Document ID: EPA-HQ-OPP-2007-0107-0004
Agency: epa
Document Type: Supporting & Related Material
Title: 
Posted Date: 2008-03-26T04:00Z

UNITED STATES ENVIRONMENTAL PROTECTION AGENCY

WASHINGTON, D.C.  20460

OFFICE OF           

PREVENTION, PESTICIDES

AND TOXIC SUBSTANCES

Date:		11/1/07

Subject:	Myclobutanil.  Human-Health Risk Assessment for Proposed Use on
Section 3 Requests for Use on Snap Bean, Mint, Papaya, Gooseberry,
Currant, Caneberry, Bell and Non-Bell Pepper, Head and Leaf Lettuce, and
Artichoke.  

Regulatory Action: Section 3 Registration

Risk Assessment Type: Single Chemical Aggregate

	PP#s: 7E4861, 7E4877, 3E6562, 8E4939, 6E7138, & 7E4866. 

DP Num:  341689

PC Code:  128857

40 CFR:  180.443

From:		W. Cutchin, Acting Branch Senior Scientist

		M. Dow, Ph. D., Biologist

		Alternative Risk Integration Assessment Team (ARIA)

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

	Registration Division (RD; 7505P)

Thru:		D. Vogel, Branch Chief

		Registration Action Branch 1 (RAB1)

		Health Effects Division (HED; 7509P)

To:		Barbara Madden, RM Team 05

		RIMUERB/RD (7505P)

INTRODUCTION

as needed, to estimate the risk to human health that will result from
proposed and registered uses of the pesticide myclobutanil
[α-butyl-α-(4-chlorophenyl)-1H-1,2,4-triazole-1-propanenitrile] as a
result of the proposed uses on crop group 8, except tomato; okra; crop
subgroup 4A, except spinach; cilantro; artichoke; papaya; black sapote;
canistel; mamey sapote; mango; sapodilla; and star apple.  In addition,
data has been submitted in support of the requests to remove the
conditions of registration for myclobutanil on bean, snap, succulent;
peppermint and spearmint; gooseberry; current; and caneberry.  A summary
of the findings and an assessment of human risk resulting from the
registered and proposed tolerances for myclobutanil is provided in this
document.  The risk assessment, residue chemistry data review, and the
dietary risk assessment is by W. Cutchin (ARIA), the
occupational/residential exposure assessment by M. Dow (ARIA), and the
drinking water assessment by J.Wolf (Environmental Fate and Effects
Division; EFED).

	Table of Contents

  TOC \o "1-3" \h \z \u    HYPERLINK \l "_Toc181668006"  1.0	Executive
Summary	  PAGEREF _Toc181668006 \h  5  

  HYPERLINK \l "_Toc181668007"  2.0	Ingredient Profile	  PAGEREF
_Toc181668007 \h  15  

  HYPERLINK \l "_Toc181668008"  2.1	Summary of Registered/Proposed Uses	
 PAGEREF _Toc181668008 \h  15  

  HYPERLINK \l "_Toc181668009"  2.2	Structure and Nomenclature	  PAGEREF
_Toc181668009 \h  17  

  HYPERLINK \l "_Toc181668010"  2.3	Physical and Chemical Properties	 
PAGEREF _Toc181668010 \h  17  

  HYPERLINK \l "_Toc181668011"  3.0	Hazard Characterization/Toxicity
Endpoint Selection	  PAGEREF _Toc181668011 \h  18  

  HYPERLINK \l "_Toc181668012"  3.1	Hazard Characterization	  PAGEREF
_Toc181668012 \h  18  

  HYPERLINK \l "_Toc181668013"  3.2	Toxicity Endpoint Selection	 
PAGEREF _Toc181668013 \h  19  

  HYPERLINK \l "_Toc181668014"  4.0	Food Quality Protection Act (FQPA)
Assessment	  PAGEREF _Toc181668014 \h  20  

  HYPERLINK \l "_Toc181668015"  5.0	Endocrine Disruption	  PAGEREF
_Toc181668015 \h  21  

  HYPERLINK \l "_Toc181668016"  6.0	Exposure Characterization/Assessment
  PAGEREF _Toc181668016 \h  21  

  HYPERLINK \l "_Toc181668017"  6.1	Dietary Exposure/Risk Pathway	 
PAGEREF _Toc181668017 \h  21  

  HYPERLINK \l "_Toc181668018"  6.1.1	Residue Profile	  PAGEREF
_Toc181668018 \h  21  

  HYPERLINK \l "_Toc181668019"  6.1.2	Drinking Water Considerations	 
PAGEREF _Toc181668019 \h  29  

  HYPERLINK \l "_Toc181668020"  6.1.3	Dietary Risks (Food and Drinking
Water)	  PAGEREF _Toc181668020 \h  29  

  HYPERLINK \l "_Toc181668021"  6.2	Residential Exposure	  PAGEREF
_Toc181668021 \h  31  

  HYPERLINK \l "_Toc181668022"  6.2.1	Residential Handler Exposures and
Risks	  PAGEREF _Toc181668022 \h  32  

  HYPERLINK \l "_Toc181668023"  6.2.2	Residential Handler Exposure Data	
 PAGEREF _Toc181668023 \h  33  

  HYPERLINK \l "_Toc181668024"  6.2.3	Residential Handler Risk Estimates
  PAGEREF _Toc181668024 \h  33  

  HYPERLINK \l "_Toc181668025"  6.2.4	Residential Handler Risk
Characterization	  PAGEREF _Toc181668025 \h  34  

  HYPERLINK \l "_Toc181668026"  6.3	Home Garden Post Application
Exposures and Risks	  PAGEREF _Toc181668026 \h  34  

  HYPERLINK \l "_Toc181668027"  6.3.1	Home Garden Post Application
Exposure Data	  PAGEREF _Toc181668027 \h  34  

  HYPERLINK \l "_Toc181668028"  6.3.2	Home Garden Post Application
Exposure Assumptions	  PAGEREF _Toc181668028 \h  37  

  HYPERLINK \l "_Toc181668029"  6.3.3	Home Garden Post Application Risk
Estimates	  PAGEREF _Toc181668029 \h  37  

  HYPERLINK \l "_Toc181668030"  6.3.4	Home Garden Post Application Risk
Characterization	  PAGEREF _Toc181668030 \h  37  

  HYPERLINK \l "_Toc181668031"  6.4	“Pick Your Own” Post Application
Exposures and Risks	  PAGEREF _Toc181668031 \h  38  

  HYPERLINK \l "_Toc181668032"  6.4.1	Pick Your Own Post Application
Exposure Data	  PAGEREF _Toc181668032 \h  38  

  HYPERLINK \l "_Toc181668033"  6.4.3	Pick Your Own Post Application
Risk Estimates	  PAGEREF _Toc181668033 \h  38  

  HYPERLINK \l "_Toc181668034"  6.4.4	Pick Your Own Post Application
Risk Characterization	  PAGEREF _Toc181668034 \h  39  

  HYPERLINK \l "_Toc181668035"  6.5	Residential Turf Post Application
Exposure and Risks	  PAGEREF _Toc181668035 \h  39  

  HYPERLINK \l "_Toc181668036"  6.5.1	Residential Turf Post Application
Exposure Data	  PAGEREF _Toc181668036 \h  39  

  HYPERLINK \l "_Toc181668037"  6.5.2	Residential Turf Post Application
Exposure Assumptions	  PAGEREF _Toc181668037 \h  40  

  HYPERLINK \l "_Toc181668038"  6.5.3	Residential Turf Post Application
Risk Estimates	  PAGEREF _Toc181668038 \h  41  

  HYPERLINK \l "_Toc181668039"  6.5.4 	Residential Turf Post Application
Risk Characterization	  PAGEREF _Toc181668039 \h  42  

  HYPERLINK \l "_Toc181668040"  7.0	Aggregate Risk	  PAGEREF
_Toc181668040 \h  42  

  HYPERLINK \l "_Toc181668041"  7.1	Acute Aggregate Risk Assessment
(Food and Drinking Water)	  PAGEREF _Toc181668041 \h  43  

  HYPERLINK \l "_Toc181668042"  7.2	Short-Term Aggregate Risk Assessment
(Food, Drinking Water and Residential)	  PAGEREF _Toc181668042 \h  43  

  HYPERLINK \l "_Toc181668043"  7.3	Intermediate-Term Aggregate Risk
Assessment (Food, Drinking Water and Residential)	  PAGEREF
_Toc181668043 \h  43  

  HYPERLINK \l "_Toc181668044"  7.4	Chronic Aggregate Risk Assessment
(Food and Drinking Water)	  PAGEREF _Toc181668044 \h  45  

  HYPERLINK \l "_Toc181668045"  8.0	Cumulative	  PAGEREF _Toc181668045
\h  45  

  HYPERLINK \l "_Toc181668046"  9.0	Occupational Exposure	  PAGEREF
_Toc181668046 \h  46  

  HYPERLINK \l "_Toc181668047"  9.1	Occupational Handler Exposure and
Risk	  PAGEREF _Toc181668047 \h  46  

  HYPERLINK \l "_Toc181668048"  9.2	Post-Application Exposure to
Agricultural Workers	  PAGEREF _Toc181668048 \h  48  

  HYPERLINK \l "_Toc181668049"  9.3	Restricted Entry Interval	  PAGEREF
_Toc181668049 \h  49  

  HYPERLINK \l "_Toc181668050"  10.0	Data Needs and Label Requirements	 
PAGEREF _Toc181668050 \h  50  

  HYPERLINK \l "_Toc181668051"  10.1	Toxicology	  PAGEREF _Toc181668051
\h  50  

  HYPERLINK \l "_Toc181668052"  10.2	Residue Chemistry	  PAGEREF
_Toc181668052 \h  50  

  HYPERLINK \l "_Toc181668053"  10.3	Occupational/Residential Exposure	 
PAGEREF _Toc181668053 \h  50  

  HYPERLINK \l "_Toc181668054"  Attachment A	  PAGEREF _Toc181668054 \h 
51  

  HYPERLINK \l "_Toc181668055"  Attachment B	  PAGEREF _Toc181668055 \h 
53  

 1.0	Executive Summary

 myclobutanil
[α-butyl-α-(4-chlorophenyl)-1H-1,2,4-triazole-1-propanenitrile] and
the establishment of permanent tolerances for the combined residues of
myclobutanil and its alcohol 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 the parent, in/on papaya, bell and non-bell pepper, head and leaf
lettuce, and artichoke.  In addition, IR-4 has submitted data in support
of the requests to remove the conditions of registration for
myclobutanil on bean, snap, succulent; peppermint and spearmint;
gooseberry; current; and caneberry.  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 aggregate risks associated with the proposed uses of
myclobutanil are not of concern to HED for the general U.S. population
or any population subgroup.  

Use Profile

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).  The proposed uses range from
caneberries treated with four applications at 0.03 to 0.60 lb ai/A (0.25
lb ai/A, total rate) with 10-14 days retreatment interval (RTI) and a
0-day preharvest interval (PHI) to papayas treated with eight
applications at 0.25 lb ai/A (2.0 lb ai/A, total rate) with 13-15 days
RTI and a 0-day PHI. 

Toxicity/Hazard

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.  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.  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 serum
glutamic pyruvic transaminase (SGPT) and gamma glutamyl transferase
(GGT).  Signs of toxicity observed in the rat 28-day dermal studies 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).

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 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].  HED evaluated the hazard
and exposure data for myclobutanil and recommended that the FQPA Safety
Factor (SF) be reduced to 1x in assessing the risk posed by this
chemical.  The doses and toxicological endpoints selected for various
exposure scenarios are summarized below.  

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	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	Decreased testicular weights and increased testicular
atrophy.

Short-Term Dermal & Inhalation (1-30 days)

(Occupational/

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

(dermal absorption rate = 50%)

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

acceptable MOE = 100 (Residential, includes the FQPA SF)	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 & Inhalation (1-6 months)

(Occupational/

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

(dermal absorption rate = 50%)

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

acceptable MOE = 100 (Residential, includes the FQPA SF)	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 & Inhalation (> 6 months)

(Occupational/

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

(dermal absorption rate = 50%)

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

acceptable MOE = 100 (Residential, includes the FQPA SF)	Decreased
testicular weights and increased testicular atrophy.

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

Dietary Exposure (Food/Water)

Food

The nature of the residue in the subject crops, water, rotational crops,
and livestock is adequately understood.  The residues of concern in
plants are the parent myclobutanil and its RH-9090 metabolite (free and
bound). 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.  The residues of concern in rotational
crops are the parent myclobutanil and its RH-9090 metabolite (free and
bound).   

An adequate enforcement method (Method 34S-88-10) is available to
enforce the proposed tolerances.  Quantitation is by gas chromatography
using a nitrogen/phosphorus detector (GC/NPD) for myclobutanil and an
electron capture detector (GC/ECD) for residues measured as the alcohol
metabolite.  Crop field trial samples were analyzed for residues of
myclobutanil and its metabolite RH-9090 using a method derived from the
enforcement method.  The lower limit of method validation (LLMV) for
both myclobutanil and its metabolite RH-9090 was 0.01 ppm in lettuce
(head and leaf) and artichoke; 0.02 ppm in pepper (bell and non-bell),
caneberry, gooseberry, and snap bean.  The LLMV for currant was 0.0199
ppm for myclobutanil and 0.0204 ppm for RH9090.  The LLMV for papaya was
0.0199 ppm for myclobutanil and 0.0204 ppm for RH9090.  The LLMV for
mint was 0.019 ppm for myclobutanil and 0.02 for RH9090.  The method
used for data collection, based on the enforcement method, 34S-88-10, is
adequate.  There are adequate storage stability data to support the
requested uses.  None of the raw agricultural commodities of the subject
petitions have associated livestock feed items of regulatory concern. 
The petitioner has submitted adequate crop field trial and processing
studies to support their requested uses of myclobutanil.  

Snap Beans

The results from the snap bean trials show that the highest total
myclobutanil residues were 0.40 ppm in samples treated at the seasonal
rate of 0.50 lb ai/A and harvested the day of the final application. 
The new snap bean data are submitted to remove the conditional
registration.  ARIA recommends that the conditional registration for
myclobutanil on bean, snap, succulent be removed.

Mint

The results from the mint trials show that the highest total
myclobutanil residues were 0.24 ppm in samples treated at the seasonal
rate of 0.382 lb ai/A and harvested at 31 days after the final
application. 

The mint data are submitted to remove the conditional registration. 
ARIA recommends that the conditional registration for myclobutanil on
mint be removed.  

Papaya

The results from the papaya trials show that the highest total
myclobutanil residues were 1.95 ppm on a sample treated at the seasonal
rate of 2.0 lb ai/A and harvested the day of the final application.
There is adequate number and geographic location of residue field trials
to support a tolerance registration on papaya and the data also support
tolerance for black sapote, canistel, mamey sapote, mango, sapodilla,
and star apple as requested by the petitioner.  However, the requested
tolerances are not appropriate.  A revised Section F is required for the
residues of myclobutanil on papaya, sapote, canistel, mamey sapote,
mango, sapodilla, and star apple at 3.0 ppm. 

Gooseberry

IR-4 has submitted field trial data for myclobutanil on gooseberry.  At
each trial location, gooseberries received eight foliar applications at
a single application rate of 0.122 to 0.136 lb ai/A (seasonal rate of
1.04 to 1.05 lb ai/A) with 10 to 14 days between applications and a
0-day PHI.  The results from these trials show that the highest total
myclobutanil residues were 0.35 ppm in samples treated at the seasonal
rate of ~1.00 lb ai/A and harvested the day of the final application.

The gooseberry data are submitted to remove the conditional
registration.  The data are adequate in number and geographic location
to satisfy the requirements as requested in the cited memo.  ARIA
recommends that the conditional registration for myclobutanil on
gooseberry be removed.  Since the additional data does not exceed the
established tolerances, no change in the existing gooseberry tolerance
is required.

Current 

IR-4 has submitted field trial data for myclobutanil on currant.  At the
trial location, currants received eight foliar applications at a single
application rate of 0.125 to 0.130 lb ai/A (1.01 lb ai/A, total rate)
with 13 and 15 days between applications and a 0-day PHI.  The results
from these trials show that the highest total myclobutanil residues were
1.05 ppm in samples treated at the seasonal rate of ~1.0 lb ai/A and
harvested the day of the final application.

The current data are submitted to remove the conditional registration. 
The data are adequate in number and geographic location to satisfy the
requirements as requested in the cited memo.  ARIA recommends that the
conditional registration for myclobutanil on current be removed.  Since
the additional data does not exceed the established tolerances, no
change in the existing current tolerance is required.

Caneberry

IR-4 has submitted field trial data for myclobutanil on caneberry.  At
each trial location, caneberries received four foliar applications at a
single application rate of 0.060 to 0.068 lb ai/A (seasonal rate of
0.244 to 0.257 lb ai/A) with 10 to 14 days between applications and a
PHI of 0 days. The results from these trials show that the highest total
myclobutanil residues were 0.62 ppm in samples treated at the seasonal
rate of ~0.25 lb ai/A and harvested the day of the final application.

The caneberry data are submitted to remove the conditional registration.
 The data are adequate in number and geographic location to satisfy the
requirements as requested in the cited memo.  ARIA recommends that the
conditional registration for myclobutanil on caneberry be removed. 
Since the additional data does not exceed the established tolerance, no
change in the existing caneberry tolerance is required.

Bell and Non-Bell Pepper

IR-4 has submitted field trial data for myclobutanil on bell and
non-bell pepper.  Bell peppers were grown in five trials and non-bell
peppers were grown in one trial.  At each trial, peppers were treated
with four foliar applications at the approximate rate of 0.125 lb ai/A
for a total of approximately 0.50 lb ai/A.  The applications were made
at 12 to16-day intervals and a 0-day PHI.  The analytical results show
that the highest total myclobutanil residues were 0.19 ppm on bell
pepper and 0.14 ppm on non-bell pepper sampled at the 0-day PHI.  Also,
RH-9090 residues were less than the LLMV of 0.02 ppm in all samples.

A total of 6 field trials on bell and non-bell peppers were previously
conducted.  Pepper plots received 4 foliar applications of myclobutanil
at rates of ~0.125 lb. ai/A (0.5 lb ai/A/season).  The applications were
made at intervals of 13-15 days and mature peppers were collected
following the final application or 1 day later.  In bell peppers,
myclobutanil and RH-9090 residues ranges were 0.02- 0.51 ppm and
<0.02-0.17 ppm, respectively.  In the non-bell peppers, myclobutanil and
RH-9090 residues ranges were 0.08-2.03 ppm and 0.03-0.39 ppm,
respectively.  The previous data are used to support a tolerance with
regional registration for myclobutanil on bell and non-bell peppers.

Using both the previously submitted data and the data in the current
submission, there is adequate number and geographic location of residue
field trials to support a tolerance with a national registration on
peppers.  In addition, the data also support a tolerance for fruiting
vegetables (except cucurbits), crop group 8, except tomato since bell
and non-bell peppers are the representative crop.  However, the
requested tolerances are not appropriate.  In addition, the commodity
definition is incorrect.  A revised Section F is required for the
residues of myclobutanil on fruiting vegetables (except cucurbits), crop
group 8, except tomato at 4.0 ppm.

Okra

No data have been submitted for the residues of myclobutanil on okra. 
Okra is not currently a member of the fruiting vegetables crop group;
however, IR-4 has submitted a Crop Group amendment to EPA to add okra to
the fruiting vegetables crop group.  HED has previously determined that
field residue data for non-bell peppers is applicable to okra (DP Num:
274312, G. Herndon, 4/30/01).  The previous bell and non-bell pepper
data are used to support an okra tolerance with regional registration
for myclobutanil in the following states: Texas, Oklahoma, Arkansas, New
Mexico, Colorado, Arizona, Utah, Nevada, and California.  

ARIA concludes that the data for the fruiting vegetables (except
cucurbits) are adequate to support the requested tolerance on okra. 
However, the proposed tolerance is not appropriate.  A revised Section F
is required for the residues of myclobutanil on okra at 4.0 ppm.

Head and Leaf Lettuce

IR-4 has submitted field trial data for myclobutanil on lettuce (head
and leaf).  Fourteen field trials including seven head lettuce trials
and seven leaf lettuce trials were conducted.  At each trial, lettuce
was treated with four foliar applications of myclobutanil at the
approximate rate of 0.125 lb ai/A for a total of approximately 0.50 lb
ai/A.  The foliar applications were made at 12 to15-day intervals. 
Commercially mature lettuce samples were collected 2-4 days after the
final application.  Leaf lettuce samples for decline determination were
also collected at approximately 0, 7, and 14 days following the final
application.  In the head lettuce trials, wrapper leaves were removed
from half of the samples. Maximum myclobutanil residues on head lettuce
at 2-4 day PHI were 1.36 ppm with wrapper leaves and 0.25 ppm without
wrapper leaves. Maximum myclobutanil residues on leaf lettuce at 2-4 day
PHI were 4.03 ppm.  Myclobutanil and RH-9090 residues declined
significantly from 0-14 day PHI on leaf lettuce.

There is an adequate number and geographic location of residue field
trials on head and leaf lettuce, the representative crops to support a
tolerance on leafy greens, crop subgroup 4A, except spinach.  However,
the requested tolerances are not appropriate.  In addition, the
commodity definition is incorrect.  A revised Section F is required for
the residues of myclobutanil on leafy greens, crop subgroup 4A, except
spinach at 9.0 ppm.

Cilantro

No data have been submitted for the residues of myclobutanil on
cilantro.  Cilantro is not currently a member of the leafy greens, crop
subgroup 4A, except spinach.  However, since data for parsley has been
determined to be adequate to support tolerances on cilantro
(Reviewer’s Guide, B. Schneider, 6/14/02) and parsley is a member of
crop subgroup 4A, the data for head and leaf lettuce are adequate to
support a tolerance on cilantro.  

ARIA concludes that the data for the head and leaf lettuce (except
cucurbits) are adequate to support the requested tolerance on cilantro. 
However, the proposed tolerance on cilantro is not appropriate.  A
revised Section F is required for the residues of myclobutanil on
cilantro at 9.0 ppm.

Artichoke

IR-4 has submitted field trial data for myclobutanil on artichokes. 
Three field trials were conducted.  At each trial, artichokes were
treated with six foliar-directed applications of myclobutanil at the
approximate rate of 0.1 lb ai/A for a total of approximately 0.6 lb
ai/A.  The foliar applications were made at 12- to 16-day intervals. 
Commercially mature artichoke samples were collected 3 days after the
final application.  The analytical results show that the highest total
myclobutanil residues were 0.60 ppm in treated artichoke samples.

There is an adequate number and geographic location of residue field
trials on artichoke.  The requested tolerances are appropriate.  ARIA
recommends for the proposed myclobutanil tolerance of 0.90 ppm on
artichokes.

There are no current Codex, Canadian or Mexican MRLs for residues of
myclobutanil in/on any crops.  Therefore, international harmonization is
not an issue with these petitions.  

Water

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 tropical fruit, 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 120.1 ppb and 46.3 ppb, respectively.  The ground
water EDWC for both acute and chronic exposures is estimated as 2.83
ppb.

Dietary Risk Analysis

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.  These assessments
conclude that the acute dietary exposure estimates (95th percentile) are
below HED’s level of concern (<100% of the acute population adjusted
dose (aPAD)) for females 13-49 years old at 4% of the aPAD.

A refined, chronic dietary exposure assessment was performed for the
general U.S. population and various population subgroups using some
monitoring data, registered and proposed tolerances for other
commodities; and some average percent crop treated (%CT) information. 
Drinking water was incorporated directly into the dietary assessment
using the chronic concentration for surface water.  This assessment
concludes that the chronic dietary exposure estimates are below HED’s
level of concern (<100% of the chronic population adjusted dose (cPAD))
for the general U.S. population (20% of the cPAD) and all population
subgroups.  The most highly exposed population subgroup is children 1-2
years old at 30% of the cPAD.

Residential Exposure

All residential handler exposures and risks resulted in margins of
exposure (MOEs) of  >100; and, therefore, are not of concern to HED. 
The residential handler assessment was based upon the residential SOPs,
the Pesticide Handlers Exposure Database (PHED), data, and Outdoor
Residential Exposure Task Force (ORETF) study data.  All residential
post-application exposures and risks resulted in MOEs of >100; and,
therefore, are not of concern to HED.  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 turf transferable residue (TTR) data, when applicable.

Aggregate Risk

The acute aggregate risk assessment takes into account exposure
estimates from dietary consumption of myclobutanil (food and drinking
water).  The acute dietary exposure estimates, which include drinking
water, are below HED’s level of concern (<100% aPAD) at the 95th
exposure percentile for females 13-49 years old at 4% of the aPAD.

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.  

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.  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 all population
subgroup, including infants and children, all short-term MOEs are
greater than 100; and, therefore, are not of concern to HED (MOE <100).

The intermediate-term aggregate risk assessment estimates risks likely
to result from 1-6 months exposure to myclobutanil residues in food,
drinking water, and residential pesticide scenarios.  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. 
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.  For the general U.S. population and all population
subgroup, including infants and children, all intermediate-term MOEs are
greater than 100; and, therefore, are not of concern to HED (MOE <100).

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 (20% of the cPAD)
and all population subgroups.  The most highly exposed population
subgroup is children 1-2 years old at 30% of the cPAD.  Therefore, the
chronic aggregate risk associated with the proposed uses of myclobutanil
are not of concern to HED for the general U.S. population or any
population subgroups.

Occupational Exposure/Risk

Based upon the proposed new use patterns, ARIA believes the most likely
methods of application are likely to be by ground boom and by airblast. 
The Rally® "parent" (i.e., not supplemental labels) label indicates
that chemigation and aerial applications are permitted.  ARIA expects
the most highly exposed occupational handlers would most likely be
mixer/loaders loading wettable powder packaged in water soluble
packaging, applicators using open-cab ground-boom and open-cab airblast
spray machinery and aerial applicators.  It is possible for agricultural
workers to have post-application exposures to pesticide residues during
the course of typical agricultural activities.  HED has identified a
number of post-application agricultural activities that may occur and
which may result in post-application exposures to pesticide residues.  A
MOE of 100 is adequate to protect occupational pesticide handlers and
agricultural workers from post-application exposures.  Since the
estimated MOEs are > 100, the proposed uses are not of concern to ARIA.

Myclobutanil is classified in Acute Toxicity Category I for primary eye
irritation and in Acute Toxicity Category IV for acute dermal toxicity,
acute inhalation toxicity and primary skin irritation.  It is a dermal
sensitizer.  The labels list a 24-hour reentry interval (REI).  The
24-hour REI listed on the product labels should be confirmed or
corrected as may be necessary.

Environmental Justice Considerations

Potential areas of environmental justice concerns, to the extent
possible, were considered in this human health risk assessment, in
accordance with U.S. Executive Order 12898, "Federal Actions to Address
Environmental Justice in Minority Populations and Low-Income
Populations,"   HYPERLINK
"http://www.eh.doe.gov/oepa/guidance/justice/eo12898.pdf"
http://www.eh.doe.gov/oepa/guidance/justice/eo12898.pdf ).

As a part of every pesticide risk assessment, OPP considers a large
variety of consumer subgroups according to well-established procedures. 
In line with OPP policy, ARIA estimates risks to population subgroups
from pesticide exposures that are based on patterns of that subgroup’s
food and water consumption, and activities in and around the home that
involve pesticide use in a residential setting.  Extensive data on food
consumption patterns are compiled by the USDA under the Continuing
Survey of Food Intake by Individuals (CSFII) and are used in pesticide
risk assessments for all registered food uses of a pesticide.  These
data are analyzed and categorized by subgroups based on age, season of
the year, ethnic group, and region of the country.  Additionally, OPP is
able to assess dietary exposure to smaller, specialized subgroups and
exposure assessments are performed when conditions or circumstances
warrant.  Whenever appropriate, non-dietary exposures based on home use
of pesticide products and associated risks for adult applicators and for
toddlers, youths, and adults entering or playing on treated areas
postapplication are evaluated.  Further considerations are currently in
development as OPP has committed resources and expertise to the
development of specialized software and models that consider exposure to
bystanders and farm workers as well as lifestyle and traditional dietary
patterns among specific subgroups.

Review of Human Research

This risk assessment relies in part on data from studies in which adult
human subjects were intentionally exposed to a pesticide or other
chemical.  These studies (listed in Attachment B) have been determined
to require a review of their ethical conduct, and have received that
review.

Regulatory Recommendations and Data Deficiencies

Recommendations

anil and its alcohol metabolite α- (3-hydroxybutyl)-α-
(4-chlorophenyl)-1H-1, 2,4-triazole-1-propanenitrile (free and bound) in

Commodity	Tolerance

(ppm)

Fruiting vegetables (except cucurbits), crop group 8, except tomato	4.0

Okra	4.0

Leafy greens, crop subgroup 4A, except spinach	9.0

Cilantro	9.0

Artichoke	0.90

Papaya	3.0

Black sapote	3.0

Canistel	3.0

Mamey sapote	3.0

Mango	3.0

Sapodilla	3.0

Star apple	3.0

In addition, the submitted data supports the removal of the conditions
of registrations for myclobutanil on bean, snap, succulent; peppermint
and spearmint; gooseberry; current; and caneberry.  Since the additional
data does not exceed the established tolerances, no change in the
existing tolerances is required.

Deficiencies

A revised Section F is required for the residues of myclobutanil on
papaya, sapote, canistel, mamey sapote, mango, sapodilla, and star apple
at 3.0 ppm. 

A revised Section F is required for the residues of myclobutanil on
fruiting vegetables (except cucurbits), crop group 8, except tomato at
4.0 ppm.

A revised Section F is required for the residues of myclobutanil on okra
at 4.0 ppm.

A revised Section F is required for the residues of myclobutanil on
leafy greens, crop subgroup 4A, except spinach at 9.0 ppm.

A revised Section F is required for the residues of myclobutanil on
cilantro at 9.0 ppm.

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

Completion of the triazole and metabolite risk assessment.

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 Nova™ 40 WSP, a
product containing 40% ai.  Table 2.1 is a summary of the proposed use
pattern.

Table 2.1.  Summary of Proposed Use Patterns.

Crop	Product

(EPA Reg. No.)	#

App.	Application Rate

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

	Per app.	Per season

	Snap Bean	Nova 40 W

(62719-411)	4	0.125	0.5	7-10	0	Rust: Begin at first observation.

Pod tip rot: Begin at pod development and continue at 7-10 day intervals

Mint	Nova 40 W

(62719-411)	3	0.125	0.375	14-21	30	Begin applications in early spring
when plants break dormancy.

Papaya	Nova 40 W

(62719-411)	8	0.25	2.0	14	0	Do not plant any crop other than those on
the label for 12 months following the last application.

Gooseberry	Nova 40 W

(62719-411	8	0.125	1.0	10-14	0	Anthracnose: Begin at unfolded first leaf
then at 10-14 intervals.

Powdery mildew: Make applications at pre-bloom, full bloom and 2 weeks
later.

Current	Nova 40 W

(62719-411)	3	0.125	1.0	NA	0	Make applications at pre-bloom, full bloom
and 2 weeks later.

Blackberry & Raspberry	Nova 40 W

(62719-411)	4	0.03-0.06	0.25	10-14	0	Apply at budbreak. Use shorter
interval under heavy disease pressure.

Fruiting vegetables, crop group 8, except tomato and okra	 NOVA 40W

(62719-411)	4	0.0625 to 0.125	1.25	10-14	0	Apply the lower rate when
plants are small. Increase the rate as plants increase in size. 

Crop subgroup 4A, except spinach	NOVA 40W

(62719-411)	4	0.0625-0.125	1.25	10-14	3	Apply the lower rate when plants
are small. Increase the rate as plants increase in size. 

Artichoke	Nova 40 W

(62719-411)	6	0.075 - 0.1	0.6	14	3	Apply the lower rate when plants are
small. Increase the rate as plants increase in size.

1 RTI = retreatment interval; PHI = preharvest interval; GPA = gallons
per acre.

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. 

Structure and Nomenclature

Table 2.2.a  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  Physicochemical Properties of the Technical Myclobutanil.

Parameter	Value	Reference

Melting range/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 (DP Num: 330235, J. Tyler, 7/12/06).  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 3.2  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, 9/13/99) to evaluate the hazard and exposure data for
myclobutanil.  The committee recommended that the FQPA 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 ORETF and PHED.  The residential post-application assessment is
based upon chemical-specific 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

6.1	Dietary Exposure/Risk Pathway

6.1.1	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 (PP#2F4155,   DP Num: 183273, D. Davis,
2/8/93).  The requirement to conduct a tomato metabolism study, in
conjunction with PP#1F4030, was waived (DP Num: 203587, J. Stokes,
7/13/94).  The residues of concern in plants are the parent myclobutanil
and its RH-9090 metabolite (free and bound).

Myclobutanil metabolism in meat, milk, poultry, and eggs has been
reviewed (PP#7F3476, M. Nelson, 2/8/88) and summarized in conjunction
with the temporary tolerance petition for almond nuts and hulls
(PP#9G3786, 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# 40803302) is available to enforce the proposed
tolerances.  Quantitation is by gas chromatography using a GC/NPD for
myclobutanil and a GC/ECD 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 were analyzed for residues of myclobutanil and its metabolite
RH-9090 using a Working Method derived from Rohm & Haas Technical Report
Number 34S-88-10, “RH-3866 Total Residue Analytical Method for Apple
and Grape.”  Briefly, samples were extracted with acidified methanol. 
The extract was made basic by adding a sodium hydroxide solution. 
Sodium borohydride was then added; the flask was shaken and allowed to
stand 20 minutes.  The sample was transferred to a separatory funnel. 
Sodium chloride solution was used to rinse the flask and the rinsate was
combined with the sample.  The sample was partitioned with hexane.  The
water-methanol layer from the separatory funnel was then partitioned
twice with dichloromethane, and the combined dichloromethane fractions
were evaporated to dryness.  The residues were dissolved in 1:4 (v/v)
methanol-water, loaded onto a ferric chloride-activated Chelex 100
column, and eluted with 1:1 (v/v) methanol-water.  Sodium chloride was
added to the eluant and it was partitioned three times with
dichloromethane.  Methylene chloride extracts were combined and rotary
evaporated to dryness.  The residues were loaded onto a preconditioned
silica gel column, and the analytes were eluted with acetone-toluene and
evaporated.  Finally, the samples were analyzed for myclobutanil and
RH-9090 by GC/NPD in nitrogen mode (also designated as thermionic
specific detector (GC/TSD)) and GC/ECD, respectively.  The LLMV for both
myclobutanil and its metabolite RH-9090 was 0.01 ppm in lettuce (head
and leaf) and artichoke; 0.02 ppm in pepper (bell and non-bell),
caneberry, gooseberry, and snap bean.  The LLMV for currant was 0.0199
ppm for myclobutanil and 0.0204 ppm for RH9090.  The LLMV for papaya was
0.0199 ppm for myclobutanil and 0.0204 ppm for RH9090.  The LLMV for
mint was 0.019 ppm for myclobutanil and 0.02 for RH9090.  The method
used for data collection, based on the enforcement method, 34S-88-10, is
adequate.

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 interval for field treated snap
bean samples in the study was 233 days.  No freezer storage stability
test was conducted with this study; however, previously submitted
storage stability data indicate that residues were stable for up to 657
days under the conditions samples were held from harvest to analysis
(PP#7E04861, DP Num: 238454, MRID: 44338201, N. Dodd, 4/24/98).

The maximum storage interval for field treated mint samples in the study
was 297 days.  No freezer storage stability test was conducted with this
study; however, previously submitted storage stability data indicate
that residues were stable under the conditions samples were held for at
least 296 days under frozen conditions (PP# 7E04877, DP Num: 238448,
MRID: 44349601, J. Rowell, 8/3/99).

The maximum storage interval for field treated papaya samples in the
study was 353 days.  Storage stability samples were fortified with
myclobutanil and RH9090 and analyzed after 378 and 379 days,
respectively.  Recoveries obtained during storage stability testing were
acceptable. 

The maximum storage interval for field treated gooseberry samples in the
study was 292 days.  No freezer storage stability test was conducted
with this study; however, previously submitted storage stability data
indicate that myclobutanil and RH-9090 metabolite are relatively stable
during frozen storage up to 279 days in/on gooseberries (PP# 8E4939, DP
Num: 242704, MRID: 44462101, J. Rowell, 9/17/99).

The maximum storage interval for field treated currant samples in the
study was 260 days.  No freezer storage stability test was conducted
with this study; however, previously submitted storage stability data
indicate that residues of myclobutanil and its RH-9090 metabolite are
stable during frozen storage for up to 202 days in/on currants (PP#
8E4939, DP Num: 242704, MRID: 44462101, J. Rowell, 9/17/99).

No freezer storage stability test was conducted with this study;
however, previously submitted storage stability data show that
myclobutanil and RH-9090 metabolite are relatively stable during frozen
storage up to 187 days (~6 months) in/on blackberries and up to 308 days
(~10 months) in/on raspberries (PP# 7E04866, DP Num: 238444, MRID:
44339201 and -02, J. Rowell, 9/17/99).

The maximum storage interval for field treated pepper samples in the
study was 238 days.  Myclobutanil and RH-9090 have previously been shown
to be sable on bell and non-bell peppers in frozen storage for up to 475
days.474-475 days in/on peppers (bell and non-bell) (PP#:1E6265, DP Num:
275142, MRID: 45334201 and -02, J. Tyler, 6/4/01).

The maximum storage interval for field treated samples was 335 days. 
The results of a freezer storage stability study demonstrated that
myclobutanil and RH-9090 residues were stable in leaf lettuce samples
stored frozen 376 days.  

The maximum storage interval for field treated artichoke samples in the
study was 583 days.  The results of a freezer storage stability study
demonstrated that myclobutanil and RH-9090 residues were stable in
artichoke samples stored frozen 610 days.

Magnitude of the Residue in Livestock:  None of the raw agricultural
commodities of the subject petitions have associated livestock feed
items of regulatory concern; therefore, a discussion of livestock
exposure to myclobutanil is not germane to this action.

Magnitude of the Residue in Plants: 

Snap Bean  

IR-4 has submitted field trial data for myclobutanil on snap bean.  At
each trial location, snap beans received four foliar applications at a
single application rate of 0.121 to 0.127 lb ai/A (0.50 lb ai/A, total
rate) with 7 to 8 days between applications and a PHI of 0 days.  The
results from these trials show that the highest total myclobutanil
residues were 0.40 ppm in samples treated at the seasonal rate of 0.50
lb ai/A and harvested the day of the final application.

The new snap bean data are submitted to remove the conditional
registration.  The data are adequate in number and geographic location
to satisfy the requirements as requested in the cited memo.  ARIA
recommends that the conditional registration for myclobutanil on bean,
snap, succulent be removed.  Since the additional data does not exceed
the established tolerance, no change in the existing bean, snap,
succulent tolerance is required.

Mint

IR-4 has submitted field trial data for myclobutanil on mint.  At the
trial location, mint received three foliar applications at a single
application rate of 0.126 to 0.129 lb ai/A (0.382 lb ai/A, total rate)
with 12 to 15 days with a PHI of 31 days. The results from these trials
show that the highest total myclobutanil residues were 0.24 ppm in
samples treated at the seasonal rate of 0.382 lb ai/A and harvested at
31 days after the final application. 

The mint data are submitted to remove the conditional registration.  The
data are adequate in number and geographic location to satisfy the
requirements as requested in the cited memo.  ARIA recommends that the
conditional registration for myclobutanil on mint be removed.  Since the
additional data does not exceed the established tolerances, no change in
the existing peppermint and spearmint tolerances are required.

Papaya

IR-4 has submitted field trial data for myclobutanil on papaya.  At each
trial location, papayas received eight foliar applications at a single
application rate of 0.23 to 0.26 lb ai/A (seasonal rate of 1.98 to 2.03
lb ai/A) with 13 to 15 days between applications and a 0-day PHI. The
results from these trials show that the highest total myclobutanil
residues were 1.95 ppm on a sample treated at the seasonal rate of 2.0
lb ai/A and harvested the day of the final application.

There is adequate number and geographic location of residue field trials
to support a tolerance registration on papaya.  In addition, since
papaya is the representative crop for the proposed tropical crop group,
the data also support tolerance for black sapote, canistel, mamey
sapote, mango, sapodilla, and star apple as requested by the petitioner.
 However, the requested tolerances are not appropriate.  A revised
Section F is required for the residues of myclobutanil on papaya,
sapote, canistel, mamey sapote, mango, sapodilla, and star apple at 3.0
ppm. 

Gooseberry

IR-4 has submitted field trial data for myclobutanil on gooseberry.  At
each trial location, gooseberries received eight foliar applications at
a single application rate of 0.122 to 0.136 lb ai/A (seasonal rate of
1.04 to 1.05 lb ai/A) with 10 to 14 days between applications and a
0-day PHI.  The results from these trials show that the highest total
myclobutanil residues were 0.35 ppm in samples treated at the seasonal
rate of ~1.00 lb ai/A and harvested the day of the final application.

The gooseberry data are submitted to remove the conditional
registration.  The data are adequate in number and geographic location
to satisfy the requirements as requested in the cited memo.  ARIA
recommends that the conditional registration for myclobutanil on
gooseberry be removed.  Since the additional data does not exceed the
established tolerances, no change in the existing gooseberry tolerance
is required.

Current 

IR-4 has submitted field trial data for myclobutanil on currant.  At the
trial location, currants received eight foliar applications at a single
application rate of 0.125 to 0.130 lb ai/A (1.01 lb ai/A, total rate)
with 13 and 15 days between applications and a 0-day PHI.  The results
from these trials show that the highest total myclobutanil residues were
1.05 ppm in samples treated at the seasonal rate of ~1.0 lb ai/A and
harvested the day of the final application.

The current data are submitted to remove the conditional registration. 
The data are adequate in number and geographic location to satisfy the
requirements as requested in the cited memo.  ARIA recommends that the
conditional registration for myclobutanil on current be removed.  Since
the additional data does not exceed the established tolerances, no
change in the existing current tolerance is required.

Caneberry

IR-4 has submitted field trial data for myclobutanil on caneberry.  At
each trial location, caneberries received four foliar applications at a
single application rate of 0.060 to 0.068 lb ai/A (seasonal rate of
0.244 to 0.257 lb ai/A) with 10 to 14 days between applications and a
PHI of 0 days. The results from these trials show that the highest total
myclobutanil residues were 0.62 ppm in samples treated at the seasonal
rate of ~0.25 lb ai/A and harvested the day of the final application.

The caneberry data are submitted to remove the conditional registration.
 The data are adequate in number and geographic location to satisfy the
requirements as requested in the cited memo.  ARIA recommends that the
conditional registration for myclobutanil on caneberry be removed. 
Since the additional data does not exceed the established tolerance, no
change in the existing caneberry tolerance is required.

Bell and Non-Bell Pepper

IR-4 has submitted field trial data for myclobutanil on bell and
non-bell pepper.  Bell peppers were grown in five trials and non-bell
peppers were grown in one trial.  At each trial, peppers were treated
with four foliar applications at the approximate rate of 0.125 lb ai/A
for a total of approximately 0.50 lb ai/A.  The applications were made
at 12 to16-day intervals and a 0-day PHI.  The analytical results show
that the highest total myclobutanil residues were 0.19 ppm on bell
pepper and 0.14 ppm on non-bell pepper sampled at the 0-day PHI.  Also,
RH-9090 residues were less than the LLMV of 0.02 ppm in all samples.

A total of 6 field trials on bell and non-bell peppers were previously
conducted.  Pepper plots received 4 foliar applications of myclobutanil
at rates of ~0.125 lb. ai/A (0.5 lb ai/A/season).  The applications were
made at intervals of 13-15 days and mature peppers were collected
following the final application or 1 day later.  In bell peppers,
myclobutanil and RH-9090 residues ranges were 0.02- 0.51 ppm and
<0.02-0.17 ppm, respectively.  In the non-bell peppers, myclobutanil and
RH-9090 residues ranges were 0.08-2.03 ppm and 0.03-0.39 ppm,
respectively.  The previous data are used to support a tolerance with
regional registration for myclobutanil on bell and non-bell peppers.

Using both the previously submitted data and the data in the current
submission, there is adequate number and geographic location of residue
field trials to support a tolerance with a national registration on
peppers.  In addition, the data also support a tolerance for fruiting
vegetables (except cucurbits), crop group 8, except tomato since bell
and non-bell peppers are the representative crops.  The MRL spreadsheet
indicates that the requested tolerances are not appropriate.  In
addition, the requested commodity definition is incorrect.  A revised
Section F is required for the residues of myclobutanil on fruiting
vegetables (except cucurbits), crop group 8, except tomato at 4.0 ppm.

Okra

No data have been submitted for the residues of myclobutanil on okra. 
Okra is not currently a member of the fruiting vegetables crop group;
however, IR-4 has submitted a Crop Group amendment to EPA to add okra to
the fruiting vegetables crop group.  HED has previously determined that
field residue data for non-bell peppers is applicable to okra (DP Num:
274312, G. Herndon, 4/30/01).  The previous bell and non-bell pepper
data are used to support an okra tolerance with regional registration
for myclobutanil in the following states: Texas, Oklahoma, Arkansas, New
Mexico, Colorado, Arizona, Utah, Nevada, and California.  

ARIA concludes that the data for the fruiting vegetables (except
cucurbits) is adequate to support the requested tolerance on okra. The
MRL spreadsheet indicates that the requested tolerances are not
appropriate.  A revised Section F is required for the residues of
myclobutanil on okra at 4.0 ppm.

Head and Leaf Lettuce

IR-4 has submitted field trial data for myclobutanil on lettuce (head
and leaf).  Fourteen field trials including seven head lettuce trials
and seven leaf lettuce trials were conducted.  At each trial, lettuce
was treated with four foliar applications of myclobutanil at the
approximate rate of 0.125 lb ai/A for a total of approximately 0.50 lb
ai/A.  The foliar applications were made at 12 to15-day intervals. 
Commercially mature lettuce samples were collected 2-4 days after the
final application.  Leaf lettuce samples for decline determination were
also collected at approximately 0, 7, and 14 days following the final
application.  In the head lettuce trials, wrapper leaves were removed
from half of the samples. Maximum myclobutanil residues on head lettuce
at 2-4 day PHI were 1.36 ppm with wrapper leaves and 0.25 ppm without
wrapper leaves. Maximum myclobutanil residues on leaf lettuce at 2-4 day
PHI were 4.03 ppm.  Myclobutanil and RH-9090 residues declined
significantly from 0-14 day PHI on leaf lettuce.

There is an adequate number and geographic location of residue field
trials on head and leaf lettuce, the representative crops to support a
tolerance on leafy greens, crop subgroup 4A, except spinach.  The MRL
spreadsheet indicates that the requested tolerances are not appropriate.
 In addition, the commodity definition is incorrect.  A revised Section
F is required for the residues of myclobutanil on leafy greens, crop
subgroup 4A, except spinach at 9.0 ppm.

Cilantro

No data have been submitted for the residues of myclobutanil on
cilantro.  Cilantro is not currently a member of the leafy greens, crop
subgroup 4A, except spinach.  However, since data for parsley has been
determined to be adequate to support tolerances on cilantro
(Reviewer’s Guide, B. Schneider, 6/14/02) and parsley is a member of
crop subgroup 4A, the data for head and leaf lettuce are adequate to
support a tolerance on cilantro.  

ARIA concludes that the data for the head and leaf lettuce (except
cucurbits) are adequate to support the requested tolerance on cilantro. 
The MRL spreadsheet indicates that the requested tolerances are not
appropriate.  A revised Section F is required for the residues of
myclobutanil cilantro at 9.0 ppm.

Artichoke

IR-4 has submitted field trial data for myclobutanil on artichokes. 
Three field trials were conducted.  At each trial, artichokes were
treated with six foliar-directed applications of myclobutanil at the
approximate rate of 0.1 lb ai/A for a total of approximately 0.6 lb
ai/A.  The foliar applications were made at 12- to 16-day intervals. 
Commercially mature artichoke samples were collected 3 days after the
final application.  The analytical results show that the highest total
myclobutanil residues were 0.60 ppm in treated artichoke samples.

There is an adequate number and geographic location of residue field
trials on artichoke.  The requested tolerances are appropriate.  ARIA
recommends for the proposed myclobutanil tolerance of 0.90 ppm on
artichokes. 

Magnitude of the Residue in Processed Commodities:  Mint oil is the only
processed commodity of regulatory concern in the subject petitions.  A
processing study was previously performed (MRID: 44349601).  The
processing study demonstrated that myclobutanil residues do not
concentrate in mint oil.  

Confined/Field Accumulation in Rotational Crops:  Myclobutanil can be
taken up directly from the soil by the plant and oxidatively metabolized
to the alcohol metabolite, RH-9090.  The alcohol metabolite can be
conjugated with endogenous sugars to form glucosides and glycosides
which in turn can be transported into the plant cell walls as bound
residues.  In addition, the alcohol metabolite can be further oxidized
to the corresponding ketone metabolite, RH-9089.  These data show that
residues of myclobutanil and its alcohol metabolite are <0.01 ppm in
lettuce with a 120-day plantback interval (PBI), radishes with a 210-day
PBI, wheat with a 120-day PBI, and soybeans with a 210-day PBI (PP#
7E4861, DP Num: 250160, MRID: 44621901, J. Rowell, 10/13/99). 

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) (DP Num:
308904, MRID: 46034003, J. Tyler, 6/29/05).

Recommendations for Tolerances/International Considerations:  A summary
of the recommended tolerances and the correct commodity definitions for
the proposed uses are listed in Table 6.1.1.  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 6.1.1  Tolerance Summary for Myclobutanil.

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

(correct commodity definition)

Crop group 8, except tomato	4.5	4.0	fruiting vegetables (except
cucurbits), crop group 8, except tomato 

Okra	4.5	4.0

	Crop subgroup 4A, except spinach	11	9.0	leafy greens, crop subgroup 4A,
except spinach.

Cilantro	11	9.0

	Artichoke	0.9	0.90

	Papaya	2.0	3.0

	Black sapote	2.0	3.0

	Canistel	2.0	3.0

	Mamey sapote	2.0	3.0

	Mango	2.0	3.0

	Sapodilla	2.0	3.0

	Star apple	2.0	3.0

	

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

6.1.2	Drinking Water Considerations

EFED provided EDWCs of myclobutanil in surface and ground water using
PRZM-EXAMS and SCI-GROW, respectively (DP Num: 336254, J. Wolf,
9/26/07).  The assessment was based on tropical fruit, 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 120.1 ppb and 46.3
ppb, respectively.  The ground water EDWC for both acute and chronic
exposures is estimated as 2.83 ppb.

It should be noted that in the 7/12/06 human-health risk assessment (DP
Num: 330235, J. Tyler, 7/12/06), HED used ground and surface water EDWCs
provided by EFED (DP Num: 290167 and 289700, T. Nguyen; 6/9/03).  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/A with
14 day RTIs (total 9.75 lb ai/A/year), while the current maximum
application rate is 1.0 lbs ai/A/year.

6.1.3	Dietary Risks (Food and Drinking Water)

	

Acute (females 13-49 years old) and chronic dietary exposure (general
U.S. population and all population 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
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 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.

	

HED’s level of concern is when the exposure is greater than 100% of
the PAD.  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
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 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, artichokes, asparagus, green beans, blackberry, 
broccoli, cantaloupe, cauliflower, cherry, cucumber, grape, hops, mint,
nectarine, peach, peppers, plum, pumpkin, raspberry, soybeans, 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
(20% of the cPAD) and all population subgroups.  The most highly exposed
population subgroup is children 1-2 years old at 30% of the cPAD.

Table 6.1.3  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	0.004912	20

All Infants (< 1 year old)

0.006254	25

Children 1-2 years old

0.007491	30

Children 3-5 years old

0.006925	28

Children 6-12 years old

0.005121	21

Youth 13-19 years old

0.003989	16

Adults 20-49 years old

0.004792	19

Adults 50+ years old

0.004634	19

Females 13-49 years old	0.025927	4	0.004787	19

1 Acute dietary endpoints 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.

	

6.2	Residential Exposure

Myclobutanil is a contact fungicide which is applied to prevent fungal
outbreaks.  In the 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 home garden uses on berries, grapes,
peppermint, spearmint,  strawberries, asparagus, cucurbits, snap beans
and tomatoes and home orchard uses on almonds, apples, mayhaw and stone
fruits.  A listing of the application rates for the existing and
proposed new uses is given in Table 6.2.

Table 6.2  Myclobutanil Application Rates 

Crop	Agricultural and Commercial Application Rate

(lb ai/A)	Home Garden Application Rate* 

(oz product per gallon)	Spray Volume 

(GPA)	Home Garden Application Rate 

(lb ai/A)* 

Asparagus	0.125	1.25	100+	0.127

Almonds	N/A	0.5	400+	0.20

Berries (Blackberries/Raspberries)	0.0625	0.66	100+	0.067

Conifer Trees	0.25	3.0	100+	0.30

Curcurbits	0.125	1.25	100+	0.127

Pome Fruit  (Apple and Mayhaw)	0.25	0.66	400+	0.27

Grapes	0.125	1.25	100+	0.127

Mint (Peppermint and Spearmint)	0.125	1.25	100+	0.127

Ornamentals	0.25	2.0	100+	0.2

Snap Beans	0.125	1.25	100+	0.127

Strawberries	0.125	1.25	100+	0.127

Stone Fruit (Apricot, Nectarine, Cherry, Peach, Plum and Prune	0.15	0.5
400+	0.20

Tomato	0.1	1.0	100+	0.10

Turf	1.36	7.0	87*	0.62

+ Assumed

* Specified on Chemsico Fungicide M Label (9688-123) 

6.2.1	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 - LP Handwand Application to Ornamentals

4 - LP Handwand Application to Vegetables

5 - 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

 

6.2.2	Residential Handler Exposure Data

Unit exposure data were either taken from PHED or the home garden and
turf application studies that were sponsored by the ORETF.  A listing of
the unit exposure data used for each scenario is given in DP Num:
319227, T. Dole, 2/8/06; Appendix A. 	

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.  These 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 GPA for
turf, 100 GPA per A for most crops and 400 GPA for fruit trees.  A
listing of these rates is included in Table 6.2.3.  

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

The area treated per day (1000 square feet) was taken from 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. 	

6.2.3	Residential Handler Risk Estimates

The residential handler exposures and MOEs were calculated as detailed
in DP Num: 319227, T. Dole, 2/8/06; Appendices A and B.  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 6.2.3.  The MOEs for all of the scenarios exceed the target MOE of
100 which indicates that the risks are not of concern. 

Table 6.2.3  Myclobutanil Residential Handler Risks

Exposure Scenario

(all are mix/load/apply)	Use Site	Application Rate 	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 lb ai/A

	0.023 A/day

(1000 square feet)

	0.0016	6200

LP Handwand

0.0023	4300

LP Handwand	Vegetables

Berries

Mint

	0.125 lb ai/A	0.023 A/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 lb ai/A	0.5 A/day	0.054	185

Hose End Sprayer - Ready to Use

0.0130	785

Hose End Sprayer - Mix Your Own	Turf	0.62 lb ai/A	0.5 A/day	0.0250	370

Hose End Sprayer - Ready to Use

0.0059	1600

Belly Grinder	Turf	1.36 lb ai/A	0.023	 0.0250	410

Broadcast Spreader

	0.5	0.0033	3000

6.2.4	Residential Handler Risk Characterization

The MOEs for residential handlers range from 185 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.

							

6.3	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 the
application of myclobutanil.  To address these risks, the following two
scenarios were assessed based upon the Residential SOP 3.0 for Garden
Plants and SOP 4.0 for Trees:

Post Application Exposure in Home Gardens

Post Application Exposure in Home Orchards

6.3.1	Home Garden Post Application Exposure Data

Two dislodgeable foliar residue (DFR) studies 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 are summarized below and the data analyses are
included in DP Num: 319227, T. Dole, 2/8/06; Appendix C.

“Determination of Dislodgeable Residues of Myclobutanil on Grape
Foliage”, MRID 404893-02; November 9, 1987; W.J. Zogorski, Performing
Laboratory: Rohm and Haas Company.

This study measured myclobutanil DFRs following airblast application of
Rally 60DF to grapes at three vineyards located in the central valley of
California.  Five applications of 0.075 to 0.125 lb ai/A to yield a
total of 0.5 lb ai/A were made 16 to 30 days apart with a spray volume
of 100 to 200 GPA.

Triplicate DFR samples were collected out to 35 days using the Iwata
method to yield a total double sided leaf surface area of 608 cm2 per
sample.  The leaf disk samples were sealed in a jar and were placed in
wet ice storage until extraction which occurred as soon as possible
after completion of each sample collection.  The leaf disks samples were
extracted three times in 100 ml of an aqueous solution of 0.01 percent
Sur-Ten wetting agent to yield a total extract of 300 ml.  This extract
was capped, frozen in dry ice and shipped to the lab for analysis. 
Field spikes and controls were prepared using separate leaf punches. 
The samples were analyzed using a GC equipped with a thermionic detector
using a method that had been validated to an LOD of 0002 ug/cm2.

Quality control data indicated good laboratory and field recovery.  The
average laboratory recovery was 103 + 6.0% (n=25) and did not vary with
respect to fortification level which ranged from 0.008 to 0.033 ug/cm2. 
The average field recovery was 95 + 8% (n=44) with a fortification level
of 0.025 ug/cm2.  The field fortification samples were analyzed
concurrently with the DFR samples.  The DFR results were not adjusted
for either laboratory or field recovery.

The results of this study are summarized in Table 6.3.1.a.  All of the
results were 35X or more above the LOD at all sampling intervals while
the control samples were below the LOD.   The DAT 0 residues ranged from
0.16 to 0.19 ug/cm2 with an average of 0.18 ug/cm2.  The percent
transferable residue ranged from 7.8 to 11.5 when the results were
corrected for pre DAT 0 residues that resulted from the previous
applications.  The percent transferable residue ranged from 11.3 to 13.4
percent when the results were not corrected. 

Table 6.3.1.a  Dissipation of Myclobutanil Applied to Grapes in
California (MRID 404893-02) 

Site 	Application Rate 

(lb ai/A)	DAT 0 DFR 

(ug/cm2)	Percent Transferable Residue	Correlation Coefficient	Half Life
(days)

McFarland

Earlimart

Madera

Avg	0.125

0.125

0.125	0.16

0.18

0.19

0.18 	10.7 (C), 11.3(NC)

11.5 (C), 12.8(NC)

7.8 (C), 13.4 (NC)

10 (C), 12,5 (NC)	0.98 (n=10)

0.98 (n=10)

0.93 (n=10)	7.2

9.5

7.2

8.0

C = Corrected for previous residues

NC = Not corrected for previous residues

“Dislodgeable Foliar Residues Following Reduce-Volume and Conventional
Myclobutanil Application to Grapes,” HS-1760, August 2000; Welsh et.
al., California Environmental Protection Agency, Dept of Pesticide
Regulation.

This study measured myclobutanil DFRs following airblast application of
Rally 40WP to grapes at five vineyard sites located in California. 
Applications were made with both conventional airblast sprayers and
reduced volume electrostatic sprayers, however, only the data for
conventional sprayer are considered here because the reduced volume
methods are less applicable to the home garden.  No applications were
made prior to the initiation of the study at sites 2 and 3 while three
to four applications were made to sites 1, 4 and 5.  Applications began
at pre-bloom with approximate 18 day treatment intervals.  The
application rate was 0.1 b ai/A with a spray volume of 80 to 100 GPA. 
No rainfall occurred at any of the sites and irrigation was provided
using drip irrigation which did not affect the foliage.

Quadruplicate DFR samples were collected out to 14 to 26 days using the
Iwata method to yield a total double sided leaf surface area of 400 cm2
per sample.  Samples were collected from both the inside and outside
regions of the leaf canopy.  The leaf disk samples were sealed in jars
stored on ice until extraction at the laboratory which occurred within
24 to 48 hours after collection.  The leaf disks samples were extracted
three times in 50 ml of a dilute aqueous solution Aerosol OT-75 wetting
agent to yield a total extract of 150 ml.  Quality control samples were
prepared by fortifying blank extracts in the laboratory.  Field
fortification samples were not prepared.  The samples were analyzed
using either a GC equipped with a Ion Trap Detector (Site 1) or HPLC
equipped with a UV detector (all other sites).  Both methods were
validated with LODs of 0.0125 ug/cm2 for sites 1 and 2, 0.005 ug/cm2 for
sites 3 and 4 and 0.0075 ug/cm2 for site 5.

The average laboratory recovery from the fortification of blank extracts
was 104 + 18% (n=59) with a range of 77.1 to 171.2 percent.  The
recoveries did not vary with respect to analytical method (GC or HPLC)
or fortification level (which ranged from 0.025 to 0.50 ug/cm2).  The
DFR results were not adjusted for laboratory recovery.

The results of this study are summarized in Table 6.3.1.b.  The DFR
sample results were generally above the LOD at all sampling intervals
while the control samples were below the LOD.   The DAT 0 residues
ranged from 0.19 to 0.26 ug/cm2 with an average of 0.20 ug/cm2.  The
percent transferable residue at previously treated sites ranged from 7.8
to 13 percent when the results were corrected for pre DAT 0 residues
that resulted from the previous applications.  The percent transferable
residue ranged from 11.3 to 15.2 percent when the results were not
corrected.  The highest percent transferable residue (23.5 percent)
occurred at site 3 which was not treated with myclobutanil prior to the
study.

Table 6.3.1.b  Dislodgeable Foliar Residues Following Myclobutanil
Applied to Grapes in California (HS-1760) 

Site 	Application Rate 

(lb ai/A)	Pre App DFR

(ug/cm2)	DAT 1 DFR 

(ug/cm2)	Percent Transferable Residue	Correlation Coefficient	Half Life
(days)

1

3

4

5	0.1

0.1

0.1

0.1	0.084

N/A

0.040

0.073	0.19

0.26

0.17

0.19	9.1 (C), 16.6(NC)

23.5 (NC)

11.3 (C), 14.9 (NC)

10.2 (C), 16.6 (NC)	0.96 (n=24)

0.95 (n=20)

0.91 (n=16)

0.87 (n=20)	16

14

     9.1

17

C = Corrected for previous residues

NC = Not corrected for previous residues.

No previous applications were made at Site 3.

Application of the DFR Study Data to the Home Garden Exposure Scenarios

The two available studies were done using airblast sprayers while the
proposed home garden applications would be made with low pressure hand
wand or hose end sprayers.  Based upon experience with other fungicides,
such as the EBDCs, however, it is anticipated that DFRs that would
result from handwand applications would be similar to DFRs from airblast
applications. 

In the case of mancozeb, for example, the percent transferable residues
were 22.1 + 7.9 (n=6) for airblast applications, 18.3 + 2.0 (n=3) for
groundboom applications and 11.7 (n=1) for high pressure hand wand
application. 

The DFR data for HS-1760 Site 3 were used to assess home garden post
application exposures.  It is acknowledged that this DFR may represent
high end residues, however, it was chosen because there was no
indication in the study report that it represented atypical conditions.

6.3.2	Home Garden Post Application Exposure Assumptions

The following assumptions and exposure factors were used for assessing
home garden post application risks:

The maximum label rates were used for all of the calculations as there
are no use data available for home gardeners.  

The transfer coefficient 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.

6.3.3	Home Garden Post Application Risk Estimates

The Myclobutanil MOEs are summarized in Table 6.3.3 and the calculations
are included in DP Num: 319227, T. Dole, 2/8/06; Appendices A and D. 
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 6.3.3  Myclobutanil Post Application Risks for Home Gardeners

Crop	Application Rate

(lb ai/A)	DAT 0 DFR

(ug/cm2)	Transfer Coefficient (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

6.3.4	Home Garden Post Application Risk Characterization 

The risk for home gardeners is conservative because it is based upon a
screening level transfer coefficient and a dermal absorption factor of
50 percent.

6.4	“Pick Your Own” Post Application Exposures and Risks

“Pick Your Own” exposures can occur at a commercially operated
“Pick Your Own” strawberry farms and orchards where Myclobutanil has
been applied.  To address these risks, the following two scenarios were
assessed based upon the Residential SOP 15.0 for “Pick Your Own”
Strawberries:

Post Application Exposure for Pick Your Own Strawberries

Post Application Exposure for Pick Your Own Tree Fruit

6.4.1	Pick Your Own Post Application Exposure Data

The DFR data that were used for the home gardener post application risks
were also used to assess “Pick Your Own” Exposures.  These are
discussed in Section 3.0 above. 

6.4.2	Pick Your Own Post Application Exposure Assumptions

The following assumptions and exposure factors were used for assessing
“pick your own” post application risks:

The maximum label rates for strawberries and tree fruit were used. 

The transfer coefficient 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.

6.4.3	Pick Your Own Post Application Risk Estimates

The Myclobutanil MOEs are summarized in Table 6.4.3 and the calculations
are included in 

DP Num: 319227, T. Dole, 2/8/06; Appendix D.  The Myclobutanil MOEs for
the “pick your own” scenarios are greater than the target MOE of 100
and are not of concern.	

Table 6.4.3  Myclobutanil Post Application Risks for Pick Your Own Crops

Crop	Application Rate

(lb ai/A)	DAT 0 DFR

(ug/cm2)	Transfer Coefficient (cm2/hr)	Exposure Time (hours/day)	Dose

(mg/kg/day)	Dermal MOE

Fruit Trees 	0.25	0.65	10000	2	0.093	110

Strawberries	0.125	0.325	10000	4	0.093	110

6.4.4	Pick Your Own Post Application Risk Characterization

The risks for pick your own exposures are conservative because they are
based upon a screening level transfer coefficient and a dermal
absorption factor of 50 percent.  The risks could be refined by
examining the recently submitted ARTF transfer coefficient studies and
calculating TCs that match the clothing worn by pick your own customers.

6.5	Residential Turf Post Application Exposure and Risks

The following exposure scenarios are assessed for residential post
application risks:

Toddlers Playing on Treated Turf

Adults Performing Yardwork on Treated Turf

Adults Playing Golf on Treated Turf

6.5.1	Residential Turf Post Application Exposure Data 

A turf transferable residue (TTR) study was used to assess the turf
exposures.  The field portion of this study was conducted by Grayson
Research LLC of Creedmoor, North Carolina and Research for Hire of
Porterville, California.  The laboratory analysis for all three studies
was conducted by Rohm and Haas Company of Springhouse, Pennsylvania. 
This study measured the dissipation of myclobutanil using the ORETF
roller technique (also called the modified California Roller).   This
study was reviewed by HED and were found to meet most of the series 875
guidelines for post application exposure monitoring.   The study is
summarized below and the data analyses are included in DP Num: 319227,
T. Dole, 2/8/06; Appendix C.

Determination of Transferable Residues on Turf Treated with
Myclobutanil, MRID 44952901

Myclobutanil (Eagle WSP) was applied at a rate of 1.31 lbs ai/A to
Bermuda grass turf plots in North Carolina and Fescue turf plots
California using groundboom sprayers with a spray volume of 43.6 GPA. 
The bermuda grass plots were maintained at a height of 1.25 to 2.5
inches and the fescue plots were maintained at a height of 2 to 4
inches; however, no mowing was required after the final application at
either site.   No rainfall occurred at the California site and it was
irrigated six days after the final application with 0.75" of water.  
Rainfall occurred starting on DAT 2 at the NC site and irrigation was
not applied.   The rainfall amounts were 0.04" on DAT 2, 0.06" on Dat 3,
0.01" on DAT 4, 0.09" on 0.15 on DAT 8, 0.03" on DAT 9 and 0.41" on DAT
14.

Sampling was conducted with a ORETF roller using a 27" X 39" percale
cotton cloth in accordance with the SOP developed by the ORETF.  The NC
samples were collected after the sprays had dried then at 0.3, 1, 4, 5,
7, 10 and 14 Days after Treatment (DAT).  The CA samples were collected
after the sprays had dried then at 0.3, 1, 2, 4, 5, 7, 10 and 14 DAT. 
The samples were analyzed using a validated method that had an LOQ of
0.027 ug/cm2.  The concurrent laboratory recoveries were close to 100
percent and were acceptable.  The average field recoveries were
acceptable with a range of 91.6 to 94.6 percent depending upon the site
and fortification level.  The TTR values were corrected using a method
recovery factor of 0.977.

The results are shown in Table 6.5.1.  The pre-application TTRs were
below the LOQ at both sites.  The initial TTRs were based upon the
average of the DAT 0 and DAT 0.3 values.  The TTR levels declined to the
LOQ by DAT 4 at the NC site and by DAT 7 at the CA site.  The decline at
the NC may have corresponded to the rainfall that occurred prior to the
DAT 4 sample but this could not be confirmed because there were no
samples collected on DAT 2 or 3.   The decline at the CA site was abrupt
and seemed to correspond with the irrigation that occurred on DAT 6. 
The calculated correlation coefficient for the NC site was 0.98,
however, this may be an artifact of the missing data between DAT 1 and
DAT 4.  The correlation coefficient for the CA site was 0.41 when all
data were considered and 0.84 when two outlier data points were
excluded.  The outlier data points were replicate C on DAT 0 which was
0.186 ug/cm2 (replicates A and B were 0.361 and 0.336 ug/cm2) and
Replicate C on DAT 0.33 which was 0.547 ug/cm2 (replicates A and B were
0.323 and 0.348 ug/cm2).

Table 6.5.1  Dissipation of Myclobutanil Applied to Turf

Site	Application Rate

(lb ai/A)	Initial TTR (ug/cm2) 	Percent Applied as TTR	Correlation
Coefficient	Half Life (days)

North Carolina	1.31	0.16 + 0.032 (n=6)	1.1	0.98 (n=12)	1.1

California - All Data Considered	1.31	0.36+ 0.12 

(n=6)	2.4	0.41 (n=15)	N/A

California - Outliers Excluded	1.31	0.34+ 0.016

(n=4)	2.4	0.84 (n=13)	8.5

Note - The Initial TTR is calculated as the average of the DAT 0 and DAT
0.3 TTR values.

6.5.2	Residential Turf Post Application Exposure Assumptions

The turf exposures were considered to be short/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 per 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 1.36 lb ai A is from non-Chemsico labels (such as 62719-463).  

The initial TTR for dermal exposures was assumed to be 2.4 percent of
the application rate and was based upon an average of the DAT 0 and DAT
0.3 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 percent)
because the outliers offset each other.

Five percent 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.

Twenty percent 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 percent is also
used.

The Jazzercise approach is the basis for the dermal transfer
coefficients 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 percent 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 transfer coefficient 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.

6.5.3	Residential Turf Post Application Risk Estimates

The myclobutanil MOEs for toddler exposures are summarized in Table 10
and the calculations are included in DP Num: 319227, T. Dole, 2/8/06;
Appendices A and E.  The total MOE is below 100 when the application
rate is 1.36 lb ai/A and it is above 100 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 100 at the higher application rate. The
myclobutanil MOEs for adult dermal exposures are summarized in Table
6.5.3.a.  The dermal MOEs are above 100 regardless of which application
rate is used. 

Table 6.5.3.a  Toddler MOEs for 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*

Playing on Lawns	1.36	0.37	0.127	0.020	0.0051	0.000068	0.15	66

	0.62	0.17	0.0579	0.0093	0.0023	0.000031	0.070	140

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

The myclobutanil MOEs for adult dermal exposures are summarized in Table
6.5.3.b.  The dermal MOEs are above 100 regardless of which application
rate is used. 

Table 6.5.3.b  Adult MOEs for Exposure to Turf Treated with Myclobutanil

Exposure Scenario	Application Rate

(lbs ai/A)	Dermal TTR (ug/cm2)	Dermal Dose (mg/kg/day)	Dermal MOE* 

Heavy Yardwork

Playing Golf	1.36	0.37	0.076

0.0052	130

1900

Heavy Yardwork

Playing Golf	0.62	0.17	0.035

0.0024	290

4200

*The NOAEL is 10 mg/kg/day 

6.5.4 	Residential Turf Post Application Risk Characterization 

The high rate of 1.36 lb ai/A is from the Eagle 20EW label (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 turfgrass (including golf course
fairways, roughs, tee boxes and greens)”.  With the rate of 1.36 lb
ai/A, the toddler post application risk is of concern at Day 0 (MOE
<100) while the adult risk is not of concern.  All residential handler
exposures and risks resulted in MOEs of >100; and, therefore, are not of
concern to HED.  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, are not of concern to HED.  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.

7.0	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. 

7.1	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% of the aPAD; see Table 6.1.3).  Therefore, the acute aggregate risk
associated with the proposed uses of myclobutanil are not of concern to
HED for females 13-49 years old.

7.2	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 6.1.3) 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 7.3.  For
the general U.S. population and all population subgroup, including
infants and children, all short-term MOEs are greater than 100; and,
therefore, are not of concern to HED (MOE <100).

7.3	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 6.1.3) 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 

For the general U.S. population and children/toddlers, the total food
and residential intermediatet-term aggregate MOEs are listed in Table
7.3.  For the general U.S. population and all population subgroup,
including infants and children, all intermediate-term MOEs are greater
than 100; and, therefore, are not of concern to HED (MOE <100).

Table 7.3.  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
0.004912	0.054	170

Short- and Intermediate-Term Post-Application Exposures

General U.S Population	Home Gardens	10	100	0.1	0.004912	0.031	280

	“Pick Your Own” Fruit Trees

	0.09	110

	Turf - Heavy Yardwork

(0.62 lb ai/A rate)

	0.076	120

	Turf -Playing Golf

(0.62 lb ai/A rate)5

	0.0052	990

Children 1-2 years old	Turf - Playing on Lawn

(0.62 lb ai/A rate) 5

0.007491	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 are not of
concern to HED.

7.4	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 (20% of the cPAD)
and all population subgroups (see Table 6.1.3).  The most highly exposed
population subgroup is children 1-2 years old at 30% of the cPAD. 
Therefore, the chronic aggregate risk associated with the proposed uses
of myclobutanil are not of concern to HED for the general U.S.
population or any population subgroups.

8.0	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.  The last update for these metabolites was
conducted in conjunction with new uses on difenconazole (DP Num: 341803,
M. Sahafeyan, 10/30/07).  That analysis indicated that the acute and
chronic risk from dietary exposure to 1,2,4-T from all registered and
proposed triazole-based pesticides are not of concern; the highest aPAD
(from food + water) was 32% from all-infants population sub-group at
95th percentile of exposure distribution and the highest cPAD (from food
+ water) was 41% from children 1-2 years old.  For TA and TAA aggregate
acute and chronic dietary risk assessment, it was also expected that the
risks from adding difenconazole new uses only change minimally from the
last aggregate dietary risk assessment; hence, no DEEM analyses were
performed.  Therefore, the aggregate dietary risk from exposure to
1,2,4-T, TA, and TAA was expected to be of no concern to HED.  The new
uses of difenoconazole did not warrant a new cumulative aggregate risk
(dietary + residential) for 1,2,4-T.  In the previous cumulative
aggregate risk assessment (DP Num: 322238, M. Doherty, 11/1/05),
triadimefon, a triazole-based pesticide, with potentially much higher
exposures to residential handlers than difenoconazole were used and the
risks were of no concern to HED; therefore, 1,2,4-T aggregate risk due
to the addition of ornamental use of difenoconazole were not of concern.
 For triazole conjugates (TA and TAA), HED did not expect residues of TA
and TAA on leaf surfaces due to the formation of TA and TAA from 1,2,4-T
within plants; therefore, HED has not conducted a residential exposure
assessment for the triazole conjugates.

The last risk assessment has not as yet been updated as a result of the
proposed new uses of myclobutanil.  ARIA recommends against the proposed
new uses of myclobutanil pending the completion of the triazole and
metabolite risk assessment. 

9.0	Occupational Exposure

The occupational residential exposure assessment was conducted in the
HED-memorandum dated (DP Num: 323673, M. Dow, 3/8/07).

9.1	Occupational Handler Exposure and Risk

Based upon the proposed new use patterns, ARIA believes the most likely
methods of application are likely to be by ground boom and by airblast. 
The Rally® "parent" (i.e., not supplemental labels) label indicates
that chemigation and aerial applications are permitted. 

ARIA expects the most highly exposed occupational handlers would most
likely be mixer/loaders loading wettable powder packaged in water
soluble packaging, applicators using open-cab ground-boom and open-cab
airblast spray machinery and aerial applicators.

Persons involved in chemigation are not formally assessed.  There is no
"applicator" per se for applications through irrigation systems.  An
occupational handler would be responsible for preparing a concentrate
solution from which pesticide is "metered" into the irrigation system
water.  As such, the handler is essentially performing similar tasks to
a mixer/loader preparing solution for application by aircraft or by
ground machinery.  ARIA believes a handler preparing for application
through irrigation machinery would not be more highly exposed than a
mixer/loader supporting aerial operations.  

Since the treatment blocks (i.e., areas treated) are relatively small
for the proposed new crop uses (as compared to typical field crops such
as cotton, corn, soybeans or wheat), ARIA believes pesticide handlers
will be exposed to short-term duration (1-30 days) exposures but not to
intermediate-term (1-6 months) duration exposures.   However, since
multiple applications are permitted, it is possible that commercial
applicators might experience intermediate-term duration exposures. 
Risks are estimated for short-term and intermediate-term duration
exposures.  

Particularly for ground applications, private (i.e., grower) applicators
may perform all functions, that is, mix, load and apply the material. 
The HED ExpoSAC SOP Number 12 (29 March 2000) directs that although the
same individual may perform all those tasks, 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 Pesticide Handler Exposure Database (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, 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, 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 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 pesticide handlers.  The estimates of exposure to pesticide
handlers are based upon surrogate study data available in the 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 HED HIARC has met to discuss the adequacy of the toxicological
database relative to myclobutanil (HED DOC NO 013740, “MYCLOBUTANIL -
Second Report of the Hazard Identification Assessment Review
Committee,” M. Copley, 9/2/99).  Subsequently, the 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 was not appropriate.  A two-generation reproduction study in
rats was selected.  With regards to the assessment herein, the
short-term duration (1-30 days) and the intermediate-term duration (1-6
months) dermal and inhalation toxicological endpoints are identified
from a 2-generation reproduction toxicity study in the rat.  The NOAEL
is 10.0 mg ai/kg bw/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.  The HIARC identified a 50% dermal
absorption factor for use in assessing dermal exposures.  The RAB 1
toxicology team cited the same study for the inhalation endpoint, noting
the same effects and NOAEL.  Inhalation absorption is assumed to be
100%.  The intermediate-term dermal and inhalation NOAELs are the same
as those noted for short-term duration exposures and are cited from the
same 2-generation rat reproduction study.  See Table 9.1 for a summary
of exposures and risks to occupational pesticide handlers.  See the
Attachment A for a summary of the toxicological endpoints used for risk
assessment.

Table 9.1 Summary of Exposure & Risk for Occupational Handlers Applying
Myclobutanil

Unit Exposure1

mg ai/lb handled	Applic. Rate2

lb ai/unit	Units Treated3	Avg. Daily Exposure4

mg ai/kg bw/day	MOE5

Mixer/Loader Using WP in Water Soluble Packaging (in support of aerial
operations)

Dermal:

SLNoGlove     0.021 LC

SLWithGlove  0.0098 LC

Inhal.              0.00024 LC	0.25	350	Dermal:

SLNoGlove    0.013

SLWithGlove 0.00613

Inhal.              0.0003	No Glove

752

With Glove

1,555

Applicator - Groundboom Open-Cab

Dermal:

SLNoGlove     0.014 HC

SLWithGlove  0.014 MC

Inhal.               0.00074 HC	0.125	200	Dermal:

SLNoGlove    0.0025

SLWithGlove 0.0025

Inhal.          0.000264	No Glove

3,617

With Glove

3,617

Applicator - Airblast Open-Cab

Dermal:

SLNoGlove     0.36 HC

SLWithGlove  0.24 HC

Inhal.              0.0045 HC	0.25	40	Dermal:

SLNoGlove    0.0257

SLWithGlove 0.017

Inhal.           0.000643	No Glove

380

With Glove

567

Aerial Applicator

Dermal:

SLNoGlove      0.0050 MC

Inhal.            0.000068 MC	0.25	350	Dermal:

SLNoGlove  0.00313

Inhal.          0.000085	No Glove

3,110

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.   Inhal. = Inhalation.  Units = mg
a.i./pound of active ingredient handled.  Data Confidence: LC = Low
Confidence, MC = Medium Confidence, HC = High Confidence.

2.  Applic. Rate. = Taken from the  IR 4 submission Sections B

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 (ADD) = Unit Exposure * Applic. Rate * Units
Treated * absorption factor (50% dermal) ( Body Weight 70 kg. 

5.  NOAEL = No Observable Adverse Effect Level (10 mg a.i./kg bw/day for
short-term and intermediate-term dermal and  inhalation)

6.  MOE = Margin of Exposure = (NOAEL = 10 mg ai/kg bw/day)  ( ADD.  
The ADD = dermal exposure + inhalation exposure.

 A MOE of 100 is adequate to protect occupational pesticide handlers
from exposures to myclobutanil.  All MOEs are > 100 therefore the
proposed uses do not exceed ARIA’s level of concern.

9.2	Post-Application Exposure to Agricultural Workers

It is possible for agricultural workers to have post-application
exposures to pesticide residues 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 and which may result in
post-application exposures to pesticide residues.  HED has also
identified Transfer Coefficients (TC) (cm²/hr) relative to the various
activities which express the amount of foliar contact over time, during
each of the activities identified.  

 For the proposed new crop use sites, the highest TC for fruiting
vegetables and artichoke is 1,000 cm2/hr for hand harvesting.  The
highest TC for root vegetables and for greens is 2,500 cm2/hr for hand
harvesting.  Tropical fruit are not named specifically in the database. 
However, ARIA assumes there would not be significant difference from the
highest TCs for hand harvesting citrus or pome or stone fruit (which is
3,000 cm2/hr).  Therefore, as a “screening” level assessment, ARIA
herein uses a TC of 3,000 cm²/hr.

The TCs used in this assessment are from an interim TC Standard
Operating Procedure (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 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.

Lacking compound specific dislodgeable foliar residue (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 a.i./kg bw/day) = DFR µg/cm2 * TC cm2/hr *
hr/day * 0.001 mg/µg * 1/70 kg bw 

 and where:

Surrogate Dislodgeable Foliar Residue (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 a.i./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 * 3,000 cm2/hr * 8 hr/day * 0.001 mg/µg * 0.50 (% dermal
absorption) ( 70 kg bw = 0.096 mg/kg bw/day.

MOE = NOAEL ( ADD then 10.0 mg/kg bw/day ( 0.096 mg/kg bw/day =  104.

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

	

9.3	Restricted Entry Interval

Myclobutanil is classified in Acute Toxicity Category I for primary eye
irritation and in Acute Toxicity Category IV for acute dermal toxicity,
acute inhalation toxicity and primary skin irritation.  It is a dermal
sensitizer.  The labels list a 24-hour REI.  

;

C

 

Â

Ê

Õ

3

4

R

x

Ÿ

 

À

Õ

Ö

ã

ä

j¸

j;

j/

j¬

j

愀Ĥ

愀Ĥ

愀Ĥ

@

@

༁搃愀϶d؀

䡅

kd

óëâëÞëÕëÞóÇóëâëÞóëÞÂ½Â·°·°·Þ©Þ·Þ¡–‹
–‚|u|‚|‚|u|

愀Ĥ

ÿ

ÿ

^

z

‰

›

ž

3ÿ

ž

@

騀ꈋꨒ阙ꄞ$騆

騀ꈋꨒ阙ꄞ$騆

騀ꈋꨒ阙ꄞ$騆

騀ꈋꨒ阙ꄞ$騆

騀ꈋꨒ阙ꄞ$騆

騀ꈋꨒ阙ꄞ$騆

騀ꈋꨒ阙ꄞ$騆

騀ꈋꨒ阙ꄞ$騆

騀ꈋꨒ阙ꄞ$騆

騀ꈋꨒ阙ꄞ$騆

騀ꈋꨒ阙ꄞ$騆

騀ꈋꨒ阙ꄞ$騆

騀ꈋꨒ阙ꄞ$騆

騀ꈋꨒ阙ꄞ$騆

騀ꈋꨒ阙ꄞ$騆

@

@

@

$

@

$

@

@

$

@

$

@

@

$

@

@

@

@

@

@

$

@

U

>

>

>

>

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.”

The 24-hour REI listed on the product labels should be confirmed or
corrected as may be necessary.

10.0	Data Needs and Label Requirements

10.1	Toxicology

None.

10.2	Residue Chemistry

A revised Section F is required for the residues of myclobutanil on
papaya, sapote, canistel, mamey sapote, mango, sapodilla, and star apple
at 3.0 ppm. 

A revised Section F is required for the residues of myclobutanil on
fruiting vegetables (except cucurbits), crop group 8, except tomato at
4.0 ppm.

A revised Section F is required for the residues of myclobutanil on okra
at 4.0 ppm.

A revised Section F is required for the residues of myclobutanil on
leafy greens, crop subgroup 4A, except spinach at 9.0 ppm.

A revised Section F is required for the residues of myclobutanil on
cilantro at 9.0 ppm.

10.3	Occupational/Residential Exposure

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

References	DP Num: 336660, M. Dow, 3/8/07

PP#s: 7E4861, 7E4877, 3E6562, 8E4939, 6E7138, & 7E4866, DP Num: 341689
MRID: 45596301, 45880301, 45883401, 45908101, 45908201, 45910601, &
46990901-03, W. Cutchin, 9/26/07

DP Num: 319227, MRID: 40489302 & 44952901, T. Dole, 2/8/06

PP#s: 7E4861, 7E4877, 3E6562, 8E4939, 6E7138, & 7E4866, DP Number:
341690, W. Cutchin, 10/2/07

HED Doc. No. 013740, M. Copley, 9/2/99

		HED Doc. No. 013734, 9/13/99

		DP Num: 330235, J. Tyler, 7/12/06

		DP Num: 336254, J. Wolf, 9/26/07

Attachment A

Toxicity Tables

Table A.1  Acute Toxicity of Myclobutanil

Guideline

 No.	

Study Type	

MRID #(S)	

Results	

Toxicity Category

81-1	

Acute Oral	

00141662	

LD50 = 1.6 g/kg (M)

LD50 = 2.29 g/kg (F)	

III

81-2	

Acute Dermal	

00141663	

LD50> 5000 mg/kg	

IV

81-3	

Acute Inhalation	

40357101	

LC50 > 5.1 m/L	

IV

81-4	

Primary Eye  Irritation	

00141663	

Severe eye irritant	

I

81-5 	

Primary Skin Irritation	

00141663	

Non-irritating to skin	

IV

81-6	

Dermal Sensitization	

40357102	

Positive sensitizer	

Table A.2  Summary of Toxicological Doses and Endpoints for Myclobutanil

EXPOSURE

SCENARIO	DOSE

(mg/kg/day)	ENDPOINT	STUDY

Acute Dietary

females 13-50 years of age	NOAEL=60

UF = 100	LOAEL = 200 mg/kg/day based on increased resorptions, decreased
litter size and a decrease in the viability index.	Developmental
Toxicity - rabbit

	Acute RfD = 0.60

Acute Dietary

general population including infants and children	none

	Acute RfD = none

Chronic Dietary	NOAEL =2.49 mg/kg/day

UF = 100	LOAEL = 10 mg/kg/day based on decreased testicular weights and
increased testicular atrophy.	Chronic Toxicity/ Carcinogenicity - rat

	Chronic RfD = 0.025 mg/kg/day

Short-Term 

(Dermal)	oral NOAEL=10 mg/kg/day1	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.	2
Generation Reproduction Toxicity - rat

Intermediate-Term 

(Dermal)	oral NOAEL=10 mg/kg/day1	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.	2
Generation Reproduction Toxicity - rat

Long-Term (Dermal)	oral NOAEL =2.49 mg/kg/day1	LOAEL = 10 mg/kg/day
based on decreased testicular weights and increased testicular atrophy.
Chronic Toxicity/ Carcinogenicity - rat

Short Term

(Inhalation)	oral NOAEL=10 mg/kg/day2	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.	2
Generation Reproduction Toxicity - rat

 Intermediate Term

(Inhalation)	oral NOAEL=10 mg/kg/day2	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.	2
Generation Reproduction Toxicity - rat

Long Term

(Inhalation)	oral NOAEL =2.49 mg/kg/day2	LOAEL = 10 mg/kg/day based on
decreased testicular weights and increased testicular atrophy.	Chronic
Toxicity/ Carcinogenicity - rat

1 Use the appropriate dermal absorption factor (50%) since the NOAEL is
from an oral study.

2 Use the appropriate absorption factor (100%) since the NOAEL is from
an oral study.



Attachment B

Review of Human Research 

No MRID - PHED Surrogate Exposure Guide

	Page   PAGE  14  of   NUMPAGE \*Arabic  53 

Page   PAGE  1  of   NUMPAGE \*Arabic  53