Document ID: EPA-HQ-OPP-2008-0714-0003
Agency: epa
Document Type: Supporting & Related Material
Title: 
Posted Date: 2008-11-28T05:00Z

UNITED STATES ENVIRONMENTAL PROTECTION AGENCY

WASHINGTON, DC  20460

OFFICE OF

PREVENTION, PESTICIDES

AND TOXIC SUBSTANCES

MEMORANDUM

Date:		September, 15 2008

Subject:	DIFLUBENZURON.  HUMAN HEALTH RISK ASSESSMENT FOR THE PROPOSED
USE OF DIFLUBENZURON FOR CONTROL OF GRASSHOPPERS INFESTING ALFALFA GROWN
FOR HAY, MIXED GRASS/ALFALFA HAY, AND GRASSES GROWN FOR SEED IN
NORTHEASTERN OREGON.  

PC Code:  	108201	DP Barcode:	355224

Decision No.:	398367	Registration No.:	400-461

Petition No.:	08OR10	Regulatory Action:	Section 18

Assessment Type:	Single Chemical	Registration Case No.:	‘None’

TXR No.:	‘None’	CAS No.:	35367-38-5

MRID No.:	‘None’	40 CFR:	§180.377

  SEQ CHAPTER \h \r 1 From:		  SEQ CHAPTER \h \r 1 John Redden, M.S.
Team Leader

			Alternative Risk Integration and Assessment (ARIA) Team

			Risk Integration, Minor Use and Emergency Response Branch (RIMUERB)

			Registration Division (RD) (7505P)

Through:		  SEQ CHAPTER \h \r 1 William Cutchin, Acting Senior Branch
Scientist

					ARIA

				RIMUERB/RD (7505P)

		

To:	Libby Pemberton/Dan Rosenblatt, RM Team 05 

			RIMUERB/RD (7505P)

ARIA/RIMUERB of RD of the Office of Pesticide Programs (OPP) is charged
with estimating the risk to human health from exposure to pesticides. 
RD of OPP has requested that ARIA evaluate hazard and exposure data and
conduct dietary, occupational, residential and aggregate exposure
assessments, as needed, to estimate the risk to human health that will
result from proposed and currently registered uses of the active
ingredient diflubenzuron.

Table of Contents

  TOC \o "1-3" \h \z \u    HYPERLINK \l "_Toc208722864"  I.	 Summary	 
PAGEREF _Toc208722864 \h  3  

  HYPERLINK \l "_Toc208722865"  II.	Background	  PAGEREF _Toc208722865
\h  4  

  HYPERLINK \l "_Toc208722866"  III.	Proposed Use	  PAGEREF
_Toc208722866 \h  4  

  HYPERLINK \l "_Toc208722867"  IV.	Human Health Risk Assessment	 
PAGEREF _Toc208722867 \h  4  

  HYPERLINK \l "_Toc208722868"  V.	Residue Chemistry	  PAGEREF
_Toc208722868 \h  5  

  HYPERLINK \l "_Toc208722869"  VI.	Dietary Risk (Food and Drinking
Water)	  PAGEREF _Toc208722869 \h  6  

  HYPERLINK \l "_Toc208722870"  VII.	Non-Occupational and Residential
Risk	  PAGEREF _Toc208722870 \h  7  

  HYPERLINK \l "_Toc208722871"  VIII.	Aggregate Risk	  PAGEREF
_Toc208722871 \h  7  

  HYPERLINK \l "_Toc208722872"  IX.	Occupational Exposure and Risk	 
PAGEREF _Toc208722872 \h  7  

  HYPERLINK \l "_Toc208722873"  X.	Environment Justice	  PAGEREF
_Toc208722873 \h  8  

  HYPERLINK \l "_Toc208722874"  XI.	Review of Human Research	  PAGEREF
_Toc208722874 \h  9  

  HYPERLINK \l "_Toc208722875"  XII.	Additional Data Needs and
Recommendations	  PAGEREF _Toc208722875 \h  9  

  HYPERLINK \l "_Toc208722876"  XIII.	 Conclusion	  PAGEREF
_Toc208722876 \h  9  

 

I.		Summary

Under provisions in Section 18 of the Federal Insecticide, Fungicide and
Rodenticide Act (FIFRA), as amended, the Oregon Department of
Agriculture has notified USEPA that a crisis exists and invoked its
authority under 40 C.F.R. 166.40 to initiate treatment against insect
pests by using the chemical diflubenzuron.  The crisis declaration was
implemented on 30 June 2008, for the use of diflubenzuron (Dimilin® 2L
Insect Growth Regulator, EPA Reg. No. 400-461) to control grasshoppers
and Mormon crickets infesting alfalfa grown for hay, mixed grass/alfalfa
hay, and grasses grown for seed in northeastern Oregon.  Diflubenzuron
acts as a chitin inhibitor that controls immature grasshopper
populations while significantly reducing (compared to registered
alternatives) the risk to other non-target species, such as honey bees,
native pollinators and applicators.

 

Applications of Dimilin®2L under this exemption are authorized to begin
at 4:00 a.m. PDT, 30 June 2008.  This exemption will expire on 14 July
2008.  

Tolerances for residues of diflubenzuron are established under 40CFR
§180.377.  Tolerances are established for combined residues of the
insecticide diflubenzuron and its metabolites 4-chlorophenlyurea and
4-chloroaniline on various food commodities including grass, forage,
fodder, and hay, group 17 at 6 ppm.

Pending the recommendation in additional data needs and recommendations
below and considering that this Section 18 is not expected to increase
human dietary exposure to diflubenzuron, ARIA concludes that no new
aggregate risk assessments are needed for this Section 18 use on alfalfa
grown for hay, mixed grass/alfalfa hay, and grasses grown for seed in
northeastern Oregon.   The proposed Section 18 request does not negate
any of the previous safety findings.  To support this Section 18 use,
time-limited tolerances for the combined residues of diflubenzuron and
its metabolites 4-chlorophenylurea (CPU) and 4-chloroaniline (PCA)
should be established as follows:

Table 1.  Recommended Tolerances

Crop (commodity)	Tolerance (ppm)

Alfalfa, hay	6.0

Alfalfa, forage	6.0

Current policy is not to establish tolerances on mixed stands.  However,
even pure stands of alfalfa become mixed with grasses as they age over
2-3 years.  The tolerance for alfalfa covers the mixed stands (email;
Dr. Bernard Schneider; 09/04/2008).  

The above recommendations are consistent with the draft 09/30/2000
document, Additional Guidance on the Crop – ‘Grasses Grown for
seed.’

 Due to the time frame of this crisis exemption, EPA has communicated
with the applicant that the necessary residue tolerances can be
established, and that EPA had no objection to this crisis exemption. 

II.	Background

Previously, HED conducted a human health risk assessment for a Section
18 use of diflubenzuron on alfalfa in Utah (DP#: 283653, G. F. Kramer,
7/9/2002).  In this assessment HED concluded that there are no direct
human feed items associated with alfalfa and residues of diflubenzuron
in/on forage or hay from alfalfa would not result in higher residues in
livestock commodities.  It was concluded in this assessment that a
previous human health risk assessment (DP#: 277608, G. Kramer, et al.;
3/21/2002) adequately covered alfalfa use.  

ARIA has since performed a human health risk assessment and determined
that the dietary risks associated with the currently registered uses of
diflubenzuron do not exceed ARIA’s level of concern (DP#: 336813, B.
Hanson, 4/16/2007).  ARIA has since evaluated a Section 18 for
diflubenzuron on alfalfa in the state of Montana (DP#: 351851, B.
Hanson, 8/10/2008).

III.	Proposed Use

Table 2. Summary of Proposed Use Pattern for Diflubenzuron

Crop/Site	Alfalfa

Formulation 	Dimilin® 2L Insect Growth Regulator Aqueous Flowable (EPA
Reg. No. 400-461);  2.0 lb (22.0 %) ai/gallon liquid.

Pest	Grasshoppers, Mormon crickets

Method of Applic.	Aerial fixed wing, groundboom

Max. Applic. Rate	2.0 fl oz product/A (0.031 lb ai/A).  

Max. No. Applications	1/season

Applic. Interval	N/A

Preharvest Interval	1 day

Restricted Entry Interval	12 hours

Manufacturer	Chemtura USA Corporation

Applications are to be made when grasshoppers have reached the second to
third instar stage of development.

IV.	Human Health Risk Assessment

Toxicology 

The acute oral, dermal and inhalation toxicity of diflubenzuron is low. 
It is a mild eye irritant and not a skin irritant in laboratory animals.
 It is negative for sensitization in the guinea pig.  In subchronic and
chronic feeding studies, the primary endpoint of concern, produced most
likely by PCA, was methemoglobinemia and/or sulfhemoglobinemia.  These
effects were evident in both sexes of mice, rats, and dogs and were
produced by more than one route of administration in rats [i.e., oral,
dermal and inhalation].  The general consequence of methemoglobinemia
and/or sulfhemoglobinemia is the impairment of the oxygen transportation
capacity of the blood, which is generally known to be caused by aromatic
amines in both humans and animals.

The overall toxicology database is sufficient for a determination of
potential hazard to infants and children.  The data provide no
indication of an increased susceptibility to rats or to rabbits from in
utero or post-natal exposure to diflubenzuron.  

Dose-Response

The acute oral, dermal and inhalation toxicity of diflubenzuron is low. 
It is a mild eye irritant and not a skin irritant in laboratory animals.
 It is negative for sensitization in the guinea pig.  In subchronic and
chronic feeding studies, the primary endpoint of concern, produced most
likely by PCA, was methemoglobinemia and/or sulfhemoglobinemia.  These
effects were evident in both sexes of mice, rats, and dogs and were
produced by more than one route of administration in rats [i.e., oral,
dermal and inhalation].  The general consequence of methemoglobinemia
and/or sulfhemoglobinemia is the impairment of the oxygen transportation
capacity of the blood, which is generally known to be caused by aromatic
amines in both humans and animals.

The overall toxicology database is sufficient for a determination of
potential hazard to infants and children.  The data provide no
indication of an increased susceptibility to rats or to rabbits from in
utero or post-natal exposure to diflubenzuron.  

FQPA Assessment

The FQPA Safety Factor Committee (SFC) recommended that the FQPA safety
factor used in human health risk assessments (as required by FQPA of
August 3, 1996) be reduced to 1x in assessing the risk posed by this
chemical (B. Tarplee, HED Document Number 012630, 06/14/1998). 
Consequently, the current chronic reference dose (cRfD) and chronic
population adjusted dose (cPAD) values are equivalent (0.02 mg/kg/day).
This decision was based on the following:  1) there is no indication of
increased susceptibility of rats or rabbits to in utero or postnatal
exposure; 2) a developmental neurotoxicity study (DNT) with
diflubenzuron is not required; 3) food and drinking water exposure
assessments will not underestimate the potential exposure for infants
and children; and 4) there are currently no registered or proposed
residential (non-occupational) uses of diflubenzuron. 

V.	Residue Chemistry

The proposed end-use product for this risk assessment is Dimilin® 2L,
EPA Reg. No. 400-461.  The maximum number of applications is 1, with a
preharvest interval (PHI) of 1 day.  A maximum of 1,500 acres of grass
grown for seed may be treated under this exemption.  In addition a
maximum of 42,000 acres of alfalfa hay + mixed grass/alfalfa hay may be
treated under this exemption.  

Only one application is allowed under this crisis exemption.  Apply, for
alfalfa and mixed grass/alfalfa grown for hay, and for grasses grown for
seed, Dimilin® 2L in a broadcast spray at the rate of 2 fl. oz. (0.031
lb. ai diflubenzuron) per acre.  Applications may be made by air, using
a minimum of 5 gallons of water per acre, or by ground, using a minimum
of 20 gallons of water per acre.  Include 1 pint to 2 quarts per acre of
emulsified vegetable or paraffinic oil to aid in canopy penetration and
minimize water evaporation.

The Interregional Project No. 4 (IR-4) conducted a residue study which
was submitted but not formally reviewed for this action.  Alfalfa hay
was treated with 3 applications of 0.0325 lb ai/A (2 fl. oz. Dimlin
2L/A).  All samples were harvested one day after treatment.  The average
residue found in alfalfa was 5.29 ppm.   ARIA has determined that
residues of diflubenzuron will not exceed 6.0 ppm in/on alfalfa forage
and hay as a result of this proposed Section 18 label use.  Therefore,
time- limited tolerances for alfalfa forage and hay should be
established at 6.0 ppm.

Although forage and hay from alfalfa are livestock feed items, they
would be substitutes for grass forage and hay.  ARIA thus concludes that
residues of diflubenzuron in/on forage and hay from alfalfa will not
result in higher livestock dietary burdens and that increased tolerances
are not required for residues in livestock commodities from this Section
18 use.

Adequate enforcement methods are available for determination of the
combined residues of diflubenzuron and its metabolites CPU and PCA in
plant and livestock commodities.

VI.	Dietary Risk (Food and Drinking Water)

Drinking Water

The Environmental Fate and Effects Division (EFED) previously provided a
drinking water assessment (A. Al-Mudallal, DP #: 321156, 08/25/2006). 
Estimated Drinking Water Concentrations (EDWCs) were generated for the
total toxic residue which includes parent diflubenzuron and the major
degradate CPU.  For chronic assessments the EDWC is 2.76 ppb.  This
scenario presented the most conservative surface water concentration due
to use of diflubenzuron.  

Acute and Chronic Dietary Exposure Results and Characterization

No toxic effects attributable to a single (i.e., acute) exposure to
diflubenzuron have been identified; therefore, an acute reference dose
(aRfD) has not been established for diflubenzuron and an acute dietary
exposure assessment has not been conducted.  

In the most recent human health risk assessment, a chronic dietary risk
assessment for diflubenzuron was conducted using the chronic drinking
water concentration of 2.76 ppb.  The assessment was based on the
assumption of recommended tolerance-level residues, 100% crop treated
(%CT) and that DEEM default processing factors were used for some
commodities.  The results of the analysis indicated that chronic risk
from the dietary (food + drinking water) exposure to diflubenzuron will
not exceed ARIA’s level of concern for the general U.S. population and
all population subgroups.

VII.	Non-Occupational and Residential Risk

Although there are no registered homeowner uses, there are registered
uses for professional applications to outdoor residential and
recreational areas to control mosquitoes, moths, and other insects. 
However, the potential for post-application residential exposure is
expected to be limited.  Due to the low dermal absorption rate (0.5%) of
diflubenzuron and since locale-specific treatment programs in these
areas involve homeowner outreach/education program, minimal bystander
contact is expected.

VIII.	Aggregate Risk

As concluded in the more recent HED memo, and further reinforced by the
ARIA memo (DP# 336813, B. Hanson, 4/16/2007), aggregate risk estimates
for chronic exposure do not exceed ARIA’s level of concern for this
use.  This Section 18 exemption should not pose an unacceptable
aggregate risk to infants, children, or adults. 

IX.	Occupational Exposure and Risk

An occupational exposure risk assessment was completed by ARIA (DP#:
352297, M. Dow, 5/6/2008) for a previous Section 18 request (DP#:
351851, B. Hanson, 8/10/2008).

  

Pesticide Handler Exposure

Based upon the proposed use pattern, ARIA believes the most highly
exposed occupational pesticide handlers will be; mixer/loaders using
open pour loading of liquids; applicator using tractor drawn ground-boom
sprayer; and aerial applicator.

Table 3.  Summary of Exposure & Risk for Occupational Handlers Applying
Diflubenzuron to Alfalfa

Unit Exposure1

mg ai/lb handled	Applic. Rate2

lb ai/unit	Units Treated3	Avg. Daily Exposure4

mg ai/kg bw/day	MOE5	Combined

MOE6

Mixer/Loader – Liquid Open-Pour (Groundboom)

Dermal:

SLNoGlove     2.9

SLWithGlove  0.023

Inhal.               0.0012	0.016 

lb ai/A	200 A/day	Dermal:

SLNoGlove      0.13

SLWithGlove   0.0011

 Inhal.                0.000055	

3,846

454,545

369,090	No glove

3,806

With glove

204,082

Applicator – Groundboom Open Cab

Dermal:

SLNoGlove     0.014

SLWithGlove  0.014

Inhal.               0.00074	0.016

 lb ai/A	200 A/day	Dermal:

SLNoGlove     0.00064 SLWithGlove  0.00064

Inhal.               0.000034	

781,250

781,250

597,058	No glove

338,423

With glove

338,423

Mixer/Loader - Liquid Open-Pour (Aerial Operations)

Dermal:

SLNoGlove     2.9

SLWithGlove  0.023

Inhal.               0.0012	0.016

 lb ai/A	1,200 A/day

	Dermal:

SLNoGlove     0.79 SLWithGlove  0.0063

Inhal.               0.00033	

633

79,365

61,515	No glove

626

With glove

34,655

Aerial Applicator 

(pilots not required to wear protective gloves)

Dermal:

SLNoGlove    0.005

Inhal.              0.000068	0.016

 lb ai/A	1,200 A/day

	Dermal:

SLNoGlove      0.0014

Inhal.                0.000019	

357,143

1,068,421	No glove

267,669

Since all margins of exposure (MOEs) > 100, the proposed use pattern
does not exceed ARIA’s level of concern.

Post-Application Exposure

It is possible for agricultural workers to have post-application
exposures to pesticide residues during the course of typical
agricultural activities.  The estimate for post-application exposure is
an MOE of 80,645.  A MOE of 100 is adequate to protect agricultural
workers from post-application exposures.  Since the estimated MOEs are >
100, the proposed uses do not exceed ARIA’s level of concern.

Restriced Entry Interval (REI)

The product label lists a 12 hour restricted entry interval. 
Diflubenzuron is classified in Acute Toxicity Category III for acute
dermal toxicity and primary eye irritation.  It is classified in
Toxicity Category IV for acute inhalation toxicity and primary skin
irritation.  It is not a dermal sensitizer.  Therefore the interim
worker protection standard REI of 12 hours is adequate to protect
agricultural workers from post-application exposures.   The product
label lists a 12 hour REI.

X.	Environment 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://homer.ornl.gov/nuclearsafety/nsea/oepa/guidance/justice/eo12898.
pdf_" 
http://homer.ornl.gov/nuclearsafety/nsea/oepa/guidance/justice/eo12898.p
df ).

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 estimates 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.  Extensive data on food
consumption patterns are compiled by the USDA under the Continuing
Survey of Food Intake by Individuals (CSFII) and are used in pesticide
risk assessments for all registered food uses of a pesticide.  These
data are analyzed and categorized by subgroups based on age, season of
the year, ethnic group, and region of the country.  Additionally, OPP is
able to assess dietary exposure to smaller, specialized subgroups and
exposure assessments are performed when conditions or circumstances
warrant.  Whenever appropriate, non-dietary exposures based on home use
of pesticide products and associated risks for adult applicators and for
toddlers, youths, and adults entering or playing on treated areas
post-application are evaluated.  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.

XI.	Review of Human Research

This risk assessment does not rely on data from studies in which adult
human subjects were intentionally exposed to a pesticide or other
chemical. The exposure scenarios used in this risk assessment are
outlined in the Pesticide Handler Exposure Database (PHED) Surrogate
Exposure Guide (August 1998)

XII.	Additional Data Needs and Recommendations

None are required for this petition.

As described in the petition this crisis exemption is subject to the
following additional conditions:

All applicable directions, precautions, recommendations, restrictions,
and worker protection requirements on the registered Dimilin® 2L
product label must be followed.

Do not exceed the application rate of 2 fl. oz. Dimilin® 2L (0.031 ib.
a.i. diflubenzuron) per acre.

Do not apply directly to or allow to drift to water or wetlands.  When
disposing of equipment wash water or rinsate, do not contaminate water.

Do not apply within 25 feet by ground or within 150 feet by air of
bodies of water such as lakes, reservoirs, rivers, permanent streams,
natural ponds, marshes, or estuaries.  All applications must include a
25-foot buffer vegetative strip within the buffer zone to decrease
runoff.

Do not apply closer than 14 days prior to harvest.

Do no enter or allow workers into treated areas during the restricted
entry interval (REI) of 12 hours.

Do not plant or feed crops in Dimilin®-treated soils within 1 month
following application under this exemption, unless Dimilin® is
authorized for those crops.

Any adverse effects resulting from the use of Dimilin® 2L under this
crisis exemption must be immediately reported to the Oregon Department
of Agriculture.

A pre-grazing interval of 1 day.

XIII.	 Conclusion

Tolerances for residues of diflubenzuron are established under 40CFR
§180.377.  Tolerances are established for combined residues of the
insecticide diflubenzuron and its metabolites 4-chlorophenlyurea and
4-chloroaniline on various food commodities including grass, forage,
fodder, and hay, group 17 at 6 ppm.

Considering that this Section 18 is not expected to increase human
dietary exposure to diflubenzuron, ARIA concludes that no new aggregate
risk assessments are needed for this Section 18 use on alfalfa grown for
hay, mixed grass/alfalfa hay, and grasses grown for seed in northeastern
Oregon.   The proposed Section 18 request does not negate any of the
previous safety findings.  To support this Section 18 use, time-limited
tolerances for the combined residues of diflubenzuron and its
metabolites 4-chlorophenylurea (CPU) and 4-chloroaniline (PCA) should be
established as follows:

Table 4.  Recommended Tolerances

Crop (commodity)	Tolerance (ppm)

Alfalfa, hay	6.0

Alfalfa, forage	6.0

 Current policy is not to establish tolerances on mixed stands.  Rather,
individual livestock commodities are evaluated on their own.  Alfalfa
and grasses will be treated under this program.  However, even pure
stands of alfalfa become mixed with grasses as they age over 2-3 years. 
The tolerance for alfalfa covers the mixed stands (email; Dr. Bernard
Schneider; 09/04/2008).  

The above recommendations are consistent with the draft 09/30/2000
document, Additional Guidance on the Crop – ‘Grasses Grown for
seed.’

 Due to the time frame of this crisis exemption, EPA has communicated
with the applicant that the necessary residue tolerances can be
established, and that EPA had no objection to this crisis exemption. 

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