Document ID: EPA-HQ-OPP-2006-0282-0006
Agency: epa
Document Type: Supporting & Related Material
Title: 
Posted Date: 2006-12-20T05:00Z

SEQ CHAPTER \h \r 1 

	UNITED STATES ENVIRONMENTAL PROTECTION AGENCY

WASHINGTON, D.C.  20460

OFFICE OF           

PREVENTION, PESTICIDES

AND TOXIC SUBSTANCES

Date:		12-JULY-2006

Subject:	Myclobutanil.  REVISED Human Health Risk Assessment for
Proposed Uses on Hops and Home Garden Fruit Trees, Nut Trees, Berries,
Mint and Vegetables.  PC Code: 128857.  PP#: 1E6265.  DP#:  D330235. 
Decision #: 357983.

From:		Jennifer R. Tyler, Chemist

		P.V. Shah, Ph.D.

		Mark I. Dow, Ph. D., Biologist

		Registration Action Branch 1

		Health Effects Division (7509C)

		Timothy C. Dole, CIH, Industrial Hygienist 

		Reregistration Branch 1 (RRB1)/HED (7509C)

Thru:		P.V. Shah, Ph.D., Branch Senior Scientist

		RAB1/HED (7509C)

		Felecia Fort, Acting Branch Chief

		RAB1/HED (7509C)

To:		Mary Waller, PM Team 21

		Fungicide Branch

		Registration Division (RD; 7505C)

Note:	The following memorandum supersedes the HED Human health risk
assessment dated 6/14/06 (J. Tyler; DP# 318501).  Dow AgroSciences
agreed to revise its current labels to include a maximum application
rate of 0.62-0.65 lb ai/A for residential use on turf (personal
communication between R. Brinkmeyer and J. Tyler, 7/10/06).  The company
will submit revised labels to include these changes.

INTRODUCTION

ct No. 4 (IR-4), on behalf of the Washington State Hops Commission that
represents all United States (U.S.) hops growers, has submitted a
request for the use of the triazole fungicide myclobutanil
[α-butyl-α-(4-chlorophenyl)-1H-1,2,4-triazole-1-propanenitrile] on
hops.  IR-4 has proposed a tolerance, expressed as the parent compound
and its alcohol metabolite α- (3-hydroxybutyl)-α-
(4-chlorophenyl)-1H-1, 2,4-triazole-1-propanenitrile (free and bound)
(RH-9090), of 10.0 ppm on dried hops.  Concurrently, the petitioner has
submitted a request for Section 3 registration of the products Rally®
40W Agricultural Fungicide (EPA Reg No. 707-215) and Nova® 40W
Agricultural Fungicide (EPA Reg No. 707-221), both of which are packaged
as water-soluble pouches containing 40% myclobutanil as the active
ingredient (ai), on hops.

In addition, Chemsico has requested a label amendment to add home garden
uses on almonds, apples, mayhaw, berries, grapes, peppermint, spearmint,
stone fruits, strawberries, asparagus, cucurbits, snap beans and
tomatoes to the Chemsico Fungicide M label (EPA Reg. No. 9688-123), a
product containing 1.55% myclobutanil as the ai.

NOTE:  HED previously completed a Section 3 human-health risk assessment
for the use of myclobutanil on several commodities (Memo, J. Rowell, et
al. 3/14/00; D244901), and RD recently completed a Section 18 Emergency
Exemption assessment for the use of myclobutanil on soybeans and legume
vegetables (Memo, W. Cutchin, 8/9/05; D317318).  This document contains
only those aspects of the risk assessment that are affected by the
addition of the proposed new uses of myclobutanil.  The following
information from the previous risk assessments on myclobutanil can be
applied directly to this action:

Physical/Chemical Properties (page 11 of 3/14/00 memo).

	

The following should also be noted that, since the completion of the
3/14/00 risk assessment,

	

RAB1 toxicologists re-evaluated the myclobutanil toxicology database and
concluded that the 28-day dermal toxicity study previously used for
short-term dermal risk assessment is not appropriate.  A two-generation
reproduction study in rats was selected because the effects of concern
(atrophy of the testes and prostate) seen at a lowest observed adverse
effect level (LOAEL) of 50 mg/kg/day may not be protective if the
endpoints were based on the 28-day dermal toxicity study.  In addition,
there were no effects of concern identified in the 28-day dermal
toxicity study [no observed adverse effect level (NOAEL) of 100
mg/kg/day was the highest dose tested].

EPA conducted a human-health assessment for aggregate exposure to
1,2,4-triazole and triazolylalanine/triazolylacetic acid in a separate
document in order to support the extension of existing and granting of
new parent triazole-derivative fungicide tolerances (Memo Doherty, et
al., 12/22/05; DP# 322215).

	

In this memo, dietary, residential, occupational and aggregate risks
were re-evaluated based on the addition of aforementioned uses to the
myclobutanil use pattern.

Conclusions/Recommendations:  Aggregate risk assessments were performed
for acute (food and drinking water), short-term (food, drinking water
and residential), intermediate-term (food, drinking water and
residential), and chronic aggregate exposure (food and drinking water). 
The acute and chronic aggregate risks associated with the proposed uses
of myclobutanil do not exceed HED’s level of concern for the general
U.S. population or any population subgroup.  For the general U.S.
population, the short-term handler and short- and intermediate-term
post-application aggregate margins of exposure (MOEs) are greater than
100; and, therefore, do not exceed HED's level of concern (MOE <100). 
For children/toddlers, the short- and intermediate-term aggregate MOE is
63 for the “playing on lawn” scenario using the turf application
rate of 1.36 lb ai/A, but is 130 for the same scenario using the 0.62 lb
ai/A turf application rate.  It should be noted that the high rate of
1.36 lb ai/A is from the Eagle® 20EW label (EPA Reg. No. 62719-463),
which appears to be primarily intended for turf use on golf courses
because it has the statement “A systemic, protective and curative
fungicide for disease control in turf grass (including golf course
fairways, roughs, tee boxes and greens).”  However, as there is no
specific language prohibiting use on residential turf, it was assumed
that this product could be used on residential turf.

The residue chemistry and toxicological databases are adequate to
support the following:

	

The requested label amendment to add home garden uses on almonds,
apples, mayhaw, berries, grapes, peppermint, spearmint, stone fruits,
strawberries, asparagus, cucurbits, snap beans and tomatoes to the
Chemsico Fungicide M label (EPA Reg. No.9688-123).

the combined residues of myclobutanil and its alcohol metabolite α-
(3-hydroxybutyl)-α- (4-chlorophenyl)-1H-1,
2,4-triazole-1-propanenitrile (free and bound) in/on hop, dried cones.

	

However, as the short- and intermediate-term aggregate risk for
children/toddlers are of concern (MOE<100), the occupational and
residential exposure database is not adequate to support the proposed
uses at this time.  The short- and intermediate-term aggregate risk
would be acceptable if the myclobutanil product labels with turf uses
are amended to specify at maximum application rate of 0.62 lb ai/A on
residential turf.

1.0	Background

	

Myclobutanil is a contact triazole fungicide, which is applied to
prevent fungal outbreaks.  In agricultural and commercial settings it
has a variety of uses including fruits, vegetables, ornamentals and
turf.  In the residential setting, the existing uses include turf and
ornamentals.  The proposed new uses include hops as well as home garden
uses on fruit trees, nut trees, berries, mint and vegetables.

2.0	Hazard Characterization/Toxicity Endpoint Selection

2.1	Hazard Characterization:  The toxicological database for
myclobutanil is adequate to support registration and tolerances.  There
are no data gaps.  Myclobutanil has low acute toxicity with the
exception for ocular irritation.  It is toxicity category III for oral
acute toxicity, category IV for dermal and inhalation acute toxicity and
dermal irritation.  Myclobutanil is category I for ocular irritation and
the technical is a dermal sensitizer. However, formulation containing
40% myclobutanil was not sensitizing.  In rat subchronic and chronic
toxicity studies, the primary target organs are liver and testes.  Liver
effects, following subchronic exposure, include hypertrophy,
hepatocellular necrosis and increased liver weight.  There is decreased
testicular weight and testicular atrophy.  Chronic exposure to the rat
also results in hepatocellular vacuolization and additional testicular
effects, which include bilateral aspermatogenesis, increased incidences
of hypospermia and cellular debris in the epididymides and increased
incidences of arteritis/periarteritis in the testes.  With the exception
of testicular effects, subchronic and chronic exposures in the mouse
result in a toxicity profile similar to the rat.  The mouse, following
chronic exposure, has, in addition, increased Kupffer cell pigmentation,
periportal punctate vacuolation, and individual cell necrosis of the
liver.  There is no evidence of carcinogenic potential in either the rat
or mouse.  In the subchronic dog, there are hepatocellular hypertrophy,
increased relative and absolute liver weight and increased alkaline
phosphatase.  In the chronic dog study, liver toxicity is similar with
the addition of “ballooned” hepatocytes and increases in SGPT and
GGT.  Signs of toxicity observed in the rat 28-day dermal studies
(studies on the 40WP and 2EC formulations) are limited to dermal
irritation.  There is no evidence of systemic toxicity in either study. 
There is no evidence of increased susceptibility in either of the
developmental toxicity studies or the reproduction study.  In the rat
developmental toxicity study, maternal toxicity, which included rough
hair coat and salivation, occurs at the same dose level as increases in
incidences of 14th rudimentary and 7th cervical ribs in the fetuses.  At
the next higher dose there is also alopecia, desquamation and red
exudate around the mouth in the dams.  In the rabbit developmental
toxicity study there is reduced body weight and body weight gain during
the dosing period, clinical signs of toxicity and a possible increase in
abortions in the does at the same dose level that there are increased
resorptions, decreased litter size and decreased viability index.  The
maternal toxicity in the rat reproduction study includes increased liver
weights and hepatocellular hypertrophy.  Reproductive effects occur at
the same dose and include increased incidences in the number of still
born pups and atrophy of the testes, epididymides and prostate. 
Developmental effects occurring at the same dose in the reproduction
study include decreased pup body weight gain during lactation. 
Myclobutanil is rapidly absorbed and excreted with complete elimination
by 96 hours.  There is extensive metabolism prior to excretion with
elimination of radiolabeled material evenly distributed between urine
and feces.  There is no evidence of tissue accumulation.  There is no
concern for mutagenic activity.  Myclobutanil was determined to be not
carcinogenic in two acceptable animal studies.  Therefore, it was
classified as a “Group E” chemical (evidence of noncarcinogenicity
for humans).



Toxicity Endpoint Selection:  The doses and toxicological endpoints
selected for

various exposure scenarios are summarized in Table 2.1.  RAB1
toxicologists recently re-evaluated the myclobutanil toxicology database
and concluded that the 28-day dermal toxicity study previously used for
short-term dermal risk assessment is not appropriate.  A two-generation
reproduction study in rats was selected because the effects of concern
(atrophy of the testes and prostate) seen at a LOAEL of 50 mg/kg/day may
not be protective if the endpoints were based on the 28-day dermal
toxicity study.  In addition, there were no effects of concern
identified in the 28-day dermal toxicity study (NOAEL of 100 mg/kg/day
was the highest dose tested).

Table 2.1.  Summary of Toxicological Dose and Endpoints for Myclobutanil
for Use in Human Risk Assessment

Exposure

Scenario	Dose Used in Risk Assessment,

UF	FQPA SF and Endpoint for Risk Assessment	Study and Toxicological
Effects

Acute Dietary

females 13-50 years of age	NOAEL = 60 mg/kg/day

UF = 100

Acute RfD = 0.60 mg/kg/day	FQPA SF = 1x

aPAD = acute RfD

              FQPA SF

= 0.60 mg/kg/day	Developmental Toxicity - rabbit1

LOAEL = 200 mg/kg/day based on increased resorptions, decreased litter
size and a decrease in the viability index.

Acute Dietary

general population including infants and children	none	not applicable
not applicable

Chronic Dietary

all populations	NOAEL= 2.49 mg/kg/day

UF = 100

Chronic RfD =  0.025 mg/kg/day	FQPA SF = 1x

cPAD = chronic RfD

                FQPA SF

= 0.025 mg/kg/day	Chronic Toxicity/ Carcinogenicity - rat

LOAEL = 9.94 mg/kg/day based on decreased testicular weights and
increased testicular atrophy.

Short-Term Dermal (1-30 days)

(Occupational/

Residential)	oral study NOAEL= 10 mg/kg/day

(dermal absorption rate = 50%)	acceptable MOE = 100 (Occupational)

acceptable MOE = 100 (Residential, includes the FQPA SF)	2 Generation
Reproduction Toxicity - rat

LOAEL = 50 mg/kg/day based on atrophy of the testes and prostate as well
as an increase in the number of stillborn pups and a decrease in pup
weight gain during lactation.

Intermediate-Term

Dermal (1-6 months)

(Occupational/

Residential)	oral study NOAEL= 10 mg/kg/day

(dermal absorption rate = 50%)	acceptable MOE = 100 (Occupational)

acceptable MOE = 100 (Residential, includes the FQPA SF)	2 Generation
Reproduction Toxicity - rat

LOAEL = 50 mg/kg/day based on atrophy of the testes and prostate as well
as an increase in the number of stillborn pups and a decrease in pup
weight gain during lactation.

Long-Term Dermal (> 6 months)

(Occupational/

Residential)	oral study NOAEL= 2.49 mg/kg/day

(dermal absorption rate = 50%)	acceptable MOE = 100 (Occupational)

acceptable MOE = 100 (Residential, includes the FQPA SF)	Chronic
Toxicity/ Carcinogenicity – rat

LOAEL = 9.94 mg/kg/day based on decreased testicular weights and
increased testicular atrophy.

Short-Term Inhalation (1-30 days)

(Occupational/

Residential)	oral study NOAEL= 10 mg/kg/day

(inhalation absorption rate = 100%)	acceptable MOE = 100 (Occupational)

acceptable MOE = 100 (Residential, includes the FQPA SF)	2 Generation
Reproduction Toxicity - rat

LOAEL = 50 mg/kg/day based on atrophy of the testes and prostate as well
as an increase in the number of stillborn pups and a decrease in pup
weight gain during lactation.

Intermediate-Term Inhalation (1 –6 months)

(Occupational/

Residential)	oral study NOAEL= 10 mg/kg/day

(inhalation absorption rate = 100%)	acceptable MOE = 100 (Occupational)

acceptable MOE = 100 (Residential, includes the FQPA SF)	2 Generation
Reproduction Toxicity - rat

LOAEL = 50 mg/kg/day based on atrophy of the testes and prostate as well
as an increase in the number of stillborn pups and a decrease in pup
weight gain during lactation.

Long-Term Inhalation (>6 months)

(Occupational/

Residential)	oral study NOAEL= 2.49 mg/kg/day

(inhalation absorption rate = 100%)	acceptable MOE = 100 (Occupational)

acceptable MOE = 100 (Residential, includes the FQPA SF)	Chronic
Toxicity/ Carcinogenicity - rat

LOAEL = 9.94 mg/kg/day based on decreased testicular weights and
increased testicular atrophy.

Cancer (oral, dermal, inhalation)	"Group E"	not applicable	not
applicable

1.  The HIARC document (dated 9/2/99) table incorrectly lists this as
rat.

3.0	Food Quality Protection Act (FQPA) Assessment

	

The FQPA Safety Factor Committee (SFC) met on August 16, 1999 (HED Doc.
No. 013734, dated 9/13/99) to evaluate the hazard and exposure data for
myclobutanil.  The committee recommended that the FQPA Safety Factor
(SF) (as required by FQPA of August 3, 1996) be reduced to 1x in
assessing the risk posed by this chemical.  The myclobutanil risk
assessment team re-evaluated the quality of the toxicology and exposure
data; and, based on these data, recommended that the FQPA SF be reduced
to 1x (Memo, J. Tyler.  The recommendation is based on the following: 

There are no toxicity data gaps in the consideration of the FQPA SF.

The Hazard Identification Assessment Review Committee (HIARC) concluded
that there was no evidence of increased susceptibility in the
developmental toxicity studies with rats and rabbits.  

HIARC determined that a developmental neurotoxicity study is not
required because neurotoxic compounds of similar structure were not
identified and there was no evidence of neurotoxicity in the current
toxicity database.

The exposure assessments will not underestimate the potential dietary
(food and drinking water) and residential (non-occupational) exposures
for infants and children from the use of myclobutanil.

The acute dietary food exposure assessment (females 13-49 years old
only) utilizes existing and proposed tolerance level residues and 100%
crop treated (CT) information for all commodities.  By using these
screening-level assessments, actual exposures/risks will not be
underestimated.

The chronic dietary food exposure assessment utilizes existing and
proposed tolerance level residues; USDA Pesticide Data Program (PDP)
monitoring data for apple juice, bananas (not plantains) and milk;
average % CT data verified by the Biological Economic and Analysis
Division (BEAD) for apple (except juice), apricots, artichokes,
asparagus, sugar beet, blackberry, and tomatoes; and 100% CT information
for all other registered and proposed uses.  The chronic assessment is
somewhat refined and based on reliable data and will not underestimate
exposure/risk.

The dietary drinking water assessment utilizes water concentration
values generated by model and associated modeling parameters, which are
designed to provide conservative, health protective, high-end estimates
of water concentrations which will not likely be exceeded.

The residential handler assessment is based upon the residential
standard operating procedures (SOPs) and utilized unit exposure data
from the Outdoor Residential Exposure Task Force (ORETF) and the
Pesticide Handlers Exposure Database (PHED).  The residential
post-application assessment is based upon chemical-specific turf
transferable residue (TTR) data and DFR data.  The chemical-specific
study data as well as the surrogate study data used are reliable and
also are not expected to underestimate risk to adults as well as to
children.  In a few cases where chemical-specific data were not
available, the SOPs were used alone.  The residential SOPs are based
upon reasonable “worst-case” assumptions and are not expected to
underestimate risk.  These assessments of exposure are not likely to
underestimate the resulting estimates of risk from exposure to
myclobutanil.

	

4.0	Endocrine Disruption

	

EPA is required under the Federal Food Drug and Cosmetic Act (FFDCA), as
amended by FQPA, to develop a screening program to determine whether
certain substances (including all pesticide active and other
ingredients) "may have an effect in humans that is similar to an effect
produced by a naturally occurring estrogen, or other such endocrine
effects as the Administrator may designate."  Following the
recommendations of its Endocrine Disruptor Screening and Testing
Advisory Committee (EDSTAC), EPA determined that there were scientific
bases for including, as part of the program, the androgen and thyroid
hormone systems, in addition to the estrogen hormone system.  EPA also
adopted EDSTAC’s recommendation that the Program include evaluations
of potential effects in wildlife.  For pesticide chemicals, EPA will use
FIFRA and, to the extent that effects in wildlife may help determine
whether a substance may have an effect in humans, FFDCA has authority to
require the wildlife evaluations.  As the science develops and resources
allow, screening of additional hormone systems may be added to the
Endocrine Disruptor Screening Program (EDSP).

	

When the appropriate screening and/or testing protocols being considered
under the Agency’s EDSP have been developed, myclobutanil may be
subjected to additional screening and/or testing to better characterize
effects related to endocrine disruption.

		

5.0	Registered/Proposed Application Scenarios

	

5.1	Registered Uses:  Myclobutanil is a contact fungicide that is
applied to prevent fungal outbreaks.  In agricultural and commercial
settings, it has a variety of uses including fruits, vegetables,
ornamentals, and turf.  In the residential setting, the existing uses
include turf and ornamentals.  Permanent tolerances are currently
established for the combined residues of myclobutanil and its RH-9090
metabolite (free and bound) in/on a variety of raw agricultural
commodities (RACs) at levels ranging from 0.02 to 25.0 ppm and in meat,
milk, poultry, and eggs at levels ranging from 0.02 to 1.0 ppm [40 CFR
§180.443(a)].  In addition, tolerances in conjunction with Section 18
registrations have been established for a number of RACs under 40 CFR
§180.443(b).  Tolerances for indirect or inadvertent residues of
myclobutanil have been established for several crop groups under 40 CFR
§180.443(d).

	

5.2	Proposed Uses:  For the proposed agricultural use on hops, specimen
labels were provided for use of myclobutanil formulated as Rally® 40W
Agricultural Fungicide (EPA Reg No. 707-215) and Nova® 40W Agricultural
Fungicide (EPA Reg No. 707-221), both of which are packaged as
water-soluble pouches containing 40% ai.  For the proposed home garden
uses, a specimen label was provided for use of myclobutanil formulated
as Fungicide M (EPA Reg. No. 9688-123), which contains 1.55% ai. 
Summaries of the proposed use patterns are provided in Attachment 1.  

 

HED Conclusions:  Labels have been provided for use of myclobutanil
formulated as Rally® 40W, Nova® 40W, and Fungicide M.  No deficiencies
in the labels were noted.  There are currently permanent tolerances
under 40 CFR §180.443 for the crops listed in Attachment 1.  Although
the proposed home garden use directions differ slightly from the
registered agricultural uses for some commodities, the current
tolerances are adequate to support the proposed home garden uses. 

	

6.0  Residue Chemistry Considerations

	

Residue chemistry memo - DP# 275142, J. Tyler, 6/4/01 

	

6.1	Nature of the Residue - Plants:  No plant metabolism data were
submitted with this petition.  Plant metabolism studies on wheat,
grapes, and apples have previously been submitted and reviewed
(PP#4G3149 and PP#7G3479), and were summarized in HED review of
PP#2F4155 (DP Barcode D183273, D. Davis, 2/8/93).  The requirement to
conduct a tomato metabolism study, in conjunction with PP#1F4030, was
waived (DP Barcode D203587, J. Stokes, 7/13/94).  By translation of
metabolism data from wheat, grapes and apples, the qualitative nature of
the residue in hops is adequately understood.  The residues of concern
are the parent myclobutanil and its RH-9090 metabolite (free and bound).
 Additionally, the Agency does have concern about potential toxicity to
1,2,4-triazole and two conjugates, triazole alanine and triazole acetic
acid, metabolites common to most of the triazole fungicides.  To support
the extension of existing and granting of new parent triazole-derivative
fungicide tolerances, EPA conducted a human-health assessment for
aggregate exposure to 1,2,4-triazole and
triazolylalanine/triazolylacetic acid in a separate document (Memo
Doherty, et al., 12/22/05; DP# 322215). 

	

6.2	Residue Analytical and Multiresidue Methods:  An adequate
enforcement method [Rohm and Haas Gas-Liquid Chromatography (GLC) Method
34S-88-10] is available for enforcement of the proposed tolerances. 
Quantitation is by GLC using a nitrogen/phosphorus (N/P) detector for
parent myclobutanil and an electron-capture detector (Ni63) for residues
measured as RH-9090.  EPA has conducted a successful method validation
of Method 34S-88-10, and the method has been forwarded to the Food and
Drug Administration (FDA) for inclusion in Pesticide Analytical Methods
(PAM), Volume II (PP#7F3476 and FAP#7H5524, M. J. Nelson, 4/14/88 and
7/18/89).  Samples of hops from the submitted field trials were analyzed
for residues of myclobutanil and the metabolite RH-9090 using Method
TR-310-84-13.  Concurrent method recovery data were acceptable.

	

Multiresidue method data are available in the 2/97 FDA PESTDATA database
PAM, Volume I, Appendix I.  Residues of myclobutanil are adequately
recovered (>80%) using Multiresidue Method Section 302 (Luke Method;
Protocol D), but are not recovered using Multiresidue Method Sections
303 (Mills, Onley, Gaither Method; Protocol E, non-fatty foods) or 304
(Mills Method; Protocol E, fatty foods).  Residues of the metabolite
RH-9090 were poorly recovered (30-55%) using Multiresidue Method Section
302 (Luke Method; Protocol D); the metabolite is not recovered using
Multiresidue Method Sections 303 (Mills, Onley, Gaither Method; Protocol
E, non-fatty foods) and 304 (Mills Method; Protocol E, fatty foods).

	

6.3	Storage Stability Data:  The concurrent storage stability data,
provided by the Interregional Research Project No. 4 (IR-4), are
marginally adequate because the storage stability at zero time was not
measured/provided; this information is vital in determining the percent
decline of residues over time.  Although marginal, the concurrent
storage stability data from the current submissions indicate that
fortified residues of myclobutanil and its RH-9090 metabolite are
relatively stable during frozen storage for up to 82 days (~ 4 months)
in/on hops.  The maximum interval that the hops samples from the residue
field trials remained in frozen storage prior to analysis was 70 days. 
HED concludes that myclobutanil and its metabolite are stable for this
time period.  HED notes that additional storage stability data from
previous myclobutanil petitions indicate that residues of myclobutanil
and its RH-9090 metabolite are stable under frozen storage conditions
for up to 3 years in/on apples (PP# 7F3476, M.J. Nelson, 2/8/88) and
grapes (PP#7F3476, M.J. Nelson, 4/26/88). 

	

6.4	Crop Field Trials and Processed Food and Feed:  The submitted
residue data on hops are adequate and indicate that the combined
residues of myclobutanil and its metabolite RH-9090 will not exceed the
proposed tolerance level of 10 ppm in/on hops, dried when harvested 14
days following the last of nine foliar applications, with 7- to 12-day
RTIs, of the 40% WP formulation at 0.125-0.25 lb. ai/A/application (1x
the maximum proposed seasonal application rate).  Therefore, the
available residue data support a tolerance of 10 ppm for residues of
myclobutanil and its alcohol metabolite in/on “hop, dried cones.” 
No processed food/feed items are associated with hops.  Therefore, data
pertaining to the magnitude of myclobutanil residues in processed
commodities are not required.

	

6.5	International Considerations:  There are no current Canadian or
Mexican maximum residue limits (MRLs) for residues of myclobutanil in/on
hops.  However, there is a Codex MRL of 2 ppm for the parent compound
myclobutanil in/on hops, dry.  HED has concluded the submitted residue
chemistry data support a tolerance of 10 ppm for residues of
myclobutanil and its alcohol metabolite RH-9090 (free and bound). 
Therefore, harmonization with the Codex MRL is not possible.

7.0 	Drinking Water Considerations

	

Drinking water assessment memo - DP# 290167 and D289700, T. Nguyen,
6/9/03

	

The Environmental Fate and Effects Division (EFED) provided Estimated
Drinking Water Concentrations (EDWCs) of myclobutanil in ground and
surface water using  Food Quality Protection Act (FQPA) Index Reservoir
Screening Tool (FIRST) and Screening Concentration in Ground Water
(SCI-GROW), respectively.  The assessment was based on hops, which has
the highest use rate among all existing uses (15 applications per year
and 0.65 lb ai/A per application at 14-day intervals).  EFED calculated
the acute (peak) and chronic (56-day) EDWCs for myclobutanil in surface
water to be 333 ppb and 86 ppb, respectively.  The ground water EDWC for
both acute and chronic exposures in estimated as 3.2 ppb.

	

8.0	Dietary Risks (Food and Drinking Water)

	

Dietary exposure and risk assessment - DP# 319228,  J. Tyler, 6/8/06

	

tabase™ (DEEM-FCID™; ver. 2.03) program which incorporates
consumption data from the United Stated Department of Agriculture’s
(USDA’s) Continuing Surveys of Food Intakes by Individuals (CSFII),
1994-1996 and 1998.  The 1994-96, 98 data are based on the reported
consumption of more than 20,000 individuals over two non-consecutive
survey days.  Foods “as consumed” (e.g., apple pie) are linked to
EPA-defined food commodities (e.g. apples, peeled fruit - cooked; fresh
or N/S; baked; or wheat flour - cooked; fresh or N/S, baked) using
publicly available recipe translation files developed jointly by
USDA/ARS and EPA.  Consumption data are averaged for the entire U.S.
population and within population subgroups for chronic exposure
assessment, but are retained as individual consumption events for acute
exposure assessment.

	

For chronic exposure and risk assessment, an estimate of the residue
level in each food or food-form (e.g., orange or orange juice) on the
food commodity residue list is multiplied by the average daily
consumption estimate for that food/food form.  The resulting residue
consumption estimate for each food/food form is summed with the residue
consumption estimates for all other food/food forms on the commodity
residue list to arrive at the total average estimated exposure. 
Exposure is expressed in mg/kg body weight/day and as a percent of the
chronic population adjusted dose (cPAD).  This procedure is performed
for each population subgroup.

	

For acute exposure assessments, individual one-day food consumption data
are used on an individual-by-individual basis.  The reported consumption
amounts of each food item can be multiplied by a residue point estimate
and summed to obtain a total daily pesticide exposure for a
deterministic (Tier 1 or Tier 2) exposure assessment, or “matched”
in multiple random pairings with residue values and then summed in a
probabilistic (Tier 3/4) assessment.  The resulting distribution of
exposures is expressed as a percentage of the acute population adjusted
dose (aPAD) on both a user (i.e., those who reported eating relevant
commodities/food forms) and a per-capita (i.e., those who reported
eating the relevant commodities as well as those who did not) basis.  In
accordance with HED policy, per capita exposure and risk are reported
for all tiers of analysis.  However, for Tiers 1 and 2, significant
differences in user vs. per capita exposure and risk are identified and
noted in the risk assessment.

	

.  That is, estimated exposures above this level are of concern, while
estimated exposures at or below this level are not of concern.  The
DEEM-FCID™ analysis estimates the dietary exposure of the U.S.
population and 26 population subgroups.  The results reported in Table
8.1 are for the U.S. Population, all infants (<1 year old), children 1-2
years old, children 3-5 years old, children 6-12 years old, youth 13-19
years old, females 13-49 years old, males 20-49 years old, and adults
50+ years old.

	

8.1	Acute Dietary Exposure Estimates:  An acute dietary exposure
assessment was performed for females 13-49 years old (no endpoint was
identified for the general U.S. population or any other population
subgroup) using tolerance-level residues and 100% CT information for all
registered and proposed uses.  Drinking water was incorporated directly
in the dietary assessment using the acute (peak) concentration for
surface water generated by the FIRST model.  These assessments conclude
that the acute dietary exposure estimates (95th percentile) are below
HED’s level of concern (<100% of the aPAD) for females 13-49 years old
at 4.2% of the aPAD.

	

8.2	Chronic Dietary Exposure Estimates:  A refined, chronic dietary
exposure assessment was performed for the general U.S. population and
various population subgroups using USDA Pesticide Data Program (PDP)
monitoring data for apple juice, bananas (not plantains) and milk,
registered and proposed tolerance for all other commodities; average %
CT information for apple (except juice), apricots, artichokes,
asparagus, sugar beet, blackberry, and tomatoes; and 100% CT information
for all other registered and proposed uses.  Drinking water was
incorporated directly into the dietary assessment using the chronic
(annual average) concentration for surface water generated by the FIRST
model.  This assessment concludes that the chronic dietary exposure
estimates are below HED’s level of concern (<100% of the cPAD) for the
general U.S. population (15% of the cPAD) and all population subgroups. 
The most highly exposed population subgroup is all infants (<1 year old)
at 36% of the cPAD.

	



Table 8.1.  Summary of Dietary Exposure and Risk for Myclobutanil.

Population Subgroup	Acute Dietary1	Chronic Dietary2

	Dietary Exposure (mg/kg/day)	% aPAD	Dietary Exposure (mg/kg/day)	% cPAD

U.S. Population (total)	NA

	0.003842	15

All Infants (< 1 year old)

0.009005	36

Children 1-2 years old

0.007697	31

Children 3-5 years old

0.006435	26

Children 6-12 years old

0.004189	17

Youth 13-19 years old

0.002840	11

Adults 20-49 years old

0.003418	14

Adults 50+ years old

0.003595	14

Females 13-49 years old	0.025154	4.2	0.003320	13

1 Acute dietary endpoint of 0.6 mg/kg/day for females 13-49 years old. 
No acute dietary endpoint was chosen for the general U.S. population,
including infants and children.

2  Chronic dietary endpoint of 0.025 mg/kg/day applies to the general
U.S. population and all population subgroups.

	

9.0	Residential Exposure

	

Residential exposure and risk assessment memo - DP# 319227, T. Dole

	

Myclobutanil, formulated as Chemsico Fungicide M, is being proposed for
use on home gardens (see Attachment 1).  In addition, end-use products
containing the active ingredient, myclobutanil, are marketed for
homeowner use on turf, roses, flowers, shrubs and trees.  The homeowner
use with the greatest potential for exposure is small-scale lawn
application.  Since myclobutanil is applied at 7- to 14-day intervals,
only short-term exposure is expected for the residential handler. 
Short- and intermediate-term residential post-application exposures are
also expected.

	

The NOAEL of 10 mg/kg/day was used for assessing short- and
intermediate-term dermal, inhalation and incidental oral exposures. 
This NOAEL is from a 2-generation reproduction toxicity study in rats
which testicular atrophy (in P2 generation), an increase in the number
of still born pups and decreased body weight gain during lactation (in
both generations) were observed with a LOAEL of 50 mg/kg/day.  A dermal
absorption factor of 50% was used because the dermal endpoint was based
upon an oral study.  Chronic exposures are not expected due to the
seasonal and intermittent nature of the existing and proposed uses.

	

A residential non-dietary exposure and risk assessment was conducted in
support of the proposed home garden uses of myclobutanil.  The
assessment addresses residential risk from these proposed uses and also
includes updated assessments for the existing residential uses of other
products on turf and ornamentals.  In addition, the assessment has been
updated to incorporate exposure factor changes that have taken place
since the last myclobutanil residential exposure assessment was
completed (Memo, D. Vogel, 3/7/00; D264191).

	

9.1	Residential Handler Exposures and Risks:  The anticipated use
patterns and current labeling indicate that a variety of application
equipment could be used by the homeowner to apply myclobutanil to
ornamental plants, shrubs, fruit trees, home garden vegetables and
lawns.  Therefore, the following scenarios were assessed.

		

	1  Aerosol Spray Can Application to Ornamentals and Fruit Trees

	2  Hose End Sprayer Application to Ornamentals and Fruit Trees

	3  Low-pressure (LP) Handwand Application to Ornamentals

	4  LP Handwand Application to Vegetables

	5  Ready to use (RTU) Sprayer Application to Vegetables

	6  Hose End Sprayer Application to Vegetables

	7  Hose End Sprayer - Mix Your Own - Application to Turf 

	8  Hose End Sprayer - Ready to Use - Application to Turf

	9  Belly Grinder Application to Turf

	10  Broadcast Spreader Application to Turf

	 

Unit exposure data were either taken from PHED or the home garden and
turf application studies that were sponsored by the Outdoor Residential
Exposure Task Force (ORETF).  The assumptions and factors used in the
risk calculations include:

	

Both the proposed uses on the Chemsico Fungicide M Label and existing
uses on other myclobutanil labels were assessed.  The other labels
include granular and aerosol can products that are used on turf and
ornamentals.

The application rates for the new uses were taken from the proposed
Chemsico fungicide label and are roughly the same as the rates on
agricultural and commercial labels if the spray volume is 87 gallons per
acre (GPA) for turf, 100 GPA for most crops and 400 GPA for fruit trees.
 A listing of these rates is included in Attachment 1.  

The application rates for the existing uses were taken from the existing
labels.

The area treated per day (1000 square feet) was taken from Scientific
Advisory Council (ExpoSAC) Policy #12 “Recommended Revisions to the
Standard Operating Procedures for Residential Exposure Assessments” of
 2/22/01.  This value is based upon the results of the National Home
Garden Survey and is applicable for the four application methods
considered.

	

 The dermal and inhalation MOEs were combined because the dermal and
inhalation endpoints were selected from the same oral study and are
summarized in Table 9.1.  The MOEs for residential handlers range from
180 to 55,000 with the highest risks (i.e. the lowest MOEs) associated
with the mixing, loading and applying myclobutanil to turf with a mix
your own hose end sprayer at the highest rate of 1.36 lb ai/A.  With the
lower application rate of 0.62 lbs ai/A, the lowest MOE is 370.



Table 9.1.  Myclobutanil Residential Handler Risks.

Exposure Scenario

(all are mix/load/apply)	Use Site	Application Rate (lb ai/A)	Amount Used
or Area Treated	Absorbed Daily Dose (mg/kg/day)	Combined MOE

Aerosol Spray Can	Ornamentals

 	0.012% ai per 

15 ounce can	1 can per day	0.00018	55000

Hose End Sprayer   	Ornamentals

Fruit Trees

Nut Trees

Grapes	0.25

	0.023 acre/day

(1000 square feet)

	0.0016	6200

LP Handwand

0.0023	4300

LP Handwand	Vegetables

Berries

Mint

	0.125	0.023 acre/day

(1000 square feet)	0.00078	13000

RTU Sprayer

0.0011	9000

Hose End Sprayer

0.00070	14000

Hose End Sprayer - Mix Your Own	Turf	1.36	0.5 acre/day	0.054	180

Hose End Sprayer - Ready to Use

0.0130	790

Hose End Sprayer - Mix Your Own	Turf	0.62	0.5 acre/day	0.0250	370

Hose End Sprayer - Ready to Use

0.0059	1600

Belly Grinder	Turf	1.36	0.023	 0.0250	410

Broadcast Spreader

	0.5	0.0033	3000

9.2	Home Garden Post-application Exposures and Risks:  Home garden
post-application exposures can occur when home gardeners perform tasks
such as weeding, pruning or hand harvesting following application of
myclobutanil.  In order to address these risks, the post-application
exposure to home gardens and orchard scenarios were assessed based upon
the Residential SOP 3.0 for Garden Plants and SOP 4.0 for Trees.

	

Two DFR studies on grapes in California were used to assess the home
garden exposures.  The studies were reviewed by HED and were found to
meet most of the series 875 guidelines for post application exposure
monitoring.  The studies were performed using airblast sprayers while
the proposed home garden applications would be made with LP handwand or
hose end sprayers.  Based upon experience with other fungicides,
however, it is anticipated that DFRs resulting from handwand
applications would be similar to DFRs from airblast applications.  The
initial DFR  was assumed as 23% of the application rate and was based
upon DFR Data for HS-1760 Site 3. 

	

In addition, the following assumptions and exposure factors were used
for assessing home garden post-application risks:

	

The maximum application rates as listed in Attachment 1 for each crop
were used for risk calculations as there are no use data available for
home gardeners.

The transfer coefficient (TC) is 10,000 cm2/hr as stated in the
Residential SOPs.

The daily exposure duration for tasks performed in the home garden or
home orchard are expected to be 40 minutes per day as stated in the
Residential SOPs.

	

The MOEs are summarized in Table 9.2.  The myclobutanil MOEs for all of
the home gardener post-application scenarios are greater than the target
MOE of 100 and are not of concern.

	

Table 9.2.  Myclobutanil Post-Application Risks for Home Gardeners.

Crop	Application Rate

(lb ai/A)	DAT 0 DFR

(ug/cm2)	TC (cm2/hr)	Exposure Time (hours/day)	Dose

(mg/kg/day)

	Dermal MOE

Home Garden Ornamental Plants and Vegetables	0.25	0.65	10000	0.67	0.031
320

Home Orchard Fruit Trees	0.25	0.65	10000	0.67	0.031	320

	

9.3	“Pick Your Own” Post-application Exposures and Risks:  “Pick
your own” exposures can occur at commercially operated “pick your
own” strawberry farms and orchards where myclobutanil has been
applied.  To address these risks, post-application exposure for pick
your own strawberries and tree fruit were assessed based upon the
Residential SOP 15.0 for “pick your own” strawberries.  The DFR data
that were used for the home gardener post-application risks were also
used to assess “pick your own” exposures .  The following
assumptions and exposure factors were used for assessing “pick your
own” post-application risks:

	

The maximum label rates as listed in Attachment 1 for strawberries and
tree fruit was used.

The TC is 10,000 cm2/hr as stated in the Residential SOPs.

The daily exposure duration for “pick your own” strawberries is 4
hours as stated in the Residential SOPs.

The daily exposure duration for “pick your own” tree fruits is 2
hours.

	

The myclobutanil MOEs are summarized in Table 9.3.  The myclobutanil
MOEs for the “pick your own” scenarios are greater than the target
MOE of 100 and are not of concern.  The risks for pick your own
exposures are conservative because that scenario is based upon a
screening-level TC and a dermal absorption factor of 50%.  This risk
could be refined by examining the recently submitted Agriculture
Research Task Force (ARTF) TC studies and calculating TCs that match the
clothing worn by pick your own customers. 

	

Table 9.3.  Myclobutanil Post-Application Risks for Pick Your Own Crops.

Crop	Application Rate

(lb ai/A)	DAT 0 DFR

(ug/cm2)	TC (cm2/hr)	Exposure Time (hours/day)	Dose

(mg/kg/day)	Dermal MOE

Fruit Trees 	0.25	0.65	10000	2	0.09	110

Strawberries	0.125	0.325	10000	4	0.093	110

	

9.4	Residential Turf Post-Application Exposure and Risks:  The following
exposure scenarios are assessed for residential post-application risks:

	

	1 - Toddlers Playing on Treated Turf

	2 - Adults Performing Yardwork on Treated Turf

	3 - Adults Playing Golf on Treated Turf

	

A TTR study was used to assess the turf exposures.  The field portion of
this study was in North Carolina and California.  This study was
reviewed by HED and was found to meet most of the series 875 guidelines
for post application exposure monitoring.  The initial TTR for dermal
exposures was assumed to be 2.4% of the application rate and was based
upon an average of the DAT-0 and DAT-3 data for the California site. 
The following assumptions and exposure factors were used for assessing
turf post-application exposure risks:

	

The turf exposures were considered to be short- and intermediate-term in
duration because myclobutanil can be used only 16 times per year and
dissipates fairly rapidly with a half-life of 8.5 days.  Acute exposures
from granule ingestion were not assessed because there is no endpoint
for acute dietary exposures for the general population, which includes
children.

The application rates of 0.62 and 1.36 lb ai/A were used for calculating
short/intermediate term risks.  The rate of 0.62 lb ai./A is from the
Chemsico product labels (such as 9688-123 and 9688-165) and the rate of
1.31 lb ai/A is from non-Chemsico labels (such as 62719-463).

The initial TTR for dermal exposures was assumed to be 2.4% of the
application rate and was based upon an average of the DAT-0 and DAT-3
data for the California site.  All of the data, including the two
outliers, were included in this average, however if the outliers had not
been included, the TTR would still have been the same (2.4%) because the
outliers offset each other;

5% of the application rate has been used to calculate the 0-day residue
levels used for defining risks from hand-to-mouth behaviors, measured
TTR values are not used because of differences in transferability versus
what would be expected during hand-to-mouth behaviors;

20% of the application rate has been used to calculate the 0-day residue
levels used for defining risks from object-to-mouth behaviors, measured
TTR values are not used because of differences in transferability versus
what would be expected during object-to-mouth behaviors, a higher
percent transfer has been used for object-to-mouth behaviors because it
involves a teething action believed to be more analogous to DFR/leaf
wash sample collection where 20%is also used;

The Jazzercise approach is the basis for the dermal TCs as described in
HED’s Series 875 guidelines, SOPs For Residential Exposure Assessment,
and the 1999 FIFRA SAP Overview document.  This approach was used for
toddlers on turf and adults on athletic fields;

Soil residues are contained in the top centimeter and soil density is
0.67 mL/gram;

Three year old toddlers are expected to weigh 15 kg;

Hand-to-mouth exposures are based on a frequency of 20 events/hour and a
surface area per event of 20 cm2 representing the palmar surfaces of
three fingers;

Saliva extraction efficiency is 50% meaning that every time the hand
goes in the mouth approximately ½ of the residues on the hand are
removed;

Risk values (i.e., MOEs) for the different kinds of toddler exposures to
turf (dermal, hand-to-mouth, object-to-mouth, and soil ingestion) were
added together per HED policy as discussed in the ExpoSac Meeting
Minutes.  These exposures are typically added together when chemicals
are used on turf  because it is logical they can co-occur;

Golfers have been assessed using a TC of 500 cm2/hour;

For golfer assessment it was assumed that the tees, greens and fairways
are treated and that the exposure time per day would be four hours.

	

The myclobutanil MOEs for toddler and adult exposures are summarized in
Table 9.4.  The myclobutanil MOEs for toddler exposures at day 0,
expressed as the total MOE, is 60 when the application rate is 1.36 lb
ai/A and it is 140 when the application rate is 0.62 lb ai/A.  The
dermal pathway is the risk driver, which causes the total MOE to be
below the target MOE of 100 at the higher application rate.  The
myclobutanil MOEs for adult dermal exposures are above 100 regardless of
which application rate is used.

	

It should be noted that the high rate of 1.36 lb ai/A is from the
Eagle® 20EW label (EPA Reg. No. 62719-463) that appears to be primarily
intended for turf use on golf courses because it has the statement “A
systemic, protective and curative fungicide for disease control in turf
grass (including golf course fairways, roughs, tee boxes and greens).”
 The risk could be refined if a label statement could be added to the
turf product labels to specify at maximum application rate of 0.62 lb
ai/A on residential turf.

Table 9.4.  Toddler and Adult MOEs for Post-Application Exposure to Turf
Treated with Myclobutanil.

Exposure Scenario	Application Rate

(lbs ai/A)	Dermal TTR

(ug/cm2)	Dermal

Dose	Hand-to Mouth Dose	Object to Mouth Dose	Soil Ingestion Dose	Total
Dose

(mg/kg/day)	Total MOE*

Toddlers

Playing on Lawns	1.36	0.37	0.127	0.020	0.0051	0.000068	0.152	65

	0.62	0.17	0.0579	0.0093	0.0023	0.000031	0.0695	140

Adults

Heavy Yardwork	1.36	0.37	0.076	Not applicable	130

Playing Golf

	0.0052

1900

Heavy Yardwork	0.62	0.17	0.035	Not applicable	290

Playing Golf

	0.0024

4200

*The NOAEL is 10 mg/kg/day for dermal and incidental oral exposures.

10.0	Aggregate Risk

	

Aggregate risk assessments were performed for acute (food and drinking
water), short-term (food, drinking water and residential),
intermediate-term (food, drinking water and residential), and chronic
aggregate exposure (food and drinking water).  Long-term and cancer
aggregate risk assessments were not performed because, based on the
current and proposed use patterns, HED does not expect residential
exposure durations that would result in long-term exposures and
myclobutanil is not carcinogenic.  All potential exposure pathways were
assessed in the aggregate risk assessment. 

	

10.1	Acute Aggregate Risk Assessment (Food and Drinking Water):  The
acute aggregate risk assessment takes into account exposure estimates
from dietary consumption of myclobutanil (food and drinking water). 
Dermal, inhalation, and incidental oral exposures resulting from
short-term residential applications are assessed separately.  The acute
dietary exposure estimates are below HED’s level of concern (<100%
aPAD) at the 95th exposure percentile for females 13-49 years old (4.2%
of the aPAD).  Therefore, the acute aggregate risk associated with the
proposed uses of myclobutanil does not exceed HED’s level of concern
for females 13-49 years old.

	

10.2	Short-Term Aggregate Risk Assessment (Food, Drinking Water and
Residential):  The short-term aggregate risk assessments estimate risks
likely to result from 1-30 days of exposure to myclobutanil residues in
food, drinking water, and residential pesticide uses.  In aggregating
short-term risk, HED considered background chronic dietary exposure
(food and drinking water; see Table 8.1) and short-term, non-dietary
oral and/or dermal exposures (see Tables 9.1-9.4).

	

For adults, there is potential for short-term dermal and inhalation
handler exposure, and short-term dermal post-application exposures from
the residential uses of myclobutanil, including orchards, “pick your
own” gardens, home fruit and vegetable gardens, and treated turf. 
However, the handler and post-application exposures were not combined as
the likelihood of the residential homeowner experiencing both short-term
handler and post-application exposure to myclobutanil is unlikely (it is
current ExpoSAC policy not to combine handler and post-application
exposures for these scenarios due to the conservative nature of each
assessment alone).  For children/toddlers, short-term dermal and
non-dietary oral post-application exposures may result from dermal
contact with treated turf as well as non-dietary ingestion/hand-to-mouth
transfer of residues from turf grass.

	

For the general U.S. population and children/toddlers, the total food
and residential short-term aggregate MOEs are listed in Table 10.1.  For
the general U.S. population, all short-term MOEs are greater than 100;
and, therefore, do not exceed HED's level of concern (MOE <100).

	

For children/toddlers, the short-term aggregate MOE is 63 for the
“playing on lawn” scenario using the turf application rate of 1.36
lb ai/A, but the MOE is 130 for the same scenario using the 0.62 lb ai/A
application rate.  It should be noted that the high rate of 1.36 lb ai/A
is from the Eagle® 20EW label (EPA Reg. No. 62719-463) that appears to
be primarily intended for turf use on golf courses because it has the
statement “A systemic, protective and curative fungicide for disease
control in turf grass (including golf course fairways, roughs, tee boxes
and greens).”  The short-term aggregate risk could be refined if the
myclobutanil turf labels are amended to specify at maximum application
rate of 0.62 lb ai/A on residential turf.

10.3	Intermediate-Term Aggregate Risk Assessment (Food, Drinking Water
and Residential):  The intermediate-term aggregate risk assessment
estimates risks likely to result from 1 to 6 months exposure to
myclobutanil residues in food, drinking water, and residential pesticide
scenarios.  In aggregating intermediate-term risk, HED considered
background chronic dietary exposure (food and drinking water) and
intermediate-term, non-dietary oral and/or dermal exposures (see Tables
9.1-9.4).

	

For adults, intermediate-term post-application exposures may result from
dermal contact with treated fruits and vegetables at “pick your own”
gardens, treated home fruit and vegetable gardens and treated turf.  As
mentioned previously, since myclobutanil is applied at 7- to 14-day
intervals, only short-term exposure is expected for the residential
handler.  Therefore, no aggregate intermediate-term exposure for the
adult handler was performed.  For toddlers, intermediate-term dermal and
non-dietary oral post-application exposures may result from dermal
contact with treated turf as well as non-dietary ingestion/hand-to-mouth
transfer of residues from turf grass.

	

However, as the NOAEL (10 mg/kg/day) from a 2-generation reproduction
toxicity study in rats was used for assessing short- and
intermediate-term dermal, inhalation and incidental oral exposures, the
short-and intermediate-term aggregate risk estimates from the
post-application exposure scenarios are the same for the general U.S.
population and children/toddlers (see Table 10.1).



Table 10.1.  Short- and Intermediate-Term Aggregate Risk Calculations
for Myclobutanil.

Population

Subgroups	Exposure Scenario	NOAEL

(mg/kg/day)	Level of Concern1	Max Exposure2

(mg/kg/day)	Average Dietary Exposure

(mg/kg/day)	Residential Exposure3

(mg/kg/day)	Aggregate MOE

(dietary and residential)4

Short-Term Handler Exposures

General US Population	Hose End Sprayer - Mix your own	10	100	0.1
0.003842	0.054	170

Short- and Intermediate-Term Post-Application Exposures

General US Population	Home Gardens	10	100	0.1	0.003842	0.031	290

	“Pick Your Own” Fruit Trees

	0.09	110

	Turf -

Heavy Yardwork

(1.36 lb ai/A rate)

	0.076	130

	Turf -

Playing Golf

(1.36 lb ai/A rate)

	0.0052	1100

Children 1-2 years old	Turf -

Playing on Lawn

(1.36 lb ai/A rate)

0.007697	0.152	63

	Turf -

Playing on Lawn

(0.62 lb ai/A rate)

	0.0695	130

1 The level of concern (target MOE) includes 10X for interspecies
extrapolation and 10X for intraspecies variation.

2  Maximum Exposure (mg/kg/day) = NOAEL/Target MOE

3  Residential Exposure = [Oral exposure + Dermal exposure + Inhalation
Exposure].

4  Aggregate MOE = [NOAEL ÷ (Avg Dietary Exposure + Residential
Exposure)]

10.4	Chronic Aggregate Risk Assessment (Food and Drinking Water):  The
chronic aggregate risk assessment takes into account average exposure
estimates from dietary consumption of myclobutanil (food and drinking
water) and residential uses.  However, due to the use patterns, no
chronic residential exposures are expected.  Therefore, the chronic
aggregate risk assessment includes exposure from food and drinking water
only.  The chronic dietary exposure estimates are below HED’s level of
concern (<100% cPAD) for the general U.S. population (15% of the cPAD)
and all population subgroups (see Table 8.1).  The most highly exposed
population subgroup is all infants (<1 year old) at 36% of the cPAD. 
Therefore, the chronic aggregate risk associated with the proposed uses
of myclobutanil does not exceed HED’s level of concern for the general
U.S. population or any population subgroups.

	

11.0 Cumulative

	

The Agency did not perform a cumulative risk assessment as part of this
tolerance action for myclobutanil.  However, the Agency does have
concern about potential toxicity to 1,2,4-triazole and two conjugates,
triazole alanine and triazole acetic acid, metabolites common to most of
the triazole fungicides.  To support the extension of existing parent
triazole-derivative fungicide tolerances, EPA conducted an interim human
health assessment for aggregate exposure to 1,2,4-triazole (M. A.
Doherty, “Interim Human Health Risk Assessment of 1,2,4-Triazole to
Support Tolerance Extensions and New Section 18 Soybean Tolerances for
Triazole-Derivative Fungicides,” June 29, 2004, DP Barcode D304288). 
The exposure and risk estimates presented in this assessment are
overestimates of actual likely exposures and therefore, should be
considered to be highly conservative.  Based on this assessment the EPA
concluded that for all exposure durations and population subgroups,
aggregate exposures to 1,2,4-triazole are not expected to exceed its
level of concern.  This assessment should be considered interim due to
the ongoing series of studies being conducted by the U.S. Triazole Task
Force (USTTF).  Those studies are designed to provide the Agency with
more complete toxicological and residue information for free triazole
and are expected to be submitted to the Agency in the future.  Upon
completion of review of these data, EPA will prepare a more
sophisticated assessment based on the revised toxicological and exposure
databases.

	

12.0	Occupational Exposure

	

Occupational exposure and risk assessment -  DP# 328188, M. Dow

	

Based upon the proposed use patterns (see Attachment 1), short-term
(1-30 days) handler exposures and short- and intermediate-term
post-application exposures are expected for the occupational worker.

	

12.1	Occupational Handler Exposure and Risk:  Based upon the proposed
use patterns,  HED believes that the most highly-exposed occupational
pesticide handler exposures are for a mixer/loader, loading wettable
powder with water soluble packages and an applicator using open-cab,
air-blast machinery.  It is expected that some private applicators may
perform all tasks, that is, mix, load and apply the material.  However,
HED ExpoSAC draft SOP (29 March 2000) directs that although the same
individual may perform all tasks, in some cases they shall be assessed
separately.  

	

The available exposure data for combined mixer/loader/applicator
scenarios are limited in comparison to the monitoring of these two
activities separately.  These exposure scenarios are outlined in the
PHED Surrogate Exposure Guide (August 1998).  HED has adopted a
methodology to present the exposure and risk estimates separately for
the job functions in some scenarios and to present them as combined in
other cases.  Most exposure scenarios for hand-held equipment (such as
handwands, 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.  The available monitoring data support this and HED
presents them in this way.  Conversely, for equipment types such as
fixed-wing aircraft, groundboom tractors,  air-blast sprayers, or
high-pressure handwand sprayers, the applicator exposures are assessed
and presented separately from those of the mixers and loaders.  By
separating the two job functions, HED determines 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 (e.g., chemical-resistant gloves may only be
necessary during the pouring of a liquid formulation).  

	

No chemical-specific data were available with which to assess potential
exposure to occupational pesticide handlers.  The estimates of exposure
to pesticide handlers are based upon surrogate study data available in
PHED (v. 1.1, 1998).  For pesticide handlers, it is HED standard
practice  to present estimates of dermal exposure for “baseline;”
that is, for workers wearing a single layer of work clothing consisting
of a  long-sleeved shirt, long pants, shoes plus socks and no protective
gloves as well as for “baseline” and the use of protective gloves or
other PPE as might be necessary.  The proposed product label involved in
this assessment directs applicators and other handlers to wear the
following PPE:  long-sleeved shirt, long pants, shoes plus socks,
chemical-resistant gloves and protective eyewear.

Table 12.1.  Estimated Handler Exposure and Risk from the Use of
Myclobutanil on Hops.

Unit Exposure1

(mg ai/lb handled)	Application Rate

(lb ai/A)2	Units Treated3

Per Day

(Acres)	ADD4

(mg ai/kg bw/day)	NOAEL5

(mg ai/kg bw/day)	Combined MOE6

Mixer/Loader - Wettable Powders with Water Soluble Bags

Dermal:

No Glove     0.021 LC

With Glove  0.0098 LC

Inhal.           0.00024 LC	0.25	40	Dermal:

No Glove  0.003

W Glove   0.0014

Inhal         0.00004	10	No Glove     3,300

W Glove      6,900

Applicator - Airblast - Open Cab

Dermal:

No Glove     0.36 HC

With Glove  0.24 HC

Inhal             0.0045HC	0.25	40	Dermal:

No Glove  0.051

W Glove   0.034

Inhal         0.00075	10	No Glove      190 

W Glove       290

1 Unit Exposures are taken from “PHED SURROGATE EXPOSURE GUIDE”,
Estimates of Worker Exposure from The Pesticide Handler Exposure
Database Version 1.1, August 1998.  Dermal =  Single Layer Work Clothing
No Gloves;  Single Layer  Work Clothing With Gloves;  Inhal.  =
Inhalation.  Units = mg ai/pound of active ingredient handled.  Data
Confidence: LC = Low Confidence, MC = Medium Confidence, HC = High
Confidence.

2 Applic. Rate.  = Taken from the IR4 petition for myclobutanil on hops

3 Units Treated are taken from “Standard Values for Daily Acres
Treated in Agriculture”; SOP  No. 9.1.   Science Advisory Council for
Exposure;  Revised 5 July 2000; 

4 Average Daily Dose = Unit Exposure * Applic. Rate * Units Treated ÷
Body Weight (70 kg used for short-term dermal; 60 kg used for 

short-term inhalation).  

5 NOAEL = No Observable Adverse Effect Level: short-term dermal and
inhalation NOAEL = 10 mg ai/kg bw/day.

6 MOE = Margin of Exposure = No Observable  Adverse Effect Level (NOAEL)
 ÷ ADD.  Short Term  MOEs are combined since the dermal and inhalation
NOAELS were identified from  the same study.  

 

All short-term MOEs are >100.  Since HED’s level of concern for
myclobutanil is for MOEs below 100, all worker exposures are expected to
be below the level of concern.

	

12.2	Occupational Post-Application Exposure :  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 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 TCs relative to the various activities that express the
amount of foliar contact over time, during each of the activities
identified.  TCs are expressed as cm²/hr.  For hops, the highest TC is
2,000 cm²/hr which results from harvest activities or stripping or
training the vines.  As a “screening-level” assessment, HED herein
uses the 2,000 cm²/hr TC.

	

The TCs used in this assessment are from an interim TC SOP developed by
HED’s ExpoSAC using proprietary data from the ARTF database (SOP #
3.1).  It is the intention of HED’s ExpoSAC that this SOP will be
periodically updated to incorporate additional information about
agricultural practices in crops and new data on TCs.  Much of this
information will originate from exposure studies currently being
conducted by the ARTF, from further analysis of studies already
submitted to the Agency, and from studies in the published scientific
literature.

	

Lacking compound-specific DFR data, HED assumes 20% of the application
rate is available as DFR on day zero after application.  This is adapted
from the ExpoSAC SOP No. 003 (7 May 1998 - Revised 7 August 2000).  

	

The following convention may be used to estimate post-application
exposure: 

	

Average Daily Dose (ADD) (mg ai/kg bw/day) = DFR μg/cm2 * TC cm2/hr *
hr/day * 0.001 mg/μg * 1/60 kg bw 

	

	and where:

	

Surrogate DFR = application rate * 20% available as dislodgeable residue
* (1-D)t * 4.54 x 108 μg/lb * 2.47 x 10-8 A/cm2 .  

	

0.25 lb ai/A * 0.20 * (1-0)0 * 4.54 x 108 μg/lb *  2.47 x10-8 A/cm² =
0.56 μg/cm2 , therefore,

	

0.56 μg/cm2 * 2,000 cm2/hr * 8 hr/day * 0.001 mg/μg  * 0.5 (% dermal
absorption) ÷ 70 kg bw = 0.128mg/kg bw/day.

	

MOE = NOAEL ÷ ADD then 10 mg/kg bw/day ÷ 0.064 mg/kg bw/day = 156.

	

A MOE of 100 is adequate to protect agricultural workers from
post-application exposures.  Since the estimated MOEs are >100, the
proposed use does not exceed HED’s level of concern.

	

a

ñ



)

<

`

a

H*

愀Ĥ

愀Ĥ

]欀⹤

p欀つ

&

&

&

&

਀

&

&

&

&

&

&

&

&

&

&

&

&

&

&

&

&

&

&

&

&

&

&

&

&

&

&

&

 

$

&

V

X



,

.

6

8

X

b

d

l

n

„

†

º

¼

x

|

”

˜

T

X

ᔀX

al sensitizer.  The Rally® label lists the REI as 24 hours, which is
sufficient to protect workers from excessive exposure.

	

cc: J. Tyler (RAB1), T. Dole (RRB1), M. Dow  (RAB1)

RDI: RA Team (5/31/06); PV Shah (7/12/06); F. Fort (7/12/06)			

J. Tyler: 809B: CM#2: (703)305-5564: 7509C: RAB1

Attachment 1.  Summaries of Proposed Use Patterns.

Summary of Proposed Directions for Use of Myclobutanil on Hops.

Crop	Maximum Application Rate

(lb. ai/A)	Maximum Number of Applications	RTI1 (days)	PHI2 (days)
Comments/Restrictions

	Per Application	Per Season

Hops	0.25	2	8	7-10	14	None.

1.  RTI = retreatment interval

2.  PHI = preharvest interval

Summary of Proposed Directions for Home Garden Uses of Myclobutanil.

Crops	Proposed Home Garden Use Pattern -

Chemsico Fungicide M (1.55% ai; EPA Reg. No. 9688-123)	Registered
Agricultural Use Pattern

Rally® 40W and Nova® 40W (40% ai; EPA Reg. No. 707-221)

Chemsico Fungicide M ((1.55% ai; EPA Reg. No. 9688-123)

	Application Rate (lb ai/A)1

[fl oz/gal]	Maximum Number of Applications	RTI (days)	PHI (days)
Application Rate (lb ai/A)	Maximum Number of Applications	RTI (days)	PHI
(days)

	Per Application	Per Season

Per Application	Per Season

	Asparagus	CA	0.127 [1.25]	0.508 [5.0]	4	14	30	0.125	0.5	4	14	30

	all other states	0.127 [1.25]	0.127 [1.25]	1	na2	180	0.125	0.75	6	14
180

Almonds	0.20 [0.5]	0.60 [1.5]	3	21	90	0.19	0.6

7-10	160

Apples and Mayhaws	0.27 [0.66]	2.7 [6.6]	10	7-10	14	0.25	2.0	8	10-14	14

Berries	Blackberry, Raspberry, Loganberry	0.067 [0.66]	0.268 [2.68]	4
10-14	0	0.0625	0.25	4	10-21

	0

	Currant, Gooseberry	0.127 [1.25]	1.02 [10.0]	8	10-14	0	0.125	1.0	8
10-14	0

Cucurbits	0.127 [1.25]	0.635 [1.25]	5	7-10	0	0.0625	0.6	10	7-10	0

Grapes	0.127 [1.25]	0.635 [6.25]	5	14-21	14	0.075-0.125	0.6	ns2	14-21	14

Peppermint, Spearmint	0.127 [1.25]	0.381 [3.75]	3	14-21	30	0.125	0.2	3
14-21	30

Snap Beans	0.127 [1.25]	0.508 [5.0]	4	7-10	0	0.125	0.5	4	7-10	0

Stone Fruit	Apricot, Plum, Prune	0.20 [0.5]	1.4 [3.5]	7	7-21	0
0.0625-0.15	1.1	ns	7-14	0

	Cherry, Nectarine, Peach	0.20 [0.5]	1.4 [3.5]	7	7-21	0	0.0625-0.15	1.3
ns	7-14	0

Strawberry	0.127 [1.25]	0.762 [7.5]	6	14-21	0	0.125	0.75	6	14-21	0

Tomato	0.10 [1.0]	0.40 [4.0]	4	21	0	0.1	0.5	5	21	0

1 Assuming spray volumes of 100 gallons per acre (GPA) for asparagus,
berries, conifer trees, grapes, mint, ornamentals, snap beans,
strawberries, and tomatoes; 400 GPA for almonds, pome fruit, and stone
fruit (Memo, T. Dole, D319227).

2  na = not applicable; ns = not specified.

Page   PAGE  24  of   NUMPAGES  25 

Page   PAGE  1  of   NUMPAGES  25 

Page   PAGE  26  of   NUMPAGES  25 

Page   PAGE  25  of   NUMPAGES  25