Number range CHAPTER**FILE NAME:** **company.wpt (1/1/2005)** **(xml)**

**Template Number P25**

**ATTENTION:**

**All commodity terms must comply with the Food and Feed Commodity
Vocabulary database (http://www.epa.gov/pesticides/foodfeed**/**).**

**All text in blue font (instructions for preparing the document),
should be removed prior to sending the document to the Federal Register
Staff. Instructional text and prompts in green font should also be
removed.**

**COMPANY FEDERAL REGISTER DOCUMENT SUBMISSION TEMPLATE**

**(1/1/2005)**

**EPA Registration Division contact: \[Tony Kish, Product Manager 22
(703)-308-9443\]**

***TEMPLATE:***

**\[BASF Corporation\]**

**\[Insert petition number\]**

EPA has received a pesticide petition (**\[insert** **petition
number\]**) from **\[BASF Corporation\]**, **\[P.O. Box 13528, Research
Triangle Park, NC 27709\]** 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. by establishing a tolerance for residues of the
fungicide pyraclostrobin, carbamic acid,
\[2-\[\[\[1-(4-chlorophenyl)-1H-pyrazol-3-yl\]oxy\]methyl\]phenyl\]methoxy-,
methyl ester and its metabolite methyl-N-\[\[\[1-(4-chlorophenyl)
pyrazol-3-yl\]oxy\]o-tolyl\] carbamate (BF 500-3); expressed as parent
compound in or on the raw agricultural commodities: **borage at 0.45
ppm, castor oil plant at 0.45 ppm, Chinese tallowtree at 0.45 ppm,
crambe at 0.45 ppm, cuphea at 0.45 ppm, echium at 0.45 ppm, euphorbia at
0.45 ppm, evening primrose at 0.45 ppm, flax seed at 0.45 ppm, gold of
pleasure at 0.45 ppm, hare's ear mustard at 0.45 ppm, jojoba at 0.45
ppm, lesquerella at 0.45 ppm, lunaria at 0.45 ppm, meadowfoam at 0.45
ppm, niger seed at 0.45 ppm, milkweed at 0.45 ppm, mustard seed at 0.45
ppm, oil radish at 0.45 ppm, poppy seed at 0.45 ppm, rapeseed at 0.45
ppm, rose hip at 0.45 ppm, safflower at 0.45 ppm, sesame at 0.45 ppm,
stokes aster at 0.45 ppm, sunflower at 0.45 ppm, sweet rocket at 0.45
ppm, tallowwood at 0.45 ppm, tea oil plant at 0.45 ppm, and vernonia at
0.45 ppm**. EPA has determined that the petition contains 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
petition. Additional data may be needed before EPA rules on the
petition.

*A. Residue Chemistry*

1\. *Plant metabolism* Plant and animal metabolism. Nature of the
residue studies (OPPTS 860.1300) were conducted in grape, potato and
wheat as representative crops in order to characterize the fate of
pyraclostrobin in all crop matrices. Pyraclostrobin demonstrated a
similar pathway and fate in all three crops. In all three crops the
pyraclostrobin Residues of Concern (ROC) of were characterized as parent
(pyraclostrobin) and BAS 500-3), methyl-N\[\[\[1-(4-chlorophenyl)
pyrazol-3yl\]oxy\]o-tolyl\] carbamate. In hens the residues of concern
were determined to be parent compound and a hydroxlated metabolite, BAS
500-16. In goats the residues of concern were determined to be parent
and a hydroxylated metabolite BAS 500-10**.\]**. **\[Insert text.\]**

2\. *Analytical method***\[**In plants the method of analysis is aqueous
organic solvent extraction, column clean up and quantitation by
LC/MS/MS. In animals the method of analysis involves base hydrolysis,
organic extraction, column clean up and quantitation by LC/MS/MS or
derivatization (methylation) followed by quantitation by GC/MS.**\]**.
**\[Insert text.\]**

3\. *Magnitude of residues*. \[Field trials were conducted in NAFTA
growing regions 5, 7, 11, and 14 to establish the magnitude of the
residues in rapeseed. EPA has already established a tolerance for
residues of this chemical in sunflower. BASF is relying on the submitted
data in rapeseed and sunflower to satisfy the requirements for tolerance
for the above-listed commodities. All field trials were carried out
using the maximum labeled rates, maximum number of applications, and the
proposed pre-harvest interval**.\]**

*B. Toxicological Profile*

1\. *Acute toxicity*. Pyraclostrobin and its formulated products have
favorable acute toxicity. The acute toxicity studies place technical
pyraclostrobin in toxicity category IV for acute oral and acute
inhalation and category III for acute dermal. Pyraclostrobin is category
III for both eye and skin irritation, and it is not a dermal sensitizer.
Two formulated end use products are proposed, an Emulsifiable
Concentrate (EC) and an Extruded Granule (EG). The EC has an acute oral
toxicity category of II, acute dermal of III, acute inhalation of IV,
eye and skin irritation categories of III, and is not a dermal
sensitizer. The EG has acute oral and dermal toxicity categories of III,
acute inhalation of IV, eye irritation of III, skin irritation of IV and
is not a dermal sensitizer.

2\. *Genotoxicty*. Pyraclostrobin was negative for inducing mutations in
both an *in vitro* Ames test and an *in vitro* CHO/HGPRT Locus Mammalian
Cell Mutation Assay. Pyraclostrobin also demonstrated no chromosomal
effects in an *in vitro* V79 Cells CHO Cytogenetic Assay and *an in
vivo* Mouse Micronucleus test. An additional *in vitro* study
investigating DNA damage and repair also showed no effects.
Pyraclostrobin has been tested in a total of 5 genetic toxicology assays
consisting of *in vitro* and *in vivo* studies. It can be stated that
pyraclostrobin did not show any mutagenic, clastogenic or other
genotoxic activity when tested under the conditions of the studies
mentioned above. Therefore, pyraclostrobin does not pose a genotoxic
hazard to humans.

3\. *Reproductive and developmental toxicity*. The reproductive and
developmental toxicity of pyraclostrobin was investigated in a
2-generation rat reproduction study as well as in rat and rabbit
teratology studies. There were no adverse effects on reproduction,
systemic toxicity to adults or developmental toxicity in the
two-generation study so the NOAEL is the highest dose tested of 300 ppm
(approximately 32.6 mg/kg bw/day).

No teratogenic effects were noted in either the rat or rabbit
developmental studies. In the rat study, maternal toxicity observed at
the mid and high dose consisted of decreased food consumption and body
weight gain. Developmental changes noted at the high dose were increased
incidences of dilated renal pelvis and cervical ribs with no cartilage.
The maternal NOAEL was 10 mg/kg bw and the developmental NOAEL was 25
mg/kg bw.

In the rabbit teratology study, maternal toxicity observed at the mid
and high doses consisted of decreased food consumption and body weight
gain (severe at the high dose). An increased postimplantation loss was
also observed at the mid and high doses due to an increase in early
resorptions. In rabbits, these types of effects are often observed with
significant stress on the mothers (as seen by the body weight gain
decrease in this study) and not indicative of frank developmental
toxicity. The NOAEL for both maternal and developmental toxicity was 5
mg/kg bw.

4\. *Subchronic toxicity*. The subchronic toxicity of pyraclostrobin was
investigated in 90-day feeding studies with rats, mice and dogs, and in
a 28-day dermal administration study in rats. A 90-day neurotoxicity
study in rats was also performed. Generally, mild toxicity was observed.
At high dose levels in feeding studies, general findings in all three
species were decreased food consumption and body weight gain and a
thickening of the duodenum. Anemia occurred at high dose levels in both
rats and mice with accompanying extramedullary hematopoiesis of the
spleen in rats. In rats only, a finding of liver cell hypertrophy was
indicative of a physiological response to the handling of the chemical.
The lowest NOAEL in the 90-day feeding studies was from the dog study
and determined to be 5.8 mg/kg bw/day.

In the 28-day repeat dose dermal study, no systemic effects were noted
up to the highest dose tested of 250 mg/kg bw/day.

In a 90-day rat neurotoxicity study, a direct neurotoxic effect was not
observed.

5\. *Chronic toxicity*. Pyraclostrobin was administered to groups of 5
male and 5 female purebred Beagle dogs in the diet at concentrations of
0, 100, 200 and 400 ppm over a period of 12 months. Signs of toxicity
were observed at the high dose. Diarrhea was observed throughout the
study period for both sexes. High dose males and females initially lost
weight and body weight gain was decreased for the entire study period
for females. Hematological changes observed were an increase in white
blood cells in males, and an increase in platelets in both sexes at the
high dose. Clinical chemistry demonstrated a decrease in serum total
protein, albumin, globulins and cholesterol in high dose animals of both
sexes possibly due to the diarrhea and reduced nutritional status of the
animals. The NOAEL was 200 ppm (ca. 5.5 mg/kg bw/day males; 5.4 mg/kg
bw/day females).

In an oncogenicity study, pyraclostrobin was administered to groups of
50 male and 50 female Wistar rats at dietary concentrations of 0; 25;
75, and 200 ppm for 24 months. In a companion chronic toxicity study, 20
rats/sex were used at the same dose levels as in the oncogenicity study.
A body weight gain depression of 10-11% in males and 14-22% in females
with an accompanying decrease in food efficiency was observed at the
high dose. There was no evidence that pyraclostrobin produced a
carcinogenic effect in rats. The NOAEL for the chronic rat and the
cancer rat study is 75 ppm (ca. 3.4 mg/kg bw/day males; 4.7 mg/kg bw/day
females).

Pyraclostrobin was administered to groups of 50 male and 50 female
B6C3F1 mice at dietary concentrations of 0, 10, 30, 120 and 180 ppm
(females only) for 18 months. Body weights were reduced at the highest
doses tested in both males and females. At the high dose, body weight
gain decreases of 27% in females and 29% in males with an accompanying
decrease in food efficiency were observed. No other signs of toxicity
were noted at any dose level. The NOAEL was found to be 30 ppm (ca. 4.1
mg/kg bw/day) for males. The Agency determined that the body weight
effect at the high dose in females was not sufficient to determine an
MTD. Therefore the NOAEL for females is considered greater than the
highest dose tested of 32.8 mg/kg bw/day. There was no evidence that
pyraclostrobin produced a carcinogenic effect in mice.

***.*\]**

6\. *Animal metabolism*. In a rat metabolism study with pyraclostrobin,
10-13% of the administered dose was excreted in the urine and 74-91% in
the feces within 48 hours. Excretion via bile was significant accounting
for 35-38% of the administered dose. By 120 hours after dosing, very
little radioactivity remained in tissues. Pyraclostrobin was rapidly and
almost completely metabolized. Very little unchanged parent was
detected. The phase one biotransformation is characterized by
N-demethoxylation, various hydroxylations, cleavage of the ether bond
and further oxidation of the two resulting molecule parts. Conjugation
of the formed hydroxyl groups by glucuronic acid or sulfate also
occurred. In summary, pyraclostrobin is extensively metabolized and
rapidly eliminated primarily via the bile, with no evidence of
accumulation in tissues.

7\. *Metabolite toxicology*. A comparison of the rat metabolism results
with the plant metabolism/residue results indicates that toxicology
studies performed with the parent pyraclostrobin are sufficient to cover
dietary exposure. Plant residues are primarily the parent compound with
a fraction (up to 10-20% at most) being the demethoxylated parent. This
metabolite is referred to as BF 500-3 in the plant studies and as 500M07
in the rat study. This metabolite in the rat is the first step in the
major biotransformation process leading to the majority of the
metabolites determined in the major excretion pathway.

8\. *Endocrine disruption*. Endocrine effects. No specific tests have
been conducted with pyraclostrobin to determine whether the chemical may
have an effect in humans that is similar to an effect produced by a
naturally occurring estrogen or other endocrine effects. However, there
were no significant findings in other relevant toxicity studies (i.e.,
subchronic and chronic toxicity, teratology and multi-generation
reproductive studies) which would suggest that pyraclostrobin produces
endocrine related effects.

*C. Aggregate Exposure*

1\. *Dietary exposure*. Exposure assessments were conducted to evaluate
the potential risk due to acute and chronic dietary exposure of the U.S.
population to residues of pyraclostrobin. This fungicide and its
desmethoxy metabolite, in or on raw agricultural commodities, and
metabolites in or on animal fat, liver, meat and meat byproducts were
expressed as the parent compound. The tolerance values previously
established for various cereals, vegetables, fruits, and animal products
are listed in the U.S. EPA final rule published in the Federal Register
October 29, 2004 (Vol 69, No. 209, p 63083 -- 63100) and U.S. 40 CFR §
180.582. This analysis included all current and proposed tolerance
values for pyraclostrobin.

The pyraclostrobin chronic reference dose (cRfD) is 0.034 mg/kg bw/day
based on the NOAEL of 3.4 mg/kg bw/day in the rat chronic toxicity study
and a 100X safety factor. The acute reference dose (aRfD) is 3 mg/kg
b.w./day for the general population based on a NOAEL from the acute
neurotoxicity study of 300 mg/kg bw/day and a 100X safety factor. For
females of child bearing years (13-49 years), the aRfD is 0.05 mg/kg
b.w./day based on the NOAEL of 5 mg/kg bw/day from the rabbit teratology
study and a 100X safety factor. The EPA determined that the FQPA safety
factor should be 1X for all exposure scenarios. Therefore, the acute
Population Adjusted Dose (aPAD) and the chronic Population Adjusted Dose
(cPAD) are the same as the aRfD and cRfD, respectively.

i\. *Food*.

[Acute Dietary Exposure Assessment]{.underline}

The acute dietary exposure estimates were based on tolerance values,
default process factors, 100% crop treated values for all commodities
except for leafy vegetables, pome fruit, stone fruit, and citrus crop
groups where the percent crop treated (%CT) values listed in the U.S.
EPA document DP Barcode No. D323632 (November 30, 2005) were utilized.
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 acute population adjusted dose (aPAD) used for females 13-49 years
of age was 0.05 mg/kg bw/day and 3.0 mg/kg bw/day for all other
sub-populations. Considering the exposure assumptions discussed above,
pyraclostobin acute dietary exposure from food is less than 5.1 % aPAD
for the U.S. population and all sub-populations except females 13-49
years of age that occupies 85.4 % of the aPAD. The results of the acute
dietary assessment are presented in Table 1.

Table 1. Results for Pyraclostrobin Acute Dietary Exposure Analysis
Considering all Current and Proposed Tolerances Including the Proposed
Crops Using DEEM-FCID at the 95^th^ Percentile

  ------------------------ ------------------------ ---------------------
  **Population**           **Exposure Estimate**    **%aPAD**

  **Subgroups**            **(mg/kg b.w./day)\***   ** **

  U.S. Population          0.056138                 1.87

  All Infants (\< 1 year   0.12302                  4.10
  old)                                              

  Children (1-2 years old) 0.148364                 4.95

  Children (3-5 years old) 0.106797                 3.56

  Children (6-12 years     0.061887                 2.06
  old)                                              

  Youth (13-19 years old)  0.042725                 1.42

  Females (13-49 years     0.042689                 85.38
  old)                                              

  Adults (20-49 years old) 0.041876                 1.40

  Adults (50+ years old)   0.041314                 1.38
  ------------------------ ------------------------ ---------------------

aPAD = acute population adjusted dose

\* Exposure Estimate (95^th^ percentile) was based on tolerance values,
default processing factors, and considering 100% crop treated for all
commodities except for leafy vegetables, pome fruit, stone fruit, and
citrus fruit groups which included the percent crop treated values
listed in U.S. EPA document DP Barcode No. D323632 (November 30, 2005)

The results of the analysis show that for all sub-populations, the
exposures are below the Agency\'s level of concern (\< 100% aPAD).
Additional refinements in the dietary risk assessment (i.e. utilizing
anticipated residue values, process factors, percent crop treated values
for all crops) would further reduce the estimated exposure values.

[Chronic Dietary Exposure Assessment]{.underline}

The chronic dietary exposure estimates were based on tolerance values
for all commodities with the exception that anticipated residues were
utilized for leafy vegetables, apples, and pears; default process
factors; % crop treated values listed in the U.S. EPA document DP
Barcode No. D323632 (November 30, 2005); and 100% crop treated values
for the proposed crop uses. 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
tolerance values included 0.45 ppm for the proposed crop uses.

The chronic population adjusted dose (cPAD) used for U.S. population and
all sub-populations is 0.034 mg/kg bw/day. Considering the exposure
assumptions discussed above, pyraclostobin chronic dietary exposure from
food for the U.S. population was 16.0 % of the cPAD. The most highly
exposure population sub group was children 1-2 years of age at 47.3%
cPAD. The results of the chronic dietary assessment are presented in
Table 2.

Table 2. Results for Pyraclostrobin Chronic Dietary Exposure Analysis
Considering all Current and Proposed Tolerances Including the Proposed
Crops Using DEEM-FCID

  -------------------------- ----------------------- --------------------
  **Population**             **Exposure Estimate**   **%cPAD**

  **Subgroups**              **(mg/kg b.w./day)**    ** **

  U.S. Population            0.005447                16.0

  All Infants (\< 1 year     0.011588                34.1
  old)                                               

  Children (1-2 years old)   0.016084                47.3

  Children (3-5 years old)   0.012817                37.7

  Children (6-12 years old)  0.007984                23.5

  Youth (13-19 years old)    0.004461                13.1

  Females (13-49 years old)  0.003899                11.5

  Adults (20-49 years old)   0.004061                11.9

  Adults (50+ years old)     0.00422                 12.4
  -------------------------- ----------------------- --------------------

cPAD = chronic population adjusted dose

\* Exposure estimates based on tolerance values for all commodities with
the exception of anticipated residues for leafy vegetables, apples, and
pears; default processing factor; and considering % crop treated values
listed in the U.S. EPA document DP Barcode No. D323632 (November 30,
2005); and 100% crop treated values for the proposed crop uses.

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 for all crops) would further reduce the
estimated exposure values.

ii\. *Drinking water*. Based on the PRZM/EXAMS and SCIGROW models, the
peak EDWCs of pyraclostrobin for acute exposure are estimated to be 22.6
ug/L (ppb) in surface water and 0.02 ug/L in shallow ground water. The
peak EDWCs for chronic exposure are estimated to be 1.9 ug/L in surface
water and 0.02 ug/L in shallow ground water. These concentrations are
based on maximum applications to turf, which have the highest labeled
application rate of any pyraclostrobin use.

Drinking water contributions were assessed based on the maximum
estimated pyraclostrobin water concentrations (acute - 22.6 ug/L,
chronic 1.9 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 pyraclostrobin occurs through drinking water with \< 0.5%
the aPAD and cPAD for all subpopulations with the exception of females
13-49 years of age with a 2.2% aPAD.

Table 3. Results for Pyraclostrobin Acute Water Exposure Analysis
Considering the Maximum Estimated Acute Drinking Water Concentration
using

> DEEM-FCID

  -------------------------- ----------------------- --------------------
  **Population**             **Water Exposure        **%aPAD**
                             Estimate**              

  **Subgroups**              **(mg/kg b.w./day)**    ** **

  U.S. Population            0.001181                0.04

  All Infants (\< 1 year     0.004451                0.15
  old)                                               

  Children (1-2 years old)   0.001852                0.06

  Children (3-5 years old)   0.001692                0.06

  Children (6-12 years old)  0.001178                0.04

  Youth (13-19 years old)    0.000958                0.03

  Females (13-49 years old)  0.001100                2.20

  Adults (20-49 years old)   0.001094                0.04

  Adults (50+ years old)     0.000988                0.03
  -------------------------- ----------------------- --------------------

aPAD = acute population adjusted dose

Based on estimated acute surface water value of 22.6 ug/L

[]{.mark}

Table 4. Results for Pyraclostrobin Chronic Water Exposure Analysis
Considering the Maximum Estimated Chronic Drinking Water Concentration
using DEEM-FCID

  -------------------------- ----------------------- --------------------
  **Population**             **Water Exposure        **%cPAD**
                             Estimate**              

  **Subgroups**              **(mg/kg b.w./day)**    ** **

  U.S. Population            0.00004                 0.1

  All Infants (\< 1 year     0.000131                0.4
  old)                                               

  Children (1-2 years old)   0.000059                0.2

  Children (3-5 years old)   0.000056                0.2

  Children (6-12 years old)  0.000038                0.1

  Youth (13-19 years old)    0.000029                0.1

  Females (13-49 years old)  0.000037                0.1

  Adults (20-49 years old)   0.000037                0.1

  Adults (50+ years old)     0.000039                0.1
  -------------------------- ----------------------- --------------------

cPAD = chronic population adjusted dose

Based on estimated chronic surface water value of 1.9 ug/L

[Acute Aggregate Exposure and Risk (Food and water)]{.underline}

The aggregate acute risk includes residues of pyraclostrobin 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 established and new
uses, and that the results clearly meet the FQPA standard of reasonable
certainty of no harm.

Table 5. Estimated Acute Aggregate Exposure and Risk of Pyraclostrobin

  ------------------ --------------- --------------- --------------- --------------- --------
  **Population       **aPAD          **Food Exposure **Water         **Total         **%
  Subgroup**         (mg/kg/day)**   (mg/kg/day)**   Exposure        Exposure        aPAD**
                                                     (mg/kg/day)**   (mg/kg/day)**   

  U.S. Population    3               0.056138        0.001181        0.057319        1.91

  All Infants (\< 1  3               0.12302         0.004451        0.127471        4.25
  yr old)                                                                            

  Children 1-2 years 3               0.148364        0.001852        0.150216        5.01

  Children 3-5 years 3               0.106797        0.001692        0.108489        3.62

  Children 6 -- 12   3               0.061887        0.001178        0.063065        2.10
  years                                                                              

  Youth 13-19 years  3               0.042725        0.000958        0.043683        1.46

  Females 13-49      0.05            0.042689        0.0011          0.043789        87.58
  years                                                                              

  Adults 20-49 years 3               0.041876        0.001094        0.04297         1.43

  Adults + 50        3               0.041314        0.000988        0.042302        1.41
  ------------------ --------------- --------------- --------------- --------------- --------

[Short- and Intermediate Term Aggregate Exposure and Risk (food,water,
and residential)]{.underline}

Short-term aggregate risk from pyraclostrobin takes into account
exposures from dietary consumption (food and water) and residential
exposure from turf use. Post application exposure from the turf use is
considered short-term. The aggregate MOE from food, water, and
residential exposure are 110 and 237 for the children 1-2 years old and
the US population, respectively. These MOE are greater than the target
MOE of 100 which indicates there is no safety concern. The results of
the analysis are shown in Table 6.

Table 6. Estimated Short/Intermediate Term Aggregate Exposure and Risk
of Pyraclostrobin

  ---------------- --------------- ---------- --------------- --------------- --------------- --------------- ------------
  **Population**   **NOAEL         **Target   **Food Exposure **Water         **Residential   **Total         **MOE^3^**
                   (mg/kg/day)**   MOE^1^**   (mg/kg/day)**   Exposure        Exposure^2^     Exposure        
                                                              (mg/kg/day)**   (mg/kg/day)**   (mg/kg/day)**   

  US               5.8             100        0.005447        0.00004         0.019           0.024487        237

  Child 1-2 yr old 5.8             100        0.016084        0.000059        0.036425        0.052568        110
  ---------------- --------------- ---------- --------------- --------------- --------------- --------------- ------------

**^1^** Target MOE is 100.

**^2^** Residential Exposure = Exposure to adult while playing golf.

**^3^** Aggregate MOE = (NOAEL / (Food + Water + Residential Exposure)

[Chronic Aggregate Exposure and Risk (food and water)]{.underline}

The aggregate chronic risk includes residues of pyraclostrobin from food
and water (Table 7). Exposures from residential uses are not included in
the chronic aggregate assessment. The results demonstrate there are no
safety concerns for any subpopulation based on established and new uses,
and that the results clearly meet the FQPA standard of reasonable
certainty of no harm.

**Table 7. Estimated Chronic Aggregate Exposure and Risk of
Pyraclostrobin**

  ------------------ --------------- --------------- --------------- --------------- --------
  **Population       **cPAD          **Food Exposure **Water         **Total         **%
  Subgroup**         (mg/kg/day)**   (mg/kg/day)**   Exposure        Exposure        cPAD**
                                                     (mg/kg/day)**   (mg/kg/day)**   

  U.S. Population    0.034           0.005447        0.00004         0.005487        16.14

  All Infants (\< 1  0.034           0.011588        0.000131        0.011719        34.47
  yr old)                                                                            

  Children 1-2 years 0.034           0.016084        0.000059        0.016143        47.48

  Children 3-5 years 0.034           0.012817        0.000056        0.012873        37.86

  Children 6 -- 12   0.034           0.007984        0.000038        0.008022        23.59
  years                                                                              

  Youth 13-19 years  0.034           0.004461        0.000029        0.00449         13.21

  Females 13-49      0.034           0.003899        0.000037        0.003936        11.58
  years                                                                              

  Adults 20-49 years 0.034           0.004061        0.000037        0.004098        12.05

  Adults + 50        0.034           0.00422         0.000039        0.004259        12.53
  ------------------ --------------- --------------- --------------- --------------- --------

[Aggregate Cancer Risk for U.S. Population]{.underline}

The aggregate MOE value (considering food and drinking water) was
calculated for pyraclostrobin and is shown in Table 8. The 36-year
average of pyraclostrobin in surface water that was estimated by
PRZM/EXAMS for use in the chronic/cancer risk assessment is 1.2 ug/L.
The results demonstrate there are no safety concerns for US population
based on established and new uses, and that the results clearly meet the
FQPA standard of reasonable certainty of no harm.

**Table 8. Aggregate Cancer Risk of Pyraclostrobin to the U.S.
Population**

  ---------------- --------------- --------------- --------------- --------------- ---------
  **Population**   **NOAEL         **Food Exposure **Water         **Total         **Total
                   (mg/kg/day)**   (mg/kg/day)**   Exposure        Exposure        MOE**
                                                   (mg/kg/day)**   (mg/kg/day)**   

  U.S. Population  32.80           0.005447        0.000025        0.005472        5994
  ---------------- --------------- --------------- --------------- --------------- ---------

2\. *Non-dietary exposure*. Pyraclostrobin is registered for use on
residential and recreational turf. The applications to turf will be made
only by professional pest control operators. Therefore, residential
handler exposure was not evaluated. The exposure assessment cited in
this notice of filing was transcribed from the most recent Federal
Register Notice on pyraclostrobin (U.S. EPA final rule published in the
Federal Register October 29, 2004 \[Vol 69, No. 209, p 63083 -- 63100).
The EPA evaluated the following post-application exposure scenarios 1)
adults and toddler post-application dermal exposure 2) toddlers'
incidental ingestion of pesticide residues on lawns form hand-to-mouth
transfer, 3) toddlers' object-to-mouth transfer from mouthing
pesticide-treated turfgrass, and 4) toddlers' incidental ingestion of
soil from pesticide-treated residential areas. The post-application
exposure assessment was based on generic assumptions specified in the
Recommended Revisions to the Residential Standard Operating Procedures
and recommended approaches by an EPA science advisory council. A dermal
absorption value of 14% was used in the assessment of pyraclostrobin.
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*

Section 408(b)(2)(D)(v) requires that, when considering whether to
establish, modify, or revoke a tolerance, the Agency consider
\`\`available information\'\' concerning the cumulative effects of a
particular pesticide\'s residues and \`\`other substances that have a
common mechanism of toxicity.\' Pyraclostrobin is a foliar fungicide
which belongs to the new class of strobilurin chemistry. It is a
synthetic analog of strobilurin A, a naturally occurring antifungal
metabolite of the mushroom *Strobillurus tenacellus* (Anke et. al.,
1977). The active ingredient acts in the fungal cell through inhibition
of electron transport in the mitochondrial respiratory chain at the
position of the cytochrome-bc1 complex. The protective effect is due to
the resultant death of the fungal cells by disorganization of the fungal
membrane system. Pyraclostrobin also acts curatively to prevent the
increase and spread of fungal infections by inhibiting mycelial growth
and sporulation on the leaf surface. Pyraclostrobin inhibits spore
germination, germ tube growth and penetration into the host tissues

The EPA is currently developing methodology to perform cumulative risk
assessments. At this time, there is no available data to determine
whether pyraclostrobin has a common mechanism of toxicity with other
substances or how to include this pesticide in a cumulative risk
assessment. Unlike other pesticides for which EPA has followed a
cumulative risk approach based on a common mechanism of toxicity,
pyraclostrobin does not appear to produce a toxic metabolite common to
other substances.

*E. Safety Determination*

1\. *U.S. population*. Based on this risk assessment, BASF concludes
that there is a reasonable certainty that no harm will result to the
general population from the aggregate exposure to pyraclostrobin
residues.

2\. *Infants and children*. Based on this risk assessment, BASF
concludes that there is a reasonable certainty that no harm will result
to infants or children from the aggregate exposure to pyraclostrobin
residues.

*F. International Tolerances*

No Codex or Mexican maximum residue levels (MRLs) have been proposed or
are established for residues of pyraclostrobin. Therefore, no tolerance
discrepancies exist between countries for this chemical. Since the
application for registration of pyraclostrobin was reviewed jointly with
the Pest Management Regulatory Agency (PMRA) of Canada, several Canadian
MRLs for pyraclostrobin are proposed and are expected to be published
soon. However, the joint review is expected to have eliminated the
potential for discrepancies between U.S. tolerances and Canadian MRLs.