Document ID: EPA-HQ-OPP-2004-0346-0033
Agency: epa
Document Type: Supporting & Related Material
Title: 
Posted Date: 2007-02-07T05:00Z

UNITED STATES ENVIRONMENTAL PROTECTION	AGENCY

	WASHINGTON, D.C.  20460

   

OFFICE OF PREVENTION,  PESTICIDES AND

TOXIC SUBSTANCES

January 10, 2007

SUBJECT: 	ETHOFUMESATE: HED Revised Human Health Risk Assessment For
Phase 5; Response to Bayer CropScience Phase 4 Comments and Review of
the Dermal Penetration Study with Ethofumesate, MRID 46866901

 

PC Code 110601.  DP Barcode DP296939/DP296953

Regulatory Action: Phase 5 Reregistration Action

Risk Assessment Type: Single Chemical Aggregate

FROM:		Nancy McCarroll, Geneticist

Toxicology Branch 

Health Effects Division (7509C)

THRU:		Alberto Protzel, PhD, Branch Senior Scientist

Toxicology Branch 

Health Effects Division (7509C)

TO:		Laura Parsons, Chemical Review Manager

Special Review and Reregistration Division (SRRD)

(7508W)

and

		Nathan Mottl, Chemical Review Manager

SRRD (7508W)

cc:  Shanna Recore and Bill Hazel,  RRB2

On June 12, 2006, Bayer CropScience submitted a Rodent In Vivo Dermal
Penetration  Study (MRID 46866901) to address the issue of unacceptable
MOEs resulting from the use of the default 100% dermal absorption for
occupational and residential dermal exposures to ethofumesate.   The
dermal absorption study has been reviewed and found to be
acceptable/guideline.   Accordingly, the dermal absorption factor of 27%
from the combined radioactivity absorbed and that remaining in/on the
skin at the 10-hour exposure duration for the low dose was used to
refine exposure and risk estimates for the unacceptable MOEs.   In
addition, the sponsor submitted a document entitled “Refined
Occupational and Residential Assessment for Ethofumesate” (MRID
46867601) based on the new dermal absorption factor.  The Agency’s
Executive Summary for the Dermal Absorption Study as well as responses
from HED regarding earlier comments associated with the use of the 100%
default dermal absorption factor and an issue related to residues of the
metabolite NC 20645 in livestock commodities are presented below.  

HAZARD CHARACTERIZATION/ASSESSMENT CONSIDERATIONS

No comments were submitted by the sponsor dealing with the Hazard
Characterization/Assessment.  However, the Executive Summary for the
dermal absorption study is presented below:  

CITATION:	Muriel Odin-Feurtet [14C]-Ethofumesate: In vivo Dermal
Absorption Study in the Male Rat;  Report of Study SA 05289  MRID
46866901, June 19, 2006. Unpublished. 

SPONSOR:	Bayer AG, Bayer CropScience, Alfred Nobel Str. 50, 40789
Monheim, Germany

EXECUTIVE SUMMARY

In a dermal absorption rat study (MRID No. 46866901), ethofumesate
(phenyl-UL-14C, >99%) was applied to Sprague-Dawley Crl:CD (SD) rats at
dose levels of 3, 9 and 20 μg/cm2.  A single dermal application of the
test material in aqueous methyl cellulose was made to the shaved dorsal
skin (12 cm2 area) of a total of 48 animals (4 per time group/16 per
dose) and the animals were monitored for absorption at 1, 10, 24 and 168
hours after dosing.  The 168 hour group underwent skin wash at 10 hours
and was carried to 168 hours before termination.  The following table
summarizes mean percent absorption at each time period for the three
dose groups. 

Table 1.  Dermal Absorption Rate Summary

Dose Level

(µg/cm2)		Mean Percentage of Dose Absorbed & In/On Skin

	1 hour	10 hours	24 hours	168 hours**

	Absorbed	skin*	absorbed	skin	absorbed	Skin	absorbed	skin

3

9

20	5.63

1.68

2.64	4.33

3.07

4.50	23.14

15.90

9.95	3.42

1.99

2.30	32.51

26.83

18.99	6.87

2.09

1.38	20.95

24.69

12.51	0.72

0.49

0.27

* amount of radioactivity in/on skin after skin wash

** washed at 10 hours and carried to 168 hours prior to termination	

Mean recoveries of applied radioactivity from all dose groups ranged
from 86 to 102%.  Mean absorption based on urinary/fecal excretion,
blood, carcass, and cage wash ranged from 1.68 to 32.51%.  Total
radioactivity absorbed clearly increased with increasing exposure time
for all doses and the highest absorption rate consistently occurred at
the 24 hour exposure duration.  Absorbed radioactivity decreased with
increasing dose for the 10 and 24 hour exposure durations indicating
that the skin was approaching saturation of penetration for these
exposure durations. The majority of the absorbed radioactivity was
consistently found in the urine for all doses and durations.  Absorbed
dose found in the urine and feces increased with increasing exposure
duration indicating that absorbed test material is increasingly absorbed
and eliminated over time. Negligible amounts were present in blood
samples analyzed for all dose/duration groups.  Amount of radioactivity
present in the carcass at 1, 10 and 24 hour exposure durations ranged
from 1.5-6.2%.  The amount of radioactively found in the carcass was
significantly reduced at 168 hr post-wash exposure duration.  

Most of the unabsorbed radioactivity was found in the skin washes from
each dose/duration (48-88%).  Amount of radioactive dose on the treated
skin after wash and termination ranged from 0.3 to 7%.  Although there
was no clearly discernable pattern of radioactivity remaining in/on
treated skin indicating the extent to which skin residues continue to be
absorbed post-wash, it is reasonable to assume that that test material
remaining in/on skin is absorbed.  Therefore, a dermal absorption factor
of 27%, from the combined radioactivity absorbed and that remaining
in/on the skin at the 10 hour exposure duration for the low dose, would
be considered appropriate for use in risk assessment.  

This study is classified as acceptable/guideline and satisfies the
guideline requirements (OPPTS 870.7600; OECD none) for a dermal
penetration study in rats.

The full DER is listed under TXR No. 0054284.

 	

RESIDUE CHEMISTRY CONSIDERATIONS

HED response to Bayer comment A7 re: analysis of metabolite NC 20645 in
livestock commodities

Bayer comment A7. In the RED (Document A, Page 17, Table 5) it is stated
that “… residues of a major animal metabolite (NC 20645) were not
determined.” This is further discussed on Page 56 of Document D. BCS
believe it can be shown that this 

metabolite is minor. The current analytical method (MRID 43412901,
Appendix 3; Bayer Report B002201, Method No. B-93R-04/05) that was used
for the cattle feeding study does recover NC 20645 as NC 9607 in milk.
The residues of ethofumesate, NC 8493, NC 9607 and NC 20645 were each
<0.01 ppm in all milk samples at up to 10X the maximum theoretical
dietary burden (MTDB). Extensive metabolism work (MRID 42364504, Bayer
Report A82968) has shown that NC 20645 exceeds 10% of the total
radioactive residue only in kidney, the tissue with the highest residue.
 Based on the conservative estimates of dietary exposure, it can be
shown that it will account for <0.01% RfD. Using appropriate ruminant
diets and transfer factors from the ruminant metabolism study (MRID
42364504, Bayer Report A82968), it can also be calculated that NC 20645
will not exceed the current tolerance level (0.05 ppm) in kidney at the
1X dosing level.  NC 20645 is, therefore, an insignificant contributor
of exposure to the human population resulting from use of ethofumesate.
Efforts to quantify NC 20645 in kidney will not lead to a significantly
improved dietary risk assessment. 

Document A.  Reregistration Eligibility Decision (RED) for Ethofumesate,
September, 2005

Document D.  Ethofumesate: HED Revised Human Health Risk Assessment For
Phase 4; Response to Bayer CropScience Phase 3 Comments. August 4, 2005.
PC Code 110601

HED response

HED continues to feel that additional data concerning residues of the
metabolite NC 20645 in livestock commodities would permit dietary risk
refinement and confirmation of assumptions in the 9/05 RED.  However, we
have taken a more risk-based and “value-added” approach as we,
again, consider Bayer’s request.  The following overriding
considerations permit taking such an approach:

Only ruminant kidney, a minor human food, could potentially bear finite
ethofumesate residues based on an exaggerated rate metabolism study
(from S. Funk, 12/3/92, D180705).

Residues in milk from an exaggerated rate (30x) cow feeding study did
not contain detectable residues of ethofumesate, NC 8493, or NC 9607
(all <0.01 ppm).  Metabolite NC 20645 would have been included (as NC
9607) since milk samples were acidified.  Milk often serves as an
indicator of mammalian tissues.  We can only assume that NC 20645 would
not have been determined in tissues as those samples were apparently not
acidified.  Only one fat sample contained residues >LOD of 0.01 ppm
(0.02 ppm of parent compound) (L. Cheng, 8/9/95, D209084 and D 210002).

The only treated feed items for cattle, goats, horses, and sheep are
sugar beet tops and the hay, forage, and regrowth of grasses grown for
seed.  [There are no treated hog or poultry feed items.]   These are
very minor, localized, and seasonal feed items.  They are esoteric feed
items that HED believes will never be fed to the same animals.

In the case of grass grown for seed, most is grown in the Pacific
Northwest which produces only 5% of the U.S. beef supply.

In the case of sugar beets, only 0.8% of the nation’s sugar beet tops
are available to be used as livestock feed (HED’s Chemistry Science
Advisory Council, Minutes of 6/30/04 meeting).

The most recent human health risk assessment (J. Morales, 7/6/05,
D296927) presented the dietary acute risk as being 4% of the aPAD
(females 13-49 were the only relevant population).  Chronic risks were
<1% of the cPAD in all population subgroups.  These were very
conservative risk estimates given that all foods were assumed to bear
tolerance-level residues and for 100% to have been treated.

Therefore, from a risk perspective, there is no basis upon which to
require a new ruminant feeding study provided that ethofumesate is not
used on major livestock feed items and/or finite residues of
ethofumesate, NC 8493, NC 9607, and NC 20645 do not result in livestock
commodities from treated feed items.  If a new ruminant feeding study
becomes necessary, analysis of all four residues of concern in tissues
and milk is to be conducted.

From a regulatory perspective, however, there remains a tolerance
enforcement consideration, i.e., uncertainty whether the livestock
tolerance enforcement method is capable of detecting NC 20645.  The
livestock tolerance enforcement method is to be validated for
ethofumesate, NC 8493, NC 9607, and NC 20645 in tissues and milk.

OCCUPATIONAL AND RESIDENTIAL EXPOSURE (ORE) CONSIDERATIONS

HED response to Bayer comments on ORE issues:

μg/lb ai handled, respectively, an application rate of 22.5 lb ai/ton,
and assuming 30 tons treated per day and a handler weight of 60 kg, the
dermal exposure estimate is 0.259 mg/kg/day and the inhalation exposure
estimate is 0.0135 mg/kg/day. Assuming 100% dermal and inhalation
absorption, the total dose is 0.273 mg/kg/day. With a NOAEL of 30
mg/kg/day, the total MOE is 110. This estimate indicates acceptable
worker risk for commercial treatment of dry bulk fertilizer with
ethofumesate for workers wearing the required PPE on the Nortron® SC
Herbicide label (single layer of clothes with water proof gloves) with
open pour mixing and loading. No engineering controls are required for
commercial mixing/loading of ethofumesate on dry bulk fertilizer. We
note two typographical errors on page 2 of the Document B in the text
above and below the Table 1 - “Handler Risks for Dry Fertilizer
Applications on Sugar Beets”: (a) the text for the maximal labeled
rate of 4.5 pts/acre (0.56 lb ai/acre) should be corrected to read as
“4.5 pts/acre (2.25 lb a.i./acre)”; (b) “the footnote 3: each ton
(2000 lb)of fertilizer would require 30 lb of ethofumesate active
ingredient”. The 30 lb value should be changed to 22.5 lb a.i. as used
in the Table above (it reflects the labeled 5.63 gallons of Nortron SC
that contains 4 lb a.i/per gallon).

HED response:  EPA researched the process of commercial impregnation of
liquid pesticides into dry bulk fertilizer during the reregistration of
alachlor, which also has this labeled use-pattern.  The Agency’s
Biological and Economic Analysis Division provided (April 28, 1998, memo
George Keitt) provided the following information obtained through the
University of Illinois Extension Service:

In commercial settings, the liquid pesticide is metered from a mini-bulk
tank (several hundred gallons) to a mixing drum via a closed system. 
The liquid pesticide is sprayed onto the fertilizer, which is stirred by
an auger that lifts it to the top of the drum.  After impregnation, the
treated fertilizer is gravity-fed through a hopper onto a conveyor belt
leading to an auger truck, which carries it to the field.  Because all
processes are mechanized, there is minimal exposure to either the
mixer/loader at the treatment site or the loader at the transfer sites.

  SEQ CHAPTER \h \r 1  Information supplied by Monsanto confirmed that
impregnation of fertilizer in a mixing tower is typically a closed
system operation.   Therefore, EPA   SEQ CHAPTER \h \r 1 estimates risk
for mixers/loaders impregnating the dry bulk fertilizer in commercial
operations by assuming use of engineering controls (metered delivery
from a mini-bulk tank).  HED notes that   SEQ CHAPTER \h \r 1 the amount
of active ingredient necessary to impregnate the tons of fertilizer that
can be processed in a day is too large to be handled by opening
individual bottles or containers.

If Bayer CropScience is aware of commercial operations that impregnate
bulk fertilizers with liquid pesticides using open mix/loading systems,
they may submit information about such commercial systems.  HED would
welcome data about the commercial impregnation of dry bulk fertilizers
with liquid pesticides.  

EPA will revise the typographical errors on page 2 of Document B.

Bayer CropScience Comment A2: On page 27 in the labels change summary
table of the RED, the Agency requires chemical resistant gloves on
ethofumesate labels. The PPE indicated on the existing labels (e.g.
Nortron SC and Prograss) for the three ethofumesate products are
appropriate for the chemical compositions of the respective products.

HED response:   SEQ CHAPTER \h \r 1 When the WPS was promulgated and PR
Notice 93-7 was developed, EPA took the opportunity to require
registrants to specify the type of glove material that was highly
protective for each specific end-use product (active ingredient and
solvent) and to select the appropriate chemical-resistance category for
that end-use product.  Registrants with end-use products that had no
solvents (dry formulations) or where the solvent was only water did not
select a chemical-resistance category and listed "waterproof" gloves on
their labeling,   since all waterproof materials are highly resistant to
such products.   In addition, in early -entry situations (a minimum of 4
hours after application is complete), solvents are presumed to have
volatilized leaving early-entry workers exposed to the dry residue
consisting mainly of active ingredient and inert carriers.  There again,
the appropriate glove type was deemed to be “waterproof” gloves. 

	Once the labels with these revised personal protective equipment
statements appeared on the market, questions from users and Extension
personnel arose about why the gloves were listed as "waterproof", but
aprons, footwear, and headgear were listed as "chemical-resistant." 
Questions also arose as to why no chemical-resistant category was listed
on labels for the dry and water-based formulations and about what types
of materials were "chemical-resistant" to that formulation, so the
correct type of material for aprons, footwear, and headgear could be
selected.   In addition, as OPP made active-ingredient-specific PPE
decisions during reregistration, registration, and special review
processes, it became increasingly complicated to list gloves as
"chemical-resistant or waterproof, as appropriate" each time gloves were
discussed.  

	Due to the confusion by users and complications during
active-ingredient-based PPE determinations, HED, SRRD, and RD personnel
decided to discontinue the "waterproof" glove language and gradually
convert to "chemical-resistant gloves" for all end-use products,
including dry and water-based formulations.  The labels for dry and
water-based formulations would list chemical resistance category "A" and
the label language would be:  "chemical-resistant gloves such as (or
“made of”) any waterproof material."  This language exactly
parallels the label language for other formulation types, i.e.,
"chemical-resistant gloves such as barrier laminate or viton." 

Bayer CropScience Comment A3:  On page 28 in the labels change summary
table of the RED, the Agency requires closed mixing/loading for on-site
mixing and loading of liquid formulations. Based on EPA’s estimates,
this statement should be limited to commercial treatment of dry bulk
fertilizers. However, BCS’ assessment in Note A1 above indicates that
this statement is not necessary for that scenario either. Therefore
statements requiring the use of closed mixing and loading systems are
not appropriate for any use of ethofumesate products.

HED response:  HED agrees that closed system mixing loading requirements
should be limited to commercial impregnation of dry bulk fertilizers.

Bayer CropScience Comment A4: On page 29 in the labels change summary
table of the RED, the Agency requires the following statement: ”Do not
enter or allow worker entry into treated areas during the restricted
entry interval (REI) of 12 hours for all crops, except turf grown for
sod. The REI for turf is 9 days. The REI for each crop is listed in the
directions for use associated with each crop.” The 9 day REI for turf
is currently appropriate for the Prograss® Herbicide label, which
allows a 3 lb ai/acre maximum application rate. However, this statement
is not appropriate for turf use of Nortron® SC Herbicide because the
maximum turf application rate for Nortron® SC Herbicide is 1.5 lb
ai/acre. The current REI for Nortron® SC Herbicide following
application to turf should be 3 days. These REIs are currently based on
the conservative assumption of 100% dermal absorption for ethofumesate.
An ethofumesate dermal absorption study is now in progress. Results of
this study are expected to allow a refinement of the dermal dose,
resulting in a decrease in the absorbed dose of ethofumesate, with a
subsequent lowering of all REIs.

HED response: It is EPA policy to regulate on the highest labeled rate. 
The 3 lb ai/acre rate is the maximum labeled turf application rate for
all ornamental turf uses.  HED has received the ethofumesate dermal
absorption study and has reassessed dermal dose and postapplication
risks using the results of that study (see Table 3 below).  Using the
new dermal absorption study restricted-entry interval will now be 3 days
at the 3 lb ai/acre rate.    

No additional harvest prohibition is necessary.

Bayer CropScience Comment A5:  On page 31 in the labels change summary
table of the RED, the Agency requires the following statement: “Do not
harvest treated sod for 16 days following application.” The 16 day
preharvest interval (PHI) for turf is currently appropriate for the
Prograss® Herbicide label, which allows a 3 lb ai/acre maximum
application rate. However, this statement is not appropriate for turf
use of Nortron® SC Herbicide because the maximum turf application rate
for Nortron® SC Herbicide is 1.5 lb ai/acre. The current PHI for
Nortron® SC Herbicide following application to turf should be 8 days.
These PHIs are currently based on the conservative assumption of 100%
dermal absorption for ethofumesate. An ethofumesate dermal absorption
study is now in progress. Results of this study are expected to allow a
refinement of the dermal dose, resulting in a decrease in the absorbed
dose of ethofumesate, with a subsequent lowering of these PHIs. 

HED response: It is EPA policy to regulate on the highest labeled rate. 
The 3 lb ai/acre rate is the maximum labeled turf application rate for
all ornamental turf uses.  HED has received the ethofumesate dermal
absorption study and has reassessed dermal dose and postapplication
risks using the results of that study (see Table 3 below).  Using the
new dermal absorption study, the restricted-entry interval will now be 3
days at the 3 lb ai/acre rate.  No additional harvest prohibition is
necessary.  

Bayer CropScience Comment A6: A Summary Note: Every occupational and
residential risk estimate in the ethofumesate RED assumes 100% dermal
absorption. An ethofumesate dermal absorption study is now in progress
and BCS will submit the report in May, 2006. Results of this study are
expected to allow a refinement of the dermal dose, resulting in a
decrease in the total absorbed dose of ethofumesate. The lower total
absorbed doses of ethofumesate will result in more accurate, lower, risk
estimates for all occupational and residential uses of ethofumesate.

HED response:  HED has received the ethofumesate dermal absorption study
and has reassessed dermal dose and handler and postapplication risks
using the results of that study.  See table 1, 2, 3, and 4 below.  



Table 1.   Summary Table for Ethofumesate Short & Intermediate – Term
Exposures

Exposure Scenarios	Crop4	Application Rate5 (lbs ai/acre or lbs ai/
gallon)	Daily Amount Treated6

(acres or gallons)	Baseline Dermal1 +Baseline Inhalation2 MOE8	PPE-G
Dermal3 + Baseline Inhalation2

MOE8	Combined Engineering Control Dermal + Baseline Inhalation

Mixer/Loader

Mixing/Loading Liquids for Aerial application	Turf: grown for seed	1.88
350	3.5	370	-

Mixing/Loading Liquids for Aerial application	Turf: grown for sod 	3	350
2.2	230	-

Mixing/Loading Liquids for Aerial application	Turf: grown for sod	1.5
350	4.4	460	-

Mixing/Loading Liquids for Aerial application	Sugar Beets	3.75	1200	0.51
54	110

Mixing/Loading Liquids for Groundboom application	Sugar Beets	3.75	200
3.1	320	-

Mixing/Loading Liquids for Groundboom application	Swiss Chard	3	80	9.6
1000	-

Mixing/Loading Liquids for Groundboom application	Table Beets grown for
seed	3	80	9.6	1000	-

Mixing/Loading Liquids for Groundboom application	Table Beets	1.9	80	15
1600	-

Mixing/Loading Liquids for Groundboom application	Carrots	2	80	14	1500	-

Mixing/Loading Liquids for Groundboom application	Spinach	1	80	29	3000	-

Mixing/Loading Liquids for Groundboom application	Turf: grown for seed
1.88	80	15	1600	-

Mixing/Loading Liquids for Groundboom application	Turf: grown for sod	3
80	9.6	1000	-

Mixing/Loading Liquids for Groundboom application	Turf: grown for sod
1.5	80	19	2000	-

Mixing/Loading Liquids for Groundboom application	Golf Course Fairways
and Tees	3	40	19	2000	-

Loading Granulars for Tractor-Drawn Spreaders application	Sod Farms	1.5
80	3800	-	-

Applicator

Applying Sprays via Aerial Equipment	Turf: grown for seed	1.88	350	N/A
N/A	1900 (closed cockpit engineering controls)

Applying Sprays via Aerial Equipment	Turf: grown for sod	3	350	N/A	N/A
1200 (closed cockpit engineering controls)

Applying Sprays via Aerial Equipment	Turf: grown for sod	1.5	350	N/A	N/A
2400 (closed cockpit engineering controls)

Applying Sprays via Aerial Equipment	Sugar Beets	3.75	1200	N/A	N/A	280
(closed cockpit engineering controls)

Applying Sprays via Groundboom Equipment	Sugar Beets	3.75	200	530	-	-

Applying Sprays via Groundboom Equipment	Swiss Chard	3	80	1700	-	-

Applying Sprays via Groundboom Equipment	Table Beets grown for seed	3	80
1700	-	-

Applying Sprays via Groundboom Equipment	Table Beets	1.9	80	2600	-	-

Applying Sprays via Groundboom Equipment	Carrots	2	80	2500	-	-

Applying Sprays via Groundboom Equipment	Spinach	1	80	5000	-	-

Applying Sprays via Groundboom Equipment	Turf: grown for seed	1.88	80
2600	-	-

Applying Sprays via Groundboom Equipment	Turf: grown for sod	3

1700	-	-

Applying Sprays via Groundboom Equipment	Turf: grown for sod	1.5	80	3300
-	-

Applying Sprays via Groundboom Equipment	Golf Course	3	40	3300	-	-

Applying Sprays via Groundboom Equipment	Golf Course Fairways and Tees
1.5	40	6600	-	-

Applying Granulars via Tractor Drawn Spreader	Turf: grown for sod	1.5	80
3900	-	-

Flagger

Flagging for Aerial Sprays Applications	Turf grown for seed	1.88	350	820
N/A	-

Flagging for Aerial Sprays Applications	Turf: grown for sod	3	350	520
N/A	-

Flagging for Aerial Sprays Applications	Turf: grown for sod	1.5	350	1000
N/A	-

Flagging for Aerial Sprays Applications	Sugar Beets	3.75	350	410	N/A	-

Mixer/Loader/Applicator

Mixing/Loading/Applying Liquid Concentrates with Low Pressure Handwand
(PHED)	Residential Lawns	3	5	4.4	820	-

Mixing/Loading/Applying Liquid Concentrates with Low Pressure Handwand
(ORETF)	Residential Lawns	3	5	30	1300	-

Mixing/Loading/Applying Liquid Concentrates with handgun sprayer (ORETF)
Residential Lawns	3	5	No data	970	-

Footnotes:

- scenario passed at previous PPE level.

1Baseline dermal represent long pants, long sleeved shirts, shoes, and
socks.  Values are reported in the PHED Surrogate Exposure Guide dated
August 1998. 

2Baseline inhalation represent no respirator.  Values are reported in
the PHED Surrogate Exposure Guide dated August 1998.

3PPE-G dermal represent long pants, long sleeved shirts, shoes, socks
and gloves.  Values are reported in the PHED Surrogate Exposure Guide
dated August 1998.

4Crops and use patterns are from product labeling.

5Application rates are based on maximum values found in various sources
including LUIS and various labels.  In most scenarios, a range of
maximum application rates is used to represent the range of rates for
different crops/sites/uses.  Application rates upon which the analysis
is based are presented as lb ai/A. 

6Amount treated is based on the area or gallons that can be reasonably
applied in a single day for each exposure scenario of concern based on
the application method and formulation/packaging type. (Standard
EPA/OPP/HED values).

7Total MOE = 1/ [1/MOE(dermal)+1/MOE(inhalation)] 

8 Target MOE is 100

Calculations used:

Dermal MOE =   Short & Intermediate-term oral NOAEL/Daily Dermal Dose;

Dermal dose (mg/kg/day) = [unit exposure (mg/lb ai) * Dermal absorption
* Application rate (lb ai/acre) * Daily area treated (acres or gallons)]
/ Body weight; 

Inhalation MOE = Short & Intermediate-term oral NOAEL/Daily Inhalation
Dose; 



Table 2.  Summary of “Days After Treatment” to Reach the Target MOE
for Short & intermediate-Term Exposure 

(Target MOE = 100)

Crop 	Application Rate 

(lbs ai/acre)	Exposure Activity Level	Transfer Coefficient (cm2/hr)a
Days After Treatment Target MOEc is Achieved 

Sugar beets	1.5	Low	100	0 (12 hours)

Medium	1500	0 (12 hours)

Beets (table grown for seed)	1.5	Low	300	0 (12 hours)

Low	300	0 (12 hours)

Beets (table)	0.33	Low	300	0 (12 hours)

Carrots	2	Low	500	0 (12 hours)

Swiss Chardb	1.5	Medium	1500	0 (12 hours)

a Transfer coefficients from Policy #003.1 “Agricultural Transfer
Coefficients”

b Swiss Chard does not occur in the ARTF survey used to develop Policy
003.1.  Typical transfer coefficient values from the leafy vegetable
transfer coefficient group were used.

c MOE = NOAEL (30 mg/kg/day; based on an oral developmental study) /
dermal dose.



Table 3.  Days After Treatment Target MOE Achieved (Target MOE = 100)

Use Pattern	Application Rate	Postapplication Activity	Transfer
Coefficient a	Days After Treatment Target MOE b Achieved

Golf Course Turf	3	Maintenance	

3,400	0

Sod Farms	3	Harvesting	

6,800	3

a Transfer coefficients from ARTF.

b MOE = NOAEL (30 mg/kg/day; based on an oral developmental study) /
dermal dose.



Table 4. Residential Exposure Estimates & MOEs for Ethofumesate Treated
Turf

resident	

activity	

DAT	

Tc or Equivalent	

Body wgt 	

ADD	

NOAEL	

MOE

toddler

(at 3 lb ai/acre)	

Playing	

0	

5200	

15	

1.17	

190	

220

toddler	

hand to mouth	

0	

PDR*	

15	

0.022	

190	4200

toddler	

object to mouth	

0	

TTR*	

15	

0.0056	

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Science Advisory Council for Exposure Policy No. 12; revised February
22, 2001.

 PAGE  1 

Ethofumesate PC110601 	  OPPTS 870.7600 	Dermal Penetration  Study –
Rats		Page   PAGE  9  of   NUMPAGES  16