Document ID: EPA-HQ-OPP-2006-0282-0004
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:		25-OCT-2006

Subject:	PP#: 5F6997.  Myclobutanil.  Human-Health Risk Assessment for
Proposed Use on Soybeans.  PC Code: 128857.  DP#: 332919.  Decision #:
361365.

From:		Jennifer R. Tyler, Chemist

		P.V. Shah, Ph.D.

		Mark I. Dow, Ph. D., Biologist

		Registration Action Branch 1 (RAB1)

		Health Effects Division (HED; 7509P)

Thru:		George F. Kramer, Ph. D., Senior Chemist

Dana Vogel, Acting Branch Chief

		RAB1/HED (7509P)

To:		Barbara Madden, RM Team 05

		Risk Integration, Minor Use & Emergency Response Branch (RIMUERB)

		Registration Division (RD; 7505P)

Lisa Jones/Mary Waller, RM Team 21

		Fungicide Branch (FB)/RD (7505P)

INTRODUCTION

 petition for the use of myclobutanil
[α-butyl-α-(4-chlorophenyl)-1H-1,2,4-triazole-1-propanenitrile],
formulated as Laredo® EW (EPA Reg. No. 62719-493), on soybeans.  In
addition, Dow has requested the establishment of permanent tolerances
for the combined residues of myclobutanil and its metabolite, RH-9090
[α-(3-hydroxybutyl)-α-(4-chlorophenyl)-1H-1,2,4-triazole-1-propanenitr
ile] 6-chloro-3-pyridinyl)methyl]-N-nitro-2-imidazolidinimine],
expressed as myclobutanil, in/on the following soybean raw agricultural
commodities (RACs):  soybean seed (0.05 ppm); soybean forage (5 ppm);
soybean hay (13 ppm); soybean aspirated grain fractions (1.1 ppm);
soybean hulls (0.06 ppm); soybean meal (0.03 ppm); and soybean oil (0.1
ppm).

NOTE:  HED previously completed a Section 3 human-health risk
assessment for the use of myclobutanil on hops and home gardens (Memo,
J. Tyler, et al., 7/12/06; D330235), 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).  The
following information from the previous risk assessments on myclobutanil
can be applied directly to this action:

Residential Exposure Assessment (pages 12-17 of 7/12/06 memo).

In this memo, dietary, occupational and aggregate risks were
re-evaluated based on the new use pattern for soybeans.

1.0	Executive Summary

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.  Based upon a maximum turf application rate of
0.62-0.68 pound active ingredient (lb ai)/acre (A), the short-and
intermediate-term aggregate margins of exposure (MOEs) are greater than
100 for the general U.S. population and all populations subgroups,
including infants and children; and, therefore, do not exceed HED's
level of concern (MOE <100).

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 soybean, seed (0.25
ppm); soybean, forage (3.5 ppm); soybean, hay (15 ppm); aspirated grain
fractions (35 ppm), and soybean, refined oil (0.40 ppm).  The
registration may be made unconditional upon submission of the requested
information from the processed food and feed study.

It should be noted that the previous human-health risk assessment (Memo,
J. Tyler, et al., 7/12/06; D330235) included two application rates for
the residential turf use – 1.36 and 0.62 lb ai/A.  In that assessment,
the short- and intermediate-term aggregate MOE for children/toddlers
exceeded HED’s level of concern for the “playing on lawn” scenario
using the turf application rate of 1.36 lb ai/A, but did not exceed
HED’s level of concern for the same scenario using the 0.62 lb ai/A
turf application rate.  Since the completion of the 7/12/06 risk
assessment, the company has revised all residential turf labels to
include a maximum application rate of 0.62-0.68 lb ai/A (personal
communication between J. Tyler and L. Jones, 10/3/06).  Therefore, the
high rate of 1.62 lb ai/A was removed from the residential exposure
assessment, resulting in aggregate short- and intermediate-term MOEs of
>100 for children/toddlers.  RD should ensure that all myclobutanil
labels with residential turf uses have been revised to include a maximum
application rate of 0.62-0.68 lb ai/A.  Additionally, the slight
increase in application rate (i.e. 0.62 lb ai/A to 0.68 lb ai/A) will
not have a significant effect on the results of the risk assessment. 
The short-and intermediate-term aggregate MOEs are greater than 100 for
the general U.S. population and all populations subgroups, including
infants and children; and, therefore, do not exceed HED's level of
concern (MOE <100).

In addition, it should be noted that the proposed label includes a
restriction on feeding treated soybean forage and hay to livestock.  The
registrant has stated that this restriction is a misprint, and will be
removed (personal communication between R. Brinkmeyer and J. Tyler,
10/12/06).  RD should ensure that a revised Section B is submitted.

HED suggests that the RD confirm or correct, as may be necessary, the 24
hour restricted entry interval (REI) listed on the product label.

2.0	Ingredient Profile

Summary of Registered/Proposed Uses 

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 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).

Proposed Uses:  A specimen label was provided for Laredo® EW, a product
containing 1.67 lb ai/gallon (gal).  Table 2.1.1 is a summary of the
proposed use pattern.

Table 2.1.1.  Summary of Proposed Use Pattern.

Crop	Product

(EPA Reg. No.)	#

App.	Application Rate

(lb ai/A)	RTI1 (days)	PHI1 (days)	REI1 (hours)	Restrictions

	Per app.	Per season

Soybean	62719-493	2	0.0625-0.125	0.25	14-21	28	24	Use adequate spray
volume to achieve good coverage and canopy penetration (for ground
applications, typically 15-20 GPA; for aerial applications, typically a
minimum of 5 GPA).

1 RTI = retreatment interval; PHI = preharvest interval; REI =
restricted-entry interval.

The label specifies the following rotational crop restrictions:  Fields
treated with myclobutanil can be rotated at any time to crops that are
listed on a registered myclobutanil label immediately after the last
treatment.  Do not plant other crops within 30 days after the last
application of a product containing myclobutanil.  The proposed use
directions are adequate and supported by the available residue chemistry
data.  It should be noted that the proposed label includes a restriction
on feeding treated soybean forage and hay to livestock.  However, the
registrant has stated that this restriction is a misprint, and will be
removed (personal communication between R. Brinkmeyer and J. Tyler,
10/12/06).  RD should ensure that a revised Section B is submitted.

Structure and Nomenclature

Table 2.2.1.  Myclobutanil Nomenclature.

Chemical structure

 

Common name	Myclobutanil

Company experimental name	RH-3866

IUPAC name
(RS)-2-(4-chlorophenyl)-2-(1H-1,2,4-triazol-1-ylmethyl)hexanenitrile

CAS name	

 

Common name	Alcohol metabolite

Company experimental name	RH-9090

2.3	Physical and Chemical Properties	

Table 2.3.1.  Physicochemical Properties of the Technical Myclobutanil.

Parameter	Value	Reference

Melting point range	63-68 oC	Product Chemistry Review (C.L. Trichilo,
1988), and Rohm and Haas Report, “Revision to: RH-3866 Technical -
Physical and Chemical Characteristics”

pH	The technical material cannot be diluted or dispersed in water.  The
pH of a saturated aqueous solution of this material is about 6-7, the
same as the background value of the water used.

	Density	1.22 g/cc @ 23 oC

1.19 g/cc @ 100 oC

	Water solubility (20 oC)	(25 (C) 142 ppm

	Solvent solubility (g/L at 20 oC)	xylene:  >50 g/100g

amyl acetate: >50 g/100g

cyclohexanone: >50 g/100g

DMF: >50 g/100g

methyl ethyl ketone: >50 g/100g

	Vapor pressure at 20 oC	

1.6 X 10-6 torr @ 25 oC for pure ai

	Dissociation constant, pKa	The pure ai does not have acidic hydrogens
and is expected to be a very weak base.  Attempts to measure pKa by
titration with acid (HCl) and base (NaOH) failed to detect any
inflection on the titration curve, indicating little or no dissociation.

	Octanol/water partition coefficient Log(KOW)	2.94 @ 25 oC for pure ai

	UV/visible absorption spectrum	not available

	

3.0	Hazard Characterization/Toxicity Endpoint Selection

3.1	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, and 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, the 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).

3.2	Toxicity Endpoint Selection:  The doses and toxicological endpoints
selected for

various exposure scenarios are summarized in Table 3.2.1.  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 (Memo, J. Tyler, et
al., 7/12/06; D330235).  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].

Table 3.2.1.  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.

4.0	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 has re-evaluated the quality of the toxicology and
exposure data; and, based on these data, recommended that the FQPA SF be
reduced to 1x.  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; United States Department of
Agriculture (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, asparagus, blackberry, cantaloupe,
cherry, cucumber, grape, nectarine, peach, plum, pumpkin, raspberry,
squash, strawberry, tomato, and watermelon; 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.

	

5.0	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.

6.0	Exposure Characterization/Assessment

The residue chemistry data submitted in support of proposed petitions
were summarized in the HED-memorandum dated 10/25/06 (J. Tyler; DP#
323503).  A drinking water assessment was provided by the Environmental
Fate and Effects Division (EFED) in a memorandum dated 6/26/06 (J. Wolf,
DP# 329419).  An acute and chronic dietary exposure assessment was
completed in a HED-memorandum dated 10/18/06 (J. Tyler, DP# 322917).  A
residential exposure assessment was conducted in conjunction with the
request for the use of myclobutanil on hops and home gardens (Memo, T.
Dole, 2/8/06; D319227).

5.1	Dietary Exposure/Risk Pathway

Residue Profile

Nature of the Residue in Plants and Livestock Commodities:  Plant
metabolism studies on wheat, grapes, and apples have previously been
submitted, and were reviewed and summarized in HED review of PP#2F4155
(Memo, D. Davis, 2/8/93; D183273).  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, the qualitative nature of the residue in soybeans is adequately
understood.  The residues of concern are the parent myclobutanil and its
RH-9090 metabolite (free and bound).

Myclobutanil metabolism in meat, milk, poultry, and eggs has been
reviewed in conjunction with PP#7F3476 (Memo, M. Nelson, 2/8/88) and
summarized in conjunction with the temporary tolerance petition for
almond nuts and hulls (PP#9G3786, Memo, J. Smith, 12/6/89).  The nature
of the residue in livestock is adequately understood.  The residues of
concern in livestock commodities except milk are myclobutanil and its
metabolite
α-(3-hydroxybutyl)-α-(4-chlorophenyl)-1H-1,2,4-triazole-1-propanenitri
le (free).  The residues of concern in milk are myclobutanil
[α-butyl-α-(4-chlorophenyl)-1H -1,2,4-triazole-1-propanenitrile] and
its metabolites,
α-(3-hydroxybutyl)-α-(4-chlorophenyl)-1H-1,2,4-triazole-1-propanenitri
le (free and bound) and α-(4-chlorophenyl)-α-(3,4-dihydroxybutyl)-1H
-1,2,4-triazole-1-propanenitrile.

Analytical Methodology:  An adequate enforcement method (Rohm and Haas
Method 34S-88-10, MRID# 408033-02) is available to enforce the proposed
tolerances on soybeans.  Quantitation is by GLC using a
nitrogen/phosphorus (N/P) detector for myclobutanil and an electron
capture detector (Ni63) for residues measured as the alcohol metabolite.
 HED 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 Method Volume II (PAM) Vol.
II (PP#7F3476 and FAP#7H5524, M. J. Nelson, 4/14/88 and 7/18/89). 
Samples from the crop field and processing studies were analyzed for
residues of myclobutanil and its alcohol metabolite RH-9090 using
analytical method GRM 05.07.  Briefly, residues of myclobutanil and its
alcohol metabolite RH-9090 were extracted from soybean samples by
homogenizing and shaking overnight with methanol.  An aliquot was
hydrolyzed to release conjugated RH-9090 by adding concentrated
hydrochloric acid (HCl) and heating for 2 hours at approximately 70 °C.
 The pH was adjusted to near neutral using 0.5 M aqueous base.  The
sample was then filtered, and the final solution analyzed using on-line
solid-phase extraction coupled to high-performance liquid chromatography
with positive-ion atmospheric pressure chemical ionization (APCI) tandem
mass spectrometry (HPLC/MS/MS).  The limit of detection (LOD) and limit
of quantitation (LOQ) for all soybean matrices were determined to be
0.003 and 0.01 ppm, respectively.

Enforcement methods for the established tolerances on livestock
commodities are Methods 34S-88-22 (MRID #408253-01), 34S-88-15 (MRID
#406458-01), 31S-87-02 (MRID #404813-01), and 34S-88-21 (MRID
#408033-01).  These methods have been submitted for publication in PAM
II (PP#7F3476, M.J. Nelson, 7/18/89).

The 2/97 FDA PESTDATA database (PAM Volume I, Appendix I) indicates that
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).

Storage Stability:  The maximum storage intervals for treated samples in
the crop field trial study were 216, 218, and 137 days for soybean
forage, hay, and seed, respectively.  Adequate storage stability studies
for myclobutanil on apples and grapes have been reviewed by HED (Memo,
M. Nelson, 2/8/88; Accession#s 266109 & 266115).  In another submission,
apples and grapes were reanalyzed for myclobutanil and its metabolite
after frozen storage (Memo, M. Nelson, 4/26/88).  Grapes and apples
treated with myclobutanil, harvested, analyzed, and stored over 3 years
and reanalyzed for both myclobutanil and its metabolite showed no change
in the levels or composition of the residues demonstrating the long-term
stability of myclobutanil and its metabolite in samples for at least 3
years under frozen conditions.  Additional storage stability studies
demonstrate that myclobutanil and its alcohol metabolite are stable
under frozen conditions for the following time periods: 288 days in/on
asparagus (Memo, G. Kramer, 12/11/98; D238442); 657 days (22 months)
in/on snap beans (Memo, N. Dodd, 4/24/98; D238454); 296 days in/on mint
(Memo, J. Rowell, 8/3/99; D238448); and 36 months in/on tomatoes (Memo,
J. Rowell, 9/13/99; D251632).  The available storage stability data are
adequate to support crop field trial data.  However, information on the
maximum storage intervals of samples in the processed food and feed
study, from harvest to analysis, for soybean seed (RAC), hulls, meal and
refined oil should be provided.

Magnitude of the Residue in Livestock:  The established ruminant
tolerances are based on an estimate of the maximum theoretical dietary
burden (MTDB) of myclobutanil and its alcohol metabolite RH-9090 (free
and bound) of 23.2 ppm, which was based on a hypothetical diet of almond
hulls, grape pomace (wet), and raisin waste (Memo, M. Peters, 2/17/94;
D193006).  The poultry tolerances are based on an estimated MTDB of 0.75
ppm, which is based on a hypothetical diet of apple and grape pomace
(Memo, M. Nelson, 4/26/88).  Grape pomace and raisin wastes are not
currently considered to be livestock feed items (Table 1 of OPPTS
Residue Chemistry Test Guidelines OPPTS 860.1000).  The livestock feed
items associated with the proposed use include soybean seed, forage,
hay, aspirated grain fractions, meal, hulls, and silage.  An updated
calculation of the MTDB resulted in dietary burdens of 13.5 ppm, and
0.074 ppm for beef and dairy cattle, and poultry.  As these dietary
burdens do not exceed the MTDB (23.2 ppm and 0.75 ppm for cattle/hogs
and poultry, respectively) used to determine the current tolerances for
livestock commodities, an increase in ruminant and poultry tolerances is
not needed to support this action.

Magnitude of the Residue in Plants:  The crop field trial data for
soybeans are classified as acceptable and satisfy the guideline
requirement for crop field trials (Residue Chemistry Guidelines OPPTS
860.1500).  Following 2 foliar applications of GF-1062 (an EW
formulation containing 19% myclobutanil as the ai) 0.125 lb ai/A (total
application rate of 0.250 lb ai/A; 1x the maximum proposed seasonal
application rate), the maximum combined residues of myclobutanil and its
alcohol metabolite RH-9090 in soybean hay, forage, and seed were 3.4354
ppm, 11.4364 ppm, and 0.2090 ppm, respectively (with 12- to 17-day RTI
and a 14-day PHI).  The forage decline study indicates that residues of
myclobutanil decline steadily with a half-life of 7-9 days; RH-9090
residues increase from the day of application until day-7 then gradually
declined.  Although the samples were harvested at 14-day PHI and the
proposed PHI is 28 days, the available residue decline data on forage
indicate that residues of myclobutanil decline steadily with a half-life
of 7-9 days, and RH-9090 decline steadily after Day-7.  Therefore, the
residue data support the establishment of permanent tolerances for the
residues of myclobutanil and its alcohol metabolite (free and bound)
in/on soybean, forage at 3.5 ppm; soybean, hay at 15 ppm; and soybean,
seed at 0.25 ppm.  A revised Section F should be submitted.

Magnitude of the Residue in Processed Commodities:  Under the conditions
and parameters used in the study, the processed food and feed data are
classified as scientifically acceptable, with the exception of the
aspirated grain fraction (AGF) data.  The results of the processing
study indicate that, following 2 foliar applications of GF-1062 at 0.625
lb ai/A/application (total application rate of approximately 1.25 lb
ai/A; 5x the maximum proposed seasonal application rate; 10- to 15-day
RTI and 14-day PHI), residues of myclobutanil and RH-9090 do not appear
to concentrate in soybean hulls (1.1x) and soybean meal (0.52x). 
Residues of myclobutanil and RH-9090 do appear to concentrate in soybean
refined oil (2.0x) and soybean AGF (70x) processed from soybean seeds
bearing detectable residues.  The maximum theoretical concentration
factor for soybean is 12x (OPPTS 860.1520, Table 1), and 11.3x, 2.2x,
and 12.0x for hulls, meal, and oil, respectively, based on separation
into components (OPPTS 860.1520, Table 3).  Therefore, tolerances on
soybean hulls and meal are not necessary.

For refined oil, using the HAFT of 0.1687 ppm for soybean seed from the
crop field trial study, the maximum expected residue level in soybean
refined oil would be 0.34 ppm (0.1687 ppm x 2.0).  Therefore, an
appropriate tolerance for residues of myclobutanil and it alcohol
metabolite (free and bound) in/on soybean, refined oil is 0.40 ppm.  A
revised Section F should be submitted.

The purpose of this distribution data is to show that the AGF typifies a
sample of commercial elevator AGF, which at least 50% has a particle
size of <400 μm.  Therefore, as a worst-case scenario, it was assumed
that all residues were in the particle sizes of <425 μm.  Therefore, if
residues of myclobutanil concentrated 70x when 15.6% of the AFG was <425
μm, then residues would presumably be ~ 200x (70 x 3) when 50% (15.6% x
3) of the AGF has a particle size of <425 μm.  Using the HAFT of 0.1687
ppm for soybean seed from the crop field trial data, the maximum
expected residue level in AGF is 34 ppm (0.1687 ppm x 200).  Therefore,
the appropriate tolerance for residues of myclobutanil and it alcohol
metabolite (free and bound) in/on aspirated grain fractions is 35 ppm. 
A revised Section F should be submitted.

Confined/Field Accumulation in Rotational Crops:  The proposed label
includes the following restriction:  Fields treated with myclobutanil
can be rotated at any time to crops that are listed on a registered
label immediately after the last treatment.  Do not plant other crops
within 30 days after the last application of a product containing
myclobutanil.  The current rotational crop restrictions are adequate,
and are supported by previously-reviewed limited field rotational crop
study conducted at a total application rate of 0.75 lb ai/A (3x the
maximum season application rate for soybeans) (Memo, J. Tyler; DP#
308904; MRID 46034003).

Recommendations for Tolerances/International Considerations:  A summary
of the recommended tolerances and the correct commodity definitions for
the proposed uses are listed in Table 5.1.1.  The appropriate tolerance
levels were calculated using the methodology formulated by the North
America Free Trade Agreement (NAFTA) Maximum Residue Limit
(MRL)/Tolerance Harmonization Workgroup for calculating statistically
based pesticide tolerances for plant commodities based on field trial
residue data.  

Table 5.1.1.  Tolerance Summary for Myclobutanil.

Commodity	Proposed Tolerance (ppm)	Recommended Tolerance (ppm)	Comments

(correct commodity definition)

Soybean seed	0.05	0.25	Soybean, seed

Soybean forage	5	3.5	Soybean, forage

Soybean hay	13	15	Soybean, hay

Soybean aspirated grain fractions	1.1	35	Aspirated grain fractions

Soybean hulls	0.06	-	Based on available processing data, a tolerance on
soybean hulls is not needed.

Soybean meal	0.03	-	Based on available processing data, a tolerance on
soybean meal is not needed.

Soybean oil	0.1	0.40	Soybean, refined oil

There are no current Codex, Canadian or Mexican maximum residue limits
(MRLs) for residues of myclobutanil in/on soybeans.  Therefore,
harmonization is not an issue.

5.1.2	Drinking Water Considerations

EFED provided Estimated Drinking Water Concentrations (EDWCs) of
myclobutanil in surface and ground water using PRZM-EXAMS 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.  EFED calculated the 1- in 10-year peak acute and 1- in 10-year
estimated annual mean non-cancer chronic EDWCs for myclobutanil in
surface water to be 15.3 ppb and 8.5 ppb, respectively.  The ground
water EDWC for both acute and chronic exposures is estimated as 0.35
ppb.

It should be noted that in the 7/12/06 human-health risk assessment
(Memo, J. Tyler, et al., 7/12/06; D330235), HED used ground and surface
water EDWCs provided by EFED in a memo dated 6/9/03 (T. Nguyen; D290167
and D289700).  The acute (peak) and chronic (56-day) EDWCs for
myclobutanil in surface water [using FQPA Index Reservoir Screening Tool
(FIRST)] were 333 ppb and 86 ppb, respectively.  The ground water EDWC
(using SCI-GROW) for both acute and chronic exposures was estimated as
3.2 ppb.  The 6/9/03 drinking water assessment was also based on hops. 
However, the major reason for difference between the current EDWCs
compared to the 6/9/03 assessments is due to changes in application
rates to hops.  The previous assessment was based upon 15 applications
at 0.65 lb ai/acre with 14 day RTIs (total 9.75 lb ai/acre/year), while
the current maximum application rate is 1.0 lbs ai/acre/year.

5.1.3	Dietary Risks (Food and Drinking Water)

	

opulation subgroups) assessments were conducted using the Dietary
Exposure Evaluation Model - Food Commodity Intake Database™
(DEEM-FCID™; ver. 2.03) program which incorporates consumption data
from 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
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.

	

l 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 5.1.3.1 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.

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 PRZM-EXAMS 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 2.4%
of the aPAD.

Chronic Dietary Exposure Estimates:  A refined, chronic dietary exposure
assessment was performed for the general U.S. population and various
population subgroups using USDA 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, asparagus, blackberry, cantaloupe, cherry, cucumber,
grape, nectarine, peach, plum, pumpkin, raspberry, squash, strawberry,
tomato, and watermelon; and 100% CT information for all other registered
and proposed uses.  Drinking water was incorporated directly into the
dietary assessment using the chronic concentration for surface water
generated by the PRZM-EXAMS 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 (10% of the cPAD)
and all population subgroups.  The most highly exposed population
subgroup is children 1-2 years old at 25% of the cPAD.



Table 5.1.3.1.  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	0.002630	10

All Infants (< 1 year old)

0.004285	17

Children 1-2 years old

0.006161	25

Children 3-5 years old

0.005125	20

Children 6-12 years old

0.003343	13

Youth 13-19 years old

0.002069	8.3

Adults 20-49 years old

0.002234	8.9

Adults 50+ years old

0.002269	9.1

Females 13-49 years old	0.14279	2.4	0.002135	8.5

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 0.025mg/kg/day applies to the general U.S.
population and all population subgroups.

5.2	Residential Exposure

All residential handler exposures and risks resulted in MOEs of >100;
and, therefore, do not exceed HED’s level of concern.  The residential
handler assessment was based upon the residential SOPs, PHED data, and
ORETF study data.  All residential post-application exposures and risks
resulted in MOEs of >\100; and, therefore, do not exceed HED’s level
of concern.  The residential post-application assessment was based upon
standard assumption from residential SOPs, the results of two
dislodgeable foliar residue (DFR) studies on grapes in California, and
TTR data, when applicable.

It should be noted that the previous residential post-application
exposure assessment included two application rates for the turf use –
1.36 and 0.62 lb ai/A.  The myclobutanil MOEs for toddler exposures at
day 0, expressed as the total MOE, exceeded HED’s level of concern
(MOE<100) when the application rate is 1.36 lb ai/A, but did not exceed
HED’s level of concern (MOE>100) when the application rate is 0.62 lb
ai/A.  Since the completion of the 7/12/06 risk assessment, the company
has revised all turf labels to include a maximum application rate of
0.62-0.68 lb ai/A (personal communication between J. Tyler and L. Jones,
10/3/06).  Therefore, the high rate of 1.62 lb ai/A has been removed
from the residential assessment, and all residential post-application
exposures and risks resulted in MOEs of >100.

6.0	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. 

6.1	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 (2.4%
of the aPAD; see Table 5.1.3.1).  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.

6.2	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 5.1.3.1) and short-term, non-dietary
oral and/or dermal exposures.

	

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 HED Science Advisory Council for Exposure (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 6.3.1. 
For the general U.S. population and all population subgroup, including
infants and children, all short-term MOEs are greater than 100; and,
therefore, do not exceed HED's level of concern (MOE <100).

6.3	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; see Table
5.1.3.1) and intermediate-term, non-dietary oral and/or dermal
exposures.

	

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 6.3.1).

Table 6.3.1.  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 U.S Population	Hose End Sprayer - Mix your own	10	100	0.1
0.002630	0.054	180

Short- and Intermediate-Term Post-Application Exposures

General U.S Population	Home Gardens	10	100	0.1	0.002630	0.031	300

	“Pick Your Own” Fruit Trees

	0.09	110

	Turf - Heavy Yardwork

(0.62 lb ai/A rate)

	0.076	130

	Turf -Playing Golf

(0.62 lb ai/A rate)5

	0.0052	1300

Children 1-2 years old	Turf - Playing on Lawn

(0.62 lb ai/A rate) 5

0.006161	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)].

5  The labels have been revised to include a maximum turf application
rate of 0.62-0.68 lb ai/A.  Although the residential exposure assessment
was conducted using an application rate of 0.62 lb ai/A, the 0.68 lb
ai/A application rate does not have a significant affect on the
short-and intermediate term aggregate assessment.  The MOEs do not
exceed HED’s level of concern. 

6.4	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 (10% of the cPAD)
and all population subgroups (see Table 5.1.3.1).  The most highly
exposed population subgroup is children 1-2 years old at 25% 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.

7.0	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.

8.0	Occupational Exposure

The occupational residential exposure assessment was conducted in the
HED-memorandum dated (M. Dow; D323673).

8.1	Occupational Handler Exposure and Risk

  SEQ CHAPTER \h \r 1 The most highly exposed occupational pesticide
handlers are expected to be mixer/loaders using open-pour loading in
support of aerial and ground operations and applicators using open-cab,
ground-boom sprayers and aircraft.  HED typically expects occupational
handlers to experience short-term duration exposures (1-30 days) since
only two applications per season are allowed.  Although there are
potentially millions of acres of soybeans that may be treated on a
national basis, that acreage would be divided among a large number of
commercial applicators as well as private, grower applicators.  In
addition, there are quite a number of other materials intended for use
against this particular soybean disease organism.  Therefore, the
likelihood of commercial applicators having intermediate-term duration
exposures (1-6 months) is diminished.  However, ExpoSAC maintains that
it is possible for commercial occupational pesticide handlers to
experience intermediate-term duration exposures. 

In some cases, HED believes that certain individuals (private growers
versus commercial applicators) may perform all three activities, that
is, mix, load, and apply the material.  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 hand wands, backpack sprayers, and
push-type granular spreaders) are assessed as a combined job function. 
With these types of hand held operations, it is assumed that all
handling activities are 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, ground-boom
tractors, or air-blast 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 may be
required for a mixer/loader (e.g., chemical-resistant gloves may only be
necessary during the pouring of a liquid formulation).

Chemical-specific data were not available with which to assess pesticide
handler exposure.  Therefore, surrogate data from studies in the PHED
Surrogate Exposure Guide (Version 1.1; August 1998) were used to
estimate mixer/loader and applicator exposure. 

For pesticide handlers, it is HED practice to present estimates of
dermal exposure for “baseline” that is, with a single layer of work
clothing consisting of a long sleeved shirt, long pants, shoes plus
socks and no protective gloves and for “baseline” and the use of
protective gloves or other PPE as might be necessary. See Table 8.1.1
for a summary of exposures and risks to occupational pesticide handlers.



  SEQ CHAPTER \h \r 1 Table 8.1.1.  Summary of Exposures and Risks to
Occupational Handlers Applying Myclobutanil to Soybean.

Unit Exposure1

(mg ai/lb handled)	Application Rate2

(lb ai/A)	Units Treated3

Per Day (A)	ADD4

(mg ai/kg bw/day)	NOAEL5

(mg ai/kg w/day)	Combined MOE6

Mixer/Loader – Liquid Open Pour

Dermal:

No Glove     2.9 LC

W Glove 0.023 MC

Inhal.     0.0012 HC	0.125	1200	Dermal:

No Glove            3.1

W Glove       0.0245

Inhal             0.0026	Dermal           10

Inhalation       10	

Dermal:

No Glove      3.2

W Glove      370

Applicator – Ground-boom – open cab

Dermal:

No Glove  0.014 HC

W Glove 0.014 MC

Inhal    0.00074 HC	0.125	200	Dermal:

No Glove 0.0025

W Glove  0.0025

Inhal        0.00026	Dermal           10

Inhalation       10	Dermal:

No Glove   1,900

W Glove    1,900

Aerial Applicator

Dermal:

No Glove 0.0050 MC

Inhal 0.000068  HC	0.125	1200	Dermal:

No Glove    0.00535

Inhal           0.00015	Dermal           10

Inhalation       10	Dermal:

No Glove  1,800

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 Laredo® supplemental labeling.

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.

 Body Weight (70 kg).  

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

6. Combined Margin of Exposure = No Observable  Adverse Effect Level
(NOAEL)   ADD.  Since the dermal and inhalation toxicological effects
are the same and are identified from the same study, the dermal and
inhalation exposures are summed, then divided into the NOAEL.

  SEQ CHAPTER \h \r 1 A MOE of 100 is adequate to protect occupational
pesticide handlers.  Provided handlers wear protective gloves where
applicable, (pilots are not required), the MOEs are >100 and the
proposed use does not exceed HED’s level of concern.

8.2	Occupational Post-Application Exposure:    SEQ CHAPTER \h \r 1 There
is a potential for agricultural workers to experience post-application
exposures to pesticides during the course of typical agricultural
activities.  HED in conjunction with the Agricultural Re-entry Task
Force (ARTF) has identified a number of post-application agricultural
activities that may occur.  HED has also identified Transfer
Coefficients (TC) expressed as cm²/hr, which describe the amount of
foliar dislodgeable pesticide residue that is available to be
transferred to agricultural workers during the course of
post-application agricultural activities.

There were no chemical specific data with which to estimate
post-application exposures of agricultural workers to dislodgeable
residues of myclobutanil.  Therefore, theoretical estimates of exposure,
based on surrogate studies, have been conducted.  The ExpoSAC (SOP
003.1, Rev. 7 Aug. 2000, Regarding Agricultural Transfer Coefficients;
Amended ExpoSAC Meeting notes - 13 Sept 01) lists a number of possible
post-application agricultural activities relative to soybeans that
result in pesticide exposure to agricultural workers.  TC are identified
for each of the post-application, agricultural activities.  The TCs are
derived from data in surrogate exposure studies conducted during the
various activities listed.

The highest TC identified for soybeans is for scouting or irrigation
activities with a TC of 1,500 cm²/hr.  For this assessment, HED uses
the 1,500 cm²/hr TC for a Tier 1, screening level estimate.

The TCs used in this assessment are from an interim transfer coefficient
procedure 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 procedure will be periodically updated to incorporate additional
information about agricultural practices in crops and new data on
transfer coefficients.  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.

Post-application worker exposure is estimated using HED procedure that
assumes 20% of the application rate is available as dislodgeable foliar
residue on the day of treatment.  HED expects post-application
agricultural exposures to scouts (i.e., crop advisors) or workers
involved in irrigation would typically be short-term. 

PDRt  =  DFRt * CF1 * Tc * ET where:

PDRt  =  potential dose rate on day “t” (mg/day)

DFRt  = dislodgeable foliar residue on day “t” (µg/cm2)

 

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>it conversion factor to convert µg units in DFR value to mg for the
daily dose     (0.001 mg/µg)

TC     =  transfer coefficient (cm2/hr) (In this case 1,500 cm2/hr;
ExpoSAC SOP 003.1 Rev. 7 Aug. 2000; amended 13 Sept 01 ExpoSAC meeting
Notes). 

ET     = Exposure Time (hrs) (8)

and

DFRt = AR * F * (1-D)t * CF2 * CF3 where:

AR  = Application rate (lb ai/A) (0.125 lb ai/A)

F     = fraction of ai retained on foliage (unitless)

D     = fraction of residue that dissipates daily (unitless)

t      = post-application day on which exposure is being assessed

CF2 = weight unit conversion factor to convert the lbs ai in the
application rate to µg for the DFR value (4.54 x 108 µg/lb)

CF3 = Area unit conversion factor to convert the surface area units
(ft2) in the application rate to cm2 for the DFR value (1.08 x 10-3 
ft2/cm2 or 2.47 x 10-8 acre/cm2 if the application rate is per acre).

 DFR = 0.125 lb ai/A * 0.20 * (1-0)0 * 4.54 x 108 µg ai/lb * 2.47 x
10-8A/cm2 = 0.28 µg/cm2

PDR = 0.28 µg/cm2 * 0.001 mg/µg * 1,500 cm2/hr * 8 hr/day = 3.36 mg
ai/day  * 0.5 (% dermal absorption) ÷ 70 kg bw = 0.024 mg ai/kg bw/day

MOE = NOAEL  PDR 

 10 mg ai/kg bw/day  0.024 mg ai/kg bw/day = 416.

An MOE of 100 is adequate to protect agricultural workers from
post-application exposure to myclobutanil.  The calculated MOE >100,
and, therefore, does not exceed HED’s level of concern.

8.3	REI:    SEQ CHAPTER \h \r 1 Myclobutanil is classified in Acute
Toxicity Category IV for acute dermal, acute inhalation and primary skin
irritation.  It is classified in Category I for primary eye irritation
and it is a “Positive” dermal sensitizer.  Therefore the interim
Worker Protection Standard (WPS) REI of 24 hours is adequate to protect
agricultural workers.  The Laredo® label lists the REI as 24 hours.  

Title 40 of the Code of Federal Regulations, § 156.208 (c) (2) states: 
If a product contains only one active ingredient and it is in Toxicity
Category I by the criteria in paragraph (c) (1) of this section, the
restricted-entry interval shall be 48 hours.”   The Federal Register
Vol. 57, No. 163,  21 August 1992  page 38104 and 38142 (For 40 CFR
Parts 156 and 170) indicates that “...a 48-hour REI is established for
any product containing an active ingredient that is in Toxicity Category
I (most acutely toxic category) because of dermal toxicity or skin or
eye irritation.”  HED suggests that the RD confirm or correct, as may
be necessary, the 24 hour REI listed on the product label.

9.0	Data Needs and Label Requirements

Toxicology

None.

Residue Chemistry

Revised Section F to include the following HED-recommended tolerances
and corresponding correct commodity definitions:  soybean, seed (0.25
ppm); soybean, forage (3.5 ppm); soybean, hay (15 ppm); aspirated grain
fractions (35 ppm), and soybean, refined oil (0.40 ppm).

਀&䘋+摧⡥â᠀imum storage intervals of samples in the processed
food and feed study, from harvest to analysis, for soybean seed (RAC),
hulls, meal and refined oil.

9.3	Occupational/Residential Exposure

HED suggests that the RD confirm or correct, as may be necessary, the 24
hour REI listed on the product label.

cc: J. Tyler (RAB1)

RDI: RAB1 (10/11/06); G. Kramer (10/25/06); D. Vogel (10/25/06)

J. Tyler: S-10943: Potomac Yard: (703) 305-5564: 7509P: RAB1

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