[Federal Register Volume 81, Number 244 (Tuesday, December 20, 2016)]
[Proposed Rules]
[Pages 92745-92747]
[FR Doc No: 2016-30019]

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DEPARTMENT OF TRANSPORTATION

Federal Aviation Administration

14 CFR Part 39

[Docket No. FAA-2016-9505; Directorate Identifier 2016-NM-155-AD]
RIN 2120-AA64

Airworthiness Directives; Learjet, Inc. Airplanes

AGENCY: Federal Aviation Administration (FAA), DOT.

ACTION: Notice of proposed rulemaking (NPRM).

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SUMMARY: We propose to adopt a new airworthiness directive (AD) for
certain Learjet Inc. Model 60 airplanes. This proposed AD was prompted
by an evaluation by the design approval holder (DAH) indicating that
the upper fuselage skin under the aft oxygen line fairing is subject to
multi-site damage (MSD). This proposed AD would require a one-time
inspection of the fuselage skin for corrosion and related investigative
and corrective actions if necessary. We are proposing this AD to
address the unsafe condition on these products.

DATES: We must receive comments on this proposed AD by February 3,
2017.

ADDRESSES: You may send comments, using the procedures found in 14 CFR
11.43 and 11.45, by any of the following methods:
     Federal eRulemaking Portal: Go to http://www.regulations.gov. Follow the instructions for submitting comments.
     Fax:<PHONE_NUMBER>.
     Mail: U.S. Department of Transportation, Docket
Operations, M-30, West Building Ground Floor, Room W12-140, 1200 New
Jersey Avenue SE., Washington, DC 20590.
     Hand Delivery: Deliver to Mail address above between 9
a.m. and 5 p.m., Monday through Friday, except Federal holidays.
    For service information identified in this NPRM, contact Learjet,
Inc., One Learjet Way, Wichita, KS 67209-2942; telephone:<PHONE_NUMBER>;
fax:<PHONE_NUMBER>; email<EMAIL_ADDRESS>Internet: http://www.bombardier.com. You may view this referenced service information at
the FAA, Transport Airplane Directorate, 1601 Lind Avenue SW., Renton,
WA. For information on the availability of this material at the FAA,
call<PHONE_NUMBER>.

Examining the AD Docket

    You may examine the AD docket on the Internet at http://www.regulations.gov by searching for and locating Docket No. FAA-2016-
9505; or in person at the Docket Management Facility between 9 a.m. and
5 p.m., Monday through Friday, except Federal holidays. The AD docket
contains this proposed AD, the regulatory evaluation, any comments
received, and other information. The street address for the Docket
Office (phone:<PHONE_NUMBER>) is in the ADDRESSES section. Comments will
be available in the AD docket shortly after receipt.

FOR FURTHER INFORMATION CONTACT: Paul Chapman, Aerospace Engineer,
Airframe Branch, ACE-118W, FAA, Wichita Aircraft Certification Office
(ACO), 1801 Airport Road, Room 100, Dwight D. Eisenhower Airport,
Wichita, KS 67209; phone:<PHONE_NUMBER>; fax:<PHONE_NUMBER>; email:
<EMAIL_ADDRESS>
SUPPLEMENTARY INFORMATION:

Comments Invited

    We invite you to send any written relevant data, views, or
arguments about this proposal. Send your comments to an address listed
under the ADDRESSES section. Include ``Docket No. FAA-2016-9505;
Directorate Identifier 2016-NM-155-AD'' at the beginning of your
comments. We specifically invite comments on the overall regulatory,
economic, environmental, and energy aspects of this proposed AD. We
will consider all comments received by the closing date and may amend
this proposed AD because of those comments.
    We will post all comments we receive, without change, to http://www.regulations.gov, including any personal information you provide. We
will also post a report summarizing each substantive verbal contact we
receive about this proposed AD.

Discussion

    We have received a report indicating that the upper fuselage skin
under the aft oxygen line fairing is subject to MSD (corrosion at
multiple sites under the fairing). This condition, if not corrected,
could result in reduced structural integrity of the airplane.

Related Service Information Under 1 CFR Part 51

    We reviewed Learjet 60 Service Bulletin 60-53-19, Revision 3, dated
August 29, 2016. The service information describes procedures for
inspections of the fuselage crown skin for corrosion and related
investigative and corrective actions, if necessary. This service
information is reasonably

available because the interested parties have access to it through
their normal course of business or by the means identified in the
ADDRESSES section.

FAA's Determination

    We are proposing this AD because we evaluated all the relevant
information and determined the unsafe condition described previously is
likely to exist or develop in other products of the same type design.

Proposed AD Requirements

    This proposed AD would require accomplishing the actions specified
in the service information described previously, except as discussed
under ``Differences Between this Proposed AD and the Service
Information.'' This proposed AD also would require sending the
inspection results to the FAA.
    Related investigative actions include a high frequency eddy current
inspection of the affected skin sections and an ultrasonic skin
thickness check. Corrective actions include repairing corrosion.

Differences Between This Proposed AD and the Service Information

    Learjet 60 Service Bulletin 60-53-19, Revision 3, dated August 29,
2016, specifies to contact the manufacturer for instructions on how to
repair certain conditions, but this proposed AD would require repairing
those conditions in one of the following ways:
     In accordance with a method that we approve; or
     Using data that meet the certification basis of the
airplane, and that have been approved by a Delegated Engineering
Representative (DER) for Learjet Inc., or a Unit Member (UM) of the
Learjet Organization Designation Authorization (ODA), whom we have
authorized to make those findings.

Interim Action

    We consider this proposed AD interim action. Because the cause of
the corrosion is not known, the inspection reports will help determine
the extent of the corrosion in the affected fleet. Based on the results
of these reports, we might determine that further corrective action is
warranted. Once further corrective action has been identified, we might
consider further rulemaking.

Costs of Compliance

    We estimate that this proposed AD affects 284 airplanes of U.S.
registry. We estimate the following costs to comply with this proposed
AD:

                                                 Estimated Costs
----------------------------------------------------------------------------------------------------------------
                                                                                Cost per      Cost on U.S.
                Action                         Labor cost           Parts cost        product        operators
----------------------------------------------------------------------------------------------------------------
Inspections...........................  46 work-hours x $85 per             $265          $4,175      $1,185,700
                                         hour = $3,910.
Reporting.............................  1 work-hour x $85 per                  0              85          24,140
                                         hour = $85.
----------------------------------------------------------------------------------------------------------------

    We have received no definitive data that would enable us to provide
cost estimates for the on-condition actions specified in this proposed
AD.
    According to the manufacturer, some of the costs of this proposed
AD may be covered under warranty, thereby reducing the cost impact on
affected individuals. We do not control warranty coverage for affected
individuals. As a result, we have included all costs in our cost
estimate.

Paperwork Reduction Act

    A federal agency may not conduct or sponsor, and a person is not
required to respond to, nor shall a person be subject to penalty for
failure to comply with a collection of information subject to the
requirements of the Paperwork Reduction Act unless that collection of
information displays a current valid OMB control number. The control
number for the collection of information required by this AD is 2120-
0056. The paperwork cost associated with this AD has been detailed in
the Costs of Compliance section of this document and includes time for
reviewing instructions, as well as completing and reviewing the
collection of information. Therefore, all reporting associated with
this AD is mandatory. Comments concerning the accuracy of this burden
and suggestions for reducing the burden should be directed to the FAA
at 800 Independence Ave. SW., Washington, DC 20591, ATTN: Information
Collection Clearance Officer, AES-200.

Authority for This Rulemaking

    Title 49 of the United States Code specifies the FAA's authority to
issue rules on aviation safety. Subtitle I, section 106, describes the
authority of the FAA Administrator. Subtitle VII: Aviation Programs,
describes in more detail the scope of the Agency's authority.
    We are issuing this rulemaking under the authority described in
Subtitle VII, Part A, Subpart III, Section 44701: ``General
requirements.'' Under that section, Congress charges the FAA with
promoting safe flight of civil aircraft in air commerce by prescribing
regulations for practices, methods, and procedures the Administrator
finds necessary for safety in air commerce. This regulation is within
the scope of that authority because it addresses an unsafe condition
that is likely to exist or develop on products identified in this
rulemaking action.

Regulatory Findings

    We determined that this proposed AD would not have federalism
implications under Executive Order 13132. This proposed AD would not
have a substantial direct effect on the States, on the relationship
between the national Government and the States, or on the distribution
of power and responsibilities among the various levels of government.
    For the reasons discussed above, I certify this proposed
regulation:
    (1) Is not a ``significant regulatory action'' under Executive
Order 12866,
    (2) Is not a ``significant rule'' under the DOT Regulatory Policies
and Procedures (44 FR 11034, February 26, 1979),
    (3) Will not affect intrastate aviation in Alaska, and
    (4) Will not have a significant economic impact, positive or
negative, on a substantial number of small entities under the criteria
of the Regulatory Flexibility Act.

List of Subjects in 14 CFR Part 39

    Air transportation, Aircraft, Aviation safety, Incorporation by
reference, Safety.

The Proposed Amendment

    Accordingly, under the authority delegated to me by the
Administrator, the FAA proposes to amend 14 CFR part 39 as follows:

PART 39--AIRWORTHINESS DIRECTIVES

0
1. The authority citation for part 39 continues to read as follows:

    Authority:  49 U.S.C. 106(g), 40113, 44701.

Sec.  39.13   [Amended]

0
2. The FAA amends Sec.  39.13 by adding the following new airworthiness
directive (AD):

Learjet Inc.: Docket No. FAA-2016-9505; Directorate Identifier 2016-
NM-155-AD.

(a) Comments Due Date

    We must receive comments by February 3, 2017.

(b) Affected ADs

    None.

(c) Applicability

    This AD applies to Learjet Inc. Model 60 airplanes, certificated
in any category, serial numbers 60-002 through 60-430 inclusive.

(d) Subject

    Air Transport Association (ATA) of America Code 53, Fuselage.

(e) Unsafe Condition

    This AD was prompted by an evaluation by the design approval
holder indicating that the upper fuselage skin under the aft oxygen
line fairing is subject to multi-site damage. We are issuing this AD
to detect and correct corrosion of the fuselage skin, which could
result in reduced structural integrity of the airplane.

(f) Compliance

    Comply with this AD within the compliance times specified,
unless already done.

(g) Inspection of the Fuselage Skin and Related Investigative and
Corrective Actions

    At the applicable time specified in paragraph (g)(1), (g)(2), or
(g)(3) of this AD: Do a fluorescent dye penetrant inspection of the
fuselage skin between stringers (S)-2L and S-2R for corrosion; and
do all applicable related investigative and corrective actions; in
accordance with the Accomplishment Instructions of Learjet 60
Service Bulletin 60-53-19, Revision 3, dated August 29, 2016, except
as required by paragraph (h) of this AD. Do all applicable related
investigative and corrective actions before further flight.
    (1) For airplanes with more than 12 years since the date of
issuance of the original airworthiness certificate or the date of
issuance of the original export certificate of airworthiness as of
the effective date of this AD: Within 12 months after the effective
date of this AD.
    (2) For airplanes with more than 6 years but equal to or less
than 12 years since the date of issuance of the original
airworthiness certificate or the date of issuance of the original
export certificate of airworthiness as of the effective date of this
AD: Within 24 months after the effective date of this AD.
    (3) For airplanes with 6 years or less since the date of
issuance of the original airworthiness certificate or the date of
issuance of the original export certificate of airworthiness as of
the effective date of this AD: Within 36 months after the effective
date of this AD.

(h) Service Information Exception

    Where Learjet 60 Service Bulletin 60-53-19, Revision 3, dated
August 29, 2016, specifies contacting Learjet Inc. for appropriate
action: Before further flight, repair using a method approved in
accordance with the procedures specified in paragraph (l) of this
AD.

(i) Reporting

    At the applicable time specified in paragraph (i)(1) or (i)(2)
of this AD: Submit a report of the findings (both positive and
negative) of the inspection required by paragraph (g) of this AD to
<EMAIL_ADDRESS>or Ann Johnson, 1801 Airport Road, Wichita, KS
67209. The report must include the name of the owner, the address of
the owner, the name of the organization incorporating Learjet 60
Service Bulletin 60-53-19, the date that inspection was completed,
the name of the person submitting the report, the address, telephone
number, and email of the person submitting the report, the airplane
serial number, the total time (hours) on the airplane, the total
landings on the airplane, whether corrosion was detected, whether
corrosion was repaired, the structural repair manual (SRM) chapter
and revision (if repaired), and whether corrosion exceeded the
minimum thickness specified in Learjet 60 Service Bulletin 60-53-19
(and specify the SRM chapter and revision that was used).
    (1) If the inspection was done on or after the effective date of
this AD: Submit the report within 30 days after the inspection.
    (2) If the inspection was done before the effective date of this
AD: Submit the report within 30 days after the effective date of
this AD.

(j) Credit for Previous Actions

    This paragraph provides credit for the actions specified in
paragraph (g) of this AD, if those actions were performed before the
effective date of this AD using Learjet 60 Service Bulletin 60-53-
19, dated November 23, 2015; Learjet 60 Service Bulletin 60-53-19,
Revision 1, dated April 4, 2016; or Learjet 60 Service Bulletin 60-
53-19, Revision 2, dated April 18, 2016.

(k) Paperwork Reduction Act Burden Statement

    A federal agency may not conduct or sponsor, and a person is not
required to respond to, nor shall a person be subject to a penalty
for failure to comply with a collection of information subject to
the requirements of the Paperwork Reduction Act unless that
collection of information displays a current valid OMB Control
Number. The OMB Control Number for this information collection is
2120-0056. Public reporting for this collection of information is
estimated to be approximately 5 minutes per response, including the
time for reviewing instructions, completing and reviewing the
collection of information. All responses to this collection of
information are mandatory. Comments concerning the accuracy of this
burden and suggestions for reducing the burden should be directed to
the FAA at: 800 Independence Ave. SW., Washington, DC 20591, Attn:
Information Collection Clearance Officer, AES-200.

(l) Alternative Methods of Compliance (AMOCs)

    (1) The Manager, Wichita ACO, FAA, has the authority to approve
AMOCs for this AD, if requested using the procedures found in 14 CFR
39.19. In accordance with 14 CFR 39.19, send your request to your
principal inspector or local Flight Standards District Office, as
appropriate. If sending information directly to the manager of the
ACO, send it to the attention of the person identified in paragraph
(m)(1) of this AD.
    (2) Before using any approved AMOC, notify your appropriate
principal inspector, or lacking a principal inspector, the manager
of the local flight standards district office/certificate holding
district office.
    (3) An AMOC that provides an acceptable level of safety may be
used for any repair, modification, or alteration required by this AD
if it is approved by a Learjet Inc. Designated Engineering
Representative (DER), or a Unit Member (UM) of the Learjet
Organization Designation Authorization (ODA), that has been
authorized by the Manager, Wichita ACO, to make those findings. To
be approved, the repair, modification deviation, or alteration
deviation must meet the certification basis of the airplane, and the
approval must specifically refer to this AD.

(m) Related Information

    (1) For more information about this AD, contact Paul Chapman,
Aerospace Engineer, Airframe Branch, ACE-118W, FAA, Wichita ACO,
1801 Airport Road, Room 100, Dwight D. Eisenhower Airport, Wichita,
KS 67209; phone:<PHONE_NUMBER>; fax:<PHONE_NUMBER>; email<EMAIL_ADDRESS>    (2) For service information identified in this AD, contact
Learjet, Inc., One Learjet Way, Wichita, KS 67209-2942; telephone:
316-946-2000; fax:<PHONE_NUMBER>; email<EMAIL_ADDRESS>
Internet: http://www.bombardier.com. You may view this referenced
service information at the FAA, Transport Airplane Directorate, 1601
Lind Avenue SW., Renton, WA. For information on the availability of
this material at the FAA, call<PHONE_NUMBER>.

    Issued in Renton, Washington, on December 2, 2016.
Michael Kaszycki,
Acting Manager, Transport Airplane Directorate, Aircraft Certification
Service.
[FR Doc. 2016-30019 Filed 12-19-16; 8:45 am]
 BILLING CODE 4910-13-P


UNITED STATES ENVIRONMENTAL PROTECTION AGENCY

WASHINGTON, D.C.  20460

     OFFICE OF

PREVENTION, PESTICIDES

AND TOXIC SUBSTANCES

November 2, 2007

MEMORANDUM

SUBJECT:	Ethalfluralin:  Human Health Risk Assessment for (IR-4) Proposed Uses on Dill and Potato.

PC Code: 113101

Petitions: 1E6326 and 2E6360

DP Barcodes: D323068 and D323069

		Regulatory Action: Section 3 Registration

		Risk Assessment Type: Single Chemical Aggregate

FROM:	J. R. Tomerlin, PhD., Plant Pathologist, ARIA Team

		Fungicide Branch

		Registration Division (7505P)

			and

		Christina Swartz, Chemist

		Registration Action Branch 2

		Health Effects Division (7509P)

THROUGH:	Karlyn J. Bailey, Toxicologist

		Registration Action Branch 2

		Health Effects Division (7509P)

			and

		Whang Phang, Toxicologist

		Reregistration Action Branch 1

		Health Effects Division (7509P)

TO:		Shaja Brothers

		Risk Integration, Minor Use and Emergency Response Branch

		Registration Division (7505P)

Table of Contents

  TOC \f  1.0	Executive Summary	4

2.0	Ingredient Profile	7

2.1	Summary of Registered/Proposed Uses	8

2.2	Structure and Nomenclature	8

2.3	Physical and Chemical Properties	8

3.0	Hazard Characterization/Assessment	10

3.1	Hazard and Dose-Response Characterization	10

3.2	FQPA Considerations	11

3.3	Developmental Toxicity Studies	12

3.4	Reproductive Toxicity Study	12

3.5	Additional Information from Literature Sources	13

3.6	Hazard Identification and Toxicity Endpoint Selection	13

3.6.1	Acute Population Adjusted Dose (aPAD) - Females age 13-49	13

3.6.2	Acute Population Adjusted Dose (aPAD) - General Population	13

3.6.3	Chronic Population Adjusted Dose (cPAD)	14

3.6.4	Incidental Oral Exposure (Short- and Intermediate-Term)	14

3.6.5	Dermal Absorption	14

3.6.6	Dermal Exposure (Short-, Intermediate- and Long-Term)	14

3.6.7	Inhalation Exposure (Short-, Intermediate- and Long-Term)	14

3.6.8	Level of Concern for Margin of Exposure	15

3.6.9	Recommendation for Aggregate Exposure Risk Assessments	15

3.6.10	Classification of Carcinogenic Potential	15

3.6.11	Summary of Toxicological Doses and Endpoints for Use in Human Risk Assessments	16

3.7	Endocrine disruption	17

4.0	Dietary Exposure/Risk Characterization	18

4.1	Pesticide Metabolism and Environmental Degradation	18

4.1.1	Metabolism in Primary Crops	18

4.1.2	Metabolism in Rotational Crops	18

4.1.3	Metabolism in Livestock	18

4.1.4	Analytical Methodology	18

4.1.5	Environmental Degradation	19

4.1.6	Pesticide Metabolites and Degradates of Concern	19

4.1.7	Drinking Water Residue Profile	20

4.1.8	Food Residue Profile	20

4.1.9	International Residue Limits	21

4.2	Dietary Exposure and Risk	21

4.2.1	Acute Dietary Exposure/Risk	21

4.2.2	Chronic Dietary Exposure/Risk	21

4.2.3	Cancer Dietary Risk	22

4.3 Anticipated Residue and Percent Crop Treated (%CT) Information	22

5.0	Residential (Non-Occupational) Exposure/Risk Characterization	23

5.1	Other (Spray Drift, etc.)	23

6.0	Aggregate Risk Assessments and Risk Characterization	23

7.0	Cumulative Risk Characterization/Assessment	23

8.0	Occupational Exposure/Risk Pathway	24

8.1	Short-Term and Cancer Handler Risk	24

8.2	Cancer Postapplication Risk	26

9.0	Data Needs and Label Recommendations	26

9.1	Toxicology	26

9.2	Residue Chemistry	26

9.3	Occupational and Residential Exposure	26

10.0	References:	27

	Appendices	28

 1.0	Executive Summary

Ethalfluralin [N-ethyl-N-(2-methyl-2-propenyl)-2,6-dinitro-4-(trifluoromethyl)-benzena mine] is a selective preemergence herbicide registered for use on a variety of food and feed crops.  Registered products containing ethalfluralin include granular (G), dry flowable (DF), and emulsifiable concentrate (EC) formulations. These formulations may be applied preplant, postplant prior to emergence, postemergence, or post-transplant as a soil incorporated, band, or broadcast application using ground equipment.  Tolerances are currently established for ethalfluralin residues in bean, dry seed; canola, seed; peanut; pea, dry, seed; safflower, seed; soybean; sunflower, seed; and vegetable, cucurbit, crop group 9, all at 0.05 ppm.

  SEQ CHAPTER \h \r 1 The Interregional Research Project No. 4 (IR-4) submitted petitions for the establishment of permanent tolerances for residues of the herbicide ethalfluralin in dill at 0.05 ppm and in potato at 0.05 ppm.  In dill, the proposed use pattern is for a single broadcast soil-incorporated application after seeding but before emergence of the dill.  The proposed application rate is a maximum of 4 pints/A (1.5 lbs ai/A; pounds active ingredient/acre).  In potato, the proposed use pattern is for a single broadcast soil-incorporated application after seeding but before emergence of potatoes; the proposed application rate in potato is a maximum of 2 2/3 pints/A (1.0 lb ai/A).  No preharvest interval (PHI) is proposed for either formulation because the proposed use patterns involve preemergence applications.

The toxicity database for ethalfluralin is complete, and indicates it has low acute toxicity by oral, dermal, and inhalation routes of exposure. It is moderately irritating to the eye and produces moderate to severe skin irritation.  In one study ethalfluralin was negative for dermal sensitization, but in another, it was considered positive.

In general, subchronic and chronic feeding studies in rats, mice, and dogs indicate the liver as the target organ, with consistent effects of enzymatic changes, liver weight increases, and histopathology (chronic mouse).  A combined chronic/carcinogenicity study in rats showed no non-neoplastic effects at the highest dose tested (32 mg/kg/day). However, mammary gland fibroadenomas were increased in a dose-related manner, and therefore ethalfluralin was classified as a possible human carcinogen in 1994. The Cancer Peer Review Committee (CPRC) recommended a quantitative approach for cancer risk assessment using a cancer potency factor, or Q1* of 8.9 x 10-2 (mg/kg/day)-1.  The mouse carcinogenicity study showed no increase in tumor incidence.  Consistent with other studies, liver effects were found in the highest dose group (163 mg/kg/day).

Ethalfluralin does not produce developmental toxicity in rats at doses up to1000 mg/kg/day.  There are several rabbit developmental toxicity studies available; together, these studies indicate the potential for ethalfluralin to induce skeletal malformations at doses of >150 mg/kg/day.  Maternal toxicity was observed at similar doses.  Ethalfluralin did not produce reproductive or offspring effects in the 3-generation reproduction studies; the parental effects consisted of decreased body weight gains.

In a rat metabolism study with oral dosing, ethalfluralin was well absorbed and rapidly and extensively metabolized, and 95% of the chemical was excreted in urine and feces within seven days.  The major route of elimination was via the feces, and the levels remaining in the tissues were negligible.

HED has fully evaluated the toxicity database of ethalfluralin with respect to the potential for special sensitivity of infants and children, and concludes that there is low concern for pre- and postnatal susceptibility for infants and children.  The FQPA safety factor has been reduced to 1X because (1) the toxicity database is complete and adequate to characterize potential pre- and postnatal risk for infants and children; (2) no reproductive or developmental effects were observed in rats; (3) there was no evidence of neurotoxicity in the submitted studies; and (4) although there were slight developmental effects observed (skeletal malformations) in rabbits (fetuses), they were seen in the presence of maternal toxicity.  Additionally, the dose chosen for acute dietary risk assessment is protective of the slight developmental effects observed in the rabbit developmental toxicity studies.  A developmental neurotoxicity study, or any other study to further elucidate potential pre- and/or postnatal effects, is not required at this time.

A single dose effect applicable to the general population was not observed in the toxicity database for ethalfluralin, and therefore, an acute dietary endpoint for the general population including infants and children was not identified.  The dose for acute dietary risk assessment for females 13-49 years old is the No Observed Adverse Effect Level (NOAEL) of 75 mg/kg/day, based on skeletal malformations observed at the Lowest Observed Adverse Effect Level (LOAEL) of 150 mg/kg/day.  The dose selected for chronic dietary risk assessment for all populations is the NOAEL of 4 mg/kg/day from a 1-year oral toxicity study in dogs, based on altered red cell morphology and urinary bilirubin observed at the LOAEL of 20 mg/kg/day.  The uncertainty factor (UF) for acute and chronic dietary assessments consists of the combined intra- and interspecies factors of 10X, for a total UF of 100.

Occupational exposures for non-cancer risk are expected to be short-term in duration.  An endpoint for dermal risk assessment was not identified in the toxicity database, and therefore dermal risks are not of concern for non-cancer effects.  A dermal absorption factor of 2.8% was used in conducting cancer risk assessments for occupational workers.  For inhalation exposures, an oral study was selected for risk assessment in order to determine screening-level risks from the inhalation route.  Inhalation toxicity of ethalfluralin is expected to be low, but in the absence of an inhalation study, the NOAEL from a 3-generation reproduction study (12.5 mg/kg/day), based on decreased body weight gains (males) at the LOAEL of 37.5 mg/kg/day was selected for short-term inhalation risk assessment.  A default assumption of 100% inhalation absorption was used to extrapolate from the oral study to the inhalation route.

Adequate residue chemistry data, including an acceptable analytical enforcement method, have been submitted to support the proposed tolerances and the risk assessment.  When ethalfluralin is used in accordance with the proposed labels, residues in or on dill (fresh and dry) are less than the limit of quantitation (LOQ) of 0.05 ppm.  Likewise, the results from potato field trials show that ethalfluralin residues are below the lowest limit of method validation (LLMV) of 0.05 ppm in potato tubers.  In the environment, ethalfluralin is expected to dissipate by binding to soil particles and then degrading both aerobically and anaerobically.  It also photodegrades rapidly in water, with a half life of 6 hours.  Modeled estimated drinking water concentrations (EDWCs) were higher for surface water sources of drinking water obtained from the PRZM-EXAMs model than ground water concentrations generated using the SciGrow model.  For both surface and ground water, the scenario chosen to represent maximum potential drinking water residues was the existing use on canola, at a maximum application rate of 1.5 lbs ai/A.  The surface water EDWCs included directly in the dietary model were 11 ppb for acute dietary exposure, and 0.4 ppb for chronic exposure; the cancer assessment was further refined with the use of drinking water monitoring data from the USDA Pesticide Data Program (PDP).

With the proposed uses, dietary exposure from food and drinking water is not of concern.  For acute dietary (food + water) exposure for females 13-49, the estimated dietary risk is <1 % aPAD at the 95th percentile of exposure.  For chronic dietary (food + water) exposure, children 1-2 was the most highly exposed subpopulation, with an estimated risk of <1% cPAD.  Finally, cancer dietary (food + water) risk for the general US population is 2 x 10-6.  Additional refinement with %CT estimates would lead to a lower estimate of dietary cancer risk.  EPA generally considers cancer risks of 10-6 or less to be below the level of concern.  The precision which can be assumed for cancer risk estimates is best described by rounding to the nearest integral order of magnitude on the log scale; for example, risks falling between 3.16 x 10-7 and 3.16 x 10-6 are expressed as 10-6.  Considering the precision with which cancer hazard can be estimated and the rounding procedure described above, cancer risk should generally not be assumed to exceed the benchmark level of concern of 10-6 until the calculated risk exceeds approximately 3 x 10-6.  Since the calculated cancer risk for ethalfluralin falls below this level, estimated cancer risk is considered to be below the level of concern.  Dietary exposure to ethalfluralin results in acute, chronic and cancer risks below HED’s level of concern.  Additional refinements are possible, since 100 % crop treated was used.  At this time, there are no current or proposed residential uses for ethalfluralin.  Therefore, aggregate exposure and risk consist of only the dietary (food + water) pathway of exposure.  Aggregate acute, chronic and cancer risks are not of concern for the proposed and existing uses.

Short-term inhalation exposure and risk to occupational handlers mixing, loading, and applying ethalfluralin are not of concern, with margins of exposure (MOEs) considerably higher than 100.  Estimates of occupational handler cancer risks (from combined inhalation and dermal exposure) range from 5.9 x 10-6 to 4.4 x 10-5, which are below HED’s level of concern (LOC) for handler cancer risk.  Estimated cancer risk from post-application exposures to workers is 1.4 x 10-5, which does not exceed HED’s LOC for occupational cancer risk.

Given these considerations, HED recommends for the establishment of ethalfluralin ((N-ethyl-N-(2-methyl-2-propenyl)-2,6-dinitro-4-(trifluoromethyl)benzena mine) herbicide tolerances of 0.05 ppm in dill and potato:

Tolerance Summary for Ethalfluralin.

Commodity	Proposed Tolerance (ppm)	Recommended Tolerance (ppm)	Commodity definition

Dill, fresh leaves	0.05	0.05	Dill, fresh and dried

Dill, dried leaves	0.05	0.05	Dill, fresh and dried

Potato	0.05	0.05	Potato

Furthermore, HED recommends for the proposed uses of CURBIT® EC on dill and Sonalan® HFP on potato.

Environmental Justice Considerations

Potential areas of environmental justice concerns, to the extent possible, were considered in this human health risk assessment, in accordance with US 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 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 Intakes 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.  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 postapplication 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.

Review of Human Research

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, which comprise the Pesticide Handlers Exposure Database (PHED), have been determined to require a review of their ethical conduct, and have received that review.  The studies in PHED were considered appropriate (ethically conducted) for use in risk assessments.

2.0	Ingredient Profile

Ethalfluralin (N-ethyl-N-(2-methyl-2-propenyl)-2,6-dinitro-4-(trifluoromethyl)benzenam ine is a dinitroaniline herbicide with established tolerances on bean, dry, seed; canola, seed; peanut; safflower, seed; soybean; sunflower, seed; and vegetable, cucurbit, group 9.  The tolerances are published under 40 CFR 180.416.  Ethalfluralin is a preemergence herbicide used to control a variety of annual grasses and broadleaf weeds on agricultural sites.

Under petition PP# 1E6326; the CURBIT® EC formulation (31.5% ai) was proposed for use on dill.  The Sonalan® HFP (31.5% ai) was proposed for use on potato under petition PP# 2E6360.

2.1	Summary of Proposed Uses

Table 2.1.  Summary of Proposed Directions for Ethalfluralin.

Applic. Timing, Type, and Equip.	Formulation	Applic. Rate

(lb ai/A)	Max. No. Applic. per Season	Max. Seasonal Applic. Rate

(lb ai/A)	PHI (days)	Use Directions and Limitations

Dill

Soil surface broadcast	CURBIT® EC	1.5	1	1.5	91 – 100	Sprinkler irrigation may be used to incorporate compound into soil

Potato

Soil surface broadcast	Sonalan® HFP	1.0	1	1	65 - 143	Sprinkler irrigation may be used to incorporate compound into soil

2.2	Structure and Nomenclature  TC \l2 "2.2	Structure and Nomenclature

The structure and nomenclature of ethalfluralin is presented in Table 2.2.

2.3	Physical and Chemical Properties  TC \l2 "2.3	Physical and Chemical Properties

The physical and chemical properties of ethalfluralin are summarized in Table 2.3.

Empirical Formula	C13H14F3N3O4

Common name	Ethalfluralin

Company experimental name	N/A

IUPAC name N-ethyl-α,α,α-trifluoro-N-(2-methylallyl)-2,6-dinitro-p-toluidine

CAS name N-ethyl-N-(2-methyl-2-propenyl)-2,6-dinitro-4-(trifluoromethyl)benzenami ne

CAS Registry Number	5523-68-6

End-use product/EP	CURBIT® EC Herbicide (Reg. No. 34704-610) and Sonalan® HFP Herbicide (Reg. No. 62719-188)

Chemical Class	Dinitroaniline herbicide

Known Impurities of Concern	N/A

TABLE 2.3.  Physicochemical Properties

Parameter	Value	Reference

Molecular Weight	333.27	Ethalfluralin Registration Eligibility Decision (RED), EPA 738-R-95-001, March 1995

Melting point/range	57ºC	Ethalfluralin RED, EPA 738-R-95-001, March 1995

pH	7.68	DP Num: 276090, MRID#’s 45406501 and 45406502

Density	4.783	Texas Risk Reduction Program

Water solubility (20°C)	4.783 mg/L	Texas Risk Reduction Program

Solvent solubility (temperature not specified), mg/L	> 0.50 in acetone

> 0.50 in acetonitrile

> 0.50 in chloroform

> 0.50 in cyclohexanone

> 0.165 in ethyl cellosolve

> 0.250 in heavy aromatic naphtha

> 0.082 in hexane

> 0.082 in methanol

> 0.50 in xylene

> 0.50 in methylene chloride	DP Num: 199662, MRID# 00135194

Vapor pressure (25°C)	8.538 x 10-6	Texas Risk Reduction Program

Octanol/water partition coefficient, log POW (25°C)	4.783	Texas Risk Reduction Program

Hazard Characterization/Assessment

Based on the proposed use pattern, the ethalfluralin toxicity database is complete for the purpose of selecting doses and endpoints for risk assessment, and for characterization of potential pre- and/or post-natal risk for infants and children. (See detailed Hazard Profile in Appendix A.3)

3.1	Hazard and Dose-Response Characterization

The data base of ethalfluralin indicates it has low acute toxicity by oral, dermal, and inhalation routes of exposure (for details, see Appendix A.2).  It is moderately irritating to the eye and produces moderate to severe skin irritation.  A guinea pig dermal sensitization study conducted by the modified Buehler method found no sensitization, whereas a study conducted by the Magnusson and Kligman maximization method was positive.

The data from the subchronic feeding studies in mice show liver to be consistently affected as indicated by increases in alanine aminotransferase (SGPT), alkaline phosphatase (ALP), and increased liver weights.  A 3-month feeding study in dogs showed liver effects as characterized by increases in ALP and slight fatty changes of the liver.  A one year feeding study in rats also showed increases in liver weights, and decreases in RBC, hematocrit, and hemoglobin.  A 21-day dermal toxicity study in rabbits indicated no systemic toxicity at the limit dose (1000 mg/kg/day).  In general, based on subchronic and chronic feeding studies in rats, mice, and dogs, liver appeared to be the target organ with consistent effects of enzymatic changes and liver weight increases.

	A chronic feeding/carcinogenicity study in rats showed no non-neoplastic effects at the highest dose tested (32 mg/kg/day). However, mammary gland fibroadenomas increased in a dose-related manner, and ethalfluralin was classified as a possible human carcinogen in 1994. The mouse carcinogenicity study showed no increase in tumor incidence. Liver effects, characterized by increase in ALP and focal hepatocellular hyperplasia, were found in the highest dose group (163 mg/kg/day). The chronic dog feeding study indicated hematological changes, elevated ALP, and siderosis of the liver in the high dose animals (80 mg/kg/day).

Ethalfluralin does not produce developmental effects in rats at doses up to ≥ 1000 mg/kg/day, but systemic effects observed were decreases in maternal body weight gains and dark urine at ≥ 250 mg/kg/day. There are several rabbit developmental toxicity studies available.  In the first pilot study no maternal or fetoxicity was seen at doses from 10 to 150 mg/kg/day, but skeletal and visceral examinations were not conducted.  In the second pilot study, abortion was seen in 1/3 dams at 500 mg/kg/day.  Like the first pilot study, no skeletal and visceral examinations were conducted. Subsequently, three full developmental toxicity studies were conducted using lower and lower dose levels because of increased incidence of abortion found in dams at all doses in the first study.  In one study, at 500 mg/kg/day, increased incidences of dwarf-like appearance, open eyelids, and cleft palate were seen.  A second study was conducted with dose levels of 75 and 250 mg/kg/day. At 250 mg/kg/day, a cluster of the external findings was reported.  No external findings were seen in the 75 mg/kg/day group.  A third study was conducted using doses ranging from 25 to 300 mg/kg/day. A slight increase in the incidence of sternal variations and incomplete cranial development was seen in 150 mg/kg/day groups. Although the increased incidence in sternal variation, incomplete cranial development, and resorption at 150 mg/kg/day appears to be slight, this suggests the potential for ethalfluralin to induce malformation at doses of 150 mg/kg/day and above.  Clear maternal effects were seen in 300 mg/kg group characterized by increased incidence of abortion (5/20); decreased body weight gain; enlarged, fatty liver; decreased food consumption, increased resorptions, and increased liver weights.  A decrease in food consumption, slight increase in abortion (1/20), and a slight increased in resorption were seen in 150 mg/kg/day dams. Therefore the dose level of 150 mg/kg/day was established as the maternal LOAEL; the maternal NOAEL was 75 mg/kg/day.  Evaluating all the results of these studies together, the developmental toxicity LOAEL was established as 150 mg/kg/day based on slight increase in the incidence of sternal variations, cranial variations, incomplete cranial development, and of resorption; the NOAEL was 75 mg/kg/day.

	Ethalfluralin did not produce reproductive or offspring effects in the 3-generation reproduction studies; the parental effects consisted of decreased body weight gains.

In metabolism studies, Fischer 344 rats were treated orally with a single low dose, a single high dose, or repeated low doses of radiolabeled ethalfluralin.  Absorption of ethalfluralin was estimated at 79-87% of the dose for all dose levels.  Ethalfluralin was rapidly and extensively metabolized, and 95% of the chemical was excreted in urine and feces by seven days.  The major route of elimination for the radiolabel was in the feces, 50.9-63.2%, and the levels remaining in the tissues after 72 hours were negligible.

3.2	FQPA Considerations

In 1999, an ad hoc FQPA Safety Factor Committee evaluated the toxicity data relevant to the determination of the FQPA Safety Factor (SF).  Based on the oral developmental toxicity study in rabbits (MRID 00250596), the ad hoc committee determined the appropriate SF for assessing acute dietary risk to be 3X and for assessing chronic dietary risk to be 1X.  In a subsequent assessment conducted in 2002, the Agency retained the 10X factor for both acute and chronic dietary exposure assessment, pending a complete evaluation of the toxicity database with respect to the special sensitivity of infants and children.  With the current proposed uses on dill and potato, HED has fully evaluated the toxicity database for ethalfluralin with respect to the FQPA SF.

In considering the FQPA SF, the hazard is evaluated in conjunction with the toxicity endpoints selected for risk assessment.  The toxicity endpoint selected for the acute dietary exposure assessment was based on slightly increased number of resorptions and increased sternal and cranial variations at the 150 mg/kg/day LOAEL of the developmental toxicity study in rabbits.  After evaluating all the information, HED concludes the 10X FQPA SF can be removed (reduced to 1X) for the following reasons:

The developmental effects seen at the LOAEL of 150 mg/kg/day are slight and are mainly sternal variations in one or two fetuses, incomplete cranial development in 2 fetuses, and a slight increase in resorptions.

The dose used for risk assessment is the NOAEL of 75 mg/kg/day, a clear NOAEL from the two developmental toxicity studies in rabbits.  The use of this NOAEL for risk assessment is protective of the effects of concern seen in the developmental toxicity studies.

There are no pre- or post-natal toxicity concerns for infants and children, based on the results of the rat and rabbit developmental toxicity studies or the 3-generation reproductive toxicity study in rats.

There is no evidence of neurotoxicity in the submitted toxicity studies, there are no data gaps, and no additional special studies have been required.

3.3	Developmental Toxicity Studies

 ≥ 150 mg/kg/day.  Clear maternal effects were seen in the 300 mg/kg group characterized by increased incidence of abortion (5/20); decreased body weight gain; enlarged and fatty liver; decreased food consumption, increased resorptions, and increased liver weights.  A decrease in food consumption, slight increase in abortion (1/20), and a slight increase in resorptions were seen in 150 mg/kg/day dams.  Therefore, the maternal LOAEL and NOAEL were established at 150 mg/kg/day and 75 mg/kg/day, respectively.  Evaluating all the results of these studies together, the developmental toxicity LOAEL was established as 150 mg/kg/day based on a slight increase in the incidence of sternal variations, cranial variations, incomplete cranial development, and of resorption; the developmental NOAEL was 75 mg/kg/day.

3.4	Reproductive Toxicity Study

In a three-generation reproduction study in Fischer 344 rats, the parental NOAEL was 12.5 mg/kg/day.  The parental LOAEL of 37.5 mg/kg/day was based on depressed mean body weight gains in males in all generations.  No treatment-related effects were noted on reproductive parameters and the NOAEL was 37.5 mg/kg/day or greater.  In a seven-month multigeneration bridging study in Fischer 344 rats, the parental NOAEL was 20 mg/kg/day.  The parental LOAEL was 61 mg/kg/day, based on increased liver weights.  No treatment-related effects were noted on reproductive parameters and the reproductive NOAEL was equal to or greater than 61 mg/kg/day.

Ethalfluralin did not produce reproductive effects in the 3-generation reproduction studies; the parental effects consisted of decreased body weight gains.

3.5	Additional Information from Literature Sources

Additional literature sources were not consulted for information related to ethalfluralin toxicity.

3.6	Hazard Identification and Toxicity Endpoint Selection

Based on the currently available toxicity data, use patterns and exposure data, the relevant toxicity endpoints and doses for risk assessment shown in Table 3.6 were selected.  These endpoints were considered the most appropriate, sensitive, and health protective.

3.6.1	Acute Population Adjusted Dose (aPAD) - Females age 13-49

The dose for risk assessment is the NOAEL of 75 mg/kg/day, a clear NOAEL from two developmental toxicity studies conducted in rabbits.  The use of this NOAEL for risk assessment is protective of the slight developmental effects seen in the rabbit developmental toxicity studies.

Study Selected:  Oral developmental toxicity study in rabbits

MRID No.:  00250596

Dose and Endpoint for Risk Assessment:  NOAEL = 75 mg/kg/day based on increased number of resorptions and increased sternal and cranial variations seen at LOAEL = 150 mg/kg/day.

Comments about Study/Endpoint/Uncertainty Factors:   A developmental toxicity study in rabbits was used to select the dose and endpoint for establishing the acute reference (aRfD) dose of 0.75 mg/kg/day.  The effects seen in the rabbit developmental study could be the result of a single dose, and therefore serve as appropriate endpoints for the subpopulation consisting of females 13-49.  Standard uncertainty factors applied are the 10X intra-species and 10X interspecies factors.  The acute population adjusted dose is the same as the acute reference dose.

3.6.2	Acute Population Adjusted Dose (aPAD) - General Population

No toxicological endpoint attributable to a single dose of ethalfluralin was identified as appropriate for any population subgroup except for females 13 to 49 years; therefore, there are no concerns for acute toxicity for the general US population, including infants and children.

3.6.3	Chronic Population Adjusted Dose (cPAD)

Study Selected:  One-year oral toxicity study in dogs

MRID No.:  00260434 and 00262711

Dose and Endpoint for Risk Assessment:  NOAEL = 4.0 mg/kg/day based on altered red cell morphology and urinary bilirubin seen at LOAEL = 20 mg/kg/day.

Comments about Study/Endpoint/Uncertainty Factors:  The combined chronic/carcinogenicity study in rats was used to select the dose and endpoint for establishing the chronic reference dose (cRfD) of 0.04 mg/kg/day.  The duration and route of exposure in the study are considered appropriate for assessing chronic dietary exposure and risk for ethalfluralin.  The NOAEL selected from the dog study is protective of liver effects seen at higher doses in both the dog study and studies in rats and mice.  The standard 100X uncertainty factor has been retained for chronic dietary exposure assessment.  The chronic reference dose is 0.004 mg/kg/day, and the cPAD is the same since the FQPA SF was reduced to 1X.

3.6.4	Incidental Oral Exposure (Short- and Intermediate-Term)

Not applicable, since there are not residential uses for ethalfluralin.

3.6.5	Dermal Absorption

A study (MRID Nos. 00132820 and 00072180) with Rhesus monkeys indicated that 2.8% of a dermal dose was absorbed through the skin.  This factor was used for estimated dermal exposure in the cancer risk assessment for occupational workers.

3.6.6	Dermal Exposure (Short-Term)

A 21-day dermal toxicity study in rabbits indicates no systemic toxicity at the limit dose of 1000 mg/kg/day.  No toxicity endpoints for short-term dermal exposure were selected, and there is no short-term dermal risk associated with the proposed or existing uses.  Since exposures associated with existing and proposed use patterns are short term in duration, no endpoints were selected for longer durations.

3.6.7	Inhalation Exposure (Short-Term)

Ethalfluralin has a low inhalation toxicity category (III).  The maximum attainable concentration (gravimetric) was tested in an acute inhalation toxicity study, and no deaths occurred to exposed rats.  Clinical signs included hypoactivity, dyspnea, ataxia, chromodacryorrhea, poor grooming, and yellow urine; these were reversible after 4 days (LC50 >0.94 mg/L; Toxicity Category III).  This maximum attainable concentration is considered to be non-lethal.  HED had previously concluded that a separate risk assessment was not required for inhalation exposure (ad hoc Hazard Identification Assessment Review Committee [HIARC], 3/4/99, W. Burnam).

HED continues to conclude that toxicity via the inhalation route of exposure is likely to be low; however, a screening level assessment was conducted for short-term inhalation exposure to occupational handlers.

Study Selected:  3-generation rat reproduction study

MRID No.:  00094784

Dose and Endpoint for Risk Assessment:  NOAEL = 12.5 mg/kg/day based on decreased body weight gains in males of all generations seen at the LOAEL = 37.5 mg/kg/day.

Comments about Study/Endpoint/Uncertainty Factors:   A 3-generation rat reproduction study was used to select the dose and endpoint for short-term inhalation exposure.  The dose and endpoint selected are considered to provide a conservative screening-level assessment, since effects on body weight gains are protective for the liver effects seen at higher doses, and because ethalfluralin is known to have low toxicity via the inhalation route of exposure.  An assumption of 100% inhalation absorption is used for route-to-route extrapolation.

3.6.8	Level of Concern for Margin of Exposure

Table 3.5.8.  Summary of Levels of Concern for Risk Assessment.

Route	Short-Term

(1 - 30 Days)	Intermediate-Term

(1 - 6 Months)	Long-Term

(> 6 Months)

Occupational (Worker) Exposure

Dermal	Not Applicable	Not Applicable	Not Applicable

Inhalation	100	Not Applicable	Not Applicable

3.6.9	Recommendation for Aggregate Exposure Risk Assessments

At this time, there are no current or proposed residential uses for ethalfluralin.  Therefore, aggregate risks consist of the dietary (food + water) pathway of exposure.

3.6.10	Classification of Carcinogenic Potential

The mouse carcinogenicity study showed no increase in tumor incidence.  Liver effects, characterized by increase in ALP and focal hepatocellular hyperplasia, were found in the highest dose group.  The chronic dog feeding study indicated hematological changes, elevated ALP, and siderosis of the liver in the high dose animals.

Ethalfluralin has been classified as a possible human carcinogen (Group C) by the CPRC (6/29/94 and 11/16/94).  The decision was based on findings from a 2-year chronic carcinogenicity study in rats, showing an increased incidence of mammary gland fibroadenomas and combined adenomas/fibroadenomas in female rats.  The CPRC recommended using the Q1* approach for risk assessment.  The Q1* is 8.9 x 10-2 (mg/kg/day)-1.

3.6.11	Summary of Toxicological Doses and Endpoints for Use in Human Risk Assessments

Table 3.6.11a.  Ethalfluralin - Summary of Toxicological Doses and Endpoints for Use in Dietary Human Health Risk Assessments.

Exposure Scenario	Point of Departure	Uncertainty/

FQPA SFs	Population Adjusted Dose for Risk Assessment	Study and Toxicological Effects

Acute Dietary (General Population, including Infants and Children)	A single dose effect relevant to the general US population including infants and children was not identified in the toxicity studies conducted with ethalfluralin.

Acute Dietary

(Females 13-49 years of age)	NOAEL = 75 mg/kg/day	UFA = 10x

UFH = 10x

FQPA SF= 1x	aPAD = 0.75 mg/kg/day	Rabbit Dev. Toxicity Study

LOAEL = 150 mg/kg/day based on increased number of resorptions and increased sternal and cranial variations

Chronic Dietary (All Populations)	NOAEL = 4 mg/kg/day	UFA = 10x

UFH =10x

FQPA SF= 1x	cPAD = 0.04 mg/kg/day	Dog, Chronic Oral Toxicity Study

LOAEL = 20 mg/kg/day based on altered red blood cell morphology and urinary bilirubin

Cancer (oral, dermal, inhalation)	Q* = 8.9 x 10-2 (mg/kg/day)-1 based on increased mammary gland fibro-adenomas & combined adenomas/fiboadenomas in female rats	Rat 2-year chronic/carcinogenicity study

Point of Departure (POD) = A data point or an estimated point that is derived from observed dose-response data and  used to mark the beginning of extrapolation to determine risk associated with lower environmentally relevant human exposures.  NOAEL = no observed adverse effect level.  LOAEL = lowest observed adverse effect level.  UF = uncertainty factor.  UFA = extrapolation from animal to human (interspecies).  UFH = potential variation in sensitivity among members of the human population (intraspecies).  FQPA SF = FQPA Safety Factor.  PAD = population adjusted dose (a = acute, c = chronic).

Table 3.6.11b  Summary of Toxicological Doses and Endpoints for Ethalfluralin for Use in Occupational Human Health Risk Assessments

Exposure/

Scenario	Point of Departure	Uncertainty Factors	Level of Concern for Risk Assessment	Study and Toxicological Effects

Dermal, Short-term durations (1 to 30 days)

	Dermal risks are not of concern because no systemic effects were observed up to the limit dose (1000 mg/kg) in a dermal study.

Inhalation, Short-term durations (1 to 30 days)	12.5 mg/kg/day	UFH=10X

UFA=10X

IA = 100%	LOC occupational = 100	3-Generation Reproduction study in Rats

The LOAEL = 37.5 based on decreased body weight gains in males in all generations.

Cancer (oral, dermal, inhalation)	Q1* = 8.9 x 10-2 (mg/kg/day)-1 based on increased mammary gland fibro-adenomas and combined adenomas/fiboadenomas in female rats. [For the dermal route, a dermal absorption factor of 2.8% was used]	Rat, 2-year chronic/carcinogenicity study

Point of Departure (POD) = A data point or an estimated point that is derived from observed dose-response data and  used to mark the beginning of extrapolation to determine risk associated with lower environmentally relevant human exposures.  NOAEL = no observed adverse effect level.  LOAEL = lowest observed adverse effect level.  UF = uncertainty factor.  UFA = extrapolation from animal to human (interspecies).  UFH = potential variation in sensitivity among members of the human population (intraspecies).  UFL = use of a LOAEL to extrapolate a NOAEL.  UFS = use of a short-term study for long-term risk assessment.  UFDB = to account for the absence of key date (i.e., lack of a critical study).  MOE = margin of exposure.  LOC = level of concern.  N/A = not applicable.  IA = inhalation absorption factor.

3.7	Endocrine disruption

The Environmental Protection Agency (EPA) is required under the Federal Food, Drug and Cosmetic Act (FFDCA), as amended by FQPA, to develop a screening program to determine whether certain substances (including all pesticide active and other ingredients) “may have an effect in humans that is similar to an effect produced by a naturally occurring estrogen, or other such endocrine effects as the Administrator may designate.”  Following recommendations of its Endocrine Disruptor Screening and Testing Advisory Committee (EDSTAC), EPA determined that there was a scientific basis for including, as part of the program, the androgen and thyroid hormone systems, in addition to the estrogen hormone system.  EPA also adopted EDSTAC’s recommendation that the Program include evaluations of potential effects in wildlife.  For pesticide chemicals, EPA will use Federal Fungicide Insecticide and Rodenticide Act (FIFRA) and, to the extent that effects in wildlife may help determine whether a substance may have an effect in humans, FFDCA authority to require the wildlife evaluations.  As the science develops and resources allow, screening of additional hormone systems may be added to the Endocrine Disruptor Screening Program (EDSP).

When additional appropriate screening and/or testing protocols being considered under the Agency’s EDSP have been developed, ethalfluralin may be subjected to further screening and/or testing to better characterize effects related to endocrine disruption.

4.0	Dietary Exposure/Risk Characterization

4.1	Pesticide Metabolism and Environmental Degradation

4.1.1	Metabolism in Primary Crops

  SEQ CHAPTER \h \r 1 The Ethalfluralin RED Document concluded that the qualitative nature of the residue in beans and peanuts is understood.  The major portion of the radioactivity was characterized as lignin, cellulose, and protein. The parent, ethalfluralin, was a minor residue.  The terminal residue of concern in plants is ethalfluralin per se; the current tolerance expression for plants is adequate.  Previously, a cucurbit metabolism study was considered outstanding and was required before plant metabolism could be considered fully understood.  A cucumber study was subsequently submitted and the metabolism data requirement was determined to be fulfilled.

In 1995, the HED Metabolism Assessment Review Committee (MARC) concluded that the residue of concern for both tolerance and risk assessment purposes is ethalfluralin per se.

4.1.2	Metabolism in Rotational Crops

Field rotational crop studies are not required since no residues of concern were found at significant levels in rotational crops.  Furthermore, tolerances for rotational crop commodities and plantback restrictions need not be established.

4.1.3	Metabolism in Livestock

  SEQ CHAPTER \h \r 1 The Ethalfluralin RED Document concluded that the qualitative nature of the residue in animals is adequately understood based on acceptable poultry and ruminant metabolism studies.  The residue of concern in milk, eggs, and animal tissues is ethalfluralin per se.  However, as a result of the low levels of radiolabeled residues found with exaggerated (200x) feeding levels, HED has waived requirements for animal feeding studies.  It was also concluded that residues of ethalfluralin from up to a 10x dietary burden would not be quantifiable (<0.05 ppm).  Therefore, according to 40 CFR §180.6 (a)(3), if there is no reasonable expectation of finite residues in livestock commodities, then no tolerances are needed for eggs, milk, fat, and meat byproducts of cattle, goats, hogs, horses, poultry, and sheep.  Previously established ethalfluralin tolerances in edible livestock commodities have been revoked.  In addition, the proposed uses do not result in the need for tolerances for ethalfluralin in livestock commodities.

4.1.4	Analytical Methodology

  SEQ CHAPTER \h \r 1 Adequate residue analytical methods are available for the purpose of tolerance enforcement.  Two gas chromatograph (GC) methods, Methods I and II, both with electron capture detection (ECD) are listed in the Pesticide Analytical Manual (PAM, Vol. II, Section 180.416).  Methods I and II are applicable for the analysis of ethalfluralin residues in/on plant and animal commodities, respectively.  The limits of detection (LODs) are 0.01 and <0.01 ppm for methods I and II, respectively.

The methods for enforcement are adequate in light of the tolerance expression and have passed Agency validation.  The method used in the dill and potato field trials is suitable for data collection.

4.1.5	Environmental Degradation

Based on laboratory studies, ethalfluralin is expected to dissipate by binding to soil particles and then degrading both aerobically and anaerobically.  There are no major degradates detected; in laboratory studies, several minor degradates were identified, all of which retain the trifluromethyl phenolic ring structure.  Freundlich Kads values ranged from 12 to 97 ml/g and in the field ethalfluralin did not leach.  Laboratory metabolism half-lives in soil were 46 days for aerobic systems and 14 days for anaerobic systems.  Ethalfluralin does not hydrolyze, but does photodegrade rapidly in water with a half-life of approximately 6 hours.  The laboratory volatility study indicates this is not a major route of dissipation.

4.1.6	Pesticide Metabolites and Degradates of Concern

Ethalfluralin per se is the only compound of toxicological significance.

Plant metabolism studies were considered in which ethalfluralin, universally radiolabeled in the benzene ring, was applied to beans, peanuts, and cucumbers.  In the beans and peanuts trials, the radiolabeled residue consisted of lignin, complex polar materials, and cellulose.  In contrast, the cucumber study yielded 42% total radioactive residue (TRR) as 2,2,2-trifluoroacetamide in vines and 86% TRR (0.014 ppm) as 2,2,2-trifluoroacetamide in cucumbers.  Ethalfluralin was 0% - 2% in these studies.  The apparent difference in cucumber versus bean and peanut metabolism may be a reflection of different post-treatment intervals.  At the time, the HED MARC concluded that the residue of concern for both regulatory (tolerance) and risk evaluation purposes is parent ethalfluralin only.

Table 4.1.6  Summary of Metabolites and Degradates to be included in the Risk Assessment and Tolerance Expression

Matrix	Residues included in Risk Assessment	Residues included in Tolerance Expression

Plants	Primary Crop	Ethalfluralin	Ethalfluralin

	Rotational Crop	Ethalfluralin	Ethalfluralin

Livestock	Ruminant	Not Applicable	Not Applicable

	Poultry	Not Applicable	Not Applicable

Drinking Water	Ethalfluralin	Not Applicable

4.1.7	Drinking Water Residue Profile

Tier II drinking water assessments for surface water for ethalfluralin were performed based on Index Reservoir settings.  The maximum simulation, the 1-in-10 year peak value, used for acute dietary exposure, was calculated for the use on canola using a maximum application rate of 1.15 lb ai/A.  The estimated drinking water concentration (EDWC) from this simulation was 11 ppb.  The maximum simulation for chronic exposures, or the 1-in-10 probability yearly, was calculated for the use on dill, with a maximum application rate of 1.5 lb ai/A.  The EDWC from this simulation was 0.4 ppb.  For cancer risk assessment, the average of yearly means was estimated to be 0.2 ppb.

For ground water sources, the Tier I drinking water assessment predicted maximum EDWCs of 0.02 ppb for both acute and chronic exposure for the use on dill, with a maximum application rate of 1.5 lb ai/A.  Table 4.1.7 summarizes the EDWC values.  These values were used directly in the DEEM dietary risk assessments, the 11 ppb value in the acute assessment and the 0.4 ppb value in the chronic assessment.

For the cancer assessment, an anticipated residue value generated from the USDA PDP drinking water monitoring data was used; there were no residues detected in 1,253 samples analyzed from 2003 – 2005.  The ½ LOD value of 23 ppt (0.023 ppb) was used directly in the dietary assessment.  These data were considered to be appropriate to use for the cancer risk assessment for the following reasons:  1) application rates for both existing and proposed uses are similar; while peak drinking water estimates differ slightly from one crop to another, EFED’s modeled drinking water numbers for the average of yearly means did not differ significantly by crop, supporting the notion that the existing monitoring data can support proposed uses; 2) the drinking water monitoring data were collected from a variety of states which include potential ethalfluralin use areas; 3) the lack of findings of detectable residues is supported by the modeled estimates and by the fate properties of ethalfluralin (e.g., 6-hour half-life for aqueous photolysis).

Table 4.1.7.  Summary of Modeled Surface Water and Groundwater Concentrations for Ethalfluralin.

	Ethalfluralin

	Surface Water Conc., ppb a	Groundwater Conc., ppb b

Acute	11	0.02

Chronic (non-cancer)	0.4	0.02

Chronic (cancer)	0.2	0.02

aFrom the Tier II PRZM-EXAMS - Index Reservoir model.  Input parameters are based on a 172.8 ha watershed draining into a 5.3 ha reservoir with a depth of 2.74 m.

bFrom the SCI-GROW model assuming Koc values ranging form 32 – 180 mL/g and half lives ranging from 13 – 1000 days.

4.1.8	Food Residue Profile

Residue data submitted in support of the proposed uses have been evaluated in a memorandum dated 9/4/07 (DP Barcode No. D306146, D306147 and D333867; J.R. Tomerlin).  The submitted field trial data are adequate to support the proposed use pattern, and were conducted in accordance to the Agency’s guidelines with respect to geographic representation.

Ethalfluralin residues in or on dill (fresh and dry) were less than the limit of quantitation (LOQ) of 0.05 ppm when ethalfluralin was applied according to the proposed use patterns.  Likewise, the results from potato field trials show that ethalfluralin residues were below the lowest limit of method validation (LLMV) of 0.05 ppm for all treatments in potato tubers when the test substance was applied according to the proposed potato use pattern; further examination of the raw data (chromatograms) indicated that residues in potato tubers and processed fractions were below the calculated limit of detection (LOD) of 0.016 ppm.  Field trials were supported by adequate storage stability data.

Regarding processed potato fractions, there was no evidence of concentration in any processed potato fraction; however, the residue profile for ethalfluralin suggests that concentration of residues is unlikely.  Given that residues were not detected (i.e., were below the calculated LOD of 0.016 ppm), no concentration was assumed in the dietary assessment, and no additional potato processing data are required.

4.1.9	International Residue Limits

There are currently no Codex, Canadian, or Mexican Maximum Residue Limits (MRLs) for residues of ethalfluralin on dill or potato, therefore there are no international harmonization issues associated with this action.

4.2	Dietary Exposure and Risk

™ model.  For the cancer dietary (food + water) assessment, monitoring data from the USDA PDP were used for soybean, watermelon, and drinking water, and the LOD value of 0.016 ppm was used for potatoes.  Risk estimates are summarized in Table 4.2.3.

4.2.1	Acute Dietary Exposure/Risk

Estimated dietary (food + water) exposure for females 13-49 years was 0.0006 mg/kg/day, equivalent to <1 % of the aPAD, at the 95th percentile of exposure, which is well below HED’s level of concern for acute dietary risk (100 % PAD).

4.2.2	Chronic Dietary Exposure/Risk

The chronic non-cancer dietary analysis for ethalfluralin resulted in an exposure estimate of 0.00006 mg/kg/day for the U.S. population, or <1 % of the cPAD, which is below HED’s level of concern.  Similarly, the exposure estimate of 0.00013 mg/kg/day for the most exposed population subgroup, children 1 to 2 years, is <1 % of the cPAD, and therefore not of concern.

4.2.3	Cancer Dietary Risk

The risk estimate for chronic cancer dietary exposure (0.000022 mg/kg/day) to ethalfluralin for the U.S. population yields a cancer risk of 2 x 10-6.  Additional refinement with %CT estimates would lead to a lower estimate of dietary cancer risk.  EPA generally considers cancer risks of 10-6 or less to be below the level of concern.  The precision which can be assumed for cancer risk estimates is best described by rounding to the nearest integral order of magnitude on the log scale; for example, risks falling between 3.16 x 10-7 and 3.16 x 10-6 are expressed as 10-6.  Considering the precision with which cancer hazard can be estimated and the rounding procedure described above, cancer risk should generally not be assumed to exceed the benchmark level of concern of 10-6 until the calculated risk exceeds approximately 3 x 10-6.  Since the calculated cancer risk for ethalfluralin falls below this level, estimated cancer risk is considered to be below the level of concern.

Table 4.2.3.  Results of Acute and Chronic Dietary (Food + Water) Exposure and Risk Estimates for Ethalfluralin.

Population Subgroup	PAD, mg/kg/day	DEEM-FCID

Exposure, mg/kg/day	% PAD

Acute Dietary Estimates 95th Percentile of Exposure

Females 13 – 49 years old	0.75	0.000604	< 1

Chronic Dietary Estimates

U.S. Population	0.04	0.000064	< 1

All infants (< 1 yr)	0.04	0.000099	< 1

Children 1-2 yrs	0.04	0.000133	< 1

Children 3-5 yrs	0.04	0.000124	< 1

Children 6-12 yrs	0.04	0.000085	< 1

Youth 13-19 yrs	0.04	0.000063	< 1

Adults 20-49 yrs	0.04	0.000054	< 1

Adults 50+ yrs	0.04	0.000053	< 1

Females 13-49 yrs	0.04	0.000051	< 1

Cancer Dietary Estimate

U.S. Population	Q1* = 0.089	0.000022	2 x 10-6

4.3	Anticipated Residue and Percent Crop Treated (%CT) Information

For the acute and chronic non-cancer dietary assessments, anticipated residues from field trials were used; studies evaluated for the RED indicated residues were below the LOD of 0.01 ppm for dry bean, peanuts, dry peas, soy beans, and sunflower seed.  Tolerance level residues were assumed for all other existing uses, and the proposed tolerances were used for dill and potato.  For the cancer dietary exposure assessment, anticipated residues from the USDA Pesticide Data Program (PDP) were used for soybean, watermelon and drinking water.  No residues were detected during monitoring of these commodities, and the ARs were based on nondetect residues, estimated at ½ LOD.  For the cancer assessment, an anticipated residue of the LOD of 0.016 ppm was used for potatoes.  For all the dietary assessments, HED used the conservative assumption of 100 % crop treated.

5.0	Residential (Non-Occupational) Exposure/Risk Characterization

An assessment is not required, since there are no existing or proposed uses of ethalfluralin in residential settings.

5.1	Other (Spray Drift, etc.)

Spray drift is a potential source of exposure to residents nearby to spraying operations.  This is particularly the case with aerial application, but, to a lesser extent, could also be a potential source of exposure from the ground application method employed for ethalfluralin.  The Agency has been working with the Spray Drift Task Force, EPA Regional Offices, and State Lead Agencies for pesticide regulation and other parties to develop the best spray drift management practices.  On a chemical by chemical basis, the Agency is now requiring interim mitigation measures for aerial applications that must be placed on product labels/labeling.  The Agency has completed its evaluation of the new database submitted by the Spray Drift Task Force, a membership of U.S. pesticide registrants, and is developing a policy on how to appropriately apply the data and the AgDRIFT computer model to its risk assessments for pesticides applied by air, orchard airblast and ground hydraulic methods.  After the policy is in place, the Agency may impose further refinements in spray drift management practices to reduce off-target drift with specific products with significant risks associated with drift.

6.0	Aggregate Risk Assessments and Risk Characterization

In accordance with the FQPA, HED must consider and aggregate (add) pesticide exposures and risks from three major sources: food, drinking water, and residential exposures.  For ethalfluralin, no residential exposure is expected, and aggregate risk consists of food and drinking water exposure only; these risks are not of concern as indicated in Table 4.2.3.

7.0	Cumulative Risk Characterization/Assessment

Unlike other pesticides for which EPA has followed a cumulative risk approach based on a common mechanism of toxicity, EPA has not made a common mechanism of toxicity finding as to ethalfluralin and any other substances and ethalfluralin does not appear to produce a toxic metabolite produced by other substances.  For the purposes of this tolerance action, therefore, EPA has not assumed that ethalfluralin has a common mechanism of toxicity with other substances.  For information regarding EPA’s efforts to determine which chemicals have a common mechanism of toxicity and to evaluate the cumulative effects of such chemicals, see the policy statements released by EPA’s Office of Pesticide Programs (OPP) concerning common mechanism determinations and procedures for cumulating effects from substances found to have a common mechanism on EPA’s website at   HYPERLINK http://www.epa.gov/pesticides/cumulative/. http://www.epa.gov/pesticides/cumulative/.

8.0	Occupational Exposure/Risk Pathway

Exposure to ethalfluralin is expected to occur for occupational handlers applying products containing the active ingredient in accordance with the proposed use pattern.  For handlers, inhalation exposure and risk were estimated for non-cancer effects, and combined dermal and inhalation exposures were assessed for cancer risks.  No chemical-specific data were submitted to support the proposed uses, so handler risks were calculated by using the proposed application rates and application parameters to determine unit exposures from the Pesticide Handlers Exposure Database (PHED).

Post-application exposure is also expected, when occupational workers re-enter treated areas to conduct crop maintenance activities.  These exposures are considered to be short-term in nature.  Since there is no non-cancer risk associated with short-term dermal exposure, only a cancer risk assessment was completed for occupational post-application.

8.1	Short-Term and Cancer Handler Risk

Based upon the proposed use patterns, HED believes the most likely methods of application will be by ground-boom spray and granular broadcast machinery.  Regarding the proposed new uses, HED further believes that the most highly exposed occupational pesticide handlers will be mixer/loaders using open-pour loading of liquid formulations, mixer/loaders using open-pour loading of granules, applicators using open-cab, ground-boom sprayers and applicators using open-cab, broadcast granular spreaders.

HED believes pesticide handlers will typically be exposed to short-term duration (1 - 30 days) exposures but not to intermediate-term (1 - 6 months) duration exposures.  Although intermediate-term exposures might be possible for commercial applicators, it is considered unlikely that pesticide handlers would be exposed continuously for 30 days or more.

Private (i.e., grower) applicators may perform all functions, that is, mix, load and apply the material.  Nevertheless, according to guidance from HED’s Exposure Science Advisory Committee (ExpoSAC; SOP Number 12, 3/29/00), handler functions were assessed separately.

No chemical specific data were available with which to assess potential exposure to pesticide handlers.  The estimates of exposure to pesticide handlers are based upon surrogate study data available in the PHED (v. 1.1, 1998).  For pesticide handlers, it is HED practice to estimate dermal exposure for workers wearing “baseline” protective clothing, namely, a single layer of work clothing consisting of a long sleeved shirt, long pants, shoes plus socks and no protective gloves.  Additionally, estimates are made for “baseline” plus protective gloves or other personal protective equipment (PPE) as might be necessary.

In addition to the PHED surrogate data used in the current assessment, HED used standard assumptions with respect to body weight, acres treated per day, and maximum application rates.

In conducting dermal and inhalation cancer risk assessments, HED typically assumes 10 days per year of exposure over a 35 year “working” lifetime and a 70 year expected lifespan for private growers who might apply/handle a compound or perform agricultural functions.  HED assumes 30 days per year of exposures for commercial occupational pesticide handlers and agricultural workers who might “follow” crops as opposed to occasional exposure from work on one or few farms by “private” individuals.  (Pers. Comm. J. Dawson to M. Dow, HED/OPP, 4 April 2005).  The Lifetime Average Daily Dose (LADD) is calculated as shown in the following equation:

LADD = ADD x 10 (or 30) working days exposed/year x 35 year working life span

365 days/year x 70 year expected life span

The Average Daily Dose (ADD) is the sum of dermal exposure + inhalation exposure.  Post-application inhalation exposure is considered negligible.  The label requires the use of protective gloves by occupational pesticide handlers, therefore exposures were estimated only for handlers wearing protective gloves.  The cancer risk estimates were below the level of concern for occupational cancer risk (1 x 10-4).

Table 8.1a.  Short-Term Occupational Exposure Estimates for Ethalfluralin.

Exposure Scenario

(Scenario #)	Crop	Daily

Dermal

Dose

(mg/kg/day)	Daily

Inhalation

Dose

(mg/kg/day)	Dermal

MOE	Inhalation

MOE

Mixer/Loader

Liquid, Open-pour	Canola, Dill and Potato	0.0028	0.0051	N/A	2450

Granular, Open-pour

0.00081	0.0051	N/A	2450

Applicator

Groundboom, Open cab	Canola, Dill and Potato	0.0017	0.0032	N/A	3900

Granular Broadcast, Open cab

0.00083	0.0051	N/A	2450

All estimates assume baseline PPE plus gloves.

Table 8.1b  Estimates of Occupational Cancer Risk for Ethalfluralin

Crop or Target	Exposure Scenario	Application Rate

(lb ai/acre)	Area Treated Daily

(acres)	Short-Term

Dermal + Inhalation

mg/kg/day 	Cancer Risk

	Private Handler	Commercial Handler

Canola, Dill and Potato	Mixer/Loader

Liquid, Open pour	1.5	200	0.0079	9.6 x 10-6	2.9 x 10-5

	Mixer/Loader

Granular, Open pour	1.5	200	0.0059	9.8 x 10-6	1.8 x 10-5

	Applicator

Groundboom, Open Cab	1.5	200	0.0049	5.9 x 10-6	2.2 x 10-5

	Applicator

Granular Broadcast, Open Cap	1.5	200	0.0059	7.2 x 10-6	4.4 x 10-5

8.2	Cancer Postapplication Risk

It is possible for agricultural workers to have post-application exposures to pesticide residues during the course of typical agricultural activities.  HED in conjunction with the Agricultural Re-entry Task Force (ARTF) has identified a number of post-application agricultural activities that may occur and which may result in post-application exposure to pesticide residues.  HED has also identified Transfer Coefficients (TC) (cm²/hr) for each activity which express the amount of foliar contact over time, during each of the activities identified.  For the proposed new crop use sites, the highest TC is 1,500 cm2/hr for scouting or irrigation activities in canola and potato.  Therefore, as a screening level assessment HED has used a TC of 1,500 cm²/hr.

Lacking compound specific dislodgeable foliar residue (DFR) data, HED typically assumes 20% of the application rate is available as DFR on day zero after application.  This is adapted from the ExpoSAC SOP No. 003 (5/7/98, Revised 8/7/00).

The following convention may be used to estimate post-application exposure.

ADD mg/kg/day = DFR µg/cm2 * TC cm2/hr * hr/day * 0.001 mg/µg * 1/70 kg

and where:

Surrogate DFR = application rate * 20% available as dislodgeable residue * (1-D)t * 4.54 x 108 µg/lb * 2.47 x 10-8 A/cm2 .

1.15 lbs ai/A * 0.20 * (1-0)0 * 4.54 x 108 µg/lb *  2.47 x10-8 A/cm² = 2.58 µg/cm2 , therefore,

2.58 µg/cm2 * 1,500 cm2/hr * 8 hr/day * 0.001 mg/µg * 0.028 (% dermal absorption) ( 70 kg bw = 0.012 mg/kg bw/day.

Estimated cancer risk from post-application exposures is 1.4 x 10-5, which does not exceed HED’s level of concern for occupational cancer risk.

9.0	Data Needs and Label Recommendations

9.1	Toxicology

None.

9.2	Residue Chemistry

None.

9.3	Occupational and Residential Exposure

None.

10.0	References:

DP Num: 199662, S. Funk, undated, MRID# 00135194

DP Num: 200166, F. Chow, 7/27/94

Memo, B. Fisher to R. Landolt, 8/3/94

DP Num: 200165, L. E. Morris, 8/18/94

MRID Nos. 00145955, 00094754, and 43394001 – cited in the Ethalfluralin RED, EPA 378-R-95-001, March 1995

Reregistration Eligibility Decision (RED): Ethalfluralin, EPA 738-R-95-00a, March, 1995

TXR 0050808, Case 2260, S. Funk, 5/25/95

DP Num: 212755, MRID No. 43532201, S. Funk, June 1995

DP Num: 233501, M. Nelson, 8/7/97

HIARC, W. Burnam, 3/4/99

DP Num: 252707, M. Nelson, S. Williams-Foy, S.-C. Wang, 3/12/99

DP Num: 272778, D. Dotson, 4/11/01

DP Num: 276090, B. F. Kitchens, 10/16/01, MRID#’s 45406501 and 45406502

DP Num: 295884, J. Lin, 10/5/05

DP Num: 296985, J. Lin, 10/5/05

DP Num: 333865, M. Dow, 12/7/06

DP Num: 339217, W. Phang, 4/23/07

DP Num: 306146, J. R. Tomerlin, 9/4/07

DP Num: 333868, C. Swartz, 10/19/07

Appendix A – Toxicity Profiles for Ethalfluralin

A.1.	Toxicology Data Requirements.

Test

	Technical

	Required	Satisfied

870.1100	Acute Oral Toxicity

870.1200	Acute Dermal Toxicity

870.1300	Acute Inhalation Toxicity

870.2400	Primary Eye Irritation

870.2500	Primary Dermal Irritation

870.2600	Dermal Sensitization		yes

yes

yes

yes

yes

yes	yes

yes

yes

yes

yes

yes

870.3100	Oral Subchronic (rodent)

870.3150	Oral Subchronic (nonrodent)

870.3200	21/28-Day Dermal

870.3250	90-Day Dermal

870.3465	90-Day Inhalation		yes

yes

yes

no

no	yes

yes

yes

---

---

870.3700a	Developmental Toxicity (rodent)

870.3700b	Developmental Toxicity (nonrodent)

870.3800	Reproduction		yes

yes

yes	yes

yes

yes

870.4100a	Chronic Toxicity (rodent)

870.4100b	Chronic Toxicity (nonrodent)

870.4200a	Oncogenicity (rat)

870.4200b	Oncogenicity (mouse)

870.4300	Chronic/Oncogenicity		yes

yes

yes

yes

yes	yes

yes

yes

yes

yes

870.5100	Mutagenicity—Gene Mutation - bacterial

870.5300	Mutagenicity—Gene Mutation - mammalian

870.5375	Mutagenicity—Structural Chromosomal Aberrations

870.5395	Mutagenicity—Other Genotoxic Effects		yes

yes

yes

yes	yes

yes

yes

yes

870.6100a	Acute Delayed Neurotox. (hen)

870.6100b	90-Day Neurotoxicity (hen)

870.6200a	Acute Neurotox. Screening Battery (rat)

870.6200b	Chronic Neurotox. Screening Battery (rat)

870.6300	Develop. Neuro		no

no

no

no

no	---

---

---

---

---

870.7485	General Metabolism

870.7600	Dermal Penetration		yes

no	yes

yes

A2. Ethalfluralin Acute Toxicity Profile.

Guideline No./ Study Type	MRID No.	Results	Toxicity Category

870.1100

Acute oral toxicity  rats	00135189	LD50 >5000 mg/kg/	IV

870.1200

Acute dermal toxicity rabbit	00135189	LD50 >5000 mg/kg/	IV

870.1300

Acute inhalation toxicity rats	00135189	LC50> 0.94 mg/L	III

870.2400

Acute eye irritation rabbits	00135189	Moderate	II

870.2500

Acute dermal irritation rabbits	41613909	Moderate to severe	II

870.2600

Dermal sensitization guinea pigs	00094788	sensitizer	--

A.3. Ethalfluralin Subchronic, Chronic and Other Toxicity Profile.

A.3. Subchronic, Chronic and Other Toxicity Table.

Guideline No.

Study Type	MRID No./(year)

Classification/Doses	Results

870.3100

90-Day Oral Toxicity, mice	0094774 (1978)

Acceptable

0, 68, 136, 285, 538, 1205 mg/kg/day	NOAEL = 136 mg/kg/day

LOAEL = 285 mg/kg/day based on increased absolute and relative liver weights and increased ALP in males.

870.3100

90-Day Oral Toxicity, rats	00135191 (1978)

0, 14, 29, 63, 146, 313 mg/kg/day	NOAEL = 29 mg/kg/day

LOAEL = 63 mg/kg/day based on increased liver weights (absolute and relative), decreased RBC, hematocrit and hemoglobin, and increased relative kidney weights

870.3150

90-Day Oral Toxicity, dogs	00135193 (1974)

Acceptable

0, 6.3, 27.5, 125 mg/kg/day

Note – dose of 125 later adjusted to 80 mg/kg/day	NOAEL = 80 mg/kg/day

LOAEL = 125 mg/kg/day based on vomiting and anorexia.

870.3200

21-Day dermal toxicity, rabbits	00145767 (1985)

Acceptable/guideline

0, 1000 mg/kg/day (6 hours/day)	NOAEL=1000 mg/kg/day (HDT)

LOAEL= >1000 mg/kg/day; no systemic effects were seen at the HDT.  Dermal effects included erythema, edema, and epidural fissures at 1000 mg/kg/day.

870.3700

Prenatal developmental toxicity, rats	0015337 (1985)

Acceptable

0, 50, 250, 1000 mg/kg/day	Maternal NOAEL=50 mg/kg/day

Maternal LOAEL=250 mg/kg/day based on decreased body weight gain and dark urine.

Developmental NOAEL=1000 mg/kg/day

Developmental LOAEL>1000 mg/kg/day, no effects seen at the HDT.

870.3700

Prenatal developmental toxicity, rabbits	00250596 (1983)

[Includes Pilot studies – R-7048, B-7438, B-7079, B-7160]

Doses ranged from 0, 10 – 1000 mg/kg/day

Taken in total, the studies are acceptable.	Maternal NOAEL=75 mg/kg/day

Maternal LOAEL=150 mg/kg/day based on abortions and decreased food consumption.

Developmental NOAEL=75 mg/kg/day

Developmental LOAEL=150 mg/kg/day based on slightly increased resorptions, and increased sternal and cranial variations.

870.3800

Reproduction and fertility effects, rats	0094784 (1981)

0, 5, 12.5, 37.5 mg/kg/day

42300301 (1992)

0, 8, 20, 61 mg/kg/day

The 2 studies together are acceptable.	Parental/Systemic NOAEL=12.5 mg/kg/day

Parental/Systemic LOAEL=37.5 mg/kg/day based on decreased body weight gains in males of all generations.

Reproductive NOAEL=37.5 mg/kg/day (HDT)

Reproductive LOAEL>37.5 mg/kg/day; no systemic effects observed at the highest dose tested.

870.4100a

Chronic toxicity, rats	00094775 (1979)

Acceptable

M: 0, 3.9, 9.7, 28.4 mg/kg/day

F: 0, 4.9., 11.9, 34.4 mg/kg/day	NOAEL=9.7/11.9 mg/kg/day

LOAEL=28.4/34.4 mg/kg/day based on significant increased blood creatinine and BUN values at termination.

870.4100a

Chronic toxicity, mice	0009477 (1981)

Acceptable, Nonguideline

M: 0, 12, 47, 173 mg/kg/day

F: 0, 12, 49, 184 mg/kg/day	NOAEL=12 mg/kg/day

LOAEL=47/49 mg/kg/day based on increased ALP and increased relative liver weights.

870.4100b

Chronic toxicity, dogs	00153371, 92062014 (1985)

Acceptable

0, 4, 20, 80 mg/kg/day	NOAEL=4 mg/kg/day

LOAEL= 20 mg/kg/day based on increased urinary bilirubin, variations in erythrocyte morphology, increased thrombocyte count, and increased erythroid series of the bone marrow.

870.4300

Combined chronic toxicity/carcinogenicity, rats	00094776 (1981)

92062013 (1981)

Acceptable

0, 4.2, 10.7, 32.2 mg/kg/day	NOAEL=32.2 mg/kg/day(HDT)

LOAEL=>32.2 mg/kg/day; no systemic effects were seen at the HDT.

Mammary gland fibroadenomas were found in dosed female rats at statistically significant incidences in mid and high doses.

870.4300

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	LOAEL=41.9 mg/kg/day based on focal hepatocellular hyperplasia in both sexes and increased liver, kidney, and heart weights in females.  No increase in neoplasms was attributed to the treatment.

870.5100

Bacterial reverse mutation test	00128693 (1983)

00128694 (1983)

Acceptable	Ethalfluralin was weakly mutagenic in activated strains TA1535 and TA100 of Salmonella typhimurium, but not in strains TA1537, TA1538 and TA98 in an Ames assay.  In a modified Ames assay with Salmonella typhimurium and Escherichia coli, ethalfluralin was weakly mutagenic in strains TA1535 and TA100, with and without activation, and in strain TA98 without activation, at the highest dose.

870.5300

In vitro mammalian cell mutation test	00128696 (1983)

Acceptable

	No mutagenicity was found in the mouse lymphoma assay for forward mutation.

870.5550

Unscheduled DNA synthesis in mammalian cells in culture	00128695 (1980)

Acceptable	Ethalfluralin did not induce unscheduled DNA synthese in rat hepatocytes.

870.5375

In vitro mammalian chromosome aberration test	00152219 (1985)

Acceptable	In Chinese hamster ovary cells, ethalfluralin was negative without S9 activation, but it was clastogenic with activation.

870.7485

Metabolism and pharmacokinetics	42822901 (1993)

Acceptable	Rats were treated orally with a single low dose, a single high dose, or repeated low doses of radiolabeled ethalfluralin.  Absorption of ethalfluralin was estimated at 79-87% of the dose for all dose levels.  Ethalfluralin was rapidly and extensively metabolized, and 95% of the chemical was excreted in the urine and feces by seven days.  The major route of elimination for the radiolabel was in the feces, 50.9-63.2%, and the levels remaining in the tissues after 72 hours were negligible.

870.7600

Dermal penetration	00132820 (1982)

Acceptable	A dermal penetration study with rhesus monkeys indicated that 2.7% of a dermal dose was absorbed through the skin.

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