	UNITED STATES ENVIRONMENTAL PROTECTION AGENCY

WASHINGTON, D.C.  20460

OFFICE OF

PREVENTION, PESTICIDES

AND TOXIC SUBSTANCES

Date: November 15, 2006

MEMORANDUM

SUBJECT:	Amended: Dimethomorph: Human Health Risk Assessment for
Proposed Uses on Brassica Stem and Head Subgroup 5A.  PC Code: 268800,
Petition No: 4E6848, DNum: D316328.

Regulatory Action: Section 3 Registration Action

Risk Assessment Type: Single Chemical Aggregate

FROM:	J. R. Tomerlin, PhD, Plant Pathologist

Fungicide Branch

Registration Division (7505P)

THROUGH:	C. Swartz, Branch Chief

Registration Action Branch 2

Health Effects Division (7509P)

TO:		B. Madden/D. Rosenblatt PM 5

RIMUERB

Registration Division (7505P)

Table of Contents

 TOC \f 1.0  Executive Summary	  PAGEREF _Toc145288070 \h  1

2.0  Ingredient Profile	  PAGEREF _Toc145288071 \h  3

2.1	Summary of Registered/Proposed Uses	  PAGEREF _Toc145288072 \h  3

2.2	Structure and Nomenclature	  PAGEREF _Toc145288073 \h  5

2.3	Physical and Chemical Properties	  PAGEREF _Toc145288074 \h  5

3.0  Metabolism Assessment	  PAGEREF _Toc145288075 \h  6

3.1 	Comparative Metabolic Profile	  PAGEREF _Toc145288076 \h  6

3.2	Nature of the Residue in Foods	  PAGEREF _Toc145288077 \h  6

3.2.1.	Description of Primary Crop Metabolism	  PAGEREF _Toc145288078 \h
 7

3.2.2	Description of Livestock Metabolism	  PAGEREF _Toc145288079 \h  7

3.2.3	Description of Rotational Crop Metabolism, including
identification of major metabolites and specific routes of
biotransformation	  PAGEREF _Toc145288080 \h  7

3.3 	Environmental Degradation	  PAGEREF _Toc145288081 \h  7

3.4	Toxicity Profile of Major Metabolites and Degradates	  PAGEREF
_Toc145288082 \h  7

3.5	Summary of Residues for Tolerance Expression and Risk Assessment
PAGEREF _Toc145288083 \h  7

4.0  Hazard Characterization/Assessment	  PAGEREF _Toc145288084 \h  8

4.1	Hazard Characterization	  PAGEREF _Toc145288085 \h  8

4.2	FQPA Hazard Considerations	  PAGEREF _Toc145288086 \h  11

4.2.1	Adequacy of the Toxicity Data Base	  PAGEREF _Toc145288087 \h  11

4.2.2	Evidence of Neurotoxicity	  PAGEREF _Toc145288088 \h  12

4.2.3	Developmental Toxicity Studies	  PAGEREF _Toc145288089 \h  12

4.2.4	Reproductive Toxicity Study	  PAGEREF _Toc145288090 \h  12

4.2.5	Additional Information from Literature Sources	  PAGEREF
_Toc145288091 \h  13

4.2.6  Pre-and/or Postnatal Toxicity	  PAGEREF _Toc145288092 \h  13

<IP_ADDRESS>	Determination of Susceptibility	  PAGEREF _Toc145288093 \h  13

4.3	Recommendation for a Developmental Neurotoxicity Study	  PAGEREF
_Toc145288094 \h  13

4.4	Hazard Identification and Toxicity Endpoint Selection	  PAGEREF
_Toc145288095 \h  13

4.4.1   Acute Reference Dose (aRfD) - Females age 13-49	  PAGEREF
_Toc145288096 \h  13

4.4.2	Acute Reference Dose (aRfD) - General Population	  PAGEREF
_Toc145288097 \h  13

4.4.3	Chronic Reference Dose (cRfD)	  PAGEREF _Toc145288098 \h  14

4.4.4	Incidental Oral Exposure (Short and Intermediate Term)	  PAGEREF
_Toc145288099 \h  14

4.4.5	Dermal Absorption	  PAGEREF _Toc145288100 \h  14

4.4.6	Dermal Exposure (Short, Intermediate and Long Term)	  PAGEREF
_Toc145288101 \h  14

4.4.7	Inhalation Exposure (Short, Intermediate and Long Term)	  PAGEREF
_Toc145288102 \h  15

4.4.8	Margins of Exposure	  PAGEREF _Toc145288103 \h  15

4.4.9	Recommendation for Aggregate Exposure Risk Assessments	  PAGEREF
_Toc145288104 \h  15

4.4.10	Classification of Carcinogenic Potential	  PAGEREF _Toc145288105
\h  15

4.5	Special FQPA Safety Factor	  PAGEREF _Toc145288106 \h  17

4.6	Endocrine disruption	  PAGEREF _Toc145288107 \h  18

5.0  Public Health Data	  PAGEREF _Toc145288108 \h  18

5.1	Incident Reports	  PAGEREF _Toc145288109 \h  18

6.0  Exposure Characterization/Assessment	  PAGEREF _Toc145288110 \h  18

6.1	Dietary Exposure/Risk Pathway	  PAGEREF _Toc145288111 \h  18

6.1.1	Residue Profile	  PAGEREF _Toc145288112 \h  18

6.1.2	Acute and Chronic Dietary Exposure and Risk	  PAGEREF
_Toc145288113 \h  20

6.2	Water Exposure/Risk Pathway	  PAGEREF _Toc145288114 \h  21

6.3	Residential (Non-Occupational) Exposure/Risk Pathway	  PAGEREF
_Toc145288115 \h  22

6.3.1	Home Uses	  PAGEREF _Toc145288116 \h  22

6.3.2	Recreational Uses	  PAGEREF _Toc145288117 \h  22

6.3.3	Other (Spray Drift, etc.)	  PAGEREF _Toc145288118 \h  22

7.0  Aggregate Risk Assessments and Risk Characterization	  PAGEREF
_Toc145288119 \h  22

7.1	Acute Aggregate Risk	  PAGEREF _Toc145288120 \h  23

7.2	Short-Term Aggregate Risk	  PAGEREF _Toc145288121 \h  23

7.3	Intermediate-Term Aggregate Risk	  PAGEREF _Toc145288122 \h  23

7.4	Long-Term Aggregate Risk	  PAGEREF _Toc145288123 \h  23

7.5	Cancer Risk	  PAGEREF _Toc145288124 \h  24

8.0  Cumulative Risk Characterization/Assessment	  PAGEREF _Toc145288125
\h  24

9.0  Occupational Exposure/Risk Pathway	  PAGEREF _Toc145288126 \h  24

9.1	Short/Intermediate/Long-Term Handler Risk	  PAGEREF _Toc145288127 \h
 25

9.2	Short/Intermediate/Long-Term Postapplication Risk	  PAGEREF
_Toc145288128 \h  26

10.0  Data Needs and Label Requirements	  PAGEREF _Toc145288129 \h  26

10.1	Toxicology	  PAGEREF _Toc145288130 \h  26

10.2	Residue Chemistry	  PAGEREF _Toc145288131 \h  26

10.3	Occupational and Residential Exposure	  PAGEREF _Toc145288132 \h
26

1.0	Executive Summary tc \l1 "1.0	Executive Summary

The Office of Pesticide Program’s Health Alternative Risk Integration
Assessment (ARIA) team has conducted an aggregate human health risk
assessment for dimethomorph.  The assessment includes evaluation of
risks for various population subgroups, including those consisting of
infants and children.  Dimethomorph ((E,Z)
4-(3-(4-chlorophenyl)-3-(3,4-dimethoxy-phenyl) acryloyl) morpholine) is
a systemic morpholine fungicide.  Its mode of action is the inhibition
of sterol (ergosterol) synthesis.  Morpholines are all systemic with
both curative and preventive properties.  There are three formulation
types: Acrobat MZ which is a wettable powder which contains mancozeb (9%
dimethomorph, 60% mancozeb), Forum WP which is a wettable powder (50%
dimethomorph) which does not contain mancozeb, and Forum DC which is a
dispersible concentrate (1.25 lb/gallon) which also does not contain
mancozeb.  The aggregate risk assessment was prompted by a submission by
the Interregional Research Project No. 4 (IR-4) of field trial data
supporting a petition for the use of dimethomorph on Brassica head and
stem vegetables, Group 5A.

The existing toxicity database for dimethomorph is complete and without
data gaps.  There is high confidence in the quality of the existing
studies and the reliability of the toxicity endpoints identified for use
in risk assessment.  Based on the toxicity profile for dimethomorph, a
developmental neurotoxicity study in rats is not required

Health Effects Division (HED) established an endpoint dose of 60
mg/kg/day to be used in risk assessments for workers for short- and
intermediate-term dermal exposures.  An NOAEL of 15 mg/kg/day was
established for workers and for short- and intermediate-term inhalation
exposures.  The dose for short-term exposure is the maternal NOAEL
established in the rat developmental toxicity study, whereas the dose
for intermediate-term exposure is the NOAEL established in the 90-day
dog feeding study.  A dermal absorption factor of 5 percent, derived
from the dermal absorption study, is included in the risk assessment to
account for the use of an oral endpoint for dermal exposures.
Inhalation absorption is assumed to be 100 percent.  HED selected an
NOAEL of 11 mg/kg/day for chronic dietary exposures, which was
established in the rat carcinogenicity study, and was supported by
similar results in the rat chronic dietary feeding study.  There were
significant body weight decrements and liver effects in female rats at
the LOAEL of 46.3 mg/kg/day.  Using an uncertainty factor of 100, the
chronic RfD was calculated to be 0.1 mg/kg/day.  At this time, there are
no residential uses for dimethomorph.  Therefore, discussion of dermal
and inhalation toxicity are moot for this risk assessment with respect
to residential exposures.

No appropriate toxicological endpoints attributable to a single exposure
were identified in oral studies.  Consequently, it was determined that
there was no basis for selecting a dose and endpoint for an acute RfD.

Dimethomorph has been classified as a Group E carcinogen with no
evidence of human carcinogenicity.  Therefore, a cancer risk assessment
is not required for dimethomorph and the RfD approach adequately
addresses chronic risk.

The toxicology data on dimethomorph provides no indication of enhanced
sensitivity of infants and children based on the results from
developmental studies conducted with rats and rabbits as well as a
two-generation reproduction study conducted with rats.  There were no
toxic effects observed in either the rat developmental toxicity or the
rat two-generation reproductive toxicity studies that were lower than
doses which produced toxic effects in the parents.  No developmental
toxicity was demonstrated in the rabbit developmental toxicity study.
The risk assessment team concluded that the 10-fold safety factor to
account for enhanced sensitivity of infants and children should be
removed.

The nature of dimethomorph residues in plants is adequately understood.
Dimethomorph per se is the only toxicologically significant residue.  No
acute dietary toxicity endpoints were identified; therefore, no risk
assessments for acute exposure were performed.

For crop applications, the chronic Estimated Drinking Water
Concentration (EDWC) for ground water is 0.30 ppb (from Tier I SCI-GROW
modeling).  The chronic (56-day average, including 3X adjustment factor)
EDWCs for surface water (from Tier I GENEEC modeling) is 28.5 ppb.  An
updated Estimated Drinking Water Concentration was calculated for the
proposed use on Brassica head and stem vegetables, but it is lower than
the previous value of 28.5 ppb, which was used in the dietary risk
assessment to account for the most conservative water exposure scenario.

IR-4 submitted field trial data for dimethomorph on broccoli and
cabbage.  Seven foliar applications of Acrobat 50WP (50% dimethomorph)
were applied to broccoli and cabbage at a rate of 0.20 lb a.i./A (0.224
kg a.i./ha).  Acrobat 50WP was applied to broccoli at 6 -8 day intervals
and to cabbage at 5 – 7 day intervals.  The number and locations of
field trials are in accordance with OPPTS Guideline 860.1500.

Broccoli was harvested at a 7-day pre-harvest interval (PHI).
Dimethomorph residues in the trials ranged from < 0.05 ppm (<LOQ) to
0.54 ppm on/in treated broccoli (heads and stalks) when the test
substance was applied at the seasonal application rate of 1.4 lb a.i./A
with a 7-day PHI.  Previously submitted storage stability studies
indicated that dimethomorph residues are stable on other Brassica
vegetables for up to 10 months.  Residue decline data show that
dimethomorph decreases in broccoli from ~0.5 ppm to below the LOQ in 21
days.

Cabbage was harvested at a 7-day PHI.  The number and locations of field
trials are in accordance with OPPTS Guideline 860.1500.  Dimethomorph
residues ranged from < 0.05 ppm (<LOQ) to 1.52 ppm on/in treated cabbage
heads (with wrapper leaves) when the test substance was applied at the
application rate of 1.4 lb a.i./A using a 7-day PHI.

The residue field trial studies were adequate in number and geographic
locations, conducted in accordance with the proposed use, and were
supported by appropriate storage stability data.  There are adequate
analytical methods available for tolerance enforcement.  The analytical
method used for data gathering is acceptable for that purpose.

Chronic dietary (food + water) exposure estimates for dimethomorph are
below the Agency’s level of concern for the U.S. population and all
population subgroups.  The most highly exposed population subgroup was
children 1 to 2 years old at 20 percent of the chronic Population
Adjusted Dose (cPAD).  In conducting this Tier 1 chronic dietary risk
assessment, ARIA made conservative assumptions: 1) all commodities
having dimethomorph tolerances contain residues of dimethomorph, 2)
residues will be at the level of the tolerance, and 3) 100% of the crops
are treated.  This conservative treatment of the data results in an
overestimate of human dietary exposure.  The chronic dietary risk
assessment also serves as the long-term aggregate risk assessment
because currently, there are no residential uses for dimethomorph.  At
this time, there are not any residential uses for dimethomorph.  Short-
and intermediate-term aggregate risk assessments are not required.

The residue chemistry data and the aggregate risk assessment support the
proposed tolerance for the residues of dimethomorph at 2.0 ppm on
Brassica, head and stem crop subgroup 5A.

2.0	Ingredient Profile tc \l1 "2.0	Ingredient Profile

Dimethomorph (E,Z) 4-[3-(4-chlorophenyl)-3-(3,4-
dimethoxyphenyl)-1-oxo-2-propenyl]morpholine is a systemic morpholine
fungicide.  Dimethomorph is formulated as a 50% wettable powder.  The
product may be applied by aerial, airblast, or ground sprays, or by
chemigation.  Five to seven foliar applications of the product, Acrobat
50WP, are applied at a rate of 0.20 lb a.i./A (0.224 kg a.i./ha) at 5
-10 day intervals for a maximum seasonal application rate of 1.0 -1.4 lb
a.i./A (1.12 -1.57 kg a.i./ha) with 0 - 7 day PHIs.  The 12-hour REI
that appears on the label is in compliance with the WPS based on
dimethomorph's acute toxicity ratings of category III for acute oral
toxicity and category IV for acute dermal toxicity.

2.1	Summary of Registered/Proposed Uses tc \l2 "2.1	Summary of
Registered/Proposed Uses

The tolerance expression as stated in 40 CFR 180.493 is dimethomorph,
(E,Z)4-[3-(4-chlorophenyl)-3-(3,4-dimethoxyphenyl)-1-oxo-2-propenyl]morp
holine.

The IR-4 has submitted field trial data for dimethomorph,
(E,Z)4-[3-(4-chlorophenyl)-3-(3,4-dimethoxyphenyl)-1-oxo-2-propenyl]morp
holine on Brassica, stem and head, subgroup 5A.  The proposed use
patterns are summarized in Table 2.1.

Table 2.1  Summary of Directions for Proposed Uses of Dimethomorph

Applic. Timing, Type, and Equip.

Formulation

[EPA Reg. No.]

Applic. Rate

lb a.i./A

(kg a.i./ha)

Max. No. Applic.  per Season

Max. Seasonal Applic.  Rate

lb a.i./A

(kg a.i./ha)

PHI

(days)

Use Directions and Limitations

Head and Stem Brassica Vegetables (Broccoli, Chinese broccoli, Brussels
sprouts, cabbage, Chinese cabbage (napa), Chinese mustard, cauliflower,
cavalo broccolo, kohlrabi)

Foliar spray

Acrobat 50WP [241-410]

0.2 (0.224)

7

1.4

(1.57)

7

5-7 day RTI

Potato

Aerial, airblast, ground, or chemigation

Acrobat 50WP [241-410]

0.2

(0.224)

5

1.0

(1.12)

4

5-10 day RTI, may be applied after vine kill

Fruiting Vegetables (except cucurbits)

Aerial, airblast, ground, or chemigation

Acrobat 50WP [241-410]

0.2

(0.224)

5

1.0

(1.12)

0

5-7 day RTI

Leafy Brassica

Aerial, airblast, ground, or chemigation

Acrobat 50WP [241-410]

0.2

(0.224)

5

1.0

(1.12)

0

(7 day RTI

Taro and Tanier

Aerial, airblast, ground, or chemigation

Acrobat 50WP [241-410]

0.2

(0.224)

5

1.0

(1.12)

7 for taro leaves and 30 for taro corms.

(7 day RTI

2.2	Structure and Nomenclature tc \l2 "2.2	Structure and Nomenclature

Table 2.2  Test Compound Nomenclature

Compound

	Chemical Structure

 (E/Z)

Common name	Dimethomorph

Company experimental name	AC 336379

IUPAC name
(E,Z)-4-[3-(4-chlorophenyl)-3-(3,4-dimethoxyphenyl)acryloyl]morpholine

CAS name
(E,Z)-4-[3-(4-chlorophenyl)-3-(3,4-dimethoxyphenyl)-1-oxo-2-propenyl]
morpholine

CAS #	110488-70-5

End-use product/EP	Acrobat 50WP  Fungicide, EPA Reg.  No.  241-410

2.3	Physical and Chemical Properties tc \l2 "2.3	Physical and Chemical
Properties

Table 2.3  Physical and Chemical Properties of Dimethomorph Technical
Grade Active Ingredient

Color	colorless - grey

Physical State	crystalline solid

Odor	odorless

Melting Point	125-149(C

Boiling Point	N/A; Dimethomorph is a solid

Density, Bulk Density, or Specific Gravity	1.318 g/cm3 at 20(C
(pycnometer method)

Solubility	  Solvent 	Solubility at 20(C

water, pH 5		19 mg/L

water, pH 7		18 mg/L

water, pH 9		16 mg/L

n-hexane		0.11 mg/mL

methanol		39.0 mg/mL

toluene			49.5 mg/mL

acetone			100 mg/mL

dichloromethane		461 mg/mL

Vapor Pressure	E-isomer: 9.7 x 10-7 Pa at 25(C

Z-isomer: 1.0 x 10-6 Pa at 25(C

Dissociation Constant	Not determinable (the solubility of dimethomorph
is very low, and the ionized and nonionized forms have identical
absorption coefficients)

Octanol/Water Partition Coefficient	E-isomer:  Kow = 430 (log Kow =
2.63) at 20(C

Z-isomer:  Kow = 543 (log Kow = 2.73) at 20(C

pH	Not applicable (dimethomorph is not soluble in water)

Stability	Thermally and hydrolytically stable.

Oxidizing or Reducing Action	Dimethomorph was determined to have
oxidizing properties in the sense that it can sustain a reaction with
cellulose at a burning rate higher than that of the reference mixture.

Flammability	Dimethomorph was determined to be not flammable, because it
could not be ignited with a flame.

Explodability	Dimethomorph was exposed to thermal and mechanical stress.
 No positive reaction was observed during the performance of the test.
From this it was concluded that dimethomorph is not explosive under the
conditions of the test.

Storage Stability	Dimethomorph was stable after 1 year of storage at
25oC in fiber drums lined with a polypropylene plastic liner.  The
percent compositional change was <1%.  The E/Z isomer ratio was stable.
The packaging material remained unchanged.  Dimethomorph  is chemically
stable when stored at 54(C for 14 days.  Decomposition of the test
substance was found to be less than 1%.

Viscosity	Not applicable (dimethomorph is a solid)

Miscibility	Not applicable (dimethomorph is a solid)

Corrosion Characteristics	See storage stability

3.0	Metabolism Assessment tc \l1 "3.0	Metabolism Assessment

DNums: D265124 and D265126, D. Dotson, SY. Williams-Foy, S.C. Wang,
7/27/00

3.1 	Comparative Metabolic Profile tc \l2 "3.1 	Comparative Metabolic
Profile

Oral administration of dimethomorph (10 mg/kg single dose; 10 mg/kg
14-day repeated dose; 10 mg/kg 7-day repeated dose; 500 mg/kg single
dose) results in rapid excretion into the urine and feces of rats.  For
all treatment protocols, most (80-90%) of the radiolabel administered
was excreted in the feces.  A considerably smaller amount (6-16%) was
excreted in the urine and only minimal levels (0.1-0.4%) were detected
in the organs and tissues.  Rapid absorption may be inferred by the
rapid excretion of metabolites in the urine and bile.  Saturation of
absorption following single high doses (500 mg/kg) was indicated by
large amounts ((50%) of radioactivity in the feces being associated with
parent compound.  For low- and high-dose treatments, urinary excretion
in female rats tended to be up to 2-fold greater (in low-dose rats) than
that of males.  Retention of dimethomorph or 14C-dimethomorph-derived
radioactivity was generally (1% for most tissues although the liver
exhibited slightly higher levels (1.4%) and higher levels in the
gastrointestinal tract organs was due to radioactivity in the lumenal
contents.  Urinary metabolites resulted from demethylation of the
dimethoxyphenyl ring and oxidation of the morpholine ring.  Biliary
excretion exhibited first-order kinetics with a low-dose half-life of
approximately 3 hours and a high-dose half-life of 11 hours for males
and about 6 hours for females.  Biliary metabolites accounted for most
of the fecal excretion following low-dose treatment.  The major biliary
metabolites were glucuronides of one and possibly two of the compounds
produced by demethylation of the dimethoxyphenyl ring.

3.2	Nature of the Residue in Foods tc \l2 "3.2	Nature of the Residue in
Foods

3.2.1.	Description of Primary Crop Metabolism tc \l3 "3.2.1.	Description
of Primary Crop Metabolism

No new plant metabolism studies were submitted.  Grape and potato
(D192776, D. Davis, 3/13/95; D219530, D. Davis, 10/31/95) and lettuce
(D237101, Y. Donovan, 5/4/2000) metabolism studies have previously been
submitted and reviewed.  In all three studies, parent dimethomorph was
the predominant residue.  No metabolites were identified that require
regulation.  For purposes of this petition, the residue of concern for
tolerance setting and risk assessment purposes is considered to be
parent dimethomorph (sum of E and Z isomers).

3.2.2	Description of Livestock Metabolism tc \l3 "3.2.2	Description of
Livestock Metabolism

Based on the results of metabolism studies in ruminants and poultry and
a cattle feeding study, tolerances are not required for residues in
meat, milk, poultry and eggs as a result of ingestion of dimethomorph
residues in the rotational cereal grains (D251605 and D252556, D.
Dotson, 7/19/00).  Furthermore, there are no head and stem Brassica feed
items of regulatory interest.  Therefore, a discussion of the nature of
the residues of dimethomorph in livestock is not germane to this action.

3.2.3	Description of Rotational Crop Metabolism, including
identification of major metabolites and specific routes of
biotransformation tc \l3 "3.2.3	Description of Rotational Crop
Metabolism, including identification of major metabolites and specific
routes of biotransformation

A dimethomorph confined rotational crop study has previously been
submitted and reviewed (D251605 and D252556, D. Dotson, 7/19/00).  As a
result, the Acrobat 50WP labeling contains rotational crop guidelines
indicating plantback intervals ranging from Any Time to Twelve Months,
depending on the crop to be rotated.

3.3 	Environmental Degradation tc \l2 "3.3 	Environmental Degradation

DNums: D265124 and D265126, D. Dotson, SY. Williams-Foy, S.C. Wang,
7/27/00

EFED used the Generic Estimated Environmental Concentration (GENEEC)
Model to estimate acute and chronic EDWCs of dimethomorph residues in
surface water.  This model simulates the transport of a pesticide off
the agricultural field.  EFED calculated a Tier I chronic (56-day
average with 3X factor) EDWC of 28.5 ppb for dimethomorph.

A revised risk drinking water assessment conducted for the proposed use
on Brassica stem and head vegetables, Group 5A (D328742, J. L.
Meléndez, 4/26/06) recommended a value of 0.264 ppb for use in the
chronic risk assessment.  However, the previous value for residues in
water of 28.5 ppb estimated for Brassica leafy vegetables (Group 5B),
and fruiting vegetables (Group 8) was used in the chronic dietary risk
assessment to ensure safety under the most conservative water exposure
scenario.

3.4	Toxicity Profile of Major Metabolites and Degradates  tc \l2 "3.4
Toxicity Profile of Major Metabolites and Degradates

As described in Section 3.2.1, parent dimethomorph is the only compound
of toxicological interest.

3.5	Summary of Residues for Tolerance Expression and Risk Assessment tc
\l2 "3.5	Summary of Residues for Tolerance Expression and Risk
Assessment

Table 3.5  Summary of Metabolites and Degradates to be included in the
Risk Assessment and     Tolerance Expression

Matrix	Residues included in Risk Assessment	Residues included in
Tolerance Expression

Plants	Primary Crop	Dimethomorph, parent	Dimethomorph, parent

Livestock	Ruminant	N/A	N/A

	Poultry	N/A	N/A

Drinking Water - values used as residue values in the DEEM dietary
exposure analysis	0.0285 ppm, surface water	Not Applicable

4.0  Hazard Characterization/Assessment tc \l1 "4.0  Hazard
Characterization/Assessment

DNums: D265124 and D265126, D. Dotson, SY. Williams-Foy, S.C. Wang,
7/27/00

4.1	Hazard Characterization tc \l2 "4.1	Hazard Characterization

At low and high doses tested, dimethomorph was rapidly absorbed and
rapidly excreted into the urine and feces.  Urinary excretion tended to
be greater in the females.

The following table summarizes the acute toxicity of the technical grade
of the active ingredient of dimethomorph.  As demonstrated, technical
dimethomorph is relatively non-toxic when administered acutely to
laboratory animals.

Table 4.1a  Acute Toxicity Profile - Test Substance

Guideline No.	Study Type	MRID(s)	Results	Toxicity Category

870.1100	Acute oral [Rat]	42233902	LD50 = 3900 (3300-4500) mg/kg (M,F)
III

870.1200	Acute dermal [Rat]	42233903	LD50 => 5000  mg/kg	IV

870.1300	Acute inhalation [Rat]	42233904	LC50 => 4.24 mg/L	III

870.2400	Acute eye irritation [Rabbit]	42233905	Conjunctival irritation
clearing in 4 days	III

870.2500	Acute dermal irritation [Rabbit]	42233907	No irritation
reported	IV

870.2600	Skin sensitization [Guinea pig]	42233906	Not a sensitizer

Table 4.1b  Subchronic, Chronic and Other Toxicity Profile

Guideline No./ Study Type	MRID No.  (year)/ Classification /Doses
Results

870.3100

90-Day oral toxicity (dog)	422339081 (1991)

Acceptable/guideline

0, 150, 450, 1350 ppm

M: 0, 5, 15, 43 mg/kg/day

F: 0, 6, 15, 44 mg/kg/day	NOAEL = 15 mg/kg/day

LOAEL = 43 mg/kg/day based on decrease in the absolute and relative
weights of the prostate and possible threshold liver effects.

870.3150

90-Day oral toxicity (rat)	42233910 (1991)

Core minimum

0, 40, 200, 1000 ppm

M: 0, 2.9, 14.2, 73 mg/kg/day

F: 0, 3.2, 15.8, 82 mg/kg/day	NOAEL >73/82 (M/F) mg/kg/day

LOAEL was not established in this study, because the highest dose tested
produced no biologically significant effects.

870.3700a

Prenatal developmental in (rabbit)	42233918 (1989)

Unacceptable/core

supplemental (Initial rating)

0, 135, 300, 650 mg/kg/day	Maternal NOAEL = 300 mg/kg/day

LOAEL = 650 mg/kg/day based on an increased incidence of abortion
confirmed in a rangefinding study.

Developmental NOAEL could not be determined.

LOAEL could not be determined.

870.3700b

Prenatal developmental in (rabbit)	4175303

Acceptable

Information supplemental to MRID# 42233918	Maternal NOAEL = 300
mg/kg/day

LOAEL = 650 mg/kg/day based on an increased incidence of abortion
confirmed in a rangefinding study.

Developmental NOAEL =650 mg/kg/day (highest dose tested).

LOAEL could not be determined - no effects observed at highest dose
tested.

870.3700c

Prenatal developmental in (rat)	42233919 (1989)

Unacceptable/core

supplemental (Initial rating)

0, 20, 60, 160 mg/kg/day	Maternal NOAEL = 60 mg/kg/day

LOAEL = 160 mg/kg/day based on reductions in food consumption, mean body
weights and body weight gain.

Developmental NOAEL could not be determined

LOAEL = could not be determined.

870.3700d

Prenatal developmental in (rat)	44175302

Acceptable

Information supplemental to MRID# 42233919	Maternal NOAEL = 60 mg/kg/day

LOAEL = 160 mg/kg/day based on reductions in food consumption, mean body
weights and body weight gain.

Developmental NOAEL = 60 mg/kg/day

LOAEL = 160 mg/kg/day based on the incidence of post implantation loss

870.3800

Reproduction and fertility effects

(rat)	42233920 (1990)

Acceptable/guideline

0, 100, 300, 1000 ppm	Parental/Systemic NOAEL = 300 ppm

LOAEL = 1000 ppm based on decreased body weights and body weight gains.

Reproductive NOAEL = 300 ppm

LOAEL = 1000 ppm based on decreased incisor eruption on day 10
postpartum.

Offspring NOAEL was not reported

LOAEL was not reported.

870.4100a

Chronic toxicity

(rat)	42233912 (1991)

Acceptable/guideline

0, 150, 450, 1350 ppm

M: 0, 9.4, 36.2, 99.9 mg/kg/day

F: 0, 11.9, 57.7, 157.8 mg/kg/day	NOAEL = 36.2/11.9 (M/F) mg/kg/day

LOAEL = 57.7/99.9 (M/F) mg/kg/day  based on decreased body weight and
increased incidence of arteritis in male rats and  decreased body weight
and significant increased incidence of "ground-glass" foci in the liver
in female rats.

870.4100b

Chronic toxicity (dog)

	42233911 (1991)

Acceptable/guideline

0, 150, 450, 1350 ppm

M: 0, 4.9, 14.7, 44.6 mg/kg/day

F: 0, 5.0, 15.7, 47.0 mg/kg/day	NOAEL = 14.7 mg/kg/day

LOAEL = 44.6mg/kg/day based on decreased prostate weight.

870.4200

Carcinogenicity

(rat)	42233916 (1991)

Acceptable/guideline

0, 200, 750, 20000 ppm

M: 0, 8.8, 33.9, 94.6 mg/kg/day

F: 0, 11.3, 46.3, 132.5 mg/kg/day	NOAEL (systemic) = 36.2/11.9 (M/F)
mg/kg/day

LOAEL (systemic) = 94.6/46.3 (M/F) mg/kg/day based on  decreased body
weight, gross and microscopic lesions in blood vessels, and liver
lesions in males and decreased body weight, gross and microscopic
lesions blood vessels, bone marrow hypercellularity, and liver lesions
in females.

There was no evidence of carcinogenicity

870.4300

Carcinogenicity

(mouse)	42233914 (1991)

Acceptable/guideline

0, 10, 100, 1000 mg/kg/day	NOAEL = 100 mg/kg/day

LOAEL (systemic) = 1000 mg/kg/day based on decreased body weight gain in
males.

There was no evidence of carcinogenicity

Gene Mutation

870.5100a	42233921 (1985)

Acceptable	Negative for inducing reverse gene mutation in either
Salmonella his- mutants or E.  coli trp-cells exposed beyond
precipitating concentrations (500 ug/plate), up to the limit dose, 5000
ug/plate, w/without metabolic activation.

Gene Mutation

870.5100b	42233926 (1989)

Acceptable	Negative for inducing reverse gene mutation in Salmonella TA
strains and E.  coli WP2 uvr A exposed, with/without activation, up to
5000 ug/plate.

In vitro mammalian cell gene mutation test

870.5300a	42233923 (1987)

Acceptable	Negative for inducing foreword mutation at the
hypoxanthine-guanine phosphoribosyl transferase locus in Chinese hamster
lung (V79) cells treated up to cytotoxic levels (230 ug/ml/-S9; 300
ug/ml/+S9).

In vitro mammalian cell gene mutation test

870.5300b	42233927 (1991)

Acceptable	Negative for inducing foreword mutation at the
hypoxanthine-guaninephosphoribosyl transferase (HGPRT) locus in Chinese
hamster lung (V79) exposed, with/without activation, up to cytotoxic
concentrations (180 ug/ml/-S9; 333 ug/ml/+S9).

In vitro mammalian chromosome aberration test

870.5375a	42233924 (1986)

Unacceptable	Reportedly positive for chromosome aberrations at the
highest doses tested (160 ug/ml/-S9; 170 ug/ml/+S9).

In vitro mammalian chromosome aberration test

870.5375b	42233925 (1987)

Acceptable	[Confirmatory repeat of Study LMP-180 C, MRID 422339-24].
Positive for increased chromosome aberrations at high doses (160
ug/ml/-S9; 170 ug/ml/+S9).

In vitro mammalian chromosome aberration test

870.5375c	42233928 (1991)

Acceptable	Presumptively (weakly) positive, but only in activated
cultures treated at the HDT, in human lymphocyte cultures treated up to
the highly toxic dose, 422 ug/ml; negative in the absence of activation
at all doses.

Mammalian erythrocyte micronucleus test

870.5395a	42233930 (1991)

Acceptable	Negative for inducing micronuclei in bone marrow cells of
mice administered test article i.p.  up to severely toxic levels (200
mg/kg).

Mammalian erythrocyte micronucleus test

870.5395b	42233931 (1989)

Acceptable	Negative for inducing micronuclei in bone marrow cells of
mice treated orally at the limit dose, 5000 mg/kg.

Mutagenicity - DNA damage/repair in vitro

870.5500	42233922 (1986)

Unacceptable	Reportedly negative for inducing unscheduled DNA synthesis
(as measured by liquid scintillation counting) in rat hepatocytes
cultured (for only 3 hours) at doses up to 250 ug/ml, a weakly cytotoxic
level.

Other Effects - Morphologic transformation of cells in culture

870.8800	42233929 (1986)

Acceptable	Negative for transformation in Syrian hamster embryo cells
treated, in the presence and absence of activation,  up to cytotoxic
concentrations (265 ug/ml/+S9; 50 ug/ml/-S9)

870.7485

Metabolism and pharmacokinetics

(rat)	42233932 (1994)

Acceptable

10 mg/kg single dose; 10 mg/kg 14-day repeated dose; 10 mg/kg 7-day
repeated dose; 500 mg/kg single dose	Oral administration of dimethomorph
results in rapid excretion into the urine and feces of rats.  For all
treatment protocols, most (80-90%) of the radiolabel administered was
excreted in the feces.  A considerably smaller amount (6-16%) was
excreted in the urine and only minimal levels (0.1-0.4%) were detected
in the organs and tissues.  Rapid absorption may be inferred by the
rapid excretion of metabolites in the urine and bile.  Saturation of
absorption following single high doses (500 mg/kg) was indicated by
large amounts ((50%) of radioactivity in the feces being associated with
parent compound.  For low- or high-dose treatment, urinary excretion in
female rats tended to be greater (up to 2-fold in low-dose rats) than
that of male rats.  Retention of dimethomorph or
14C-dimethomorph-derived radioactivity was generally (1% for most
tissues although the liver exhibited slightly higher levels (1.4%) and
higher levels in the gastrointestinal tract organs was due to
radioactivity in the lumenal contents.  Urinary metabolites resulted
from demethylation of the dimethoxyphenyl ring and oxidation of the
morpholine ring.  Biliary excretion exhibited first-order kinetics with
a low-dose (10 mg/kg) half-life of approximately 3 hours and a high-dose
(500 mg/kg) half-life of 11 hours for males and about 6 hours for
females.  Biliary metabolites accounted for most of the fecal excretion
following low-dose treatment.  The major biliary metabolites were
glucuronides of one and possibly two of the compounds produced by
demethylation of the dimethoxyphenyl ring.  The report provided a
proposed metabolic pathway for dimethomorph.

870.7600

Dermal penetration

(rat)	43917221 (1995)

Acceptable/guideline

7.73 (2.5% w/v aqueous suspension) or 79.62 (25% w/v aqueous suspension)
mg/kg.	The total amount of dimethomorph absorbed (expressed as percent
of 14C-dose) from rats at various times following dermal administration
of 14C-CL 336,379 at 7.73 (0.15 mg/cm2) or 79.62 mg/kg (1.58 mg/cm2) is
less than 5% of the dose and it appears that the absorption is
concentration dependent.  Dermal absorption was 0.05%, 0.07% and 0.27%
of the administered dose from rats 4, 8, and 24 hours after dermal
treatment at 7.73 mg/kg, respectively.  Dermal absorption was 0.02%,
0.16% and 0.12% of the dose 4, 8, and 24 hours after dermal treatment at
79.62 mg/kg, respectively.  Dermal absorption was approximately 0.4 and
1 mg/kg in terms of weight equivalent at 7.73 and 79.62 mg/kg,
respectively.  Six days after dermal treatment, the percent total
absorption of the dose in the 7.73 and 79.62 mg/kg was 4.76 and 1.20%,
respectively.  Mean percent recovery of 14C for dose levels of 7.73 and
79.62 mg/kg was 104.1% and 92.1%, respectively.  Majority of the
radioactivity was found in skin swabs and gauze wash (80.9 to 81.8%).
The percent of the dose in the skin decreased with dose; at 7.73 mg/kg
17.5% and at 79.62 mg/kg 9.99%

4.2	FQPA Hazard Considerations tc \l2 "4.2	FQPA Hazard Considerations

TXR# 012616, J. E. Stewart and J. Rowland, 5/13/98

TXR# 012649, B. Tarplee and J. Rowland, 6/10/98

4.2.1	Adequacy of the Toxicity Data Base tc \l3 "4.2.1	Adequacy of the
Toxicity Data Base

There are no data gaps for the assessment of the effects of dimethomorph
following in utero and/or postnatal exposure.  Based on the toxicity
profile for dimethomorph, a developmental neurotoxicity study in rats is
not required.

4.2.2	Evidence of Neurotoxicity tc \l3 "4.2.2	Evidence of Neurotoxicity

There are no series 81-8 (acute, OPPTS 798.6050) and 82-7 (subchronic,
OPPTS 798.6200) neurotoxicity studies available.  However, there was no
evidence of neurotoxicity observed in the submitted studies.  It is
noted that the post implantation loss in the rat developmental toxicity
study is not considered to be of toxicological significance since it was
not supported by decreased litter size in the high dose group as
compared to the controls; there was no developmental toxicity in the
rabbit developmental toxicity study, and no effect in the pups in the
two generation reproduction study.

4.2.3	Developmental Toxicity Studies tc \l3 "4.2.3	Developmental
Toxicity Studies

It has been determined that the available studies indicate no increased
susceptibility of rats or rabbits to in utero and/or postnatal exposure
to dimethomorph.  In the prenatal developmental toxicity studies in rats
and rabbits and in the two-generation reproduction study in rats,
developmental toxicity to the offspring occurred at equivalent or higher
doses than maternal toxicity

4.2.4	Reproductive Toxicity Study tc \l3 "4.2.4	Reproductive Toxicity
Study

In a multi-generation reproductive toxicity study, the P generation
animals were mated in a one to one ratio and given the test material for
15 weeks before they were mated.  Selection of the parents for the F1
generation was made shortly after weaning on day 21 post-partum.  The P1
animals were mated when they were approximately 21 weeks of age, while
the F1 generation was mated at about 15 weeks of age.

No clinical signs or necropsy findings were noted at any dose level in
parental animals which could be associated with administration of the
test material.  At 1000 ppm, P generation females weighed consistently
less than controls throughout the 15 week premating period (p <0.05).
Statistically significant reductions in food consumption were also noted
in 1000 ppm females during the premating period.  In F1 females, body
weights were slightly lower in all the dose groups but differences were
not statistically significant.  At the 1000 ppm level, during several
intervals of the premating period, female weight gain was reduced (p <
0.05).  No effects were apparent in males of the P or F1 generations.
For parental systemic toxicity, the NOEL was 300 ppm and the LOEL was
1000 ppm based upon decreased body weights and body weight gains.

Reproductive indices were not affected by treatment at any dose level or
mating.  The percentage of pups with incisor eruption was noted at the
1000 ppm dose level in the F1, F2a and F2b generations with
non-significant delays observed at the lower dose levels.  During the
second mating of the F1 generation to produce the F2b generation, a
large number of inseminated females failed to deliver.  This finding
appeared to occur in a dose related manner at all dose levels but was
not apparent during other matings.  It should be noted that the prostate
gland was apparently affected by the test material in the dog chronic
feeding study and the organ was not weighed in the chronic rat study.
No organ weight data were presented for the prostate gland in this
reproduction study but no dose related histopathology data were apparent
in this study.  For reproductive toxicity, the NOAEL was 300 ppm and the
LOAEL was 1000 ppm based upon decreased incisor eruption on day 10
postpartum.

4.2.5	Additional Information from Literature Sources tc \l3 "4.2.5
Additional Information from Literature Sources

There is no additional information available from the literature to
influence FQPA safety findings.

4.2.6  Pre-and/or Postnatal Toxicity tc \l3 "4.2.6  Pre-and/or Postnatal
Toxicity

<IP_ADDRESS>	Determination of Susceptibility tc \l4 "<IP_ADDRESS>	Determination of
Susceptibility

The data available do not provide evidence of any increased
susceptibility in the offspring in either of the two developmental
toxicity studies, or in the two generation reproduction study.  In none
of these studies was any toxicity seen in the offspring which occurred
at doses lower than in the parents.

4.3	Recommendation with Respect to a Developmental Neurotoxicity Study
tc \l2 "4.3	Recommendation for a Developmental Neurotoxicity Study

None of the submitted studies indicate that dimethomorph is a neurotoxic
chemical.  Neither the subchronic or chronic toxicity studies in rats or
dogs, nor the developmental toxicity studies indicated that the nervous
system was affected by treatment with dimethomorph.  There is no
indication that dimethomorph is a neurotoxic chemical and there is no
need for additional uncertainty factors to account for neurotoxicity.

4.4	Hazard Identification and Toxicity Endpoint Selection tc \l2 "4.4
Hazard Identification and Toxicity Endpoint Selection

4.4.1   Acute Reference Dose (aRfD) - Females age 13-49 tc \l3 "4.4.1
Acute Reference Dose (aRfD) - Females age 13-49

In a developmental toxicity study in rats (MRID No. 42233919), the NOAEL
for developmental toxicity was 60 mg/kg/day based on post implantation
loss at 160 mg/kg/day.  It was determined that this endpoint is not
appropriate for use in this risk assessment, since the effect at the
high dose was minimal and was not supported by decrement in litter size
(12.4 fetuses per dam in the control compared to 11.3 fetuses per dam at
the high dose).  The maternal effects (decreased body weight gain and
food consumption) were not considered to be attributable to a single
exposure and thus not appropriate for this risk assessment.  No
appropriate toxicological endpoints attributable to a single exposure
were identified in other oral studies.  Consequently, it was determined
that there was no basis for selecting a dose and endpoint for an acute
RfD.  An acute dietary risk assessment is not required for females 13 to
49 years old.

4.4.2	Acute Reference Dose (aRfD) - General Population tc \l3 "4.4.2
Acute Reference Dose (aRfD) - General Population

No appropriate toxicological endpoints attributable to a single exposure
were identified in oral studies.  Consequently, there was no basis for
selecting a dose and endpoint for an acute RfD.  An acute dietary risk
assessment is not required for any segment of the US population,
including infants and children.

4.4.3	Chronic Reference Dose (cRfD)  tc \l3 "4.4.3	Chronic Reference
Dose (cRfD)  (MRID Nos.  42233912 and 42233916)

The Data Evaluation Records (DERs) for the rat chronic and rat
carcinogenicity studies established identical NOAELs (11 mg/kg/day) and
endpoints of  increased incidences of pigmented or hypertrophied
hepatocytes and “ground glass” foci in livers of female rats.
Females appeared to be more sensitive in these studies.  A comparable
NOAEL (15 mg/kg/day) was also established in the chronic toxicity study
in which the liver was the target organ (increased alkaline phosphatase
activity).

Dose and Endpoint for Establishing the RfD : NOAEL= 11 mg/kg/day based
on decreased body weight and statistically significant increases in
liver lesions in female rats at 46.3 mg/kg/day (LOAEL).

Uncertainty Factor(s):  100 (10 for inter-species extrapolation and 10
for intra-species variation)

Chronic RfD = 	11 mg/kg/day (NOAEL) = 0.1 mg/kg/day

				100  (UF)

4.4.4	Incidental Oral Exposure (Short and Intermediate Term) tc \l3
"4.4.4	Incidental Oral Exposure (Short and Intermediate Term)

There are no residential uses for dimethomorph, and a toxicity endpoint
for incidental oral exposure is not necessary.

4.4.5	Dermal Absorption tc \l3 "4.4.5	Dermal Absorption

The total amount of dimethomorph absorbed (expressed as percent of
14C-dose) from rats at various times following dermal administration of
14C-CL 336,379 at 7.73 (0.15 mg/cm2) or 79.62 mg/kg (1.58 mg/cm2) is
less than 5% of the dose and it appears that the absorption is
concentration dependent.  Dermal absorption was 0.05%, 0.07% and 0.27%
of the administered dose from rats 4, 8, and 24 hours after dermal
treatment at 7.73 mg/kg, respectively.  Dermal absorption was 0.02%,
0.16% and 0.12% of the dose 4, 8, and 24 hours after dermal treatment at
79.62 mg/kg, respectively.  Dermal absorption was approximately 0.4 and
1 mg/kg in terms of weight equivalent at 7.73 and 79.62 mg/kg,
respectively.  Six days after dermal treatment, the percent total
absorption of the dose in the 7.73 and 79.62 mg/kg was 4.76 and 1.20%,
respectively.  Mean percent recovery of 14C for dose levels of 7.73 and
79.62 mg/kg was 104.1% and 92.1%, respectively.  Majority of the
radioactivity was found in skin swabs and gauze wash (80.9 to 81.8%).
The percent of the dose in the skin decreased with dose; 17.5 % at 7.73
mg/kg and 9.99% at 79.62 mg/kg dose.

The dermal absorption coefficient factor is 5%.

4.4.6	Dermal Exposure (Short, Intermediate and Long Term) tc \l3 "4.4.6
Dermal Exposure (Short, Intermediate and Long Term)

No dermal toxicity studies are available.  The maternal toxicity NOAEL
is 60 mg/kg/day based on decreased body weight, decreased body weight
gain, and decreased food consumption at 160 mg/kg/day (LOAEL) in an oral
developmental toxicity study.  The effects seen in the dams during
gestation days 10-15 (i.e., after 4-5 dosing) are appropriate for use
for short-term exposure periods (i.e., 1-30 days).  Since an oral NOAEL
was selected, a dermal absorption factor of 5% should be used in
calculating the risk from dermal exposure.

The NOAEL is 15 mg/kg/day, based on decreased absolute and relative
prostate weight and possible threshold liver effects at the LOAEL of 43
mg/kg/day in a subchronic oral feeding study in dogs.  A subchronic
feeding study was selected, so a dermal absorption factor of 5% should
be chosen from the dermal penetration study in performing
intermediate-term (30 days to six months) risk assessments.

The current use pattern does not indicate a concern for long-term
exposure/risk and no long-term uses are proposed.  Therefore, this risk
assessment is not required.

4.4.7	Inhalation Exposure (Short, Intermediate and Long Term) tc \l3
"4.4.7	Inhalation Exposure (Short, Intermediate and Long Term)

There are no inhalation studies, except for the acute toxicity study
(MRID No. 43917246).  Therefore, the oral NOAELs described above for
dermal risk assessment were selected for short-and intermediate term
inhalation risk assessments.  The use pattern does not indicate a need
for long-term risk assessment.  Since oral NOAELs were selected,
appropriate route-to-route extrapolation should be followed as shown
below:

Step I.		The inhalation exposure component (i.e. μg a.i. /day) using
100% absorption rate should be converted to an equivalent oral dose
(mg/kg/day).

Step II.		The dermal exposure component (mg/kg/day) using a 100% dermal
absorption rate should be converted to an equivalent oral dose.  This
dose should then be combined with the oral dose in Step I.

Step III.  	The combined dose from Step II should then be compared to
the  oral NOAEL of 60 mg/kg/day for short-term and 15 mg/kg/day for
intermediate term risk assessments.

4.4.8	Margins of Exposure tc \l3 "4.4.8	Margins of Exposure

Target Margins of Exposure are 100 for dermal (short- and
intermediate-term) and inhalation (short- and intermediate-term)
exposures.

4.4.9	Recommendation for Aggregate Exposure Risk Assessments tc \l3
"4.4.9	Recommendation for Aggregate Exposure Risk Assessments

There are no registered residential uses at the present time, nor are
any proposed.  Therefore, at this time, dietary (food + water) exposure
will be the only component of an aggregate exposure analysis and risk
assessment.

4.4.10	Classification of Carcinogenic Potential tc \l3 "4.4.10
Classification of Carcinogenic Potential

In a carcinogenicity study in rat, there was no evidence of increased
incidence of any neoplasms at the doses tested.  The chemical was tested
at adequate dosage, based on the high incidence of arteritis in males,
and the pronounced decrease in body weight in females at the mid and
high dose levels.

In a carcinogenicity study in mice, there was no dose related decrease
in survival or in any parameter examined on necropsy.  The LOAEL for
systemic toxicity was 1000 mg/kg/day based on decreased body weight gain
in males.  The NOAEL was 100 mg/kg/day.  There was no evidence of
carcinogenicity.  The high dose tested (1000 mg/kg/day), while probably
not the maximum tolerated dose, especially in females, is the maximum
dose required by the test guidelines for a dietary oncogenicity study.

Dimethomorph has been classified “Not Likely” to be a human
carcinogen.

The toxicity endpoints pertinent to an assessment of risk for
dimethomorph are summarized in Table 4.4.

TableTable 4.4  Summary of Toxicological Dose and Endpoints for
Dimethomorph 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 13-49)	No endpoint attributable to a single dose
was identified	Not applicable	No study selected.

Acute Dietary (general population)	No endpoint attributable to a single
dose was identified	Not applicable	No study selected

Chronic Dietary (all populations)	NOAEL= 11 mg/kg/day

UF = 100

Chronic RfD =

0.1 mg/kg/day

	FQPA SF = 1

cPAD =

chronic RfD

 FQPA SF

= 0.1 mg/kg/day	Oncogenicity Study in the Rat

LOAEL = 46.3 mg/kg/day based on decreased body weight and statistically
significant increases in liver lesions in female rats.

Dermal Short-Term (1 - 30 days)	oral study NOAEL=

60 mg/kg/day

(dermal absorption factor = 5 %)	LOC for MOE =

100 	Developmental Toxicity Study in the Rat

LOAEL = 160 mg/kg/day based on decreased body weight, decreased body
weight gain, and decreased food consumption.

Dermal Intermediate-Term (1 - 6 months)	oral study NOAEL=

15 mg/kg/day

(dermal absorption factor = 5 %	LOC for MOE =

100	Subchronic Feeding Study in Dogs

LOAEL = 43 mg/kg/day based on decreased absolute and relative prostate
weight and possible threshold liver effects.

Dermal Long-Term (> 6 months)	The current use pattern does not indicate
a concern for long-term exposure/risk.	Not applicable	No study selected

Inhalation Short-Term (1 - 30 days)	oral study NOAEL=

60 mg/kg/day

(inhalation absorption factor = 100 %)	LOC for MOE =

100	Developmental Toxicity Study in the Rat

LOAEL = 160 mg/kg/day based on decreased body weight, decreased body
weight gain, and decreased food consumption.

Inhalation Intermediate-Term (1 to 6 months)	oral study NOAEL=

15 mg/kg/day

(inhalation absorption rate = 100%)	LOC for MOE =

100	Subchronic Feeding Study in Dogs

LOAEL = 43 mg/kg/day based on decreased absolute and relative prostate
weight and possible threshold liver effects.

Inhalation Long-Term (> 6 months)	The current use pattern does not
indicate a concern for long-term exposure/risk.	Not applicable	No study
selected

Cancer (oral, dermal, inhalation)	Classification: This chemical is
classified as “not likely” to be a human carcinogen.

UF = uncertainty factor, FQPA SF = FQPA safety factor, NOAEL = no
observed adverse effect  level, LOAEL = lowest observed adverse effect
level, PAD = population adjusted dose (a = acute, c = chronic) RfD =
reference dose, MOE = margin of exposure, LOC = level of concern, NA =
Not Applicable

* Refer to Section 4.5

4.5	FQPA Safety Factor tc \l2 "4.5	Special FQPA Safety Factor

Initially (May 4, 1998), the former FQPA Safety Committee determined
that a safety factor is necessary based on the lack of environmental
fate data required for the drinking water exposure assessment of
dimethomorph.  However, EFED assured the Committee that even assuming
the worst possible model input parameters for dimethomorph, risk levels
for drinking water exposure are not of concern.  Considering this, on
June 8, 1998, the Committee recommended that the 10x Safety Factor
should be removed.

The environmental fate data issue was addressed in an EFED Memorandum
(D285766, D288920 and D286100; Section 3 and IR-4 registration for the
New Uses of dimethomorph for use on fruiting vegetables (except
cucurbits), leafy brassica greens subgroup, taro and anier; N.E.
Federoff & José Luis Meléndez).

Additionally: 1) the developmental and reproductive toxicity data did
not indicate increased susceptibility of rats or rabbits to in utero
and/or postnatal exposure to dimethomorph; 2) the dietary (food only)
exposure assessment did not indicate a concern for potential risk to
infants and children since unrefined field study data are used,
resulting in an overestimate of dietary exposure; and 3) there are
currently no registered residential uses for dimethomorph.

4.6	Endocrine disruption tc \l2 "4.6	Endocrine disruption

EPA is required under the 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 recommendations of its Endocrine Disruptor and Testing
Advisory Committee (EDSTAC), EPA determined that there was a scientific
basis 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 to 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 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).

In the available toxicity studies on dimethomorph, there was no
estrogen, androgen, and/or thyroid mediated toxicity.

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

5.0	Public Health Data tc \l1 "5.0	Public Health Data

5.1	Incident Reports tc \l2 "5.1	Incident Reports

A review of the Incident Data System (1992 to August, 2005), California
(1982-2003), NIOSH state data (1998-2003), and the scientific literature
did not report any dimethomorph incidents.  Of over a million exposures
reported from 1993 through 2003, the poison Control Center data

6.0  Exposure Characterization/Assessment tc \l1 "6.0  Exposure
Characterization/Assessment

6.1	Dietary Exposure/Risk Pathway tc \l2 "6.1	Dietary Exposure/Risk
Pathway

DNum: D316591, W. Cutchin, 7/18/05

6.1.1	Residue Profile tc \l3 "6.1.1	Residue Profile

Residues of dimethomorph were quantitated using BASF Draft Method M
3502, “LC/MS/MS Method for the Determination of BAS 550 F in Broccoli,
Cabbage, Celery, and Spinach.”  Broccoli samples are extracted with
acetone and purified by solid phase extraction.  Quantitation was
accomplished by liquid chromatography and positive ion electrospray
two-stage mass spectrometry (LC/MS/MS).  Samples of control broccoli
were fortified at levels ranging from 0.05 to 5.0 ppm.  The LOQ was 0.05
ppm and the LOD was 0.01 ppm for broccoli.  The percent recovery of
dimethomorph in broccoli ranged from 73-110%.  The method is adequate
for data collection.

IR-4 submitted field trial data for dimethomorph on broccoli.  Seven
foliar applications of Acrobat 50WP (50% dimethomorph) were applied at a
rate of 0.20 lb a.i./A (0.224 kg a.i./ha) at 6 -8 day intervals (1.4 lb
a.i./A/season, 1.57 kg a.i./ha/season).  The number and locations of
field trials are in accordance with OPPTS Guideline 860.1500.

Broccoli was harvested at a 7-day pre-harvest interval (PHI).  The
results from these trials show that dimethomorph residues ranged from <
0.05 ppm (<LOQ) to 0.54 ppm on/in treated broccoli (heads and stalks),
when the test substance was applied at the seasonal application rate of
1.4 lb a.i./A with a 7-day PHI.  Previously submitted storage stability
studies indicated that dimethomorph residues are stable on other
Brassica vegetables for up to 10 months.  Residue decline data show that
dimethomorph decreases in broccoli from ~0.5 ppm to below the LOQ in 21
days.

IR-4 also submitted field trial data for dimethomorph on cabbage.  Seven
foliar applications of Acrobat 50WP (50% dimethomorph) were applied at a
rate of 0.20 lb a.i./A (0.224 kg a.i./ha) at 5 -7 day intervals (1.4 lb
a.i./A/season, 1.57 kg a.i./ha/season).  No adjuvants or additives were
added to the spray mixture for any of the above applications, except the
Georgia trial, in which the adjuvant Latron B-1956 was added.  Cabbage
was harvested at a 7-day pre-harvest interval (PHI).  The number and
locations of field trials are in accordance with OPPTS Guideline
860.1500.

The results from these trials show that dimethomorph residues ranged
from < 0.05 ppm (<LOQ) to 1.52 ppm on/in treated cabbage heads (with
wrapper leaves), when the test substance was applied at the application
rate of 1.4 lb a.i./A using a 7-day PHI.  Cabbage was stored frozen for
a maximum of 11.1 months at < –10ºC.  The petitioner indicated that
in an interim storage stability study, residues of dimethomorph in
broccoli are stable for the duration of the study.  However, no data
were submitted.  Previously submitted storage stability studies
indicated that dimethomorph residues are stable on other Brassica
vegetables for up to 10 months.  Residue decline data show that
dimethomorph decreases in cabbage from 1.30 ppm to 0.324 ppm in 21 days.

The residue field trial studies were adequate in number and geographic
locations, conducted in accordance with the proposed use, and were
supported by appropriate storage stability data.  There are adequate
analytical methods available for tolerance enforcement.  The analytical
method used for data gathering is acceptable for that purpose.  The
residue chemistry data support the proposed tolerance for the residues
of dimethomorph at 2.0 ppm on Brassica, head and stem crop subgroup 5A

This chronic assessment was based on the assumption of tolerance-level
residues for all commodities with existing and proposed tolerances.  The
existing dimethomorph tolerances are listed in 40 CFR §180.493.  The
registrant is currently proposing tolerances for Brassica, head and
stem, crop subgroup 5A at 2.0 ppm.  For this analysis the proposed
tolerance levels and 100 % crop treated (CT) for all commodities were
used.  Tolerances are not being recommended for animal commodities as a
result of the proposed uses.

DEEM default processing factors from DEEM (Version 7.76) were used for
all processed commodities that do not have individual tolerances.

6.1.2	Acute and Chronic Dietary Exposure and Risk tc \l3 "6.1.2	Acute
and Chronic Dietary Exposure and Risk

An acute dietary risk assessment was not conducted because an acute
endpoint was not identified for any segment of the U.S. population.

A chronic dietary risk assessment was conducted using the Dietary
Exposure Evaluation Model (DEEM-FCID(, Version 2.00), which uses food
consumption data from the USDA’s Continuing Surveys of Food Intakes by
Individuals (CSFII) from 1994-1996 and 1998.  The analysis was performed
to support the Section 3 requests for the use on Brassica, head and stem
crop subgroup 5A.

The Tier 1 chronic dietary analysis for dimethomorph is a conservative
estimate of dietary exposure with tolerance level residues and 100% crop
treated.  The risk estimate from chronic dietary exposure to
dimethomorph as represented by the % population adjusted dose (PAD) is
below the Agency’s level of concern for the U.S. population and all
population subgroups.  The exposure estimate of the U.S. population is
9% of the cPAD.  The exposure estimate for the most highly exposed
subpopulation (children 1-2 years) is 20% of the cPAD.

Cancer Dietary Exposure Results and Characterization

Dimethomorph is classified as a “not likely” human carcinogen.
Therefore, a cancer dietary exposure analysis is not required.

Water Contribution

EFED calculated the surface water Tier I Drinking Water Estimated
Concentrations (EDWC) for dimethomorph as chronic 56-day EDWC at 28.5
ppb.  The EDWC of 28.5 ppb was used directly in the chronic dietary risk
assessment.  Details are provided in section 6.2.

Table 6.1  Summary of Chronic Dietary (Food + Water) Exposure and Risk
for Dimethomorph

Population Subgroup a	Chronic Dietary

	cPAD,  mg/kg/day	Exposure,

mg/kg/day b	% cPAD

General U.S.  Population	0.1	0.0086	8.6

All Infants (< 1 yr)	0.1	0.0070	7.0

Children 1-2 yrs	0.1	0.020	19.9

Children 3-5 yrs	0.1	0.016	15.5

Children 6-12 yrs	0.1	0.0091	9.1

Youth 13-19 yrs	0.1	0.0067	6.7

Adults 20-49 yrs	0.1	0.0080	8.0

Adults 50+ yrs	0.1	0.0077	7.7

Females 13-49 yrs	0.1	0.0075	7.5

a The values for the population with the highest risk is bolded.

b Reported to 2 significant figures.

6.2	Water Exposure/Risk Pathway tc \l2 "6.2	Water Exposure/Risk Pathway

The Agency lacks sufficient monitoring exposure data to complete a
comprehensive dietary exposure analysis and risk assessment for
dimethomorph in drinking water.  Because the Agency does not have
comprehensive monitoring data, drinking water concentration estimates
are made by reliance on simulation or modeling taking into account data
on the physical characteristics of dimethomorph.

EFED used the SCI-GROW (Screening Concentration In Ground Water) Model
to estimate the EDWC of dimethomorph residues in ground water.  The EDWC
reported for dimethomorph residues in ground water using SCI-GROW is
0.30 ppb.  EFED used the Generic Estimated Environmental Concentration
(GENEEC) Model to estimate acute and chronic EDWCs of dimethomorph
residues in surface water.  EFED calculated the surface water Tier I
estimated EDWCs for dimethomorph as the chronic 56-day (with 3X) factor
EDWC at 28.5 ppb.  It should be noted that an updated drinking water
assessment was conducted for the proposed use on Brassica head and stem
subgroup 5A (DNum: D328740, J. L. Meléndez, 4/26/06).  However, the
EDWC of 0.264 ppb reported in that document is lower than the value of
28.5 ppb determined in the previous drinking water assessment.  To
account for exposure to residues in water under the most conservative
scenario, the previous value of 28.5 ppb was used in the dietary
exposure assessment rather than the value for the more recent
assessment.

Table 6.2  Summary of Estimated Surface and Ground Water Concentrations
for Dimethomorph

Exposure Duration	Surface Water Conc., ppb a	Ground Water Conc., ppb b

Acute	Not applicable	Not applicable

Chronic (non-cancer)	28.5	0.30

Chronic (cancer)	Not applicable	Not applicable

a From the Tier I GENEEC Model

b From the SCI-GROW Model

6.3	Residential (Non-Occupational) Exposure/Risk Pathway tc \l2 "6.3
Residential (Non-Occupational) Exposure/Risk Pathway

6.3.1	Home Uses tc \l3 "6.3.1	Home Uses

There are not any residential uses for dimethomorph at this time, nor
are any proposed.  Therefore, no risk assessments for
non-occupational/residential handler and postapplication exposures are
required.  There are no post-application residential uses for
dimethomorph that result in residential exposure to infants and
children.

6.3.2	Recreational Uses tc \l3 "6.3.2	Recreational Uses

There are not any registered uses of dimethomorph that would result in
treatment of recreational areas.

6.3.3	Other (Spray Drift, etc.) tc \l3 "6.3.3	Other (Spray Drift, etc.)

Spray drift is always a potential source of exposure to residents nearby
to spraying operations.  This is particularly the case with aerial
application, but, to a lesser extent, could also be a potential source
of exposure from the ground application method employed for
dimethomorph.  The Agency has been working with the Spray Drift Task
Force, EPA Regional Offices and State Lead Agencies for pesticide
regulation and other parties to develop the best spray drift management
practices.  On a chemical by chemical basis, the Agency is now requiring
interim mitigation measures for aerial applications that must be placed
on product labels/labeling.  The Agency has completed its evaluation of
the new data base submitted by the Spray Drift Task Force, a membership
of U.S.  pesticide registrants, and is developing a policy on how to
appropriately apply the data and the AgDRIFT computer model to its risk
assessments for pesticides applied by air, orchard airblast and ground
hydraulic methods.  After the policy is in place, the Agency may impose
further refinements in spray drift management practices to reduce
off-target drift with specific products with significant risks
associated with drift.

7.0	Aggregate Risk Assessments and Risk Characterization tc \l1 "7.0
Aggregate Risk Assessments and Risk Characterization

In accordance with the FQPA, EPA must consider and aggregate (add)
pesticide exposures and risks from three major sources: food, drinking
water, and residential exposures.  In an aggregate assessment, exposures
from relevant sources are added together and compared to quantitative
estimates of hazard (e.g., a NOAEL or PAD), or the risks themselves can
be aggregated.  When aggregating exposures and risks from various
sources, HED considers both the route and duration of exposure.

For most pesticide active ingredients, water monitoring data are
considered inadequate to determine surface and ground water drinking
water exposure estimates, so model estimates have been used to estimate
residues in drinking water (EDWCs).  In order to determine if aggregate
risks are of concern, ARIA incorporated EDWC values directly into the
dietary risk assessment.  Because there are no residential uses for
dimethomorph, the chronic dietary risk assessment is, in effect, the
aggregate risk assessment as well.

7.1	Acute Aggregate Risk tc \l2 "7.1	Acute Aggregate Risk

An acute oral endpoint was not identified for any segment of the U.S.
population.  Therefore, an assessment of acute aggregate risk is not
required.

7.2	Short-Term Aggregate Risk tc \l2 "7.2	Short-Term Aggregate Risk

An assessment of short-term aggregate risk is not required because there
are no registered residential uses for dimethomorph.

7.3	Intermediate-Term Aggregate Risk tc \l2 "7.3	Intermediate-Term
Aggregate Risk

An assessment of intermediate-term aggregate risk is not required
because there are no registered residential uses for dimethomorph.

7.4	Long-Term Aggregate Risk tc \l2 "7.4	Long-Term Aggregate Risk

Long-term aggregate risk for dimethomorph is assessed using chronic
dietary exposure from residues in food and drinking water.  The
assessment takes into account average exposure estimates from dietary
ingestion of dimethomorph (food and drinking water).  Since there
aren’t any residential uses of dimethomorph, there are no other
contributors to long-term aggregate risk.

EFED and HED have agreed that chronic and cancer EDWCs can be used
directly in chronic/cancer dietary exposure assessments to calculate
aggregate dietary (food + water) risk.  This is done by using the
relevant modeled value as a residue for water (direct and indirect, all
sources) in the dietary exposure assessment.  The principal advantage of
this approach is that the actual individual body weight and water
consumption data from the CSFII are used, rather than assumed weights
and consumption for broad age groups.  This refinement has been used for
the dimethomorph chronic aggregate risk assessment for surface water.

There are no residential uses for dimethomorph at this time, so that the
chronic dietary (food + water) risk assessment provides a suitable
estimate of long-term aggregate risk, as well.  Long-term aggregate risk
is summarized in Table 6.1.

7.5	Cancer Risk tc \l2 "7.5	Cancer Risk

An assessment of aggregate cancer risk is not required because
dimethomorph has been classified “Not Likely” to be a human
carcinogen.

8.0	Cumulative Risk Characterization/Assessment tc \l1 "8.0	Cumulative
Risk Characterization/Assessment

Unlike other pesticides for which EPA has followed a cumulative risk
approach based on a common mechanism of toxicity, EPA has not made a
common mechanism of toxicity finding as to dimethomorph and any other
substances and dimethomorph does not appear to produce a toxic
metabolite produced by other substances.  For the purposes of this
tolerance action, therefore, EPA has not assumed that dimethomorph has a
common mechanism of toxicity with other substances.  For information
regarding EPA’s efforts to determine which chemicals have a common
mechanism of toxicity and to evaluate the cumulative effects of such
chemicals, see the policy statements released by EPA’s Office of
Pesticide Programs concerning common mechanism determinations and
procedures for cumulating effects from substances found to have a common
mechanism on EPA’s website at
http://www.epa.gov/pesticides/cumulative/.

9.0	Occupational Exposure/Risk Pathway tc \l1 "9.0	Occupational
Exposure/Risk Pathway

Based upon the proposed use pattern, EPA believes the most highly
exposed occupational pesticide handler activities are likely to be for
1) a mixer/loader using open pour technique for a wettable powder in
support of aerial operations, 2) an applicator using open-cab,
ground-boom machinery, 3) and an aerial applicator.

Due to a smaller volume of compound handled per day, EPA believes a
mixer/loader supporting ground operations will experience less exposure
than a mixer/loader supporting aerial operations. Similarly, EPA
believes the estimated exposure for a mixer/loader supporting aerial
operations would be greater than that of a mixer/loader supporting
application by chemigation.  Therefore, the estimates of mixing and
loading in support of aerial operations are suggested as the “worse
case” surrogate for mixing/loading in support of ground operations or
chemigation.

It is expected that some private (i.e., grower) applicators may perform
all tasks, that is, mix, load and apply the material.  However, HED
Science Advisory Council for Exposure (ExpoSAC) draft Standard Operating
Procedure (SOP) (29 March 2000) directs that although the same
individual may perform all tasks, in some cases they shall be assessed
separately.

The available exposure data for combined mixer/loader/applicator
scenarios are limited in comparison to the monitoring of these two
activities separately.  These exposure scenarios are outlined in the
Pesticide Handler’s Exposure Database (PHED) Surrogate Exposure Guide

(v. 1.1, 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 may 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 Pesticide
Handler’s Exposure Database (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 Personal Protective Equipment
(PPE) as might be necessary.  The registered product label involved in
this assessment directs pesticide handlers to wear long-sleeved shirt,
long pants, chemical resistant gloves made of any waterproof material
such as polyethylene or polyvinyl chloride and shoes plus socks.

The HED Hazard Identification Assessment Review Committee (HIARC) met on
8 APRIL 1998 to discuss the adequacy of the toxicological database,
relative to dimethomorph (Memo, J.  Stewart, HED DOC.  NO.  012616,
“DIMETHOMORPH - Report of the Hazard Identification Assessment Review
Committee”, 13 MAY 1998).  The Hazard Identification Assessment Review
Committee (HIARC) identified short-term dermal and inhalation
toxicological endpoints (60 mg a.i./kg bw/day) from a rat developmental
study in which the effects seen were decreased body weight and weight
gain and decreased food consumption in maternal rats.  Since fetal
effects were noted in the developmental study, a body weight of 60 kg is
used in calculating estimated risks.  The HIARC identified a 5.0 %
dermal absorption factor which was derived from a dermal absorption
study.  HED assumes inhalation absorption is 100 %.  The HIARC
identified dimethomorph as “not likely” to be a human carcinogen,
therefore a cancer risk assessment was not conducted.  Table 9.1
contains a summary of the estimated exposures and risks to occupational
pesticide handlers from the proposed uses of dimethomorph.

9.1	Short/Intermediate/Long-Term Handler Risk tc \l2 "9.1
Short/Intermediate/Long-Term Handler Risk

Table 9.1  Short/Intermediate/Long-Term Occupational Exposure and Risk
             Estimates for Dimethomorph

Exposure Scenario

Crop	Daily

Dermal + Inhalation

Dose, mg/kg/day

Combined Inhalation

and Dermal

MOE

Mixer/Loader - Wettable Powder - Open Pour

Supporting Aerial Operation

0.2 lb a.i./A with gloves	Brassica Head and Stem Vegetables	0.06012	998

0.2 lb a.i./A without gloves

0.2662	225

Applicator - Aerial

Note: Pilots are not required to wear gloves

0.2 lb a.i./A without gloves	Brassica Head and Stem Vegetables	0.0003713
161,600

Applicator - Ground-boom - Open Cab

0.2 lb a.i./A with gloves	Brassica Head and Stem Vegetables	0.00096
62,500

0.2 lb a.i./A without gloves

0.00096	62,500

9.2	Short/Intermediate/Long-Term Postapplication Risk tc \l2 "9.2
Short/Intermediate/Long-Term Postapplication Risk

Table 9.2  Postapplication Occupational Exposure and Risk Estimates for
Dimethomorph,                  Zero Days After the Final Application

Crop	Work Activity	Daily Dose (mg/kg/day)	 MOE

Brassica Head and Stem Vegetables	Hand harvesting	0.0149	4026

10.0	Data Needs and Label Requirements tc \l1 "10.0	Data Needs and Label
Requirements

10.1	Toxicology tc \l2 "10.1	Toxicology

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10.2	Residue Chemistry tc \l2 "10.2	Residue Chemistry

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10.3	Occupational and Residential Exposure tc \l2 "10.3	Occupational and
Residential Exposure

None

 PAGE

 PAGE

 PAGE  ii

  PAGE  26


[Federal Register Volume 79, Number 99 (Thursday, May 22, 2014)]
[Notices]
[Page 29438]
[FR Doc No: 2014-11871]

-----------------------------------------------------------------------

DEPARTMENT OF ENERGY

Federal Energy Regulatory Commission

[Docket No. OR14-30-000]

White Cliffs Pipeline, L.L.C.; Notice of Petiton for Declaratory
Order

    Take notice that on May 9, 2014, pursuant to Rule 207(a)(2) of the
Commission's Rules of Practice and Procedure, 18 CFR
385.207(a)(2)(2013), White Cliffs Pipeline, L.L.C. (White Cliffs) filed
a petition requesting a declaratory order approving the overall tariff,
rate and priority service structure for a proposed expansion of White
Cliffs' existing crude oil pipeline as more fully explained in the
petition.
    Any person desiring to intervene or to protest in this proceeding
must file in accordance with Rules 211 and 214 of the Commission's
Rules of Practice and Procedure (18 CFR 385.211 and 385.214) on or
before 5:00 p.m. Eastern time on the specified comment date. Protests
will be considered by the Commission in determining the appropriate
action to be taken, but will not serve to make protestants parties to
the proceeding. Anyone filing a motion to intervene or protest must
serve a copy of that document on the Petitioner.
    The Commission encourages electronic submission of protests and
interventions in lieu of paper, using the FERC Online links at http://www.ferc.gov. To facilitate electronic service, persons with Internet
access who will eFile a document and/or be listed as a contact for an
intervenor must create and validate an eRegistration account using the
eRegistration link. Select the eFiling link to log on and submit the
intervention or protests.
    Persons unable to file electronically should submit an original and
14 copies of the intervention or protest to the Federal Energy
Regulatory Commission, 888 First St. NE., Washington, DC 20426.
    The filings in the above proceeding are accessible in the
Commission's eLibrary system by clicking on the appropriate link in the
above list. They are also available for review in the Commission's
Public Reference Room in Washington, DC. There is an eSubscription link
on the Web site that enables subscribers to receive email notification
when a document is added to a subscribed docket(s). For assistance with
any FERC Online service, please email<EMAIL_ADDRESS>or
call<PHONE_NUMBER> (toll free). For TTY, call<PHONE_NUMBER>.
    Comment Date: 5:00 p.m. Eastern time on June 2, 2014.

    Dated: May 15, 2014.
 Kimberly D. Bose,
 Secretary.
[FR Doc. 2014-11871 Filed 5-21-14; 8:45 am]
BILLING CODE 6717-01-P


[Federal Register Volume 82, Number 149 (Friday, August 4, 2017)]
[Rules and Regulations]
[Page 36335]
[FR Doc No: 2017-16492]

=======================================================================
-----------------------------------------------------------------------

ENVIRONMENTAL PROTECTION AGENCY

40 CFR Part 62

[EPA-R08-OAR-2017-0171; FRL-9965-78-Region 8]

Approval and Promulgation of State Plans for Designated
Facilities and Pollutants: Colorado, Montana, North Dakota, South
Dakota, Utah, and Wyoming; Negative Declarations

AGENCY: Environmental Protection Agency (EPA).

ACTION: Withdrawal of direct final rule.

-----------------------------------------------------------------------

SUMMARY: The Environmental Protection Agency (EPA) is withdrawing a
direct final rule published on June 5, 2017, because one adverse
comment was received during the public comment period. The withdrawn
rule pertained to the EPA's receipt and approval of 20 negative
declaration letters from EPA Region 8 states. These letters of negative
declaration are statements by the state certifying the absence of
designated facilities of a certain solid waste incinerator category or
class within its jurisdiction, which obviates the statutory requirement
for the state to develop a Clean Air Act (CAA) section 111(d)/129 State
plan for the regulation of designated facilities of that particular
category or class.

DATES: Effective August 3, 2017, the direct final rule published at 82
FR 25734, June 5, 2017 is withdrawn.

FOR FURTHER INFORMATION CONTACT: Gregory Lohrke,<PHONE_NUMBER>,
<EMAIL_ADDRESS>
SUPPLEMENTARY INFORMATION: On June 5, 2017, the EPA published a direct
final rule (82 FR 25734) approving several negative declarations
submitted by Region 8 states, certifying the absence of designated
facilities regulated under various Emissions Guidelines found in 40 CFR
part 60. The promulgation of each negative declaration was to serve in
lieu of a CAA section 111(d)/129 State plan, given the declared absence
of facilities that would require such a State plan. The direct final
rule was published without prior proposal because the EPA anticipated
no adverse comments on a noncontroversial action. The direct final rule
stated that if the action received adverse comment on or before July 5,
2017, the EPA would publish a timely withdrawal in the Federal
Register. The EPA received one adverse comment and is accordingly
withdrawing the direct final rule. In a separate, subsequent final
rulemaking action, the EPA will address the comment received.

List of Subjects in 40 CFR Part 62

    Environmental protection, Administrative practice and procedure,
Air pollution control, Commercial industrial solid waste incineration,
Intergovernmental relations, Municipal solid waste combustion, Other
solid waste incineration, Reporting and recordkeeping requirements.

    Dated: July 28, 2017.
Debra H. Thomas,
Acting Regional Administrator, Region 8.

0
Accordingly, the amendments to 40 CFR part 62, subpart G, subpart BB,
subpart JJ, subpart QQ, subpart TT, and subpart ZZ, published in the
Federal Register on June 5, 2017 (82 FR 25734), are withdrawn as of
August 3, 2017.

[FR Doc. 2017-16492 Filed 8-3-17; 8:45 am]
 BILLING CODE 6560-50-P


[Federal Register Volume 80, Number 224 (Friday, November 20, 2015)]
[Rules and Regulations]
[Pages 72587-72589]
[FR Doc No: 2015-29660]

-----------------------------------------------------------------------

DEPARTMENT OF HEALTH AND HUMAN SERVICES

Food and Drug Administration

21 CFR Part 880

[Docket No. FDA-2015-N-3838]

Medical Devices; General Hospital and Personal Use Devices;
Classification of the Ultraviolet Radiation Chamber Disinfection Device

AGENCY: Food and Drug Administration, HHS.

ACTION: Final order.

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SUMMARY: The Food and Drug Administration (FDA or the Agency) is
classifying the ultraviolet (UV) radiation chamber disinfection device
into class II (special controls). The special controls that will apply
to the device are identified in this order and will be part of the
codified language for the UV radiation chamber disinfection device
classification. The Agency is classifying the device into class II
(special controls) in order to provide a reasonable assurance of safety
and effectiveness of the device.

DATES: This order is effective November 20, 2015. The classification
was applicable on December 20, 2011.

FOR FURTHER INFORMATION CONTACT: Elizabeth Claverie, Center for Devices
and Radiological Health, Food and Drug Administration, 10903 New
Hampshire Ave., Bldg. 66, Rm. 2508, Silver Spring, MD 20993-0002, 301-
796-6298.

SUPPLEMENTARY INFORMATION:

I. Background

    In accordance with section 513(f)(1) of the Federal Food, Drug, and
Cosmetic Act (the FD&C Act) (21 U.S.C. 360c(f)(1)), devices that were
not in commercial distribution before May 28, 1976 (the date of
enactment of the Medical Device Amendments of 1976), generally referred
to as postamendments devices, are classified automatically by statute
into class III without any FDA rulemaking process. These devices remain
in class III and require premarket approval, unless and until the
device is classified or reclassified into class I or II, or FDA issues
an order finding the device to be substantially equivalent, in
accordance with section 513(i) of the FD& C Act, to a predicate device
that does not require premarket approval. The Agency determines whether
new devices are substantially equivalent to predicate devices by means
of premarket notification procedures in section 510(k) of the FD&C Act
(21 U.S.C. 360(k)) and part 807 (21 CFR part 807) of the regulations.
    Section 513(f)(2) of the FD&C Act, as amended by section 607 of the
Food and Drug Administration Safety and Innovation Act (Pub. L. 112-
144), provides two procedures by which a person may request FDA to
classify a device under the criteria set forth in section 513(a)(1) of
the FD&C Act. Under the first procedure, the person submits a premarket
notification under section 510(k) of the FD&C Act for a device that has
not previously been classified and, within 30 days of receiving an
order classifying the device into class III under section 513(f)(1) of
the FD&C Act, the person requests a classification under section
513(f)(2) . Under the second procedure, rather than first submitting a
premarket notification under section 510(k) of the FD&C Act and then a
request for classification under the first procedure, the person
determines that there is no legally marketed device upon which to base
a determination of substantial equivalence and requests a
classification under section 513(f)(2) of the FD&C Act. If the person
submits a request to classify the device under this second procedure,
FDA may decline to undertake the classification request if FDA
identifies a legally marketed device that could provide a reasonable
basis for review of substantial equivalence with the device or if FDA
determines that the device submitted is not of ``low-moderate risk'' or
that general controls would be inadequate to control the risks and
special controls to mitigate the risks cannot be developed.
    In response to a request to classify a device under either
procedure provided by section 513(f)(2) of the FD&C Act, FDA will
classify the device by written order within 120 days. This
classification will be the initial classification of the device. In
accordance with section 513(f)(1) of the FD&C Act, FDA issued an order
on October 28, 2010, classifying the Vioguard Self-Sanitizing Keyboard
into class III, because it was not substantially equivalent to a device
that was introduced or delivered for introduction into interstate
commerce for commercial distribution before May 28, 1976, or a device
which was subsequently reclassified into class I or class II. On
November 2, 2010, Vioguard submitted a request for classification of
the Vioguard Self-Sanitizing Keyboard under section 513(f)(2) of the
FD&C Act. The manufacturer recommended that the device be classified
into class II (Ref. 1).
    In accordance with section 513(f)(2) of the FD&C Act, FDA reviewed
the request in order to classify the device under the criteria for
classification set forth in section 513(a)(1) of the FD&C Act. FDA
classifies devices into class II if general controls by themselves are
insufficient to provide reasonable assurance of safety and
effectiveness, but there is sufficient information to establish special
controls to provide reasonable assurance of the safety and
effectiveness of the device for its intended use. After review of the
information submitted in the request, FDA determined that the device
can be classified into class II with the establishment of special
controls. FDA believes these special controls will provide reasonable
assurance of the safety and effectiveness of the device.
    Therefore, on December 20, 2011, FDA issued an order to the
requestor classifying the device into class II. FDA is codifying the
classification of the device by adding 21 CFR 880.6600.
    Following the effective date of this final classification order,
any firm submitting a premarket notification (510(k)) for a UV
radiation chamber disinfection device will need to comply with the
special controls named in this final order. The device is assigned the
generic name UV radiation chamber disinfection device, and it is
identified as a UV chamber disinfection device intended for the low-
level surface disinfection of non-porous equipment surfaces by dose-
controlled UV irradiation. This classification does not include self-
contained open chamber UV disinfection devices intended for whole room
disinfection in a health care environment.
    FDA has identified the following risks to health associated
specifically with this type of device, as well as the mitigation
measures required to mitigate these risks in table 1.

  Table 1--Ultraviolet Radiation Chamber Disinfection Device Risks and
                           Mitigation Measures
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            Identified risks                   Mitigation measures
------------------------------------------------------------------------
Inadequate Equipment Disinfection......  Performance Testing.
                                         Labeling.

UV Radiation Exposure..................  Performance Testing.
                                         Labeling.
Electrical Shock.......................  Electrical Safety Testing.
Electromagnetic Interference...........  Electromagnetic Compatibility
                                          (EMC) Testing.
                                         Labeling.
Ozone Exposure.........................  Ozone Generation Limits.
                                         Labeling.
Processed Equipment Incompatibility....  Performance Testing.
                                         Labeling.
Contamination of Device................  Cleaning and Disinfection
                                          Validation.
                                         Labeling.
Software Malfunction...................  Hazard Analysis of Software.
                                         Software Verification and
                                          Validation.
------------------------------------------------------------------------

    FDA believes that the special controls in Sec.  880.6600(b)(1)
through (4), in addition to the general controls, address these risks
to health and provide reasonable assurance of the safety and
effectiveness.
    Section 510(m) of the FD&C Act provides that FDA may exempt a class
II device from the premarket notification requirements under section
510(k) of the FD&C Act, if FDA determines that premarket notification
is not necessary to provide reasonable assurance of the safety and
effectiveness of the device. For this type of device, FDA has
determined that premarket notification is necessary to provide
reasonable assurance of the safety and effectiveness of the device.
Therefore, this device type is not exempt from premarket notification
requirements. Persons who intend to market this type of device must
submit to FDA a premarket notification, prior to marketing the device,
which contains information about the UV radiation chamber disinfection
device they intend to market.

II. Environmental Impact

    We have determined under 21 CFR 25.34(b) that this action is of a
type that does not individually or cumulatively have a significant
effect on the human environment. Therefore, neither an environmental
assessment nor an environmental impact statement is required.

III. Paperwork Reduction Act of 1995

    This final order establishes special controls that refer to
previously approved collections of information found in other FDA
regulations. These collections of information are subject to review by
the Office of Management and Budget (OMB) under the Paperwork Reduction
Act of 1995 (44 U.S.C. 3501-3520). The collections of information in
part 807, subpart E, regarding premarket notification submissions have
been approved under OMB control number 0910-0120, and the collections
of information in 21 CFR part 801, regarding labeling have been
approved under OMB control number 0910-0485.

IV. Reference

    The following reference is on display in the Division of Dockets
Management (see ADDRESSES) and is available for viewing by interested
persons between 9 a.m. and 4 p.m., Monday through Friday; it is also
available electronically at http://www.regulations.gov.

    1. DEN100013: de novo request per 513(f)(2) from Vioguard, dated
November 2, 2010.

List of Subjects in 21 CFR Part 880

    Medical devices.

    Therefore, under the Federal Food, Drug, and Cosmetic Act and under
authority delegated to the Commissioner of Food and Drugs, 21 CFR part
880 is amended as follows:

PART 880--GENERAL HOSPITAL AND PERSONAL USE DEVICES

0
1. The authority citation for 21 CFR part 880 continues to read as
follows:

    Authority: 21 U.S.C. 351, 360, 360c, 360e, 360j, 371.

0
2. Section 880.6600 is added to subpart G to read as follows:

Sec.  880.6600  Ultraviolet (UV) radiation chamber disinfection device.

    (a) Identification. An ultraviolet (UV) radiation chamber
disinfection device is intended for the low-level surface disinfection
of non-porous equipment surfaces by dose-controlled UV irradiation.
This classification does not include self-contained open chamber UV
radiation disinfection devices intended for whole room disinfection in
a health care environment.
    (b) Classification--Class II (special controls). The special
controls for this device are:
    (1) Performance testing must demonstrate the following:
    (i) The chamber's ability to control the UV radiation dose during
operation.
    (ii) The chamber's disinfection performance through microbial
challenge testing.
    (iii) Evidence that the equipment intended to be processed is UV
compatible.
    (iv) Validation of the cleaning and disinfection procedures.
    (v) The ability of the device to continue to perform to all
specification after cleaning and disinfection.
    (vi) Whether the device generates ozone (if so, 21 CFR 801.415,
Maximum acceptable level of ozone, applies).
    (2) Appropriate software verification, validation, and hazard
analysis must be performed.
    (3) Appropriate analysis and/or testing must validate electrical
safety, mechanical safety, and electromagnetic compatibility of the
device in its intended use environment.
    (4) The labeling must include:
    (i) UV hazard warning labels.
    (ii) Explanation of all displays and/or labeling on user interface.
    (iii) Explanation of device safety interlocks.
    (iv) Explanation of all disinfection cycle signals, cautions and
warnings.
    (v) Device operating procedures.
    (vi) Identification of the expected UV lamp operational life and
instructions for procedures on replacement of the UV lamp when needed.
    (vii) Procedures to follow in case of UV lamp malfunction or
failure.
    (viii) Procedures for disposing of mercury-containing UV lamps, if
applicable.
    (ix) Identification of specific equipment that is compatible with
the UV radiation dose generated by the device and that can safely
undergo UV

radiation low-level disinfection in the chamber device.
    (x) Description of the required preparation of equipment for
disinfection in the UV radiation chamber device.
    (xi) Identification of the specific microbes used in successful
performance testing of the device.
    (xii) Validated instructions for cleaning and disinfection of the
device.

    Dated: November 17, 2015.
Leslie Kux,
Associate Commissioner for Policy.
[FR Doc. 2015-29660 Filed 11-19-15; 8:45 am]
BILLING CODE 4164-01-P