Document ID: EPA-HQ-OPP-2009-0316-0007
Agency: epa
Document Type: Supporting & Related Material
Title: 
Posted Date: 2009-06-24T04:00Z

UNITED STATES ENVIRONMENTAL PROTECTION AGENCY

WASHINGTON, D.C. 20460      

	OFFICE OF PREVENTION, PESTICIDE

	AND TOXIC SUBSTANCES

	

  SEQ CHAPTER \h \r 1 MEMORANDUM

Date: February 17, 2009

SUBJECT:	Phosmet: Revision To The Occupational Postapplication Exposure
and Risk Calculations for Phosmet; D296595; Case #838564.

PC Code:  059201	DP Barcode:   D296595

Decision No.: 396111	Registration No.: NA

Petition No.: NA	Regulatory Action: Post-RED Submission

Risk Assessment Type: Single Chemical	Case No.: NA

TXR No.: NA	CAS No.: 732-11-6

MRID No.: 45138201, 44811801, 44673301, 47262502, 47083001, 47262501,
44795810, 40122201, 40425301, 42595800.	40 CFR: NA

		              								Ver.Apr.08

          	

FROM:	Matthew Lloyd

		Linda Taylor	

		Risk Assessment Branch 7

		Health Effects Division (7509P)  SEQ CHAPTER \h \r 1 

		

THROUGH:	Michael Metzger

		Risk Assessment Branch 7

		Health Effects Division (7509P)  SEQ CHAPTER \h \r 1 

TO:		Veronique LaCapra, Chemical Review Manager

	Special Review and Reregistration Division (7508P)

  SEQ CHAPTER \h \r 1 

This memo updates the occupational postapplication risk calculations
already examined in past HED documents [D355152, D333957, D262366,
D268141, D277160] using recently updated hazard information for phosmet.

Table of Contents:

  TOC \o "1-3" \h \z \u  

  HYPERLINK \l "_Toc203474546"  1.	Occupational Postapplication Exposure
  PAGEREF _Toc203474546 \h  3  

  HYPERLINK \l "_Toc203474547"  1.1.	Occupational Postapplication
Exposures and Risks	  PAGEREF _Toc203474547 \h  3  

  HYPERLINK \l "_Toc203474548"  1.1.1.	Hazard Information	  PAGEREF
_Toc203474548 \h  3  

  HYPERLINK \l "_Toc203474549"  1.1.2.	Occupational Postapplication
Exposure Scenarios and Calculation Methods	  PAGEREF _Toc203474549 \h  5
 

  HYPERLINK \l "_Toc203474550"  1.1.3.	Data Used for Occupational
Postapplication Exposure Scenarios	  PAGEREF _Toc203474550 \h  9  

  HYPERLINK \l "_Toc203474551"  1.1.4.	Application of the Study Data to
the Exposure Scenarios	  PAGEREF _Toc203474551 \h  12  

  HYPERLINK \l "_Toc203474552"  1.1.5.	Exposure Assumptions, Factors and
Transfer Coefficients	  PAGEREF _Toc203474552 \h  12  

  HYPERLINK \l "_Toc203474553"  1.1.6.	Occupational Postapplication
Exposure and Risk Estimates	  PAGEREF _Toc203474553 \h  13  

  HYPERLINK \l "_Toc203474554"  1.1.7.	Summary of Occupational
Postapplication Risk Concerns and Data Gaps	  PAGEREF _Toc203474554 \h 
17  

  HYPERLINK \l "_Toc203474555"  1.1.8.	Occupational Postapplication Risk
Characterization	  PAGEREF _Toc203474555 \h  18  

  HYPERLINK \l "_Toc203474556"  2.	Environmental Justice and Human
Studies	  PAGEREF _Toc203474556 \h  19  

 

 Appendix A – Occupational Postapplication Calculations

 Appendix B – Human Studies Identification

Occupational Postapplication Exposure

  SEQ CHAPTER \h \r 1 Occupational Postapplication Exposures and Risks

  SEQ CHAPTER \h \r 1 The Agency uses the term “postapplication” to
describe exposures to individuals that occur as a result of working in
an environment that has been previously treated with a pesticide (also
referred to as reentry exposure).  The Agency believes that there are
distinct job functions or tasks related to the kinds of activities that
occur in previously treated areas such as harvesting vegetables in a
treated field.  Job requirements (e.g., the kinds of jobs to cultivate a
crop), the nature of the crop or target that was treated, and how
chemical residues degrade in the environment can cause exposure levels
to differ over time.  Each factor has been considered in this
assessment.

   SEQ CHAPTER \h \r 1 Hazard Information

     Since the 2001 IRED, two new toxicological studies pertinent to the
postapplication exposure assessment were submitted to the Agency for
review. These include:

a new 21-day dermal toxicity study (MRID 47262502) in rats, and 

an in vitro comparative dermal penetration study (MRID 47262501) in rat
and human skin. 

     OPP does not currently have a final policy describing the use of in
vitro dermal absorption data for determining risks from human dermal
exposure; however, the data considered are useful for this purpose.  In
the absence of a more fully developed policy, HED will take a protective
approach when using the phosmet in vitro dermal data (MRID 47262501;
TXR# 0053048) to inform the postapplication worker risk assessment for
the chemical.  Thus, HED selected the 2-sided lower 95% confidence
interval of the ratio of the rat mean 24-hour cumulative absorption to
the human mean 24-hour cumulative absorption (4.5-fold factor).  This
value is chosen because it is both consistent with HED's current
approach of using 24-hour cumulative absorption in estimating dermal
absorption values, and it is a protective assumption considering the
median ratio of 8.21 and the variability seen in the data
(ToxSacMeetingNotes, dated February 21, 2008; Sielken & Associates
Consulting, Inc. letters dated April 24 and 25, 2008 to Gowan).  This
ratio can be used to modify risk assessment points of departure for
worker postapplication risk assessments to account for the difference in
permeability between human skin and rat skin.

     HED has deemed the new 21-day dermal toxicity study (MRID 47262502;
TXR# 0053048 and TXR# 0054871) unacceptable for use in risk assessment
based on the lack of consistency and reproducibility of the
cholinesterase activity measurements and the lack of a clear rationale
for the reanalysis that took place (data submissions of February 13,
2008, March 23, 2008, and May 5, 2000; conference call on January 30,
2008; and meetings on April 9, 2008 and May 8, 2008). The registrant
(Gowan letter dated December 10, 2007) provided new information
regarding the MPI dermal toxicity study (MRID 44795801) in support of
their decision to perform another dermal study. The MPI study was used
in the previous risk assessment. Gowan indicated, among other things,
that the MPI study used a non-validated cholinesterase assay. Although
the method used was not cross-validated for rat tissues, based on
discussions with ORD, HED considers the brain data to be of sufficient
quality for risk assessment. There is low confidence in the RBC data
from this study, which stems from the spectrophotometric assay used to
measure cholinesterase levels.  The use of a spectrophotometric assay
often creates difficulties with the analysis of rat RBC cholinesterase,
causing considerable variability. Rat RBC samples present with a high
background (because of the hemoglobin interference) and low activity
(about 10 times lower than human RBCs), create considerable inaccuracy
in the assay. Conversely, rat brain cholinesterase measurements do not
have these problems; consequently, those data are often less variable
and more accurate.   Furthermore, confidence in the RBC data is low due,
in part, to the fact that in this study the brain appeared to be the
most sensitive compartment for cholinesterase inhibition.  This is in
contrast to the overall phosmet database, which indicates that the RBC
is the most sensitive compartment for this compound.  Therefore, HED
concludes that only the brain data from the MPI study are of sufficient
quality for risk assessment.

New dermal endpoints and points of departure were selected for the
short- and intermediate-term dermal exposure scenarios using the
subchronic oral neurotoxicity (SCN) study in rats (MRID 44811801) as the
primary study, supported by the MPI 21-day dermal study in rats (MRID
44795801) as co-critical (ToxSac memo; meeting date January 22, 2009). A
BMDL10 of 1 mg/kg/day (3 week assessment) for RBC cholinesterase from
the SCN study will be used for the point of departure (PoD). Although
the SCN study is an oral study and not route specific, there is high
confidence in the cholinesterase data from this study with less
confidence in the 21-day dermal MPI study for the reasons described in
the January 22nd, 2009 ToxSac meeting memo.  

Overall, the quality of the SCN cholinesterase data outweighed the
uncertainties associated with route-to-route extrapolation.  Thus,
ToxSAC concluded that using the more sensitive RBC BMDL10 data from the
oral SCN study, instead of the brain cholinesterase data from the 21-day
dermal study, is warranted and would result in a health protective PoD
for these risk assessments.  

     In recent years, OPP has increased its understanding and
implementation of benchmark dose (BMD) techniques. BMD methods provide a
more robust approach for developing points of departure (PoD) for risk
extrapolation, for evaluating relative potency, and evaluating
life-stage sensitivity.  A Bench Mark Dose (BMD) analysis of the red
blood cell (RBC) cholinesterase data from the subchronic neurotoxicity
study 3-week assessment provides the most consistent and defensible
point of departure (PoD) of 1.0 mg/kg/day (BMDL10) for both the short-
and intermediate-term dermal assessments. A BMD analysis of the brain
cholinesterase data from the MPI dermal study provides a BMDL10 of 9.97
mg/kg/day, which is consistent with that found for the SCN RBC data (10%
dermal absorption in the rat).

     To account for differences in permeability between rat and human
skin, the data from the in vitro dermal penetration study (MRID
47262501) and the in vivo dermal absorption study (MRID 40122201) were
applied to the point of departure (PoD) to obtain the human equivalent
dermal dose for the short- and intermediate-term dermal risk
assessments. The in vitro dermal penetration study provides a comparison
of permeability between rat and human skin (in vitro correction factor).
The in vivo dermal absorption study shows a 10% dermal absorption factor
for the rat. The resulting Human Equivalent Dose for both the short- and
intermediate-term dermal assessments is 45 mg/kg/day.

 Table   SEQ Table \* ARABIC  1  – Summary of Hazard Information for
Assessing Phosmet Occupational Postapplication Risks   SEQ CHAPTER \h \r
1 

Exposure

Scenario	PoD Dose

(mg/kg/day)	

Endpoint	

Study	Dermal Absorption Factor	In Vitro Correction Factor	Human
Equivalent Dose Used to Quantify Risk

(mg/kg/day)

Short- and Intermediate Term Dermal

	Oral

BMDL10 = 1.0	cholinesterase inhibition

(3-week RBC)	subchronic neurotoxicity/ rat

(MRID 44811801)

co-critical MPI 21-day dermal/rat (MRID 44795801)	10%	4.5	45

Occupational Postapplication Exposure Scenarios and Calculation Methods

  SEQ CHAPTER \h \r 1 Exposure Scenarios

The current postapplication occupational exposure assessment is
conducted for the nine crops specified in the Reregistration Decisions
on Nine Phosmet “Time Limited” Uses, dated January 18, 2007. The
calculations for postapplication exposure in this document focus on
dermal exposures alone because inhalation exposures are thought to be a
negligible contribution to postapplication exposure. Applications are
typically around two times per year, although phosmet can be used more
frequently.

The Agency uses a concept known as the transfer coefficient to
numerically represent the postapplication exposures one would receive
(i.e., generally presented as cm2/hour).  These transfer coefficients
are listed in Policy 3.1 Science Advisory Council for Exposure Policy
Regarding Agricultural Transfer Coefficients.  In this policy, transfer
coefficients were selected to represent the activities associated with
18 distinct crop/agronomic groupings based on different types of
vegetables, trees, berries, vine/trellis crops, turf, field crops, and
bunch/bundle crops (e.g., tobacco). The transfer coefficients for
highbush blueberries were taken from a study submitted by the ARTF
(ARF-020, MRID 451382-01) on blackberries.

 

The relevant crop groups associated with the nine “time-limited”
uses of phosmet include: 

Tree/fruit, deciduous (e.g., apples, pears, peaches, nectarines, plums,
prunes, apricots);

Vine/trellis (e.g., grapes)

Vine/trellis (highbush blueberries)

	Within each agronomic group, a variety of cultural practices are
required to maintain the included crops. These practices are varied and
typically involve light contact with immature plants and heavy contact
with more mature plants.

For phosmet, the Agency has completed short- and intermediate-term
postapplication assessments because of concerns over extended periods of
exposure for a segment of the user population. The Agency believes that
phosmet exposures can occur over a single day or up to several weeks at
a time for postapplication workers, even though many crops are likely
treated only a couple of times per season.  This is supported by the
length of time residues take to decline in the phosmet dislodgeable
foliar residue studies used in past HED risk assessment documents
(D262365) and the concept that several areas within a work environment
may be treated at different times.  For example, parts of agricultural
fields in a localized area might be treated over several weeks because
of an infestation with a concurrent need for hand labor activities. 
Therefore, individuals working in those fields might be exposed from
contact with treated foliage over an extended period of time that could
be categorized as an intermediate-term exposure as they work on
different sections of the localized field areas.

Calculation Methods

Postapplication exposures are calculated by considering transferable
residue levels in areas where people work and the kinds of jobs or tasks
that are required to produce agricultural commodities. These factors are
represented by dislodgeable foliar residue (DFR) concentrations and by
activity-based transfer coefficients. Exposures are calculated by
multiplying these factors by a time component (i.e., an 8 hour work day
assumed for seasonal reentry work).  Exposures are then normalized by
body weight and adjusted for dermal absorption (if necessary) to
calculate absorbed doses. Risk estimates were then calculated. 
Postapplication risks diminish over time because phosmet residues
dissipate in the environment.  

Estimation of Residue Levels Using Dissipation Kinetics 

The first step in the postapplication risk assessment was to complete an
analysis of the available DFR data. Best fit DFR levels were calculated
based on empirical data using the equation D2-16 from Series
875-Occupational and Residential Test Guidelines: Group
B-Postapplication Exposure Monitoring Test Guidelines. Half-lives were
calculated using the algorithm (T1/2 = -Ln 2/slope). The results of
those statistical analyses were used to calculate best fit
concentrations over time using the following pseudo-first order
equation:

Cenvir(t) = Cenvir(0)e(PAI(t) * M)

Where:

 (μg/cm2) that represents the amount of residue on the surface of a
contacted leaf surface that is available for dermal exposure at time
(t);

Cenvir(0) = same as above at time (0);

e =natural logarithms base function;

PAI(t)  = postapplication interval or dissipation time (e.g., days after
treatment or DAT); and

M = slope of line generated during linear regression of data [ln(Cenvir)
versus PAI].

	

The data were not corrected for recovery in any calculation by the
Agency and it appears that the data also were not corrected by the
investigators (i.e., overall field recoveries are around 90%).  The same
datapoints were used by the Agency in the development of this risk
assessment as were used in various risk assessments by the Gowan
Corporation in previous submission to the Agency.  Analysis of the data
can be summarized by the following:



Table   SEQ Table \* ARABIC  2  – “Best Fit” Dissipation Kinetics
Data for Phosmet Postapplication Risk Calculations

Crop	

Application

Rate

(lb ai/A)	

Correlation Coefficient	

Slope	

C0

(µg/cm2)	

Half-Life

(days)

Pears	

5	

0.97905	

-0.06621	

5.04	

10.5

Grapes	

1	

0.94075	

-0.06810	

1.70	

10.2

Note: This analysis is based on cumulative residues of phosmet and
phosmet oxon.

In cases where no chemical-specific residue dissipation data are
available, the Agency typically uses a generic dissipation model to
complete risk calculations.  In this case, the Agency has determined
that it is more appropriate; however, to extrapolate using
phosmet-specific dissipation data in the risk assessment for other
currently labelled crops than it is to use the generic dissipation
model.  This approach is consistent with current Agency policies for
generating transferable/dislodgeable residue data.  The existing residue
data were extrapolated to the currently labelled crops as follows:

(	Pear Data: These data have been used to complete all occupational
assessments that were based on exposures worker reentry activities
around tree fruit crops.   This extrapolation was completed because of
similarities in the application method, the crop canopy, and application
rates (i.e., between the study and current labels).  These data were
extrapolated to various application rates including 4.0 lb ai/acre for
pears and apples, 3.0 lbs ai/acre for peaches, nectarines, plums, and
apricots, and 2.0 lb ai/acre for apples in the northeast (tank mixed
with methomyl [lannate]). Therefore, four different calculations were
completed for these postapplication assessments to account for
differences between crops due to application rates in order to provide
for a more informed risk management decision.  

(	Grape Data: These data have been used to complete the remaining
occupational assessments (i.e., postapplication scenarios for highbush
blueberries and grapes).  This extrapolation was completed because of
similarities in the application method, the crop canopy, and application
rates (i.e., between the study and current labels).  These data were
extrapolated to various application rates including 1.5 lbs ai/acre for
grapes (to reflect the most recent proposed label rates). No
extrapolation was necessary for highbush blueberries because the study
was conducted at 1 lb ai/acre and the current label rate is 1 lb ai/A.
These calculations for the different label rates were completed for
these postapplication activities to account for differences between
crops due to application rates in order to provide for a more informed
risk management decision.  

	Daily Exposure:  The next step in the risk assessment process was to
calculate dermal exposure values on each postapplication day after
application using the following equation (see equation D2-20 from Series
875-Occupational and Residential Test Guidelines: Group
B-Postapplication Exposure Monitoring Test Guidelines. 

DE(t) (mg/day) = (DFR(t) (µg/cm2) x TC (cm2/hr) x Hr/Day)/1000 (µg/mg)

Where:

	DE(t)	=	Daily exposure or amount deposited on the surface of the skin
at time (t) attributable for activity in a previously treated area, also
referred to as potential dose (mg ai/day);

	DFR(t)	=	Dislodgeable foliar residue at time (t) (µg/cm2);

	TC	= 	Transfer Coefficient (cm2/hour); and

	Hr/day	=	Exposure duration meant to represent a workday (8 hours).

	Margins of Exposure:  Finally, the calculations of daily dermal dose
received by postapplication workers were then compared to the
appropriate PoD (e.g., NOAEL or BMDL10 ) to assess the total risk to
postapplication workers for dermal exposure.  All risk estimate (MOE)
values were calculated for dermal exposure levels using the formula
below:

 

Where:

MOE 	= Margin of exposure, value used by HED to represent risk or how
close a chemical exposure is to being a concern (unitless);

ADD 	= (Average Daily Dose) or the amount as absorbed dose received from
exposure to a pesticide in a given scenario (mg pesticide active
ingredient/kg body weight/day); and

PoD	= Dose level in a toxicity study, where no observed adverse effects
occurred (e.g., NOAEL or BMDL10) in the study (mg/kg/day).

     A body weight of 70 kg was used to estimate occupational exposures
for the postapplication assessment since the relevant toxicological
points of departure are not gender specific. The Agency’s level of
concern (LOC) for phosmet postapplication risk assessment is 100 (i.e, a
margin of exposure less than 100 is considered a risk of concern). The
LOC is based on a factor of 100 to account for inter-species
extrapolation to humans from the animal test species (10X) and to
account for the intra-species sensitivity (10X).

   SEQ CHAPTER \h \r 1 Data Used for Occupational Postapplication
Exposure Scenarios

Chemical-Specific Data: tc \l4 "Chemical-Specific Data   The
postapplication risk assessment for phosmet has been developed using
chemical-specific dislodgeable foliar residue data on pears and grapes.
In the previous assessments for phosmet, these data were used to
calculate risk estimates for the risk manager to set Restricted Entry
Intervals (REIs) for occupational exposures. 

In order to present a transparent postapplication exposure assessment,
it is necessary to present the data upon which it is based.  The studies
used to determine the dislodgeable foliar residue levels and human
exposure levels for risk assessment purposes can be identified below:

Dislodgeable Residue Dissipation and Reentry Interval Calculations For
Crops Treated With Products Containing Phosmet: Submitted by Stauffer
(now Zeneca) Chemical Company; Study Completion Date: 10/22/86; Report
Date: 1/16/87; Authors: Dick Knarr, Yutaka Iwata, and Kay Curry; EPA
MRID 404253-01.

This study was reviewed by the Agency in 1991.  The review indicated
that this study was considered acceptable to the Agency based on the
review criteria appropriate for that era.  The review can be identified
by the following information:

(	Review of Postapplication/Reentry Data Submitted to Support the
Reregistration of Phosmet and Revision of Data Required by the 8/30/91
DCI for Phosmet (HED Project # 9-0839): A memo from Peg Perreault of the
former Occupational and Residential Exposure Branch of HED to Lois
Rossi, Special Review and Reregistration Division.  

This document is a review of the data included in MRIDs 401223-01 and
404253-01.  Release of this review memo from the Agency to the
registrants prompted two additional chemical-specific submissions
including:

(	Phosmet Dermal Passive Dosimetry Exposure Addendum to MRID 404253-01:
Submitted by the Gowan Company, Yuma Arizona; Completion Date: 12/8/92;
Author: E. Codrea; EPA MRID 425958-01 (submitted with 12/14/92 letter
described below).

(	Letter from Gowan Company, Yuma Arizona to Ms. Brigid Lowery of
EPA/OPP/SRRD (Phosmet CRM) Dated December 14, 1992: Author: Elizabeth
Codrea, Regulatory Product Manager; EPA MRID 425958-00.

MRID 404253-01: Dislodgeable foliar residue levels were quantified from
two crops (pears and Zinfandel variety grapes) that were selected to
represent the crops for which phosmet is registered.  Phosmet,
formulated as Imidan 50-WP, was used to make all applications.  All
study sites were located in California. Pears, representing the
remaining tree fruits and nut crops, were treated at an application rate
of 5 lb ai/acre which is the current label maximum for pears.  Grapes,
representing the remaining crops, were treated at an application rate of
1 lb ai/acre which is the current maximum application rate for
blueberries, and near the maximum application rate of 1.5 lbs ai/acre
for grapes. The Iwata leaf punch/aqueous surfactant method was used to
collect all samples.  A 1 inch diameter punch was used in all cases and
48 punches were collected in each sample for a total double-sided
surface area per sample of 480 cm2.  Based on sample surface area and
the available recovery data (i.e., a low fortification level of
1µg/sample), the limit of quantification was defined as 0.002 µg/cm2
(i.e., this applies to both phosmet and phosmet oxon residue levels that
were both screened for).  All field samples collected in this study were
above the limit of quantification.  

Pears:	Imidan 50-WP was applied to a commercial, established planting of
Bartlett pears located near Walnut Grove, California.  Imidan 50-WP was
applied once using an airblast sprayer at a rate of 4.8 lb ai/acre. 
Samples were collected on days 0, 1, 2, 3, 4, 5, 7, 10, 14, 21, and 28
days postapplication    Weather conditions were typical, and no rainfall
was reported during the study.  Based on the labeling information for
pears and other tree crops at the time of the study, the high
application rate is 5.0 lb ai/acre, the preharvest interval is 7 days,
and phosmet can be applied as needed.  The dissipation data for pears
are presented in Table 2 of Appendix C of “The Revised Occupational
and Residential Exposure Aspects of the HED Chapter of the
Reregistration Eligibility Decision Document (RED) for Phosmet”
(DP262366) [Available: Special Docket EPA-HQ-OPP-2007-0151, at  
HYPERLINK "www.regulations.gov"  www.regulations.gov ].

Field and laboratory recovery data were generated in this aspect of the
study.  Field recovery for phosmet was 82.5 percent (CV 9.3, n = 8)
while field recovery for phosmet oxon was 93.2 percent (CV 6.9, n=10). 
Laboratory recovery for phosmet was 89.4 percent (CV 6.7, n = 7) while
laboratory recovery for phosmet oxon was 95.1 percent (CV 5.0, n=7). The
residue levels presented in Table 2 were not apparently corrected for
recovery by the investigators.

Grapes: Imidan 50-WP was applied to a commercial, established planting
of Zinfandel grapes located near Lodi, California.  Imidan 50-WP was
applied by an airblast sprayer at a rate of 0.94 lbs ai/acre.  One
application was made.  Samples were collected on days 0, 1, 3, 4, 6, 9,
13, 20, and 27 days postapplication    Weather conditions were typical
during the study (i.e., no unusual events).  Based on the labeling
information for grapes and other crops, the high application rate is 1.5
lb ai/acre, the preharvest interval is 7 days, and phosmet can be
applied as needed between egg hatch and pupation for leaffolder,
leafroller, and western grape skeletonizer.  The dissipation data for
grapes are presented in Table 3 of Appendix C of “The Revised
Occupational and Residential Exposure Aspects of the HED Chapter of the
Reregistration Eligibility Decision Document (RED) for Phosmet”
(DP262366) [Available: Special Docket EPA-HQ-OPP-2007-0151, at  
HYPERLINK "www.regulations.gov"  www.regulations.gov ]. Field and
laboratory recovery data were generated in this aspect of the study. 
Field recovery for phosmet was 96.9 percent (CV 6.4, n = 7) while field
recovery for phosmet oxon was 98.0 percent (CV 5.2, n=9).  Laboratory
recovery for phosmet was 90.2 percent (CV 7.9, n = 5) while laboratory
recovery for phosmet oxon was 93.8 percent (CV 10.6, n=5). The residue
levels presented in Table 3 were not apparently corrected for recovery
by the investigators.

These studies are of sufficient quality to be used for exposure and risk
assessment purposes and have been used in a number of past occupational
and residential exposure risk assessment documents and in the July, 2006
IRED. 

  SEQ CHAPTER \h \r 1 Application of the Study Data to the Exposure
Scenarios

This assessment pertains to the nine crops specified in the
Reregistration Decisions on Nine Phosmet Restricted Entry Intervals of
January, 2007. Dislodgeable foliar residue studies were submitted for
only two crop groups (deciduous tree crops and vine/trellis crops). It
is relevant to note for risk characterization that the DFR studies took
place at California-based sites, in dry conditions. Generalizing the DFR
dissipation to other locations, any ambient conditions with additional
precipitation would generally mean less residue is available for
transfer to the skin of field workers. Based upon the available DFR
field trial information, the data were extrapolated from the DFR studies
to the labeled crops.  

   SEQ CHAPTER \h \r 1 Exposure Assumptions, Factors and Transfer
Coefficients

       SEQ CHAPTER \h \r 1 The following assumptions, factors and
transfer coefficients were used for calculating the occupational
postapplication risk estimates: 

Short- and intermediate-term exposures were assessed for all available
postapplication scenarios.

The relevant toxicological information used for occupational
postapplication short- and intermediate-term assessment (i.e., same PoD
for assessing both exposure durations) are addressed above in section
1.1.1. 

The exposure durations for short- and intermediate-term and transfer
coefficients reflect current Agency policy. 

Maximum application rates were used to calculate risk estimates for the
postapplication scenarios. 

When the Agency extrapolated the available DFR data to other crops, the
data are adjusted for differences in application rate using a simple
proportional approach.  This approach seems to be the most appropriate
given the data available.  This approach is commonly used by the Agency
to conduct postapplication risk assessments.

  

Risks were calculated using generic transfer coefficients that represent
many different types of cultural practices.  A listing of the transfer
coefficients used in this assessment is given in Table 3, below.  Most
of these transfer coefficients were taken from the Agency’s revised
Policy 3.1 Science Advisory Council for Exposure Policy Regarding
Agricultural Transfer Coefficients (August 7, 2000).  The transfer
coefficients for highbush blueberries were taken from a study recently
submitted by the ARTF (MRID 45138201) on blackberries.

Blackberry ARTF data (ARF-020) is used as a surrogate for the blueberry
transfer coefficient and the activity groups used for the other transfer
coefficients are not directly comparable. This study has a primary
review by Versar and a secondary review from PMRA (MacMillan, PMRA).

Discussion around the risk estimates for both short- and
intermediate-term risks are based upon the restricted entry intervals
identified in Reregistration Decisions on Nine Phosmet
“Time-Limited” Uses, January, 2007.

The use of personal protective equipment or other types of equipment to
reduce exposures for postapplication workers is not considered a viable
alternative for the regulatory process except in specialized situations
(e.g., a rice scout will wear rubber boots in flooded paddies).  This is
described in some detail in the Agency’s Worker Protection Standard
(40 CFR 170).

Table   SEQ Table \* ARABIC  3    SEQ CHAPTER \h \r 1 - Postapplication
Exposure Scenarios and Transfer Coefficients

  SEQ CHAPTER \h \r 1 

Crop Type (Specific Crops)	Postapplication Exposure Scenarios	Transfer
Coefficient (cm2/hr)

Tree, Fruit, Deciduous

(pears, apples, apricots, peaches, nectarines, plums, prunes,)	Very Low
- propping

Low - Irrigation, scouting, weeding

High – Pruning, training, tying, harvesting

Very High – Thinning	100

1000

1500

3000

Vine/Trellis (Grape) 	Low - Hedging, irrigation, scouting, hand weeding

Medium - Scouting, training, tying

High – Leaf  pulling, thinning, pruning, training/tying

Very High – Cane Turning and Tabling Grapes	

  SEQ CHAPTER \h \r 1 500

1000

5000

100001

Vine/Trellis

(Highbush Blueberries) 	High Exposure	

11002

1 – TC for short-term exposures only; BEAD has provided HED with
information that this activity pattern does not occur for the 
intermediate-term exposure duration

2 - ARTF surrogate Transfer Coefficient (MRID 451382-01)

  SEQ CHAPTER \h \r 1 Occupational Postapplication Exposure and Risk
Estimates

  SEQ CHAPTER \h \r 1 Phosmet Risk Summary:   

The post application risks for phosmet are summarized in Table 4 and
details are presented in Appendix A. Both the short- and intermediate
term postapplication risk estimates are based on a toxicological PoD
(oral BMD10 – 1 mg/kg/day) selected from a subchronic neurotoxicity
study in rats (MRID 44811801) and considered co-critical with the 21-day
MPI study (MRID 44795801).  The LOC for short- and intermediate-term
postapplication exposures is an MOE of 100. Within each crop group,
differing transfer coefficients were used to represent different types
of cultural practices which were applicable to each crop group. Most of
the risk estimates for “very high” exposure activities (i.e.,
thinning) and one of the “high exposure” activities (i.e.,
harvesting) for phosmet exceed HED’s level of concern (i.e., MOEs are
less than 100) at the REIs specified in the Agency decision document,
Reregistration Decisions on Nine Phosmet “Time Limited” Uses, dated
January 18, 2007. The time needed to achieve MOEs of 100 for short-term
risks for the “very high” exposure category ranges from 7 to 24
days, with the longest time needed for cane turning and girdling grapes
(Applicable on to grapes grown East of the Rocky Mountains).

 While the PoD is the same for short- and intermediate-term
postapplication risk assessment, there are some activity-based
differences in the potential exposure patterns that are of interest.
According to information provided by BEAD, cane turning and girdling of
grapes is an exposure activity that occurs for the short-term exposure
duration, but not the intermediate-term exposure duration. Therefore,
the time needed to achieve MOEs of 100 for intermediate-term term risks
for the “very high” exposure category ranges from 7 to 17 days, with
the longest time needed for thinning deciduous tree fruits. 

Table   SEQ Table \* ARABIC  4    SEQ CHAPTER \h \r 1  -   SEQ CHAPTER
\h \r 1 Phosmet Postapplication Short- & Intermediate-Term Risks

(Reflecting Label Maximum Application Rates)

Crop Group	Application Rate

 (lb a.i/acre)	MOE; (days till MOE>100)

Very Low	Low	High

(Harvesting)	Very High

(Thinning)

	MOE on REI [Day 7]*

(Days when MOE > 100)

Tree, Fruit, Deciduous

Pears/Apples (West of Rockies)	4	1550	 160 	 100 	 52 (17)

	MOE on REI [Day 4]*

(Days when MOE > 100)

Tree, Fruit, Deciduous

Apples (East of Rockies)	4	1270	130	85 (7)1	42 (17)

	MOE on REI [Day 7]* 

   (Days when MOE > 100)

Tree, Fruit, Deciduous

Peaches, nectarines (West of the Rockies)	3	2070	 210	 140 2	 N/A3

	MOE on REI [Day 4]* 

   (Days when MOE > 100)

Tree, Fruit, Deciduous

Peaches, nectarines (East of the Rockies)	3	1700	170 	110 4 	57 (13) 

	MOE on REI [Day 7]*  

  (Days when MOE > 100)

Tree, Fruit, Deciduous

Plums, prunes (West of the Rockies)

	3	2070	 210 	 140 5	 N/A6

	MOE on REI [Day 7]*   

 (Days when MOE > 100)

Tree, Fruit, Deciduous

Plums, prunes (East of the Rockies)	3	2070	210	 140 7	 69 (13)

	

MOE on REI [Day 7]*   

 (Days when MOE > 100)

Tree, Fruit, Deciduous

Apricots (West of the Rockies)	3	2070	207	140 8 	N/A 9

	MOE on REI [Day 7]*   

 (Days when MOE > 100)

Tree, Fruit, Deciduous

Apricots (East of the Rockies)	3	2070	210  	140 10 	69 (13) 

	MOE on REI [Day 4]* 

   (Days when MOE > 100)

Tree, Fruit, Deciduous

North east Apples (tank mix with methomyl [lannate], only)	2	2550	260
17011	85 (7)

	MOE on REI [Day 14]*

(Days when MOE > 100)

Vine/trellis

Grapes (West of the Rockies)	1.5	N/A	52012	N/A13	N/A13

	MOE on REI [Day 14]*

(Days when MOE > 100)

Vine/trellis

Grapes (East of the Rockies)	1.5	N/A	52012	100	51(24)14

	MOE on REI [Day 1]*  

  (Days when MOE > 100)

Vine/trellis

Blueberries	1	N/A	N/A15	22516	N/A

+ Bolded MOEs exceed HED’s level of concern (i.e., MOEs<100)

* - Reregistration Decisions on Nine Phosmet “Time-Limited” Uses,
January 18, 2007

1 - The PHI for apples is 7 days, so no hand harvesting would take place
at 4 days. The MOE at 7 days is 100.

2- The PHI for peaches is 14 days, so no hand harvesting would take
place at 7 days. The MOE at 14 days is 220.

3 - In the January 18, 2007 decision document for phosmet, thinning is
prohibited as a postapplication exposure activity after phosmet
applications to peaches West of the Rockies.

4 - The PHI for peaches is 14 days, so no hand harvesting would take
place at 7 days. The MOE at 14 days is 220.

5 - In the January 18, 2007 decision document for phosmet, hand
harvesting of plums and prunes is prohibited for 14 days after
application, so no hand harvesting would take place at 7 days. The MOE
at 14 days is 220.

6 - In the January 18, 2007 decision document for phosmet, thinning is
prohibited as a postapplication exposure activity after phosmet
applications to plums and prunes West of the Rocky Mountains.

7 - In the January 18, 2007 decision document for phosmet, hand
harvesting of plums and prunes is prohibited for 14 days after
application,

8 - The PHI for apricots is 14 days, so no hand harvesting would take
place at 7 days. The MOE at 14 days is 220.

9 – In the January 18, 2007 decision document for phosmet, thinning is
prohibited as a postapplication exposure activity after phosmet
applications to apricots West of the Rockies.

10 – The PHI for apricots is 14 days, so no hand harvesting would take
place at 7 days. The MOE at 14 days is 220.

11 – The PHI for northeast apples (tank mix with methomyl, only) is 8
days, so no hand harvesting would take place at 4 days. The MOE at 8
days is 220.

12 – The MOE of 520 relates to medium exposure activities for grapes.
(See Table 3 for additional information).

13 – In the January 18, 2007 decision document for phosmet, all hand
labor activities EXCEPT for scouting, hand weeding, and irrigating, are
prohibited after phosmet application to grapes West of the Rockies. 

14 – According to information provided by BEAD, cane turning and
girdling of grapes occurs only as a short-term exposure activity, not an
intermediate-term exposure activity 

15 – ARTF ARF-020 data used for surrogate TC; HED expects other
blueberry postapplication work to result in lower exposures than the
“high” exposure activity shown. 

16 – The PHI for blueberries is 3 days, so no hand harvesting would
take place on the first day after application. The MOE at 3 days is 260.

Risk estimates for workers tending blueberries are represented for both
short- and intermediate-term exposure durations use data extrapolated
from the Agricultural Rentry Task Force's ARF-020 [MRID 451382-01]. The
ARTF transfer coefficient (TC) studies do not present TC data that are
directly comparable to the HED’s default TC values on a exposure
category basis. The TC value used to estimate phosmet risk most closely
approximates the "high" exposure potential used in the default TC
studies, and are presented in that category in the risk estimate summary
table. Reentry workers conducting activities with a lower exposure
potential (e.g., scouting and irrigation) than harvesting and pruning
would have a lower exposure estimate than risk estimates presented in
this document (ST/IT MOE @ Day 0: 210). The risks for reentry workers
for irrigation and scouting using the default TC value of 500 would be
roughly 2x lower (i.e., a 2x higher MOE) than the risk estimates
presented for workers harvesting highbush blueberries in this document.

   SEQ CHAPTER \h \r 1 Summary of Occupational Postapplication Risk
Concerns and Data Gaps

  SEQ CHAPTER \h \r 1 A summary of all the occupational postapplication
risks of concern for phosmet is included in Table 5, below. 

 The risk estimates exceed HED’s level of concern (i.e., MOEs are
below the LOC of 100) in all the “very high” activity grouping.
Typical activities for the “very high” activity grouping includes
thinning fruit trees.

The risk estimates exceed HED’s level of concern (i.e., MOEs are below
the LOC of 100) for one postapplication activity scenario in the
“high” activity grouping for both exposure durations. That activity
pattern represents workers harvesting deciduous tree fruits
(specifically apples east of the Rocky Mountains). 

 For the remainder of the postapplication exposure scenarios, the risk
estimates do not exceed HED’s level of concern (i.e., MOEs are above
the LOC of 100) for all postapplication worker activity patterns in the
“very low”, “low” and “medium” exposure activity groupings.
Typical activities in those activity groupings include propping,
irrigation, and scouting.

Table 5 - Summary of Phosmet Postapplication Risks of Concern per Crop
and Activity Groups

Crop Group	Exposure Duration	Exposure Activity Grouping – Risk of
Concern Identified?

Very Low	Low	Medium	High 	Very High

Deciduous Fruit Trees

(Pears )	ST/IT	No	No	N/A	No	Yes

Deciduous Fruit Trees

(Apples – west of Rockies )	ST/IT	No	No	N/A	No	Yes

Deciduous Fruit Trees

(Apples – east of Rockies )	ST/IT	No	No	N/A	Yes	Yes

Deciduous Fruit Trees

(Apples – northeast )

[ for tank mix]	ST/IT	No	No	N/A	No	Yes

Deciduous Fruit Trees

(Peaches, nectarines – west of Rockies)	ST/IT	No	No	N/A	No	Yes

Deciduous Fruit Trees

(Peaches, nectarines – east of Rockies)	ST/IT	No	No	N/A	No	Yes

Deciduous Fruit Trees

(Apricots – west & east of Rockies)	ST/IT	No	No	N/A	No	Yes

Deciduous Fruit Trees

(plums/prunes – west of Rockies)	ST/IT	No	No	N/A	No	Yes

Deciduous Fruit Trees

(plums/prunes - east of Rockies)	ST/IT	No	No	N/A	No	Yes

Vine/trellis

(blueberries)	ST/IT	N/A	N/A	N/A	No	N/A

Vine/trellisA

(grapes)	ST	No	No	No	No	Yes

	IT	N/A	N/A	No	No	N/A

Representative

Exposure Activities per Activity Grouping	Propping	Irrigation, Scouting
Grape Scouting, training grapesB	Harvesting	Thinning, cane
turning/girdling [grapes only]C

A – Vine/trellis risk summary has been broken into two line items to
reflect the difference in activity patterns based on exposure duration.

B - The “medium” exposure activity grouping is relevant to scouting
and training of  grapes only.

C – Cane turn/girdling is an activity relevant to grapes only
[short-term exposure duration only].

  SEQ CHAPTER \h \r 1 Occupational Postapplication Risk Characterization

The Agency has completed a risk assessment for both short- and
intermediate-term exposures; the PoD is the same for both cases. The
intermediate-term exposure assessment represents an exposure duration of
greater than 30 days (i.e., intermediate-term exposures between 30 days
and 6 months).  It should be noted that even though the Agency has
completed this assessment, it is unlikely that many individuals will be
exposed in this manner given the way that phosmet is likely used and
based on the recent use and usage data provided that indicate (in
agriculture) that phosmet is generally used up to about a maximum of 5
times per year. Even with a relative few number of applications per
growing season, postapplication exposure activities like harvesting and
thinning can take place over a course of several weeks. HED does not
expect postapplication workers to be exposed to maximum residues every
day over the course of the short-term exposure duration (up to 30 days).
For the intermediate-term exposure duration, risk estimates are likely a
conservative estimate of risk (i.e., intermediate-term risk calculations
likely overestimate exposure and risk). 

The chemical-specific exposure and dislodgeable foliar residue studies
submitted by the registrant were reviewed by the Agency and determined
to be acceptable for risk assessment purposes.  The surrogate transfer
coefficients used to calculate occupational postapplication exposures
are based on published empirical data and are generally considered to
represent reasonable estimates of dermal exposure.  These transfer
coefficient values are based on the use of normal long sleeved work
clothing.  

Environmental Justice and Human Studies

Environmental Justice: 

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

As a part of every pesticide risk assessment, OPP considers a large
variety of consumer subgroups according to well-established procedures. 
In line with OPP policy, HED risk assessments typically estimate risks
to population subgroups from pesticide exposures that are based on
patterns of that subgroup’s food and water consumption, and activities
in and around the home that involve pesticide use in a residential
setting. This document deals exclusively with occupational
postapplication risk estimates for the nine crops specified in the
Reregistration Decisions on Nine Phosmet “Time Limited” Uses, dated
January 18, 2007. Further considerations are currently in development as
OPP has committed resources and expertise to the development of
specialized software and models that consider exposure to bystanders and
farm workers as well as lifestyle and traditional dietary patterns among
specific subgroups.

Human Studies:

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

References:

General

U.S. Environmental Protection Agency. (January 18th, 2007) 
Reregistration Decisions on Nine “Time-Limited” Uses.

The Revised Occupational and Residential Exposure Aspects of the HED
Chapter of the Reregistration Eligibility Decision Document (RED) For
Phosmet, Case 818976, PC Code 059201, DP Barcode 262366, Author: Jeff
Dawson, Issued: January 27, 2000.

http://   HYPERLINK "www.regulations.gov"  www.regulations.gov 

*  Special Docket EPA-HQ-OPP-2007-0151

Hazard Information

Barnett Jr.  J. F. (2005). Oral (Gavage) Acute Time of Peak
Cholinesterase Depression Study of Phosmet Technical in Neonatal Rats.
Charles River Laboratories Preclinical Services, Horsham PA Protocol 
No. WJ100010. March 9, 2007. MRID 47083001. Unpublished.

Barnett, J. F., Jr. (2007). Cholinesterase Response of Crl:CD(SD) Rats
Following Repeated Dermal Applications of Imidan™ 70-W at Multiple
Dose Levels. Charles River Laboratories, Preclinical Services, Horsham,
PA. Laboratory Project ID WJI00021, October 18, 2007. MRID 47262502.
Unpublished.

Cappon, G. D. (1998). An Acute Neurotoxicity Study of Phosmet in Rats.
WIL Research Laboratories, Inc. Ashland, OH. Laboratory Study No.
WIL-331004, October 8, 1998. MRID 44673301. Unpublished.

Cappon, G. D. (1999). A Dietary Subchronic (90-Day) Neurotoxicity Study
of Phosmet in Rats. WIL Research Laboratories, Inc. Ashland, OH.
Laboratory Study No. WIL-331002, April 21, 1999. MRID 44811801.
Unpublished.

Fasano, W.J., Sr. (2007) Imidan® 70 WP In Vitro Absorption  in Rat and
Human Skin. E. I. duPont de Nemours and Company, DuPont Haskell SM
Global Center for Health and Environmental Sciences, Delaware.
Laboratory Project ID 22742, September 5, 2007 (revision October 8,
2007). MRID 47262501. Unpublished.

Letter from Gowan Company, Yuma Arizona to Ms. Margaret Rice of
EPA/OPP/SRRD (Phosmet CRM) Dated December 10, 2007: Author: Elizabeth
Codrea, Director of Regulatory Science. 

Letter from Gowan Company, Yuma Arizona to Ms. Margaret Rice of
EPA/OPP/SRRD (Phosmet CRM) Dated February 13, 2008: Author: Elizabeth
Codrea, Director of Regulatory Science.

Letter from Gowan Company, Yuma Arizona to Ms. Margaret Rice of
EPA/OPP/SRRD (Phosmet CRM) Dated March 23, 2008: Author: Elizabeth
Codrea, Director of Regulatory Science. 

Letter from Gowan Company, Yuma Arizona to Ms. Margaret Rice of
EPA/OPP/SRRD (Phosmet CRM) Dated May 5, 2008: Author: Elizabeth Codrea,
Director of Regulatory Science. 

Letter from Gowan Company, Yuma Arizona to Ms. Margaret Rice of
EPA/OPP/SRRD (Phosmet CRM) Dated , January 14, 2009: Author: Elizabeth
Codrea, Director of Regulatory Science. 

Letter from Sielken & Associates Consulting, Inc. to Gowan Company,
Dated April 24, 2008: Author: Robert L. Sielken, Jr. Biostatistician.

Letter from Sielken & Associates Consulting, Inc. to Gowan Company,
Dated April 25, 2008: Author: Robert L. Sielken, Jr. Biostatistician.

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