Document ID: EPA-HQ-OPP-2008-0173-0002
Agency: epa
Document Type: Supporting & Related Material
Title: 
Posted Date: 2008-04-16T04:00Z

<EPA REGISTRATION DIVISION COMPANY NOTICE OF FILING FOR PESTICIDE
PETITIONS PUBLISHED IN THE FEDERAL REGISTER  (2/18/2008)>

<EPA Registration Division contact: 

[Akiva Abramovitch,  

Registration Division (7505P) 

Office of Pesticides Programs

Environmental Protection Agency

1200 Pennsylvania Avenue

Washington, DC 20460-0001

Telephone: 703-308-8328

E-Mail Address: abramovitch.akiva@epa.gov>

 

<INSTRUCTIONS:  Please utilize this outline in preparing the pesticide
petition.  In cases where the outline element does not apply, please
insert “NA-Remove” and maintain the outline. Please do not change
the margins, font, or format in your pesticide petition. Simply replace
the instructions that appear in green and brackets, i.e., “[Dow
AgroSciences, LLC],” with the information specific to your action.>

<TEMPLATE:>

<[ Dow Agro Sciences LLC]>

<[7F7248, 3F4188 and 3H5662]>

<	EPA has received pesticide petitions (7F7248, 3F4188 and 3H5662]) from
[Dow Agro Sciences LLC], [9330 Zionsville Road, Indianapolis, IN-46268]
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.>

<(Options (pick one)>

<	1. by establishing a tolerance for residues of>

<	[chlorpyrifos] in or on the raw agricultural commodity [Crop group 17,
grass, forage] at [11] parts per million (ppm), [Crop group 17, grass,
hay] at [30] parts per million (ppm), [barley, grain] at [0.5] parts per
million (ppm), [barley, straw] at [2] parts per million (ppm), [barley,
hay] at [3] parts per million (ppm), and [barley, milled feed fractions]
at [1] parts per million (ppm).  A tolerance amendment is also needed
for [Cattle, fat] at [0.6] parts per million (ppm), [Goat, fat] at [0.4]
parts per million (ppm), [Horse, fat] at [0.5] parts per million (ppm),
[Hog, fat] at [0.4] parts per million (ppm) and [Sheep, fat] at [0.4]
parts per million (ppm).  EPA has determined that the petition contains
data or information regarding the elements set forth in section 408
(d)(2) of  FDDCA; 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. [The qualitative nature of chlorpyrifos residues
in plants and animals is adequately understood and was previously deemed
acceptable by the US-EPA in the publication of June 20, 2000,
Chlorpyrifos. Revised Product and Residue Chapters of the HED Chapter of
RED.  The primary metabolite is known to be 3,5,6-trichloro-2-pyridinol
(TCP).]>

<	2. Analytical method. [Adequate enforcement methods are available for
determination of chlorpyrifos residues in plant and animal commodities. 
The available Analytical Enforcement Methodology was previously reviewed
in the June 20, 2000, Chlorpyrifos. Revised Product and Residue Chapters
of the HED Chapter of RED.]>

<	3. Magnitude of residues. [Complete residue data for chlorpyrifos on
mixed-grasses, (Crop group 17: Grass, hay and Grass, forage) has been
submitted by Dow AgroSciences (R. W. McCormick, G. A. Schelle, 2005,
Magnitude of Residue of Chlorpyrifos and 3.5.6-Tricloro-2-pyridinol
(TCP) in Grass Forage and Hay, Dow AgroSciences unpublished report study
ID 040028).   The magnitude of residue of chlorpyrifos were determined
by twelve trials following three foliar broadcast applications of
Lorsban* 75 and Lorsban* 4E insecticide, at rates of 0.25, 0.5 and 1.0
lb ai/A. The PHI was 7, 14, and 21 days for the three tested rates,
respectively.

The impact on animal dietary burden from the use on grasses has
previously been assessed by Dow AgroSciences and submitted to the EPA
(C. Tiu, Chlorpyrifos in or on Mixed Grasses: Section E, F and G of the
Petition for Permanent Tolerances, Dow AgroSciences Internal Report,
Study # 061039).  Existing and newly proposed uses involve crops
commonly used as feed for livestock: non-grass animal feed crops, such
are alfalfa and clover, mixed grasses, corn, soybeans, cereals, etc.
were considered.  The animal dietary burden was reviewed and only a
doubling of the meat fats was proposed to accommodate the new uses. 
Poultry was not affected.  This current NOF now clarifies the doubling
for each individual meat fat type based on the tolerances announced by
EPA via the Proposed Rule of August 2007 (Federal Register, Vol 72 No
152, Section 180.342, August 8, 2007).  The requested meat fat
tolerances are adequately supported.

Residue data for chlorpyrifos in and on barley has previously been
submitted by Dow AgroSciences in two studies (C. K. Robb, B. A. Schotts,
Residues of Chlorpyrifos in Barley After Ground and Aerial Applications
of LORSBAN 4E Insecticide – Residue Study to Provide Data fro
Tolerance and Registration, Internal Report of Dow AgroSciences, GH-C
2756, 1992; E. M. Bargar, Magnitude of Residue of Chlorpyrifos in
Barley, Internal Report of Dow AgroSciences, GH-C 4132, 1996).  Jointly
these studies provide information on ground applications at 11 sites. 
The maximum observed residues of chlorpyrifos in or on barley hay,
barley grain, and barley straw were 1.79, 0.26 and 1.09 ppm,
respectively.  The estimated dietary burden input for barley was
reviewed relative to the previously submitted animal feeding studies. 
The existing residue tolerance for meat, milk, poultry and eggs are not
expected to be exceeded by the proposed use of chlorpyrifos on barley
crops (E. Bargar, E. Day, Amendment to Tolerance Petition for
Chlorpyrifos in Barley, GH-C 4180, Internal Report of DowAgroSciences,
GH-C 4180, 1996).  Substitution of barley into the mix of existing
animal feeds with potential chlorpyrifos residues does not impact the
tolerance.  The requested tolerances are adequately supported.]>

<B. Toxicological Profile [The toxicological profile and endpoints for
chlorpyrifos which supports this petition to establish tolerances were
previously published in the IRED document published as of July 31, 2006,
Finalization of Interim Reregistration Eligibility Decision (IREDs) and
Interim Tolerance Reassessment and Risk Management Decisions (TRED’s)
for the Organophosphate Pesticides, and Completion of the Tolerance 
Reassessment and Reregistration Eligibility Process for the
Organophosphate Pesticides.]>

<	1. Acute toxicity.  [as per the IRED, February, 2002 (EPA
738-R-01-007), an acute toxicological endpoint was established by the
agency based on cholinesterase (ChE) inhibition (28-40%) after exposure
of male rats to 1 mg/kg/day (Mendrala and Brzak, 1998). The acute
reference dose was established by the Agency, aRfD = 0.005 mg/kg/day,
based on a NOAEL = 0.5 mg/kg/day, and uncertainty factor of 100. The
reference dose was adjusted for susceptible population subgroups
(infants, children, females 13-50) by applying an additional FQPA = 10x
(aPAD = 0.0005 mg/kg/day).]>

<	2. Genotoxicty. [Per the Human Health Risk Assessment for chlorpyrifos
issued by the EPA June 8, 2000, chlorpyrifos was evaluated for
carcinogenic potential in both rats (2 >studies), and mice (2 studies).
There was no evidence of carcinogenicity.  Chlorpyrifos is not mutagenic
in bacteria, or mammalian cells, but did cause slight genetic
alterations in yeast and DNA damage to bacteria. In addition,
chlorpyrifos did not induce chromosome aberrations in vitro, was not

clastogenic in the mouse micronucleus test in vivo, and failed to induce

unscheduled DNA synthesis in isolated rat hepatocytes.]

<	3. Reproductive and developmental toxicity. [Per the Human Health Risk
Assessment for chlorpyrifos issued by the EPA June 8, 2000, based on
review of several studies for developmental toxicity in rats, mice and
rabbits, the EPA retained the 10X FQPA safety factor.  Their assessment
is summarized as follows:  In one rat study, developmental effects were
noted at 15 mg/kg/day (highest dose tested, HDT), that were also
associated with maternal toxicity, while another rat study failed to
observe developmental effects at 15 mg/kg/day.  Developmental effects
were also noted at higher doses in mice at 25 mg/kg/day and rabbits at
140 mg/kg/day. In both mice and rabbits, the developmental effects
occurred at maternally toxic doses.  Relative to evaluation of
reproductive toxicity using standard guideline methods, chlorpyrifos
induced reproductive toxicity in one generation of rats, but only at
dose levels that induced parental toxicity.>

From the June, 2000 risk assessment, the EPA reported that chlorpyrifos
was associated with delayed alterations in rat brain development in
offspring of exposed mothers from the developmental neurotoxicity study.
 Specifically, pups of the 1 mg/kg/day group exhibited significant dose-
and treatment-related decreases in measurements of the parietal cortex
in female offspring.  Subsequest historical control morphometric data
have since been generated and submitted that indicate this observation
was within the range of normal variation.

In the June 2000 risk assessment, the EPA notes that several studies in
the peer reviewed literature and results of the guideline developmental
neurotoxicity study are supportive of the possibility that chlorpyrifos
exposure may affect brain development.  The EPA noted that there are
suggestive data that these effects may arise independent of
cholinesterase inhibition.  After subsequent review, (USEPA, Revised OP
Cumulative Risk Assessment, June 10 2002) of this literature, the EPA
reported that developmental effects are not likely to occur at doses
below those associated with inhibition of cholinesterase.]

<	4. Subchronic toxicity. [Per the Human Health Risk Assessment for
Chlorpyrifos issued by the EPA June 8, 2000, the EPA has established a
Dermal NOAEL of 5 mg/kg/day with for short-term dermal regulation based
on the 21-day dermal rat study.  Likewise, the EPA has established an
Inhalation NOAEL = 0.1 mg/kg/day based on two 90 day rat inhalation
studies and the developmental neurotoxicity study.  An MOE of 100 is
established for worker and males.   An MOE of 1000 is established for
susceptible population subgroups (infants, children, females 13-50).]>

<	5. Chronic toxicity. [The reference for chronic toxicological endpoint
(cRfD) was set by the Agency based on significant plasma and red blood
cells (RBC) ChE inhibition at a LOAEL = 0.22 to 0.3 mg/kg/day across
five studies (1 year dog, 90 day dog, 2 year rat, 90 day rat,
developmental neurotoxicity in rat). Therefore the cRfD = 0.0003
mg/kg/day. The reference dose was adjusted for susceptible population
subgroups (infants, children, females 13-50) by applying an additional
FQPA = 10x (cPAD = 0.00003 mg/kg/day).]>

<	6. Animal metabolism. [Nature of residue studies, conducted in goats
and hens have shown that the metabolic pathway involves the conversion
of chlorpyrifos to 3,5,6-trichloropyridinol (TCP).

>

<	7. Metabolite toxicology. [The primary metabolite is known to be
3,5,6-trichloropyridinol (TCP).  The EPA Toxicology Branch has concluded
that TCP is not of toxicological concern.  TCP is not included in the
tolerance expression or considered for dietary assessment purposes.]>

<	8. Endocrine disruption. [Chlorpyrifos has been extensively studied
for a wide range of biological effects, including effects on endocrine
function.  No endocrine effects have been found in experimental animals
that have been exposed to very high levels of chlorpyrifos (several
thousands of times higher than human exposure) from conception to birth
to adulthood to old age.  Toxicologists at regulatory agencies
throughout the world evaluate these chlorpyrifos studies, and endocrine
effects have not been identified as an issue.]>

<C. Aggregate Exposure [

>

xposure Evaluation Model™ (DEEM-FCID, version 2.16, Exponent, Inc.,
Washington, DC-20036) was used for conduct of acute and chronic dietary
risk analyses.  DEEM is used to estimate exposure to a pesticide
chemical in foods comprising the diets of the U.S. population, including
population subgroups.  DEEM contains food consumption data as reported
by respondents to the USDA Continuing Surveys of Food Intake by
Individuals (CSFII) conducted in 1994-1996 and 1998 and food translation
to Raw Agricultural Commodities (RACs), as indicated by EPA/USDA FCID
recipe set as of August, 2002.  Exposures were assessed against the aPAD
and the cPAD, for the acute and chronic scenarios, respectively.]>

<	i. Food. [The highly refined Tier III/IV dietary assessments issued by
EPA (US EPA, Memorandum Chlorpyrifos, Acute Dietary Risk Assessment for
Chlorpyrifos, Revised after Public Comments: Chemical No. 59101: DP
Barcode D263890, June 22, 2000; US EPA, Memorandum Chlorpyrifos. Chronic
Exposure Assessment for Chlorpyrifos RED with Updated Values for
Anticipated Residues, Revised After Public Comments: Chemical No. 59101:
DP Barcode D263889, June 22, 2000) have been updated by Dow
AgroSciences.  General methodology established by the EPA (Human Health
Risk Assessment for Chlorpyrifos issued by the EPA June 8, 2000) was
followed for the highly refined acute probabilistic dietary exposure and
the corresponding chronic exposure analysis.  PDP (  HYPERLINK
"http://www.ams.usda.gov/science/pdp/Download.htm" 
http://www.ams.usda.gov/science/pdp/Download.htm ) and FDA Pesticide
Program Residue Monitoring (  HYPERLINK
"http://www.cfsan.fda.gov/~dms/pesrpts.html" 
http://www.cfsan.fda.gov/~dms/pesrpts.html ) data were used to the
greatest extent possible, along with field trial data, and cooking and
processing factors to assess dietary exposures.

The updated assessment covers the comprehensive listing of tolerances
announced by EPA via the Proposed Rule of August 2007 and incorporates
new monitoring data which is available primarily from USDA PDP (2002 to
2006).  Data from FDA has been incorporated for a few key commodities. 
For several blended commodities, average residue data from trials was
adjusted for percent crop treated (PCT).  In a few instances tolerance
values were used instead of residue or monitoring data.  Most notably
the grape tolerance of 0.01 ppm was employed; with enforcement of the
tolerance, exposure is reduced and the PDP monitoring data is not
applicable.  Based on market data from Doane, minor shifts in overall
percent crop treated (PCT) values which have occurred have been included
in the updated assessments.  Over 60 individual residue (RDF) files were
used in the updated acute assessment; most were created from the newer
monitoring data; a very few were reused from the older 2000 assessment
previously conducted by EPA.

The updated assessments were used as a starting point to assess the
impact of the proposed uses in barley and grasses for this petition. 
The updated assessment relied on the 2002 PDP data of beef adipose with
no detection of chlorpyrifos above the LOD of 2.8 ppb to derived an
average residue value for the chronic assessment and to create a RDF
file for the acute assessment.  These were used for the fats of beef,
goat, and sheep.   The 2005 PDP data on 353 pork adipose samples with
only 1 residue at 2.5 ppb above the LOD of 1.5 ppb was used in a similar
fashion for pork fat.  To assess the dietary impact of the grasses, the
monitoring average for these fats was doubled for the chronic assessment
and a factor of 2 was applied in DEEM to the RDF files for the acute
assessment.  A doubling of the value derived from the monitoring is
believed to be adequate, given the extremely low detection rate
historically observed.

The anticipated residue in barley is based upon average field trial
results of 0.084 ppm and an estimate of 10.0 % crop treated; current
grain crops (corn, sorghum and wheat) have PCT values of 5% or less. 
The resulting average anticipated residue of 0.0084 ppm was applied
barley.  As applicable, wheat processing factors from the 2000
assessment were adopted.]>

<	ii. Drinking water. [To account for water exposure, the most recent
PDP data sets for various water analyses over all years from 2002 to
2005 were used as direct input to DEEM.  PDP results were reported as
four types of water: bottled water, finished water, drinking water and
unfinished water in a total of 3614 analyzed samples.  In all cases, no
observable residues were reported.  The LODs ranged from 30 ppt to 6
ppt, so an average weighted LOD of 15.45 ppt was calculated from all
observations.  A value of ½ this LOD was used in DEEM for both
“Water, direct, all sources” and “Water, indirect, all sources”.
 The recent PDP data information on water is congruent with historical
drinking water monitoring data which shows no detectable residues in
finished drinking water supplies. (Blomquist, et al., 2001. Pesticides
in Selected Water-Supply Reservoirs and Finished Drinking Water,
1999-2000: Summary of Results from a Pilot Monitoring Program. 
Open-File Report 01-456, US Geological Survey).]>

<	2. Non-dietary exposure. [Non-dietary exposure to chlorpyrifos is now
extremely limited.  Containerized baits in child-resistant packaging is
the only residential use which may be applied by the homeowners. The
Agency has concluded that this use is not expected to results in
exposures of concern.  Therefore, there is no non-dietary acute,
chronic, short- or intermediate-term exposure applicable.  For further
details, refer to the Human Health Risk assessment for Chlorpyrifos,
June 8, 2000.

Residential post application exposure may occur when people enter a
treated golf course, or following application for mosquito control by a
public agency. This residential exposure is expected to be of short-term
duration (one day to one month). The Agency has published the conclusion
of the residential assessment.  For residential post application risk,
the target MOE is 1000, or greater.  In summary for golfers exposed post
application of 1 lb ai/A, MOE’s are 1,500 to 2,400. Following aerial
and ground-based fogger mosquito adulticide use, MOEs are 17,000 and
29,000 for children and adults, respectively. For further details, refer
to the Human Health Risk assessment for Chlorpyrifos, June 8, 2000.

An aggregate risk assessment combines risk from dietary exposure (food
and drinking water) and residential exposure (post-application of adults
and children from treated golf courses and mosquito control campaigns). 
The acute, short-term and chronic aggregate assessments by the Agency in
the published IRED for chlorpyrifos remain sufficient.  The resulting
values of this updated assessment for current dietary and water
exposures are comparable or less than those assumed post-mitigation for
the previous aggregate assessment.  No additional assessments are needed
and adequate MOEs are achieved.]>

<D. Cumulative Effects>

<	[Section 408(b)(2)(D)(v) requires that, when considering whether to
establish, modify, or revoke a tolerance, the Agency considers
“available information” concerning the cumulative effects of a
particular pesticide’s residues and “other substances that have a
common mechanism of toxicity.”  EPA has completed its assessment of
cumulative risks from the organophosphate (OP) class of pesticides, as
required by the Food Quality Protection act (FQPA) of 1996.  In
addition, the individual OP’s have also been subject to individual
review process, which resulted in the issuance of Interim Reregistration
Eligibility Decisions (IREDs) for 22 OP’s, interim Tolerance
Reassessment and Risk Management Decisions (TREDs) for 8 OP’s and a
Reregistration Eligibility Decision (RED) for one OP.  EPA has concluded
after completing its assessment that pesticides covered by IREDs and
TREDs are eligible for reregistration and meet the safety standard under
Section 408(b)(2) of the FFDCS.  The cumulative risk assessment and
supporting documents are available on the Agency’s website at  
HYPERLINK "http://www.epa.gov/pesticides/cumulative" 
www.epa.gov/pesticides/cumulative  and in the docket
(EPA-HQ-OPP-2006-0618.  Based on the updated dietary assessment, the
proposed uses for barley and grasses do not increase potential exposure
in a way that would alter the conclusions of the previous cumulative
assessment.]>

<E. Safety Determination>

<	1. U.S. population. [Using the exposure assumptions described above,
Dow AgroSciences has concluded the estimated chronic dietary exposure
and risk from the current and proposed new tolerances do not exceed
HED's level of concern [i.e., >100 % of the chronic population adjusted
dose (cPAD)] for the general US population.  The estimated dietary
exposure for the general U.S. population was estimated to be 0.000006
mg/kg/day or 2% of the chronic reference dose.  EPA generally has no
concern for exposures below 100% of the chronic PAD because the chronic
PAD represents the level at or below which daily aggregate dietary
exposure over a lifetime will not pose appreciable risks to human
health.  

The estimated acute dietary exposure and risk do not exceed HED's level
of concern [i.e., >100 % of the acute population adjusted dose (aPAD)]
for the general US population at the 99.9th %ile of exposure.  The
estimated dietary exposure and risk for the general U.S. population at
the 99.9th percentile exposure was 0.000177 mg/kg/day, or 3.5% aPAD.

Dow AgroSciences concludes that there is a reasonable certainty that no
harm will result to US-general population from aggregate exposure to
chlorpyrifos residues.  When exposures are aggregated for adults for
diet, drinking water and post-applications to golf courses and mosquito
control campaigns, the MOE’s are above the Agency’s threshold of
concern.]>

<	2. Infants and children. [The FQPA = 10X has been maintained by the
EPA for additional protection to infants, children and females 13-50
years old.  The aPAD is 0.0005 mg/kg/day and the cPAD is 0.00003
mg/kg/day for infants, children and females at the age of conceiving
(13-50 year).

Using the exposure assumptions described above, Dow AgroSciences has
concluded the estimated chronic dietary exposure and risk from the
current and proposed new tolerances do not exceed HED's level of concern
[i.e., >100 % of the chronic population adjusted dose (cPAD)] for all
subpopulations.  For children 1 – 2 years old, the most highly exposed
population subgroup, dietary exposure was 0.00016 mg/kg/day, or 54.4% of
the cPAD.  EPA generally has no concern for exposures below 100% of the
chronic PAD because the chronic PAD represents the level at or below
which daily aggregate dietary exposure over a lifetime will not pose
appreciable risks to human health.

At the 99.9th percentile, acute risks are not of concern for the most
highly exposed population sub-group, children 1-2 years old.  For
children 1 – 2 years old, estimated dietary exposure was 0.00036
mg/kg/day, or 71% aPAD.

Dow AgroSciences concludes that there is a reasonable certainty that no
harm will result to children from aggregate exposure to chlorpyrifos
residues.  When the exposures are aggregated for children for diet,
drinking water and mosquito control campaigns, the MOE’s are above the
Agency’s threshold of concern.]>

<F. International Tolerances>

f

g

s

t

®

¯

	

-

3

4

d

e

g

h

q

r

t

u

v

w

B*

ఞܪ栖䖰

 

 

 

 

 

#

$

M

N

O

W

[

B*

B*

B*

ༀ[

j

k

o

p

r

s

‹

Œ

Ž

—

›

§

¨

¬

¯

°

Ç

B*

B*

B*

B*

B*

B*

B*

B*

 Ç

È

Ê

Ë

Ø

Ù

Ý

Þ

á

â

ù

ú

ü

ý

B*

h

B*

B*

h

B*

B*

B*

B*

B*

B*

h

B*

B*

B*

B*

B*

B*

B*

B*

hy

B*

! hy

hy

B*

B*

B*

B*

B*

B*

B*

B*

B*

B*

B*

B*

B*

B*

B*

B*

B*

B*

B*

B*

B*

B*

B*

B*

B*

B*

B*

B*

B*

B*

B*

B*

B*

B*

B*

B*

B*

B*

B*

B*

B*

B*

B*

B*

B*

B*

B*

B*

B*

B*

B*

B*

B*

B*

B*

h¯

B*

B*

B*

B*

B*

B*

h¯

B*

B*

B*

B*

B*

B*

B*

B*

B*

B*

B*

h¯

B*

B*

B*

B*

B*

B*

B*

B*

B*

B*

B*

B*

B*

B*

B*

B*

B*

B*

B*

B*

B*

B*

B*

B*

B*

B*

B*

B*

B*

B*

B*

hc

B*

B*

B*

B*

B*

B*

B*

B*

B*

B*

B*

B*

B*

B*

B*

B*

B*

B*

B*

B*

B*

B*

B*

B*

B*

B*

B*

B*

B*

B*

B*

B*

B*

B*

B*

ఀܪ栖䏋䨰"࠼喁Ĉ⪐∁t the MRLs established by different
agencies are not harmonized.  The differences may be attributable to a
diverse set of use patterns, local efficacy needs, variations in
guidelines for conducting field crop residue studies and varying
calculation methods to propose tolerances.] 

>

 PAGE   

 PAGE   9