Document ID: EPA-HQ-OPP-2008-0718-0002
Agency: epa
Document Type: Supporting & Related Material
Title: 
Posted Date: 2008-12-30T05:00Z

FILE NAME:   Valent USA.wpt   (11/15/2007) (xml)

Template Number P25	

COMPANY FEDERAL REGISTER DOCUMENT SUBMISSION TEMPLATE

(1/1/2005)

EPA Registration Division contact: David A. Wustner, (925)256-2820

TEMPLATE:

Valent U.S.A. Corporation

[Insert petition number]

	EPA has received a pesticide petition [insert petition number] from
Valent U.S.A. Company, 1600 Riviera Ave., Suite 200, Walnut Creek, CA
94596-8025 proposing, pursuant to section 408(d) of the Federal Food,
Drug, and Cosmetic Act (FFDCA), 21 U.S.C. 346a(d), to amend 40 CFR part
180.617 by establishing a tolerance for residues of metconazole,
5-[(4-chlorophenyl)-methyl]-2,2-dimethyl-1-(1H-1,2,4-triazol-1-ylmethyl)
cyclopentanol, measured as the sum of cis- and trans- isomers in or on
the raw agricultural commodity canola seed of 0.04 parts per million
(ppm).

EPA has determined that the petitions contain data or information
regarding the elements set forth in section 408(d)(2) of the FFDCA;
however, EPA has not fully evaluated the sufficiency of the submitted
data at this time or whether the data supports granting of the
petitions.  Additional data may be needed before EPA rules on the
petitions.

A. Residue Chemistry                                      

	1. Plant metabolism. Nature of the residue studies (OPPTS Harmonized
Guideline 860.1300) were conducted in wheat, canola, banana, peas, and
mandarin oranges as representative crops in order to characterize the
fate of metconazole in all crop matrices. Two radiocarbon labeling
positions were studied in each crop. In all crops triazole ring labeling
was used, and the other label was positioned either in the
p-chlorophenyl or the cyclopentyl rings In all five crops the
metconazole Residue of Concern was identified as parent metconazole.
Confined and field rotational crop studies have determined that no
significant metconazole-unique residues occur in following crops. 



	2. Analytical method. Independently validated analytical methods have
been submitted for analyzing parent metconazole residues with
appropriate sensitivity for all canola crop and processed commodities
for which a tolerance is being requested.

	3. Magnitude of residues. Field trials were carried out in canola to
determine the magnitude of the residue in/on canola seed and in
processed products canola meal and canola refined oil. The number and
locations of field trials are in accordance with OPPTS Guideline
860.1500. Field trials were carried out on canola using the maximum
label rate, a single application, and the minimum pre-harvest interval
(PHI). Detected residues of metconazole in canola seed and processed
products support the proposed tolerance.

B. Toxicological Profile

A complete, valid and reliable database of mammalian and genetic
toxicology studies has been submitted to EPA that supports the proposed
tolerance for metconazole on canola seed. Two geometric isomers of
metconazole exist. The technical material is a mixture of cis- and
trans- isomers in an 85 to 15 ratio (85:15). The fungicidal activity of
metconazole is associated primarily with the cis-isomer. Toxicology
studies submitted in support of this petition were conducted on the
metconazole technical material composed of the 85:15 isomer mixture.
Additional studies using test material composed of a more purified
sample of the cis-isomer (greater than 95%, WL 136184) provide
additional toxicological support for this tolerance. 

1. Acute Toxicity. Metconazole technical is considered to be slightly
toxic (Toxicity Category III) to the rat by the oral route of exposure.
In an acute oral study in rats, the LD50 value of metconazole technical
was 727 milligrams per kilogram of body weight (mg/kg b.w.) for males
and 595 mg/kg b.w. for females. The oral LD50 for combined sexes was 660
mg/kg b.w. Metconazole technical demonstrates no acute toxicity via the
dermal route of exposure [LD50 value >2000 mg/kg (highest dose tested)]
(Toxicity Category III) or inhalation route of exposure [LC50 >5.6 mg/L]
(Toxicity Category IV). The material is mildly irritating to the eye
(Toxicity Category III) and is not irritating to the skin (Toxicity
Category IV), nor is it a skin sensitizer.

2. Genotoxicity.  Both metconazole technical and  WL 136184 technical
(greater than 95% cis isomer) have been tested in an extensive battery
of in vitro and in vivo genotoxicity assays measuring several different
endpoints of potential genotoxicity. Collective results from these
studies indicate that metconazole does not pose a genotoxic risk, and
therefore, is not likely to be a genotoxic carcinogen.

3. Reproductive and developmental toxicity. Several developmental
toxicity studies in rats conducted with metconazole technical and WL
136184 showed no evidence of teratogenic effects in fetuses, and no
evidence of developmental toxicity in the absence of maternal toxicity.
Thus, metconazole is neither a selective developmental toxicant nor a
teratogen in the rat. Two rat developmental toxicity studies have been
conducted with metconazole technical. In the first study, the
no-observable-adverse-effect-level (NOAEL) for maternal toxicity was 12
mg/kg b.w./ day, based on decreased body weight gain at 30 mg/kg
b.w./day, the next highest dose tested, and the NOAEL for developmental
toxicity was also 12 mg/kg b.w./day, based on decreased fetal body
weights and an increased incidence of skeletal ossification variations
at 30 mg/kg b.w./day. In the second study, the maternal and fetal NOAEL
was 16 mg/kg/day based on findings similar to the first study at the
next higher dose level of 65 mg/kg/day. In the rat developmental
toxicity study conducted with WL 136184 technical, the NOAEL for
maternal toxicity was 24 mg/kg b.w./day based on decreased body weight
gain at 60 mg/kg b.w./day, the highest dose tested, and the NOAEL for
developmental toxicity was also 24 mg/kg b.w./day, based on an increase
in the total number of resorptions, reductions in fetal body weights and
an increased incidence of skeletal ossification variations at 60 mg/kg
b.w./day. 

Results from a developmental toxicity study in rabbits metconazole
technical also indicated no evidence of teratogenicity or developmental
toxicity in the absence of maternal toxicity. Thus, metconazole
technical is neither a selective developmental toxicant nor a teratogen
in the rabbit. In this rabbit developmental study, the NOAEL for
maternal toxicity was 20 mg/kg b.w./day based on decreased food
consumption and body weight gain, reductions in hemoglobin, hematocrit
and corpuscular volume, increases in platelet counts and alkaline
phosphatase activity, and increased absolute and relative liver weights
at 40 mg/kg b.w./day (the highest dose tested). The NOAEL for
developmental toxicity was also 20 mg/ kg b.w./day, based on an increase
in the total number and mean number of resorptions and decreased fetal
body weight at 40 mg/kg b.w./day.

Two multi-generation reproduction studies were conducted with
Metconazole Technical -- one with the >95% cis form and one with the
85/15 cis/trans form.  Dose levels and results in both studies were
similar, although the 95% cis study diet was adjusted to maintain a
constant dose.  Dose levels in the >95% cis study were 0, 2, 8, 32 and
48 mg/kg/day and in the 85/15 cis study were 0, 30, 150 and 750 ppm
(approximately 0, 2.1, 10.6 and 52.8 mg/kg/day for pre-mating growth
period).  For the >95% cis study, the results support a NOAEL for
parental toxicity of 8 mg/kg/day based on increased ovarian weight and
increased gestation length at the next highest dose tested (32
mg/kg/day).   The NOAEL for growth and development of the offspring is
also 8 mg/kg/day, based on reductions in live litter size for F2 litters
at 32 mg/kg/day.  The NOAEL for reproductive performance and fertility
was 48 mg/kg/day (the highest dose tested).  In the 85/15 cis/trans
study, the NOAEL identified for parental toxicity, offspring growth and
development and reproductive toxicity was 10.8 mg/kg/day (150 ppm) based
on effects observed at the highest dose tested of 52.8 mg/kg/day (750
ppm).

Results of reproduction and developmental toxicity studies conducted
with metconazole technical show no increased sensitivity to developing
offspring as compared to parental animals.

4. Subchronic toxicity.  Subchronic (90-day) dietary studies in rats
were conducted with metconazole technical.  In the study the NOAEL was
100 ppm (approximately 6.8 mg/kg b.w./day) based on hepatic fatty
vacuolation in males at 300 ppm, the next highest concentration tested.

In a 90-day dietary study in mice conducted with metconazole technical,
the NOAEL was 30 ppm (approximately 5.5 mg/kg b.w./day), based on
increased aspartate and alanine aminotransferase activities in males,
increased absolute and relative weights of the liver and spleen of
females, and increased incidences of hepatocellular vacuolation and
hypertrophy for males and females at 300 ppm, the next highest
concentration tested. 

In a 90-day dietary study in beagle dogs with metconazole technical the
NOAEL was 60 ppm (approximately 2.5 mg/kg b.w./day) based on decreased
body weight gain and food consumption for females, and a slight increase
in reticulocyte count for males at 600 ppm, the next highest
concentration tested. 

[NOTE: At the 90-day timepoint of the chronic (one-year) toxicity study
in the dog, the NOAEL for decreased body weight gain is 300 ppm
(approximately 11.1 mg/kg b.w./day).]

5. Chronic toxicity.  Findings similar to those observed in the
short-term and subchronic studies were apparent in the long-term dietary
toxicity studies conducted in rats, dogs and mice. 

In a chronic toxicity study, long-term (104-weeks) administration of
metconazole technical to rats supported a NOAEL for systemic toxicity of
100 ppm (approximately 4.8 mg/kg b.w./day), based on increased adjusted
liver weight, clinical chemistry changes, and increased incidences of
hepatocellular lipid vacuolation and centrilobular hypertrophy at
interim sacrifice for males at 300 ppm, the next highest concentration
tested. 

In a 104-week carcinogenicity study in rats fed diets containing 0, 100,
300 or 1000 ppm metconazole technical, the NOAEL for carcinogenicity was
1000 ppm (50 mg/kg/day) the highest dose tested.  The NOAEL for chronic
systemic toxicity was 100 ppm (5.6 mg/kg/day) based on increased
incidences of centrilobular hypertrophy and pigment disposition in the
liver and increased incidences of cortical vacuolation in the adrenal at
300 ppm.

In a one-year dietary study in beagle dogs, the NOAEL was 300 ppm
(approximately 11.1 mg/ kg b.w./day), based on decreased body weight
gain for males during weeks 1 to 13 and increased alkaline phosphatase
activity for males and females at 1,000 ppm, the next highest
concentration tested. 

A 91-week carcinogenicity study in mice with metconazole technical
supports a NOAEL for non-neoplastic effects of 30 ppm (approximately 4.8
mg/kg b.w./ day), based on increased white blood cell count for males,
increased aspartate and alanine aminotransferase activities and
increased absolute and adjusted liver weight for females, and
microscopic changes in the liver, spleen and adrenal gland for males and
females at 300 ppm (the next highest concentration tested). The NOAEL
for carcinogenicity was 300 ppm (approximately 48.3 mg/kg b.w./day)
based on increased incidences of hepatocellular adenomas in males and
females and hepatocellular carcinomas in females at 1,000 ppm, the
highest concentration tested. The increased incidences of hepatic
adenomas and carcinomas at the highest concentration tested are
considered to occur through promotional and non-genotoxic secondary
mechanisms following toxicity and induction of mixed function oxidase in
mice. Consequently, metconazole is not likely to be oncogenic in humans
at the low levels of exposure that will result from its use as a
fungicide.

6. Animal metabolism. The rat metabolism studies show that the
qualitative nature of the fate of metconazole in animals is adequately
understood. In studies conducted with radiolabeled metconazole (85:15
isomer mixture) or radiolabeled WL 136184 radioactivity was rapidly
eliminated in urine and feces within 48 hours of dosing. Biliary
excretion was shown to be a prominent route of elimination. At both high
and low doses of metconazole, male rats generally excreted lower amounts
of radioactivity in the urine, and greater amounts of radioactivity in
the feces as compared to females. The pattern of metabolites detected in
males and females was similar at high and low doses, and little or no
parent compound was found in either feces or urine. Five days following
oral dosing of metconazole at the highest dose, low levels of
radioactivity were detected in the majority of tissues analyzed; however
higher concentrations of radioactivity were found in the adrenal glands,
gastro-intestinal tract and liver. A comparison of radioactivity levels
in the adrenal glands following oral administration of low and high
doses indicates that uptake in the adrenal may be saturable. No
differences in tissue levels were noted between males and females.

7. Metabolite toxicology. The metabolism of metconazole is similar in
plants and mammals with extensive hydroxylation being the predominate
reactions. Due to the similar structural nature of most metabolites, the
toxicity of the plant metabolites is adequately estimated from the
results of studies performed with the technical in various animals. EPA
concern for unique plant metabolites common to most triazole fungicides
is being addressed with research conducted by the U.S. Triazole Task
Force. On the basis of this research, an interim human health risk
assessment for aggregate exposure to 1, 2, 4-triazole was published in
the Federal Register (40 CFR Part 180, Vol. 69 No. 149 Page 47005,
8/4/04) and will be refined once the research is complete.

 

8. Endocrine disruption The toxicology database for metconazole
technical is current and complete. This includes a thorough evaluation
of the potential effects on reproduction and development, and the
pathology of the endocrine organs following short-term and long-term
exposures. The battery of tests included as part of this petition fully
characterizes potential endocrine-related in vivo effects, clearly
defines NOAEL/LOAEL values, and indicates no increased sensitivity to
developing offspring.

C. Aggregate Exposure

	1. Dietary exposure. Exposure assessments have been conducted to
evaluate the potential risk due to acute and chronic dietary exposure of
the U.S. population and various subgroups to residues of metconazole.
The proposed tolerance on canola seed is 0.04 ppm, the sum of the limits
of quantitation of the analytical method for each of the metconazole
isomers. The only canola incremental dietary exposure to metconazole is
directly from the processed product refined canola oil, or as secondary
residues from food animals fed canola seed meal. In both cases these
residues are negligible, and incremental exposure will be near zero.
Thus, a previous dietary exposure and risk analysis without canola
commodities added will be used to estimate total dietary exposures. 
This exposure analysis considered both the cis -and trans-isomers, in or
on raw agricultural commodities, was expressed as the parent compound. 
The analysis included all the proposed tolerance values (except canola)
for soybean, sugar beet, barley, wheat, oats, rye, triticale, cotton,
corn (field, pop, sweet) stone fruit (crop group 12), tree nuts (crop
group 14), peanuts, bananas, milk, meat, and eggs.

	i. Food.  

Acute Dietary Exposure Assessment

Acute dietary exposure estimates were based on proposed tolerance
values, default process factors with the exception of a determined
process factor for sugar beet molasses, and 100% of all crops treated.
Canola commodities are not included. The consumption data was from the
USDA Continuing Survey of Food Intake by Individuals (CSFII 1994 - 1996,
1998) and the EPA Food Commodity Ingredient Database (FCID) using
Exponent's Dietary Exposure Evaluation Module (DEEM-FCID) software.  

The resulting exposure estimates were compared against the metconazole
acute Population Adjusted Dose (aPAD) of 0.16 mg/kg b.w./day for females
13-49 years of age.  This endpoint is based on the NOAEL from a rat
developmental toxicity study of 16 mg/kg/day with an FQPA safety factor
of 1. An acute oral toxicological endpoint could not be determined for
all other sub-populations. Considering the exposure assumptions
discussed above, metconazole acute dietary exposure from food is only
1.00 % aPAD for females 13-49 years of age. The results of the acute
dietary assessment are presented in Table 1.

 ADVANCE \d6 

 ADVANCE \d6 Table 1.	Results for Metconazole Acute Dietary Exposure
Analysis Considering all Proposed Tolerances using DEEM-FCID at the 95th
Percentile 

Population	

Exposure Estimate	

%aPAD

Subgroups	(mg/kg b.w./day)*	 

U.S. Population	

0.003046	

NA

All Infants (< 1 year old)	0.005407	NA

Children (1-2 years old)	0.005796	NA

Children (3-5 years old)	0.00463	NA

Children (6-12 years old)	0.002858	NA

Youth (13-19 years old)	0.001688	NA

Females (13-49 years old)	0.0016	1.00

Adults (20-49 years old)	0.002776	NA

Adults (50+ years old)	0.001738	NA

The results of the analysis show that for females 13-49 years of age,
the estimated exposure is well below the Agency's level of concern (<
100% aPAD).  Additional refinements in the dietary risk assessment (i.e.
utilizing anticipated residue values, percent crop treated values) would
further reduce the estimated exposure values.

Chronic Dietary Exposure Assessment

Chronic dietary exposure estimates were based on proposed tolerance
values, default process factors with the exception of a determined
process factor for sugar beet molasses, and 100% crop treated values for
all commodities. Canola commodities are not included. The consumption
data was from the USDA Continuing Survey of Food Intake by Individuals
(CSFII 1994 - 1996, 1998) and the EPA Food Commodity Ingredient Database
(FCID) using Exponent's Dietary Exposure Evaluation Module (DEEM-FCID)
software.  

The chronic Population Adjusted Dose (cPAD) used for U.S. population and
all sub-populations is 0.048 mg/kg bw/day. This endpoint is based on the
NOAEL values from both a 104-week rat chronic toxicity study and a mouse
78-week carcinogenicity study of 4.8 mg/kg/day with an FQPA safety
factor of 1. Considering the exposure assumptions discussed above,
metconazole chronic dietary exposure from food for the U.S. population
was 2.0 % of the cPAD.  The most highly exposure population sub group
was children 1-2 years of age at 5.6 % cPAD   The results of the chronic
dietary assessment are presented in Table 2. 

 ADVANCE \d6 Table 2. Results for Metconazole Chronic Dietary Exposure
Analysis Considering all Proposed Tolerances using DEEM-FCID 

Population	

Exposure Estimate	

%cPAD

Subgroups	(mg/kg b.w./day)	 

U.S. Population	

0.000953	

2.0

All Infants (< 1 year old)	0.001556	3.2

Children (1-2 years old)	0.002672	5.6

Children (3-5 years old)	0.002124	4.4

Children (6-12 years old)	0.001306	2.7

Youth (13-19 years old)	0.000734	1.5

Females (13-49 years old)	0.000837	1.7

Adults (20-49 years old)	0.000636	1.3

Adults (50+ years old)	0.000617	1.3

 The results of the analysis show that for all sub-populations, the
exposures are below a level of concern (< 100% cPAD).  Additional
refinements in the chronic dietary risk assessment (i.e. utilizing
anticipated residue values and percent crop treated values) would
further reduce the estimated exposure values.

	ii. Drinking water. Potential drinking water exposure was estimated
using PRZM/EXAMS and SCI-GROW models. The concentrations were determined
based on the most intense use pattern, that is the maximum number of
applications at the maximum label rate and minimum interval for turf.
The chronic EDWC has been adjusted for the mitigated use pattern in turf
(a yearly maximum of 3 lb ai/a reduced to 2 lb ai/a). The turf use still
allows for the highest single application rate and greatest seasonal
amount of metconazole to be applied of any proposed use.

The acute Estimated Drinking Water Concentrations (EDWC)  for
metconazole exposure are estimated to be 48.22 ug/L (ppb) in surface
water and 0.42 ug/L in shallow ground water. The chronic EDWC=s for
exposure are estimated to be 16.21 ug/L in surface water and 0.28 ug/L
in shallow ground water.

Drinking water contributions were assessed based on the maximum
estimated metconazole water concentrations (acute - 48.22 ug/L, chronic
16.21 ug/L), and water consumption and body weights reported in CSFII,
using DEEM-FCID software.  The acute and chronic estimated water
exposure values are summarized in Tables 3 and 4, respectively.  Minimal
exposure of metconazole occurs through drinking water with 1.47% of the
aPAD for females 13-49 years of age and less than 2.33% of the cPAD for
all other subpopulations.

  

 ADVANCE \d6  ADVANCE \u6 Table 3. Results for Metconazole Acute Water
Exposure Analysis Considering the Maximum Estimated Acute Drinking Water
Concentration using DEEM-FCID 

Population	

Water Exposure Estimate	

% aPAD

Subgroups	(mg/kg b.w./day)	 

U.S. Population	

0.002519	

NA

All Infants (< 1 year old)	0.009497	NA

Children (1-2 years old)	0.003952	NA

Children (3-5 years old)	0.003611	NA

Children (6-12 years old)	0.002514	NA

Youth (13-19 years old)	0.002044	NA

Females (13-49 years old)	0.002347	1.47

Adults (20-49 years old)	0.002334	NA

Adults (50+ years old)	0.002108	NA

 ADVANCE \d6 

 ADVANCE \d6 Table 4. Results for Metconazole Chronic Water Exposure
Analysis Considering the    Maximum Estimated Chronic Drinking Water
Concentration using DEEM-FCID 

Population	

Water Exposure Estimate	

%cPAD

Subgroups	(mg/kg b.w./day)	 

U.S. Population	

0.000341	

0.71

All Infants (< 1 year old)	0.00112	2.33

Children (1-2 years old)	0.000507	1.06

Children (3-5 years old)	0.000475	0.99

Children (6-12 years old)	0.000327	0.68

Youth (13-19 years old)	0.00037	0.51

Females (13-49 years old)	0.000317	0.66

Adults (20-49 years old)	0.000319	0.66

Adults (50+ years old)	0.000335	0.70

cPAD = chronic  population adjusted dose

Based on estimated chronic surface water value of 16.21 ug/L

Acute Aggregate Exposure and Risk (food and water)

The aggregate acute risk includes residues of metconazole from food and
water (Table 5). Exposures from residential uses are not included in the
acute aggregate assessment.  The results demonstrate that there are no
safety concerns for any subpopulation based on the proposed uses and the
results clearly meet the FQPA standard of reasonable certainty of no
harm.   

 ADVANCE \d6  ADVANCE \u6 Table 5. 	Estimated Acute Aggregate Exposure
and Risk of Metconazole  

Population Subgroup	

aPAD (mg/kg/day)	

Food Exposure (mg/kg/day)	

Water Exposure (mg/kg/day)	

Total Exposure (mg/kg/day)	

% aPAD

U.S. Population	NA	0.003046	0.002519	0.005565	NA

All Infants (< 1 yr old)	NA	0.005407	0.009497	0.014904	NA

Children 1-2 years	NA	0.005796	0.003952	0.009748	NA

Children 3-5 years	NA	0.00463	0.003611	0.008241	NA

Children 6 B 12 years	NA	0.002858	0.002514	0.005372	NA

Youth 13-19 years	NA	0.001688	0.002044	0.003732	NA

Females 13-49 years	0.16	0.0016	0.002347	0.003947	2.47

Adults 20-49 years	NA	0.002776	0.002334	0.00511	NA

Adults + 50	NA	0.001738	0.002108	0.003846	NA

 

Chronic Aggregate Exposure and Risk (food and water)

The aggregate chronic risk includes residues of metconazole from food
and water (Table 6). Exposures from residential uses are not included in
the chronic aggregate assessment. For the U. S. Population at 2.70 % of
the cPAD or for the most highly exposed population subgroup, Children
1-2 years at 6.62 % of the cPAD, the results demonstrate there are no
safety concerns for any subpopulation based on the proposed uses and the
results clearly meet the FQPA standard of reasonable certainty of no
harm. 

  Table 67. 	Estimated Chronic Aggregate Exposure and Risk of
Metconazole 

Population Subgroup	

cPAD (mg/kg/day)	

Food Exposure (mg/kg/day)	

Water Exposure (mg/kg/day)	

Total Exposure (mg/kg/day)	

% cPAD

U.S. Population	0.0483	0.000953	0.000341	0.001294	2.70

All Infants (< 1 yr old)	0.0483	0.001556	0.00112	0.002676	5.58

Children 1-2 years	0.0483	0.002672	0.000507	0.003179	6.62

Children 3-5 years	0.0483	0.002124	0.000475	0.002599	5.41

Children 6 B 12 years	0.0483	0.001306	0.000327	0.001633	3.40

Youth 13-19 years	0.0483	0.000734	0.00037	0.000981	2.04

Females 13-49 years	0.0483	0.000617	0.000317	0.000934	1.95

Adults 20-49 years	0.0483	0.000837	0.000319	0.001156	2.41

Adults + 50	0.0483	0.000636	0.000335	0.000838	1.75

μg/cm2, present immediately after the spray treatment has dried (Time
0).  The exposure and risk estimates for the residential exposure
scenarios are assessed for the day of application because adults and
toddlers could contact treated turf immediately after application.  All
short-/intermediate term MOE were greater than 100 which indicates that
exposure from all residential scenarios result in exposures below a
level of concern.

D. Cumulative Effects

Metconazole is a triazole fungicide. There are several triazole
fungicides registered for use within the United States. Although
metconazole and other triazole fungicides may have similar modes of
action, no data areis available to determine if these compounds have
common mechanisms of mammalian toxicity or information on how to include
metconazole in a cumulative risk assessment.  Therefore, for the
purposes of this tolerance petition no assumption has been made with
regard to cumulative exposure with other compounds having a common mode
of action.

Further, triazole fungicides, including metconazole, have a common
primary metabolite, 1,2,4-triazole, with secondary metabolites
triazolylalanine and triazolacetic acid. EPA=s concern with these common
metabolites is being addressed with research conducted by the US
Triazole Task Force.  On the basis of this research, an interim human
health risk assessment for aggregate exposure to 1, 2, 4-triazole was
published in the Federal Register (40 CFR Part 180, Vol. 69 No. 149 Page
47005, 8/4/04) and will be refined once the research is complete.]	

	

E. Safety Determination

	1. U.S. population. Based on this risk assessment, Valent USA concludes
that there is a reasonable certainty that no harm will result to the
general population from the aggregate exposure to metconazole from the
pending and proposed use on canola.

	2. Infants and children. Based on this risk assessment, Valent USA
concludes that there is a reasonable certainty that no harm will result
to infants or children from the aggregate exposure to metconazole from
the pending and proposed use on canola.

F. International Tolerances

There are no CODEX maximum residue levels established or proposed for
residues of metconazole in canola.