Document ID: EPA-HQ-OPP-2007-1106-0002
Agency: epa
Document Type: Supporting & Related Material
Title: 
Posted Date: 2008-01-23T05:00Z

<EPA REGISTRATION DIVISION COMPANY NOTICE OF FILING FOR PESTICIDE
PETITIONS PUBLISHED IN THE FEDERAL REGISTER  (1/1/2007)>

<EPA Registration Division contact: Susan Stanton (703) 305-5218>

<Interregional Research Project No. 4 (IR-4)>

<PP 7E7270>

<	EPA has received a pesticide petition (PP 7E7270) from Interregional
Research Project No. 4 (IR-4), Rutgers University; 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 180.275 by establishing tolerances for
residues of Chlorothalonil in or on the raw agricultural commodities
vegetables, fruiting, group 8 at 5.0 parts per million (ppm); okra at
5.0 ppm; persimmon at 1.9 ppm; horseradish at 4.0 ppm; rhubarb at 5.0
ppm; ginseng at 3.0 ppm; yam at 5.0 ppm; lupine at 0.1 ppm; lentil at
0.1 ppm; vegetable, cucurbit, group 9 at 5.0 ppm; and Brassica, head and
stem, subgroup 5A at 5.0 ppm.  The petition also proposes that
previously approved tolerances for residues of chlorothalonil in or on
broccoli, Brussels sprouts, cabbage, cauliflower, cucumber, melon,
nonbell pepper, pumpkin, summer squash, winter squash and tomato be
deleted, since the proposed tolerances on fruiting vegetables, cucurbit
vegetables or Brassica head and stem vegetables would apply to these
commodities.  EPA has determined that the petition contains data or
information regarding the elements set forth in section 408 (d)(2) of 
FDDCA; 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 metabolism of Chlorothalonil as well as the
nature of the residues in plants is adequately understood for purposes
of the proposed tolerance. Plant metabolism has been evaluated in five
diverse crops: Carrots, celery, lettuce, snap beans, and tomatoes, which
should serve to define the similar metabolism of Chlorothalonil in a
wide range of crops. The qualitative nature of residues in plants for
Chlorothalonil is adequately understood. The 

residue of concern is Chlorothalonil and its metabolite, 4-hydroxy-

2,5,6-trichloroisophthalonitrile (SDS-3701). Parent metabolite CGA-

64250 is the major compound found in crops. >

<	2. Analytical method. An adequate residue analytical method (gas
chromatography) is available for enforcement purposes. The method is 

listed in the Pesticide Analytical Manual (PAM) Vol. II (PAM II).>

<	3. Magnitude of residues. All samples were analyzed for residues of
Chlorothalonil, its metabolite SDS-3701, and the manufacturing impurity
HCB.

The limit of quantitation (LOQ) for Chlorothalonil in all matrices was
0.030 ppm.  The limit of quantitation for SDS-3701 and HCB were 0.030
ppm and 0.010 ppm, respectively.  

i.  Peppers (Bell):  

Nine field trials were conducted in New Jersey, Florida, Texas, South
Carolina, Ohio, California, and Georgia to collect data on the residues
of Chlorothalonil on bell peppers following treatment with Bravo Weather
Stik. Seven or eight applications of the test substance were made 6 to
10 days apart at a rate of 1.125 lb ai/A ± 5% each. The total rate
applied at eight of the trials was approximately 9.0 lb ai/A per trial. 
In the Georgia trial, seven applications were made for a total

application rate of 8.0 lb ai/A.  In each trial, mature bell peppers
were collected from each plot 2 to 3 days following the final
application.

Samples collected 2 to 3 days following the final application contained
residues

ranging from 0.33 to 3.5 ppm. By approximately 28 days after the last
application,

residues ranged from 0.055 to 1.0 ppm Chlorothalonil. No quantifiable
residues of SDS-3701 or HCB were observed in any of the samples.  A
method suitability test was performed to validate the analysis. 

ii.   Peppers (Non-Bell):   

Non-bell peppers received a total of approximately 9 lb ai/A Bravo
Ultrex 82.5WG in six or eight foliar applications of approximately 1.125
lb ai/A each. (In the California trial, one of six applications was made
at approximately 3.375 lb ai/A to shorten the application period.) All
applications were made 4 to 9 days apart, and marketable non-bell
peppers were collected 2 to 3 days following the final application. 

Chlorothalonil residues ranged from 0.42 to 1.8 ppm in samples collected
2 to 3 days

following the final application. In the New Jersey and 99-TX28 Texas
trials, residues had declined by approximately 14 days, from a high of
1.8 ppm and 0.64 ppm (New Jersey and Texas, respectively) to a low of
0.40 ppm and 0.18 ppm (respectively). In the California trial, 7-day
residues were <0.030 ppm, but had increased to 0.93 ppm and 1.1 ppm
approximately 1 week later.  No residues above the limit of quantitation
of 0.030 ppm for SDS-3701 or 0.010 ppm for HCB were observed in

any of the samples.  A method suitability test was performed to validate
the analysis. 

iii.   Persimmon:      

Persimmons were treated five times with Bravo® 720 at 1.0 lb ai/A ± 5%
per application, for a total application rate of approximately 5.0 lb
ai/A.  Samples were collected 14 and 28 days following the final
application. 

Chlorothalonil residues in 14-day treated samples ranged from 0.350 to
1.05 ppm. The 28-day samples contained Chlorothalonil residues ranging
from <0.100 ppm (the LOQ) to 0.550 ppm.  No quantifiable residues of the
metabolite SDS-3701 or the manufacturing impurity HCB were observed in
the samples.  A method suitability test was performed to validate the
analysis. 

iv.   Horseradish:   

Three residue field trials were conducted in Maryland, New Jersey, and
Wisconsin. A total of approximately 18 lb ai/A was applied to the
treated plots in eight foliar applications of Bravo Weather Stik at a
rate of approximately 2.25 lb ai/A each. Commercially mature horseradish
was collected 12 to 15 days after the final application.  

The maximum Chlorothalonil and SDS-3701 residues were 0.48 ppm and 0.29
ppm, respectively.  No quantifiable HCB residues were detected.  A
method suitability test was performed to validate the analysis. 

v.    Rhubarb:    

Four residue field trials were conducted in Michigan and Oregon. A total
of approximately 13.5 lb ai/A was applied to the treated plots in six
foliar applications of Bravo Weather Stik at a rate of approximately
2.25 lb ai/A each. 

Mature rhubarb petioles were collected 27 to 34 days after the final
application.

No quantifiable SDS-3701 or HCB residues were detected. The maximum
Chlorothalonil residue was 3.9 ppm.

vi.   Ginseng:   

Three field trails were conducted in Marathon County, WI, the major
ginseng

producing region of the U.S.  The pesticide was applied under conditions
simulating

commercial application techniques. The roots were harvested and dried
simulating

commercial practices.  The dried roots were analyzed for residues of
Chlorothalonil, HCB and SDS 3701. 

The results indicate a maximum total residue of 1.76 ppm (2.27 ppm

after correction for freezer storage losses).   Method validation and
concurrent recoveries were all mostly within the acceptable (70% - 120%)
range with one recovery of Chlorothalonil at 121%. Storage stability
(SS) recoveries indicate that there could have been some degradation
during the storage period however; the SS recoveries were fairly
consistent enabling easy correction of the residue results for apparent
degradation. Therefore, the results reported in this study are
considered reliable.>

<B. Toxicological Profile>

	1. Acute toxicity.  An assessment of the toxic effects caused by
Chlorothalonil is discussed in Unit III.A. and Unit III.B. in the
Federal Register of 

March 12, 2001 (66 FR 14330) (FRL-6759-4).

	2. Genotoxicty. An assessment of the toxic effects caused by
chlorothalonil is 

discussed in Unit III.A. and Unit III.B. in the Federal Register of 

March 12, 2001 (66 FR 14330) (FRL-6759-4).

	3. Reproductive and developmental toxicity. An assessment of the toxic
effects caused by chlorothalonil is discussed in Unit III.A. and Unit
III.B. in the Federal Register of March 12, 2001 (66 FR 14330)
(FRL-6759-4).

<	4. Subchronic toxicity. An assessment of the toxic effects caused by
chlorothalonil is discussed in Unit III.A. and Unit III.B. in the
Federal Register of 

March 12, 2001 (66 FR 14330) (FRL-6759-4).>

<	5. Chronic toxicity. An assessment of the toxic effects caused by
chlorothalonil is discussed in Unit III.A. and Unit III.B. in the
Federal Register of 

March 12, 2001 (66 FR 14330) (FRL-6759-4).>

<	6. Animal metabolism. The metabolism of chlorothalonil in the rat 

is adequately understood.>

<	7. Metabolite toxicology. The residues of concern for tolerance 

setting purposes in or on raw agricultural commodity are the parent 

compound and its metabolite, 4-hydroxy-2,5,6-trichloroisophthalonitrile 

(SDS-3701). The residue of concern in meat and milk is SDS-3701.>

<	8. Endocrine disruption. Chlorothalonil does not belong to a class 

of chemicals known or suspected of having adverse effects on the 

endocrine system. Developmental toxicity studies in rats and rabbits 

and a reproduction study in rats gave no indication that chlorothalonil 

might have any effects on endocrine function related to development and 

reproduction. The subchronic and chronic studies also showed no evidence
of a long-term effect related to the endocrine system.>

<C. Aggregate Exposure>

<	1. Dietary exposure. Tier II/III chronic aggregate and short-term
aggregate exposure evaluations were made for Chlorothalonil using the
Dietary Exposure Evaluation Model software with the Food Commodity
Intake Database (DEEM-FCID™, version 2.16) from Exponent.  Empirically
derived processing factors were used for beans (babyfood, 0.05X),
cabbage (0.2X), carrots (babyfood, 0.005X), cherries (babyfood, 0.05X),
cherry juice (0.075X), cocoa (0.1X), coffee (0.1X), cranberry juice
(0.25X), cucumbers (cold canned, 0.2X), cucumbers (hot canned, 0.04X),
plums (0.33X), pumpkin (0.002X), squash (0.001X), tomato juice (0.25X),
and tomato paste/puree (0.02X).  All other processing factors used were
default values taken from DEEMTM version 7.87.  All consumption data for
these assessments was taken from the USDA’s Continuing Survey of Food
Intake by individuals (CSFII) with the 1994-96 consumption database and
the Supplemental CSFII children’s survey (1998) consumption database. 
These exposure assessments included all current uses for Chlorothalonil
and new uses proposed by the Interregional Research Project 4 (IR4)
including fruiting vegetables (Crop Group 8), cucurbits (Crop Group 9),
persimmons, rhubarb, horseradish, ginseng, , yams, lupines, lentils, and
Brassica, head and stem subgroup 5A.

Residue data for currently registered crops were obtained from a number
of sources including field trial data and monitoring data from the
Pesticide Data Program (PDP), FoodContam (FC), and the FDA monitoring
program.  The current tolerance definition expression for Chlorothalonil
includes Chlorothalonil plus metabolite SDS3701; residue values for
Chlorothalonil in the PDP and other monitoring databases may not include
residues of SDS3701; samples that had detectable residues of
Chlorothalonil were conservatively assigned a value of 10% of the
reported Chlorothalonil residue for SDS3701 based upon the maximum ratio
of metabolite SDS 3701 to Chlorothalonil in radio-labeled plant studies
(6.5%).  Proposed tolerances were used for all proposed new IR4 uses
including fruiting vegetables (5 ppm), cucurbits  (5 ppm), persimmon
(1.9 ppm), rhubarb (5 ppm), horseradish (4 ppm), ginseng (3 ppm), yam (5
ppm), lupines (0.1 ppm), lentils (0.1 ppm), and brassica, head and
stem, subgroup 5A (5 ppm).  Percent of crop treated values were
estimated based upon economic, pest and competitive pressures. 
Tolerance-level residues were assumed for all meat commodities.  For
milk and milk-derived commodities, PDP monitoring database residue
values were used.>

<	i. Food. Food Acute Exposure:  Acute dietary (food only) assessments
were not performed, since an endpoint of concern attributable to a
single oral dose has not been identified.

Food Chronic Exposure:  The Chlorothalonil chronic dietary (food only)
risk assessment was performed for all population subgroups using a
chronic reference dose of 0.003 mg/kg-bw/day, based upon a LOAEL of 0.9
mg/kg-bw/day from a chronic rat toxicity study and an uncertainty factor
of 300X (100X for intra- and inter-species variability and an additional
3X for absence of a NOAEL).  No additional FQPA safety factor was
applied.  For the purpose of the aggregate risk assessment, exposure
values were expressed in terms of margin of exposure (MOE), calculated
by dividing the 0.9 mg/kg-bw/day endpoint by the exposure for each
population subgroup.  In addition, exposures were expressed as a percent
of the chronic reference dose (%cRfD).  Chronic dietary (food only)
exposure to the U.S. population resulted in a MOE of 4,592 (6.5% of the
cRfD).  The most sensitive sub-population was children 1-2 years old,
with a MOE of 2,885 (10.4% of the cRfD).  Since the benchmark MOE for
this assessment was 300 and since EPA generally has no concern for
exposures below 100% of the cRfD, Syngenta believes that there is a
reasonable certainty that no harm will result from dietary (food)
exposure to residues arising from all current and proposed uses for
Chlorothalonil.

Cancer.  Chlorothalonil is listed as “likely” to be a human
carcinogen by all routes of exposure, however the SAP decision of
6/30/98 supports the use of a MOE approach.  The current chronic
population adjusted dose/reference dose (cPAD, cRfD) is based upon a new
chronic/carcinogenicity study that provides a lower endpoint (LOAEL =
0.9 mg/kg/day) that that used previously and is therefore protective of
all cancer and non-cancer chronic effects.>

<	ii. Drinking water. Estimated Drinking Water Concentrations (EDWCs)
for Chlorothalonil TTR were calculated using the Tier II Model, PRZM
(Pesticide Root Zone Model) / EXAMS (Exposure Analysis Modeling
Systems), to provide surface water exposure estimates.  The existing sod
farm turf use provided the highest EDWCs and was the driving crop use,
exceeding the EDWCs for all proposed new crop uses (fruiting vegetables,
cucurbits, persimmon, rhubarb, horseradish, ginseng, yams, and lentils).
 The use on sod farms consisted of six ground applications of 2.17 lbs.
a.i./A and this use was modeled using the PRZM Crop Scenarios, FL and PA
Turf.  The PRZM/EXAMS modeling provided an annual average (chronic)
surface water EDWC of 36.2 ppb (0.0362 ppm), which was input directly
into the DEEM-FCID™ software as “water, direct and indirect, all
sources” to model anticipated chronic drinking water exposures. 

 

Acute Exposure from Drinking Water:  Acute drinking water assessments
were not performed, since an endpoint of concern attributable to a
single oral dose has not been identified.

Chronic Exposure from Drinking Water:  The chronic EDWC of 0.0362 ppm
was used to calculate the chronic drinking water exposure values for the
U.S. Population and all population subgroups.  Chronic drinking water
exposures to the U.S. Population resulted in a MOE of 1,180 (25.4% of
the cRfD).  The most sensitive sub-population was all infants <1 year,
with a MOE of 360 (83.4% of the cRfD).  Since the benchmark MOE for this
assessment was 300 and since EPA generally has no concern for exposures
below 100% of the cRfD, Syngenta believes that there is a reasonable
certainty that no harm will result from chronic drinking water exposures
to residues arising from all current and proposed uses of
Chlorothalonil.>

<	2. Non-dietary exposure. Chlorothalonil is a broad spectrum fungicide
that can be applied to ornamentals and non-residential turfgrass and can
also be formulated into paints for interior and exterior applications. 
There is a potential for residential exposure to adult handlers making
applications to ornamentals and/or from using treated paint.  There is
also a potential for residential exposure to children from ingestion of
paint chips containing Chlorothalonil, although ingestion of paint chips
is considered to be episodic in nature and is generally not included in
aggregate risk so it was therefore excluded from these assessments as
well.  The Chlorothalonil non-dietary risk assessment was performed
using a short-term incidental oral and inhalation endpoint of 30.8
mg/kg-bw/day, based upon a LOAEL from a 2-generation reproductive tox
study in the rat and an uncertainty factor of 1,000X (100X for intra-
and inter-species variability and an additional 10X for absence of a
NOAEL).  No additional FQPA safety factor was applied.  For the purpose
of the aggregate risk assessment, exposure values were expressed in
terms of margin of exposure (MOE), calculated by dividing the 30.8
mg/kg-bw/day endpoint by the exposure for each population subgroup.  The
most exposed population subgroups from the non-dietary (residential)
assessments was all male and female youths and adults 13 years and
older, attributable to inhalation exposures from applications of alkyd
exterior paint with an airless sprayer, with a MOE of 1,291.  Since the
benchmark MOE for this assessment was 1,000 and since EPA generally has
no concern for non-dietary exposures above the benchmark MOE, Syngenta
believes that there is a reasonable certainty that no harm will result
from non-dietary (residential) exposures from all current uses for
Chlorothalonil.>

<D. Cumulative Effects>

<	Cumulative Exposure to Substances with a Common Mechanism of Toxicity.
 Section 408(b)(2)(D)(v) requires that, when considering whether to
establish, modify, or revoke a tolerance, the Agency consider
“available information” concerning the cumulative effects of a
particular pesticide’s residues and “other substances that have a
common mechanism of toxicity”.  Syngenta did not perform a cumulative
risk assessment as part of this tolerance action for chlorothalonil
because HED has not yet determined that there are any other chemical
substances that have a mechanism of toxicity common with that of
chlorothalonil.  For purposes of this tolerance action, EPA has assumed
that chlorothalonil does not have a common mechanism of toxicity with
any other substance(s).>

<E. Safety Determination>

<	1. U.S. population. The chronic aggregate exposure analysis (food plus
water exposures) showed that exposure from all established and proposed
uses of Chlorothalonil resulted in a MOE of 938 (32.0% of the cRfD)
which exceeds the benchmark MOE of 300.  The short-term aggregate
exposure analysis (food plus water plus non-dietary residential
exposures) showed that exposure from all established and proposed uses
of Chlorothalonil resulted in a MOE of 1,242 for adults 50 years and
older, which exceeds the benchmark MOE of 1,000.  Based on the
completeness and reliability of the toxicity data supporting these
petitions, Syngenta believes that there is a reasonable certainty that
no harm will result to the U. S. population from aggregate exposures
arising from all current and proposed uses for Chlorothalonil.>

<	2. Infants and children. The chronic aggregate exposure analysis (food
plus water exposures) showed that exposure from all established and
proposed uses of Chlorothalonil resulted in a MOE of 348 (86.1% of the
cRfD) for all infants <1 year, which exceeds the benchmark MOE of 300. 
The short-term aggregate exposure analysis (food plus water plus
non-dietary residential exposures) showed that exposure from all
established and proposed uses of Chlorothalonil resulted in a MOE of
11,920 for infants <1 year, which exceeds the benchmark MOE of 1,000. 
Based on the completeness and reliability of the toxicity data
supporting these petitions, Syngenta believes that there is a reasonable
certainty that no harm will result to infants and children from
aggregate exposures arising from all current and proposed uses for
Chlorothalonil.>

3. Females 13-49 Years.  The chronic aggregate exposure analysis (food
plus water exposures) showed that exposure from all established and
proposed uses of Chlorothalonil resulted in a MOE of 1106 (29.5% of the
cRfD) for females 13-49 years, which exceeds the benchmark MOE of 300. 
The short-term aggregate exposure analysis (food plus water plus
non-dietary residential exposures) showed that exposure from all
established and proposed uses of Chlorothalonil resulted in a MOE of
1,245 for females 13-49 years, which exceeds the benchmark MOE of 1,000.
 Based on the completeness and reliability of the toxicity data
supporting these petitions, Syngenta believes that there is a reasonable
certainty that no harm will result to females 13-49 years from aggregate
exposures arising from all current and proposed uses for Chlorothalonil.

<F. International Tolerances>

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 sprouts, carrots, celery, cherries, cranberries, cucumbers, melons,
onions, peaches, squash, and tomatoes.  Some incompatibilities exist
between Codex MRLs and U.S. tolerances for bananas, cabbage,
cauliflower, peanuts, and sweet corn.  No questions of compatibility
exist with respect to commodities where no Codex MRLs have been
established but U.S. tolerances exist, or where Codex MRLs have been
established but U.S. tolerances do not exist.>

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