Document ID: EPA-HQ-OPP-2007-0107-0002
Agency: epa
Document Type: Supporting & Related Material
Title: 
Posted Date: 2007-04-04T04:00Z

EPA Registration Division contact: 

Barbara Madden, Registration Division (7505P), Office of Pesticide
Programs, Environmental Protection Agency, 1200 Pennsylvania Ave., NW.,
Washington, DC 20460-0001; telephone number (703) 305-6463; e-mail:
Madden.Barbara@epa.gov.

Interregional Research Project No. 4 (IR-4)

PP# 6E7138 and 3E6562

	EPA has received pesticide petitions (6E7138 and 3E6562) from
Interregional Research Project No. 4 (IR-4), 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 180.443 by
establishing tolerances for residues of myclobutanil in or on the raw
agricultural commodities fruiting vegetables, crop group 8, except
tomato at 4.5 parts per million (ppm) (6E7138); leafy vegetables, crop
subgroup 4A, except spinach at 11 ppm (6E7138); globe artichoke at 0.9
ppm (6E7138); cilantro at 11 ppm (6E7138); okra at 4.5 ppm (6E7138); and
black sapote, canistel, mamey sapote, mango, papaya, sapodilla, star
apple at 3 ppm (3E6562).  EPA has determined that the petition contains
data or information regarding the elements set forth in section 408
(d)(2) of the 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.  Based on the four metabolism studies in wheat,
apples, sugar beets and grapes, which indicate a similar metabolic route
for crops in four different crop groups, Dow AgroSciences (the
registrant) concludes that the nature of the residue is adequately
understood for the purpose of these tolerances.

	2. Analytical method.  The residue analytical method used was Rohm and
Haas Company method 34S-88-10, “RH-3866 Total Residue Analytical
Method for Apple and Grape” for artichokes, lettuce, pepper, and
tropical fruits; and Rohm and Haas Company method TR34S-88-21,
“Analytical Method for the Measure of RH-3866 in Various Crops, Soil,
Meat, Milk and Eggs”.  The lowest level of method validation (LLMV) in
this study was 0.01 ppm for each analyte. Based on recoveries of samples
fortified at the LLMV, the limit of detection (LOD) and limit of
quantitation (LOQ were estimated as 0.0036 ppm and 0.011 ppm,
respectively, for myclobutanil and as 0.018 ppm and 0.054 ppm,
respectively, for RH-9090.

	3. Magnitude of residues.  Magnitude of residue studies were conducted
by USDA’s program IR-4 at field sites located within the major growing
regions in the U.S. as recommended by the EPA’s guidelines.  These
studies have been submitted separately by IR-4 to the Agency. To provide
the residue chemistry data to support the establishment of a tolerance
for myclobutanil in or on lettuce, 14 field trials were conducted for
this study during the 2000 and 2001 growing season. In each trial, four
foliar applications of Rally 40W at a rate of approximately 0.125 lb
ai/A each were applied, for a total of approximately 0.50 lb ai/A. The
applications were made 12 to 15 days apart and timed so that
commercially mature lettuce could be collected 2 to 4 days after the
final application. Leaf lettuce samples for decline determination were
collected at approximately 0, 7, and 14 days following the final
application in the Florida and California leaf trials. In the head
lettuce trials, wrapper leaves were removed from half of the samples.
Myclobutanil residues in head lettuce were highest in the California 
trials with residues ranging from 0.02 ppm to 1.3 ppm for samples with
wrapper leaves.  For samples without wrapper leaves, residues from the
California trials ranged from less than the LLMV (0.01 ppm) to 0.24 ppm.
 Myclobutanil residues in 3-day leaf lettuce samples were highest in the
New Hampshire trials (with residues in samples from 0.16 to 3.95 ppm.  A
tolerance on cilantro at 11 ppm is based on the leaf lettuce data.  

Myclobutanil is used on bell and non-bell peppers for control of powdery
mildew.  Two sets of data were reported separately. In one set of data,
six field trials were conducted for this study during the 2002 growing
season, one in New Jersey (EPA Region 2), two in Florida (Region 3), one
in North Carolina (Region 2), one in California (Region 10), and one in
Wisconsin (Region 5). Bell peppers were grown in five trials and
non-bell peppers in one (Florida). At each trial, four foliar
applications at a rate of approximately 0.125 lb ai/A each were made for
a total of approximately 0.50 lb ai/A. Applications were made 12 to 16
days apart, and commercially mature peppers were collected following the
final (fourth) application, after the test substance had dried. The
results from the five bell pepper trials show that the maximum residue
following a total application of approximately 0.50 lb ai/A and a
pre-harvest interval (PHI) of 0 days was 0.17 ppm myclobutanil. In 0-day
non-bell peppers, the maximum residue was 0.12 ppm myclobutanil. No RH
9090 residues > 0.02 ppm (the lowest level of method validation) were
observed.  In a second study, the magnitude of residue data were
collected from six field trials, three each in Texas (EPA region 6) and
California (region 10).  Each of the field trial sites consisted of one
untreated control plot and one treated plot.  Bell peppers were grown in
two trials and non-bell peppers in four.  The treated plots received
four foliar directed applications of the test substance at a rate of
approximately 0.125 lb ai/A each, for a total of approximately
0.50 lb ai/A.  Applications were made 13 to 15 days apart, and mature
peppers were collected following the final (fourth) application, after
the test substance had dried (California trials) or 1 day later (Texas
trials).  In one non bell trial, additional samples were collected 3,
7, and 14 days following the final application.  For both types of
peppers, higher residues of each analyte were observed in samples grown
in Texas.  In bell peppers, residues ranged from 0.02 to 0.51 ppm
myclobutanil and from <0.02 to 0.17 ppm RH-9090.  In the 0-1 day PHI
non-bell peppers, residues ranged from 0.08 to 2.03 ppm myclobutanil and
from 0.03 to 0.39 ppm RH-9090.  In the 97-CA82 trial, myclobutanil
residues of the parent in 0-day samples were 0.10 ppm and 0.22 ppm; by
14 days, residue levels were 0.08 ppm and 0.14 ppm.  RH-3866 residues
ranged from 0.42 to 1.13 ppm, and RH-9090 residues ranged from 0.24 to
0.82 ppm. Total myclobutanil residues were from 0.79 to 1.95 ppm.
Residues of RH-9090 increased slightly, from 0.03 ppm and 0.04 ppm
(0 days) to 0.05 ppm and 0.08 ppm (14 days). 

Artichoke magnitude of residue data were collected from three field
trials conducted in California (EPA region 10).  Each of the three field
trial sites consisted of one untreated control plot and one treated
plot.  In each trial, the test substance was applied six times as a
foliar-directed spray at a rate of approximately 0.1 lb ai/A per
application, for a total of approximately 0.6 lb ai/A.  All applications
were made 12 to 16 days apart, and mature artichokes were collected 3
days after the final (sixth) application. In treated samples,
myclobutanil residues ranged from 0.24 to 0.59 ppm; residues of RH-9090
ranged from <0.01 to 0.01 ppm (the lowest level of method validation,
or LLMV. 

Magnitude of residue data were collected from four field trials
conducted in Hawaii (EPA region 13).  Each of the field trial sites
consisted of one untreated control plot and one treated plot. The
treated plot received eight foliar directed applications of the test
substance at a rate of approximately 0.25 lb ai/A per application, for a
total of approximately 2.0 lb ai/. All eight applications were made at
fruiting stages. The intervals between applications were 13 to 15 days.
Green to color break papaya fruit were collected on the day of the final
(eighth) application.  RH-3866 residues ranged from 0.42 to 1.13 ppm,
and RH-9090 residues ranged from 0.24 to 0.82 ppm. Total myclobutanil
residues were from 0.79 to 1.95 ppm.

B. Toxicological Profile

	1. Acute toxicity. According to Dow AgroSciences, myclobutanil wettable
powder formulations are essentially non-toxic after administration by
the oral, dermal and respiratory routes moderately irritating to the
eyes, and no-skin sensitizers.  Of these test results, ocular irritation
at Toxicity Category III (Caution) was shown to be the worst case acute
toxicity.

	2. Genotoxicity.  Myclobutanil was negative (non-mutagenic) in an Ames
assay with and without hepatic enzyme activation.  Myclobutanil was
negative in a hypoxanthine guanine phosphoribosyl transferase (HGPRT)
gene mutation assay using Chinese hamster ovary (CHO) cells in culture
when tested with and without hepatic enzyme activation.  In isolated rat
hepatocytes, myclobutanil did not induce unscheduled DNA synthesis (UDS)
or repair.  Myclobutanil did not produce chromosome effects in vivo
using mouse bone marrow cells or in vitro using CHO cells.  On the basis
of the results from this battery of tests, it is concluded that
myclobutanil is not mutagenic or genotoxic.

	3. Reproductive and developmental toxicity.  [i.  Developmental
toxicity in the rat.  Myclobutanil has been evaluated in a standard
two-generation reproduction study at dietary concentrations of 0, 4, 16,
and 80 mg/kg bw/day.  At a dietary concentration of 80 mg/kg bw/day,
myclobutanil was associated with reproductive effects as noted by
reduced numbers of females delivering litters and increased incidences
of still-born pups.  In addition, testicular atrophy in P2 males and
decreased weight gain for offspring during lactation were observed. 
General systemic effects were observed at 16 mg/kg bw/day as noticed by
increased liver weight (P1, P2 males) and hepatocellular hypertrophy (P2
males), although these changes were not considered adverse.  The NOEL
for reproductive effects in this study was 16 mg/kg bw/day, while the
NOAEL for both systemic toxicity and developmental toxicity was 16 mg/kg
bw/day.

	

Developmental toxicity in the rabbit.  A developmental study was 

conducted in rabbits with myclobutanil at orally administered dosages of
0, 20,60, and 200 mg/kg bw/day.  At dosages of 60 and 200 mg/kg bw/day,
myclobutanil was maternally toxic to rabbits when administered on Day 6
through 19 of gestation as evidenced by transient body weight loss.  At
a dose level of 200 mg/kg bw/day, myclobutanil was embryotoxic, although
fetuses that survived to Day 29 were grossly normal in appearance and
weight.  Embryotoxicity was manifested as decreases in litter size,
viability index, and fetal weight and an increase in the number of
resorptions per litter.  The material (dam) NOAEL in this study was 20
mg/kg bw/day, while the litter NOAEL was 60 mg/kg bw/day.

	4. Subchronic toxicity.  i.  Rat 90-day oral study.  A 13-week
subchronic feeding study was conducted in rats using dietary
concentrations of 0, 10, 30, 100, 300, 1000, 3000, 10,000, and 30,000
ppm.  Equivalent mg/kg bw/day compound intake was 0.52, 1.60, 5.22,
15.3, 51.5, 158, 585 and 1730 for males and 0.67, 2.03, 6.85, 19.7,
65.8, 195.2, 665, and 1811 for females.  Toxicologically adverse
findings were observed at 3000 ppm (158 and 195 mg/kg bw/day for males
and females, respectively) and greater following 90 days of dietary
exposure to myclobutanil.  Findings included decreased body weights,
increased organ weights, and gross and histopathological changes
primarily in the liver and kidneys.  A NOAEL for this study was 1000 ppm
(52 and 66 mg/kg bw/day for males and females, respectively).

ii.  Dog 90-day oral study.  A 13-week subchronic feeding study was
conducted in dogs using dietary concentrations of 0, 10, 200, 800, 1600
ppm which corresponded to mg/kg bw/day intakes of 0.34, 7.26, 29.13, and
56.8 for males and 0.42, 7.88, 32.43, and 57.97 for females. 
Treatment-related changes were observed in the livers of dogs treated at
200 ppm or greater, and included increased relative liver weights and
centrilobular hepatocellular hypertrophy, accompanied by minimal changes
in serum clinical chemistry.  However, these were considered to be
adaptive changes, and not adverse to the general clinical condition of
the animals.  Based on these findings, the NOAEL in dogs is considered
to be 1600 ppm (57 mg/kg bw/day) for males and females.

iii.  Rat 28-day dermal study.  The toxicological endpoint selected for
dermal exposure was based on studies using two formulations of
myclobutanil, at doges of 1, 10, and 100 mg/kg bw/day and 100 mg/kg
bw/day, respectively.  When applied dermally to rats for 4 weeks under
non-occluded conditions, no changes indicative of systemic toxicity were
observed.  Skin irritation and/or minimal gross and microscopic changes
in the treated skin were observed after application of both
formulations.  The NOAEL in this study for systemic toxicity for both
formulations was 100 mg/kg bw/day.

The in vivo dermal absorption of 14C-myclobutanil was determined in male
Crl:CD BR rats following a 10 hr and 24 hr dermal exposure period. 
Groups of rats were dermally exposed to a representative undiluted
commercial formulation of myclobutanil, as well as to a 1:400 dilution
of the same formulation, which is representative of a use dilution of
the product.  Following dermal administration to male rats, 7.7 - 9.4%
(10 hour exposure) and 9.8 - 10.9% (24 hours exposure) of the low dose
(0.19 mg a.i./kg) were absorbed.  Similarly, 14% (10 hour exposure) and
22.1% (24 hour exposure) of the high dose (75 mg a.i./kg) were absorbed.

iv.  Mouse 90-Day Oral Study.  A 13-week subchronic feeding study was
conducted in mice using dietary concentrations of 0, 3, 10, 30, 100,
300, 1000, 3000, and 10,000 ppm.  Equivalent mg/kg bw/day compound
intake was 0.40, 1.54, 4.79, 14.1, 42.7, 132, 542, and 2035 for males
and 0.62, 2.11, 6.94, 22.9, 65.5, 232, 710, and 2027 for females.  The
liver was the primary target organ in the mouse following 3 months
dietary exposure to myclobutanil.  The primary changes were related to
hypertrophy or necrosis and inflammation, as evidenced by changes in
clinical pathology, hepatic MFO activity, organ weights, and
histopathology.  The NOAEL for these effects in mice is 300 ppm (43
mg/kg bw/day) in males and 1000 ppm (232 mg/kg bw/day) in females.]

	5. Chronic toxicity. [i.  Dog.  A 1-year dog feeding was conducted
using dietary concentrations of 0, 10, 100, 400 and 1600 ppm with
corresponding mg/kg bw/day equivalents of 0.34, 3.09, 14.28, and 54.22
in males and 0.40, 3.83, 15.68 and 58.20 in females.  Treatment-related
changes were observed in the livers of dogs treated at 400 ppm, and
included increased relative liver weights (females only), and minimal
centrilobular hepatocellular hypertrophy (both sexes), accompanied by
increases in serum ALP (females only).  However, these were considered
to be adaptive changes, and not adverse to the general clinical
condition of the animals.  In addition to these effects, dogs at 1600
ppm also showed effects on ALT (males), GGT (females), albumin,
inorganic phosphorous, RBC (males) and platelets (males), and an
accentuated lobular architecture of the liver and ballooning of
hepatocytes (females).  Based on the limited effects, the NOAEL in
beagle dogs is considered to be 400 ppm (14.3-15.7 mg/kg bw/day) for
males and females.

ii.  Mouse.  A two-year carcinogenicity study was conducted in mice
using dietary concentrations of 0, 20, 100, and 500 ppm (equivalent to
0, 2.7, 13.7, and 70.2 mg/kg bw/day for males and 0, 3.2, 16.5, and 85.2
mg/kg bw/day for females).  The NOEL for chronic effects other than
carcinogenicity was 20 ppm while the LOEL was 100 ppm, based on a slight
increase in liver mixed-function oxidase (MFO).  Microscopic changes in
the liver were evident in both sexes at the top dose of 500 ppm.  There
were no carcinogenic effects in either sex at any dose level tested. 
The highest dose level selected was satisfactory for evaluating
carcinogenic potential in male mice, but was considered lower than MTD
for females.  Accordingly, a second carcinogenicity study was conducted
with female mice using a top dose of 2000 ppm (393.5 mg/kg bw/day),
which approaches the MTD, to evaluate carcinogenic potential.  At this
dose level, no carcinogenic effects were observed.

iii.  Rat.  A two-year oncogenicity study in rats at dose levels of 0,
2.5, 9.8, 39.2 (males) and 0, 3.2, 12.8, 52.3 (females) revealed a
marginal effect on body weight of high dose males and possibly females. 
Absolute liver weights were slightly decreased for high dose males and
females, although statistical significance for this finding was only
evident at 6 months.  Hepatic MFO activity was slightly increased in
high-dose males and females up to 12 months.  Testicular weights were
significantly decreased in mid-dose males at termination, and in
high-dose males at 12 months and at termination.  Testicular atrophy was
slightly and moderately increased in mid and high-dose males,
respectively at 24 months.  No other significant effects were observed
in either sex at the dose levels employed over the 24-month period. 
There was no increased incidence of neoplastic lesions in any organ for
either sex.  The NOAEL in male rats is 2.5 mg/kg bw/day, based on the
testicular findings, while the female NOAEL is 52.3 mg/kg bw/day.  The
Agency has classified myclobutanil as a " Group E - not likely a human
carcinogen” and, therefore, quantification of human cancer risk is not
required.]

	6. Animal metabolism. [The adsorption, distribution, excretion, and
metabolism of myclobutanil was completely and rapidly absorbed,
extensively metabolized to at least seven major metabolites, and rapidly
excreted evenly distributed between urine and feces.  Myclobutanil did
not accumulate in tissues.]

	7. Metabolite toxicology.  [Common metabolic pathways for myclobutanil
have been identified in both plants (grapes, apples, wheat, sugar beets)
and animals (rat, goat, hen).  The metabolic pathway common to both
plants and animals involves oxidation of the n–butyl alkyl side-chain
in the 3- and 4- positions, oxidation of the cyano-group, and subsequent
conjugation.  Extensive degradation and elimination of polar metabolites
occurs in animals such that residues are unlikely to accumulate in
humans or animals exposed to these residues through the diet.]

	8. Endocrine disruption.  [The mammalian endocrine system includes
estrogen and androgens as well as other hormonal systems.  Myclobutanil
is not known to interfere with reproductive hormones; thus, the
registrant believes that myclobutanil should not be considered to be
estrogenic or androgenic.  Dow AgroSciences is not aware of any
instances of proven or alleged adverse reproductive or developmental
effects to people, domestic animals, or wildlife as a result of exposure
to myclobutanil or its residues.]

C. Aggregate Exposure

	1. Dietary exposure.  The exposure and risk resulting from agricultural
uses of myclobutanil was considered for the U.S. population and special
sub-populations.  There are three direct sources of exposure to humans
considering myclobutanil's uses across all labels:  from food intake,
from consuming drinking water, and from residential applications around
homes.  The exposure and risk are estimated in this report for different
durations of all three routes of exposure and their aggregated
contribution. An acute Tier-III probabilistic assessment was done using
highly refined estimates of food residues using a combination of PDP
residues and tolerances for inadvertent residues and proposed uses.  In
addition, tolerances for emergency exemptions (i.e. Section 18 uses),
were included to provide as complete an assessment as possible.  In an
aggregate assessment, exposures from food residues were combined with
conservative estimates of potential water residues.  The current
approach of the EPA Office of Pesticide Programs (OPP) is to use a
tiered approach for acute dietary risk assessment that proceeds from
very conservative assumptions about food residues, to inclusion of more
realistic residue values measured closer to the point of consumption.

	i. Food.  The process of dietary risk assessment of pesticides
considers chronic and acute exposures to the U.S. population and
sensitive population sub-groups.  Critical to any dietary assessment is
residue and consumption data.  Because of the number of years
myclobutanil has been used on crops, a substantial public dataset exists
of food residues as measured by the USDA's Pesticide Data Program (PDP).
 The PDP monitoring data realistically estimate the magnitude of
pesticide residue on food as it is purchased by the consumer, since
samples are taken closer to the point of consumption, and more
accurately represent actual patterns of use and food distribution than
measurements from a typical field trial.  Additional exposures from
potential residues in drinking water were also estimated.

The Dietary Exposure Evaluation Model (DEEM-FCID, version 2.04), a
commercially available software package, was used to estimate exposure
to myclobutanil via food consumption by the general U.S. population and
certain subgroups.  The model combined the consumption data and residue
data for a given pesticide to analyze dietary risk.  For the tier III
acute assessment, DEEM developed a conditional, joint probability
function from the individual pesticide residues and the food intake
information.

Food consumption data from the USDA Continuing Survey of Food Intakes by
Individuals (CSFII) conducted from 1994 through 1998 including the
children's supplemental survey were used in this assessment.  The food
consumption data, i.e., foods as consumed, were translated into raw
agricultural commodities and their food forms using recipe translation
files contained within the DEEM software.  For acute assessments,
individual, daily, food consumption amounts by each survey respondent
were use to establish a probability distribution of exposures; for
chronic assessments, food consumption values averaged across the
populations of interest were used. Because of the number of years that
myclobutanil has been used in agriculture, the PDP data provides the
best available information on residues that may result from established
uses on food crops.  It should be noted that a number of the
myclobutanil uses are supported by residue data supplied by the IR-4
program.  The section 3 tolerance value was used for those foods that
were not sampled by the PDP residue program, and for which there is no
established policy for surrogation from another crop.  These crops
include such uses as almonds, cane berries, and peppermint.

a.  Acute dietary exposure.  A summary of the results of the acute
exposures from food consumption is provided.  All estimates are given
for the upper 99.9%tile of females of child bearing age, i.e., the
subpopulation considered susceptible to acute exposures from
myclobutanil. Exposures from all existing, proposed, and inadvertent
residues result in very low acute exposures.  Consumption of food by
females of child bearing age is expected to result in approximately
0.0377 mg/kg-bw/day exposure to myclobutanil or approximately six
percent of the acute reference dose.

The acute drinking water estimates were estimated using FIRST, GENEEC
and SCIGRO and are known to overestimate potential water residues.  Such
water estimates are very sensitive to the input parameters; however,
they can still serve as a screening estimate for exposure
considerations. Water residues were incorporated as a single point
estimate for both direct and indirect water sources assuming a constant
value of 115 ppb (0.115 ppm). The potential, acute, aggregate exposures
from food and drinking water for females of child bearing age is
approximately 0.0377 mg/kg-bw/day or 6.3% of the acute reference dose
for the upper 99.9%tile of the population.

b.  Chronic dietary exposure.  After considering all existing and
proposed uses, exposures from all existing, proposed, and inadvertent
residues from myclobutanil result in low chronic exposures.  Consumption
of food by children 1-2 years old is expected to result in approximately
0.008  mg/kg-bw/day exposure to myclobutanil or approximately 32 percent
of the chronic reference dose.  Potential chronic exposure to water
residues was estimated using the highest averaged water value of 92 ppb
(0.092 ppm) for surface water. After considering all existing and
proposed uses, the exposure to myclobutanil residues is approximately
56% of the chronic population adjusted dose (cPAD) for the most exposed
population sub-group, non nursing infants.  Although this is much below
the acceptable level, it is a very conservative assessment, since about
56% of the total exposure to non-nursing infants (32% of the cPAD) comes
from the addition of drinking water as estimated for the worst possible
scenario.  For children 1-2 years old, water intake represents
approximately 36% of the total daily estimated intake or 12% of the
cPAD.  For the US population, water from direct and indirect sources
represents 53% of the total exposure and approximately 8% of the cPAD. 

Cancer dietary exposure. The Agency has classified myclobutanil as a
"Group E - not likely a human carcinogen" and, therefore, quantification
of human cancer risk is not required.

]	

ii. Drinking Food. Direct measurements of myclobutanil in drinking water
were not available.  Estimates of potential water concentrations
resulting from agricultural use of myclobutanil were estimated using
three environmental models, assuming certain environmental degradation
properties for myclobutanil and modeled dynamics of ground water and
surface water bodies.  These three models provide conservative,
screening level estimates of water concentrations.  SciGrow2.1 is used
for ground water while GENEEC2 and FIRST is used to give estimates of
ground water concentrations.  Assuming a myclobutanil  application rate
of 0.25 lbs/acre and a measured field half life of 66 days, SciGrow2.1
gave a ground water estimate of 0.27 parts per billion (ppb).  Assuming
a half life of 354 days, derived from laboratory studies, the estimate
was 1.1 ppb.  Both GENEEC2 and FIRST gave comparable peak and average
surface water concentration estimates.  Using an environmental half life
of 66 days gave a peak concentration of 48 ppb with GENEEC2 and 60 ppb
for FIRST.  The average, long term concentrations were 60 ppb and 41 ppb
respectively.  These values differ somewhat from the values used by the
USEPA in their 2001 assessment.  In their document, based on the GENEEC2
and FIRST models the estimated environmental concentrations (EECs) of
myclobutanil for acute exposures are estimated to be 115 parts per
billion (ppb) for surface water and 2 ppb for ground water. The EECs for
chronic exposures are estimated to be 92 ppb for surface water and 2 ppb
for ground water.

	2. Non-dietary exposure.  i.  Residential uses.  Myclobutanil is a
fungicide registered for use on turfgrass (including established lawns,
and golf courses), landscape ornamentals, greenhouse and nursery
ornamentals, home orchards, vineyards, or fruit trees, and
non-commercial tree fruits and vines.  The exposure and risk from the
home use application of myclobutanil were estimated for hose-end
sprayer, back pack sprayer and low pressure hand wand sprayer when used
for garden, trees and vines and turf treatments.  The resultant MOEs for
mixer/loader-applicator (M/L/A) range from 11,000 (low pressure hand
wand) to 210,000 (backpack) for garden and fruit tree applications. 
MOEs for turf application are 770 for the hose end sprayer, 2,000 for
low pressure hand wand, and 39,000 for the back pack sprayer.  MOEs were
acceptable for all post-application activities in all crops.  MOEs for
garden activities ranged from 5,800 for grape girdling and vine turning
to 370,000 for limb propping of fruit trees.  Exposure for children of
an age to be expected to be working in the garden (i.e. body weight 39.1
kg) resulted in a similar range of MOEs.  These ranged from 3,800 for
grape girdling and vine turning to 200,000 for limb propping of fruit
trees.  Reentry into treated lawns, home orchards, vineyards, and
gardens also resulted in acceptable MOEs for all crops and scenarios. 
Aggregated reentry into lawns by children resulted in MOEs > 570 and
MOEs > 1,600 for adults (based on CA data).  Working in the garden
resulted in MOEs that ranged from 5,800 to 370,000 for adults and from
3,800 to 200,000 for children.

Recreational uses.  Myclobutanil is used on golf courses.  Use on golf 

courses is very low.  Therefore, as a conservative estimate, the MOE for
residential lawns (above) is used. Since myclobutanil is a Group E (not
likely a human carcinogen), no human cancer risk was calculated.

D. Cumulative Effects

	Myclobutanil is a member of the triazole derivative (T-D) fungicides. 
At this time, there is no data available to determine whether
myclobutanil exhibits a common mechanism of toxicity with other T-D
fungicides.  For the purpose of this assessment therefore, it is assumed
that myclobutanil does not have a mechanism of toxicity common with
other substances and no cumulative risk assessment is required.

E. Safety Determination

	1. U.S. population. Using the above conservative exposure assumptions
and taking into account the completeness and reliability of the toxicity
data, chronic dietary exposure to myclobutanil from all registered and
proposed uses and drinking water will utilize 14.5% of the cRfD for the
U. S. population (total).  Generally, EPA has no concern for exposures
below 100% of the cRfD because the chronic RfD represents the level at
or below which daily dietary exposures over a lifetime will not pose
appreciable risks to human health.  Likewise, the acute dietary food
exposure at 99.9th percentile for females 13+ yrs, the population
sub-group of concern is 6% of aRfD which is well below 100% of the aRFD.
 Therefore, there is no concern for exposure because the acute RfD
represents the level at or below which a single daily exposure will not
pose appreciable risks to human health.  Additionally, the potential
contribution of myclobutanil from residential uses in home gardens,
orchards, vineyards and turf showed acceptable margin of exposures to
homeowners (MOE > 770, during the application and MOE > 1,600 for
post–application).  The aggregate exposure from diet, drinking water
and residential exposure to adults has also resulted in a safe margin of
exposure to homeowners (MOE > 360).  Short-term and intermediate-term
risks are considered to be negligible because of lack of significant
toxicological effects and exposure.  Therefore, based on these risk
assessments, Dow AgroSciences concludes that there is reasonable
certainty that no harm will result to the U. S. population from
aggregate exposure to myclobutanil residues from all supported
registered uses.

	2. Infants and children.  EPA uses a weight of evidence approach in
determining what safety factor is appropriate for assessing risks to
infants and children.  This approach takes into account the nature and
severity of the effects observed in pre- and post-natal studies and
other information such as epidemiological data.  The completeness and
adequacy of the toxicity database is also considered. Toxicity database
and exposure data for myclobutanil are complete.  No indication of
increased susceptibility of rats or rabbits to in utero and/or postnatal
exposure was noted in the acceptable developmental toxicity studies in
rats and rabbits as well as in a 2-generation reproductive toxicity
study in rats.  EPA has previously determined that no additional safety
factor to protect infants and children is necessary for myclobutanil and
that the cRfD at 0.025 mg/kg/day is appropriate for assessing risk to
infants and children.

Using the conservative assumptions described above, the chronic dietary
exposure to myclobutanil including all existing and proposed uses and
water will utilize 45.4% of the cRfD for all infants (<1 yr old), 56.4%
of the cRfD for non-nursing infants, and 31.9% of the cRfD for children
1-2 yrs.  The aggregate risk estimated acceptable MOEs of 220 for
children exposed from diet, drinking water and residential
post-application from dermal, soil ingestion, hand to mouth and object
to mouth activities.  Therefore, based on the completeness and
reliability of the toxicity data and the conservative exposure
assessment, Dow AgroSciences concludes with reasonable certainty that no
harm will result to infants and children from the aggregate exposure to
myclobutanil residues from registered uses.

F. International Tolerances

	International CODEX values are established for hops, bananas, prunes,
pears, apples, plums, apricots, cherries, peaches, nectarines, quince,
tomatoes, table grapes, wine grapes, strawberries, currants, cattle fat,
meat, milk and edible offal, poultry meat, fat, and edible offal, and
eggs.