicty. All salmonella assays testing the appropriate
technical quinclorac were negative. Technical quinclorac was also
negative in the in vivo cytogenetics (Chinese hamster) at dose levels
ranging from 2,000 to 8,000 mg/kg and did not induce unscheduled DNA
synthesis in the UDS assay at levels ranging from 101 to 1,520 ug/ml.>

<	3. Reproductive and developmental toxicity. Teratology - Rat: A
developmental study in rats fed dosages of 0, 24.4, 146, and 438
mg/kg/day (HDT) resulted in a developmental toxicity NOEL of 438
mg/kg/day and a maternal toxicity NOEL of 146 mg/kg/day based on reduced
food consumption, increased water intake, and mortality at 438 mg/kg/day
(HDT).  Under the conditions of this study, quinclorac did not produce
any sign of embryo/fetal toxicity and did not alter fetal morphological
development.> 

Teratology - Rabbits:  A developmental study in rabbits fed dosages of
0, 70, 200, and 600 mg/kg/day resulted in a developmental toxicity NOEL
of 200 mg/kg/day based on an increase in resorptions and
postimplantation loss; a decrease in the number of live fetuses and
decreased fetal body weights at the 600 mg/kg/day dose level (HDT). At
all other treatment levels no embryo/fetal toxicity was observed. The
maternal toxicity NOEL is 70 mg/kg/day based on decreased body weight
gain and food consumption at 200 mg/kg/day; and increased water
consumption, increased mortality, and discoloration of the kidney at 600
mg/kg/day.  

Two-Generation Reproduction - Rats:  A two-generation reproduction study
with rats fed dosages of 0, 50, 200, and 600 mg/kg/day resulted in a
reproductive NOEL of 200 mg/kg/day based on reduced pup viability and
pup weight, and delay in development (pinna unfolding and eye opening)
at 600 mg/kg/day with a maternal NOEL of 200 mg/kg/day based on reduced
body weights at 600 mg/kg/day. At treatment levels of 50 and 200
mg/kg/day no substance related findings were noted either in the parent
animals or the offspring.

<	4. Subchronic toxicity. [NA-Remove]>

<	5. Chronic toxicity. Chronic Feeding - Nonrodent:  A 1-year feeding
study in dogs fed 0, 34, 142, and 513 (males) and 0, 35, 140, and 469
(females) milligrams/kilogram/day (mg/kg/day) resulted in a
no-observed-effect level (NOEL) of 140 mg/kg/day based on reduced body
weight gains, adverse effect on food efficiency, hematological and
clinical chemistry values, increased liver and kidney weights, and
microscopic findings in liver and kidneys at 513 mg/kg/day (males) and
469 mg/kg/day (females), the highest dosages tested (HDT). 

Chronic Feeding/Oncogenicity - Rats:  A chronic feeding/carcinogenicity
study in rats fed dosages of 1, 56, 186, 385, and 487 mg/kg/day (males)
and 0, 60, 235, 478, and 757 mg/kg/day (females) resulted in a NOEL of
478 mg/kg/day (females) and 385 mg/kg/day (males) based on slight
decreases in weight for females at 757 mg/kg/day (HDT) and an equivocal
(uncertain) increase in acinar cell hyperplasia of the pancreas in males
at 487 mg/kg/day (HDT). There were no carcinogenic effects noted for
female rats under the conditions of the study up to 757 mg/kg/day (HDT).

 Oncogenicity - Mice:  A carcinogenic study in mice fed dosages of 0,
37.5, 150, 600, and 1,200 mg/kg/day resulted in no carcinogenic effects
observed under the conditions of the study up to and including 1,200
mg/kg/day (HDT) and a systemic NOEL of 37.5 mg/kg/day based on a
reduction of body weight at 150 mg/kg/day.

>

<	6. Animal metabolism. A metabolism study with rats receiving dosages
of 15, 100, 600 and 1200 mg/kg/day resulted in more than 90% of the
administered radioactivity eliminated in the urine within 5 days (most
within 24 hours) and 0.7 - 3.7% in the feces. Radioactivity was mainly
associated with the unchanged parent compound. The glucuronic acid
conjugate of quinclorac was a minor (2 - 5%) metabolite in urine.>

<	7. Metabolite toxicology. [NA-Remove]>

<	8. Endocrine disruption. No specific scientific studies were conducted
to determine endocrine effects.  However, the toxicity testing described
above and conducted on three different animal species demonstrate no
apparent estrogenic effects or treatment-related effects of quinclorac
on the endocrine system.>

<C. Aggregate Exposure>

<	1. Dietary exposure. EPA has established the RfD for quinclorac at 0.4
mg/kg/day. This RfD is based on a carcinogenicity study in mice with a
NOAEL of 37.5 mg/kg/day and an uncertainty factor of 100 based on
decreased body weights in male and female mice at the LOEL of 150
mg/kg/day.

Cancer Classification and Risk Assessment: The cancer classification of
quinclorac has been reviewed by the FIFRA Scientific Advisory Panel
(SAP). The Panel recommended that the compound be classified as a Group
D carcinogen (not classifiable as to human carcinogenicity). The EPA
Health Effects Peer Review Committee (PRC) evaluated the carcinogenic
potential of quinclorac and the conclusions of the SAP and has
classified quinclorac as a Group D carcinogen.>

<	i. Food. Chronic Dietary Exposure: BASF has estimated aggregate
dietary exposure based on the Theoretical Maximum Residue Contribution
(TMRC) calculation. The TMRC is a "worst case" estimate of dietary
exposure since it is assumed that 100 percent of all crops for which
tolerances are established are treated and that residues are at the
tolerances level. 

The quinclorac TMRC for the overall US population from the currently
established and proposed  tolerance represents approximately 2 percent
of the RfD.]>

<	ii. Drinking water. EPA has determined that quinclorac is rather
persistent in soils and prone to leach into groundwater. There is no
entry for quinclorac in EPA's Pesticides in Ground Water Database. No
established Maximum Contaminant Level or health advisory levels have
been established for residues of quinclorac in drinking water.

Acute exposure and risk. For purposes of acute risk assessment, the
maximum estimated environmental concentration (EEC) for quinclorac in
drinking water (26.8 ppb in surface water, GENEEC peak value) was used
for comparison to the back-calculated human health Drinking Water Level
of Comparison (DWLOC) for acute dietary exposure (52,000 micrograms/L
for the only population of concern, females (13+ years/nursing). The
estimated peak concentration in surface water (26.8 micrograms/L) is
significantly less than EPA's level of concern for quinclorac residues
in drinking water as a contribution to acute aggregate exposure.

Chronic exposure and risk. For purposes of chronic risk assessment, the
maximum EEC for quinclorac residues in drinking water (25.4 ppb in
surface water, rather than 13.8 in ground water, GENEEC average 56-day
concentration) was used for comparison to the back-calculated human
health DWLOCs for chronic dietary exposure (12,000 micrograms/L for U.S.
population; 2,700 micrograms/L for infants/children). The estimated
average concentration in surface water (25.4 micrograms/L) is
significantly less than EPA's level of concern for quinclorac residues
in drinking water as a contribution to chronic aggregate exposure and
does not result in an unacceptable level of chronic aggregate human
health risk estimate at this time.

 >

<	2. Non-dietary exposure. Quinclorac is registered for use in turf. 
Available dermal toxicity data (21 day exposure as well as acute
exposure) indicate that there is no concern for exposure from this
route, therefore, BASF expects no additional risk resulting from
non-dietary exposure.>

<D. Cumulative Effects>

<	BASF is not aware of any other EPA registered active ingredient that 

is structurally similar to quinclorac or has a common mechanism of
toxicity.>

<E. Safety Determination>

<	1. U.S. population. Using the conservative exposure assumptions
described above and based on the completeness and the reliability of the
toxicity data, a risk assessment for chronic dietary exposure from food
and feed uses was made for all subpopulations. The percent of the RfD
occupied was approximately 2% for the general population.  The most
exposed sub-group was children 1-6 where approximately 3.5% of the RfD
was occupied.>

<	2. Infants and children. No signs of teratogenicity were observed in
either the rat or rabbit developmental studies.  The NOEL values from
the developmental studies are significantly higher than the NOEL from
the 2-year feeding study in mice (threshold NOEL of 37.5 mg/kg/day) used
to establish the RfD.

In the Reproductive Toxicity study, quinclorac elicited signs of
embryotoxicity only at dose levels where clear maternal toxicity was
observed. Fertility and reproduction parameters were not affected even
at the highest treatment levels (1155 mg/kg/day). The NOEL values from
the reproduction study are significantly higher than the NOEL from the
2-year feeding study in mice (threshold NOEL of 37.5 mg/kg/day) used to
establish the RfD. 

Based on the complete database and the demonstrated lack of significant
developmental or reproductive toxicity, BASF believes that the
children’s safety factor of 10 should be removed. The RfD used to
assess safety to the general population is adequate to assess safety to
children. BASF has calculated the dietary exposure for the subgroup
exposed to the highest dietary risk, children 1-6 years old.  The TMRC
represents approximately 3.5 percent of the RfD.  BASF concludes that
there is a reasonable certainty that no harm will result to infants and
children from aggregate exposure to the residues of quinclorac,
including all anticipated dietary exposure and all other
non-occupational exposures.>

<F. International Tolerances>

<	There are no CODEX or Mexican maximum residue limits established for
quinclorac on grass forage or hay.>

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