Document ID: EPA-HQ-OPP-2004-0387-0178
Agency: epa
Document Type: Supporting & Related Material
Title: 
Posted Date: 2007-10-29T04:00Z

RESPONSE TO COMMENTS to 

Part 158 Rule Proposed March 11, 2005

Docket ID:  OPP-2004-0387

SUMMARY:  

EPA proposed to limit the applicability of revised part 158 to
conventional chemicals, in anticipation of additional revisions tailored
to biochemical, microbial and antimicrobial pesticides.   EPA is
promulgating a final rule establishing data requirements for biochemical
and microbial pesticides at the same time it is promulgating a final
rule establishing data requirements for conventional pesticides. 
However, EPA has not yet issued a proposed rule that would create
separate data requirements tailored to antimicrobial pesticides.  

If EPA were to maintain the proposed rule’s exclusive application to
conventional pesticides, the result would be that there would be no data
requirements established by regulation for antimicrobial pesticides. 
Registrants of antimicrobial pesticides would have to rely solely on
consultations with EPA to determine the data requirements for their
products without the benefit of regulatory data requirements.  However,
EPA has decided to preserve the current data requirements to provide
regulatory coverage for antimicrobial pesticides until the Agency can
propose and promulgate a final regulation.  To accomplish this, EPA has
transferred intact the current data requirements of part 158 into a new
part 161, entitled “Data Requirements for Antimicrobial Pesticides.”
 New part 161 will only apply to antimicrobial pesticides.  Part 158 as
promulgated will only apply to conventional pesticides.  EPA received no
key comments concerning the proposed limited applicability of part 158,
and accordingly, EPA is adopting its proposal.  

	Comments that would be of wide interest were considered key and
summarized in the preamble.  Comments that were tangential or of
marginal interest were not considered key and therefore not summarized
in the preamble; instead, these were addressed in the Response to
Comments document.  In many areas of the preamble, readers were reminded
to access the Response to Comments document for a more complete view of
comments and responses. 

	A commenter is identified by the number of his comment document in
Docket ID OPP-2004-0387.

ACRONYMS/INITIALISMS USED IN THIS DOCUMENT

ACSA		Agricultural Chemical Safety Assessment

AHETF	Agricultural Handlers Exposure Task Force	

CARB		California Air Resources Board

ChEI		Cholinesterase inhibitors

CNS		Central Nervous System

CFR		Code of Federal Regulations

CR		Conditionally Required

DCI		Data Call-In

DOI		Department of Interior

DFR		Dislodgeable Foliar Residue

DNT		Developmental Neurotoxicity

EDSP		Endocrine Disruptor Screening Program

EP		End-use Product

EPA		Environmental Protection Agency

EU		European Union

EUP		Experimental Use Permit

FDA		Food and Drug Administration

FFDCA	Federal Food, Drug and Cosmetic Act

FHE		Food Handling Establishment

FIFRA		Federal Insecticide, Fungicide, and Rodenticide Act

FIFRA SAP	FIFRA Science Advisory Panel

FQPA		Food Quality Protection Act

FWS		Fish and Wildlife Service

GLP		Good Laboratory Practice

HESI		Health and Environmental Sciences Institute

HSRB	  	Human Subjects Review Board 

ICCVAM	Interagency Coordinating Committee on Validation of Alternative
Methods

ILSI		International Life Sciences Institute

ILV		Independent Laboratory Validation

LOAEL	Lowest Observed Adverse Effect Level

MAD		Mutual Acceptance of Data

MBS		Market Basket Survey

MOE		Margin of Exposure

MOR		Magnitude of Residue

MP		Manufacturing Use Product 

MRID		Master Record Identification		

NAFTA	North American Fair Trade Act

NAS		National Academy of Sciences

NCAP		Northwest Coalition for Alternatives to Pesticides 

NDTEF	Non-Dietary Exposure Task Force

NICEATM	National Toxicology Program Interagency Center for the
Evaluation of Alternative Toxicological Methods	

NOAEL	No Observed Adverse Effect Level

NRC		National Research Council

NSCEP	National Center for Environmental Publications 

NTIS		National Technical Information Services

OECD		Organisation for Economic Co-Operation and Development

OPP		Office of Pesticide Programs

OPPTS	Office of Prevention, Pesticides, and Toxic Substances

ORD		Office of Research and Development 

ORETF	Outdoor Residential Exposure Task Force

OSHA		Occupational Safety and Health Administration	

PAI		Pure Active Ingredient

PAIRA		Pure Active Ingredient Radio-labeled

PCC		Poison Control Center

PDP		USDA’s Pesticide Data Program

PHED		Pesticide Handlers Exposure Database	

PMRA		Pesticide Management Regulatory Agency

PPDC		Pesticide Policy Dialogue Committee	

PR		Pesticide Registration	

QSAR		Quantitative Structure-Activity Relationship

R		Required

REJV		Residential Exposure Joint Venture

RfD		Reference Dose

RQ		Risk Quotient

SAP		Science Advisory Panel

SAR		Structural-activity Relationships

SOP		Standard Operating Procedures for Residential Exposures

TEP		Typical End-use Product

TGAI		Technical Grade of the Active Ingredient

TSCA		Toxic Substances Control Act

TTR		Turf Transferable Residue

UDS		Unscheduled DNA Synthesis 

UV		Ultraviolet

I.	Discussion of Comments on General Provisions of Part 158 (Subpart A)

Changes to Subpart A 

	EPA proposed revising subpart A by adding new material, deleting some
portions, and revising the portions that were retained or relocated. 
The new material included definitions for “applicant” and
“registration,” with references to definitions in FIFRA and FFDCA
that apply to part 158.  Deletions from subpart A to eliminate
redundancy included:  timing of the imposition of data requirements;
consultation with the Agency; agricultural versus non-agricultural
pesticides; and biochemical and microbial pesticides.  The remaining
sections of the current subpart A were retained and updated or
streamlined.

B.	Format for Data Submissions 

	EPA proposed minor revisions to §158.32, which describes how data are
to be formatted for submission to EPA.  

COMMENT:  Commenter 48 encouraged EPA to be as flexible as possible in
revising Pesticide Registration (PR) Notice 86-5 (Standard Format for
Data Submitted Under FIFRA and Certain Provisions of FFDCA), by not
rejecting studies due to minor points of presentation.  Commenter 123
asked for regulatory language to ensure data will not be rejected for
formatting reasons.  This commenter urged the Agency to integrate the
formatting recommendations from PR Notice 86-5 with §158.32 and either
include them in 40 CFR part 158 or include them only in a PR notice. 
Commenter 120 supported flexibility in determining what data are needed
but wanted the Agency to confirm its willingness to abide by agreements
made during consultation.  This commenter requested a clear set of
required or core data requirements for each use pattern & a clear set of
conditionally required data requirements

RESPONSE:	EPA made no revisions to §158.32 in the final rule. The
Agency intends to update the guidance provided in PR Notice 86-5 to help
further clarify the different elements of the submission process.  The
improved guidance, together with consultation with the Agency, should
help reduce the formatting uncertainties. Linking a set of data
requirements to each use pattern would be misleading since the
conditionalities vary depending on the product under consideration. 

Confidential Business Information	

FFDCA Sec. 408 information

	EPA proposed to make all information not designated as confidential
eligible for disclosure by operation of FIFRA sec. 10(d)(1), without
prior notice to the submitter.  This was a change from current
regulations, under which information not designated confidential must be
evaluated on a case-by-case basis at the time disclosure is requested. 

 

COMMENT:  A commenter, while not disagreeing generally with the
Agency’s proposal, suggested that certain data, such as market basket
surveys and computer modeling systems, are types of data that are not
within the scope of FIFRA sec 10(d)(1), and thus should continue to be
the subject of case-by-case confidentiality determinations.  

RESPONSE:  EPA disagrees that such data are not within the scope of
FIFRA sec. 10(d)(1), as they provide significant exposure information
that affects the risk assessments performed by the Agency.

COMMENT:	This same commenter read FIFRA sec 10(b) and (c) as requiring
the initial non-disclosure of all information submitted by an applicant.
 Thus, he asserted, subsequent notification to the submitter is required
to allow disclosure.  

RESPONSE:  FIFRA sec. 10(b) and (c) do not provide for such broad
non-disclosure.  Non-disclosure is limited to information for which a
claim of confidentiality has been made and where the information is
eligible for confidential treatment, not to all information.

Since 1988, current regulations have required that data submitters
assert a claim of  confidentiality at the time of submission of data,
and appropriately mark the information claimed as confidential.  Absent
such a claim, this final rule would consider that no claim of
confidentiality had been made for any data submitted after May 4, 1988. 
The current system of post-submission notification and case-by-case
determination is inefficient and cumbersome for the Agency, and
discourages the disclosure of information that FIFRA clearly intends to
be releasable.  EPA believes it should not be perpetuated.	

Safety and efficacy information

COMMENT:	One commenter disagreed with the decision of the court in the
case of NCAP v. Browner, cited by EPA as the basis for its proposal.  

RESPONSE:  EPA intends to abide by the Court’s decision, which
supports the Agency’s interpretation of FIFRA sec. 10(d).

Information pertaining to unregistered pesticides

	With respect to unregistered pesticides, EPA stated that information
relating to effects of unregistered pesticides would infrequently be
eligible for confidential treatment. 

 

COMMENT:  Commenters were concerned that EPA’s release of such
information could give an advantage to competitors by providing leads
that would allow them to produce similar pesticides, or make marketing
decisions.  

RESPONSE:  EPA acknowledges that certain information about unregistered
pesticides may be eligible for confidentiality, but continues to believe
that such instances will be infrequent, and in such cases the Agency
will prevent an unauthorized release of information.  EPA also notes
that it is required under FIFRA sec. 3(c)(4) to make public certain
information concerning new, unregistered pesticides, including identity
and proposed use patterns.

Confidentiality claims for plant-incorporated protectant information.

	There were no comments on confidentiality claims for plant-incorporated
protectant information.

Disclosure of data to multinational entities

COMMENT:  Two commenters were concerned that EPA’s proposal to release
less than complete, or summarized, information about unpublished
studies, or Agency reviews of studies, without a declaration of
non-multinational status, could allow a multi-national company the free
and wholesale use of data to their advantage.  

RESPONSE:  Under FIFRA sec. 10(g), a requestor of data from EPA must
declare that he is not a multi-national corporation.  Sec. 10(g) is a
statutory provision intended to ensure that EPA data is not used to
attain marketing rights in other countries without adequate compensation
to the data-producer for use of the data.  

Release to state & foreign governments with consent

	There were no comments on releasing information to state and foreign
governments with consent.  

D.	Flagging Requirements

COMMENT:	Commenters 48, 120, and 124 commented on the proposed changes
to the flagging criteria.  Commenter 48 also requested clarification
when specific criteria would apply to specific studies.

RESPONSE:  All of the listed flagging criteria for a study need not
apply.  If any of the criteria listed is applicable to the study, then
the corresponding criteria number should be included in the flagging
statement submitted with the study.  In the example provided by the
commenter, the following flagging statement would be included with the
prenatal developmental toxicity study submission:

“I have applied the criteria of 40 CFR 158.34 for flagging studies for
potential adverse effects to the results of the attached study.  This
study meets or exceeds Criterion No. 5.”

COMMENT:	Commenter 120 requested an indication when a positive flagging
statement is appropriate for proposed Criterion No. 7.

RESPONSE:  Proposed Criterion No. 7 simplifies the flagging process with
respect to No Observed Adverse Effect Levels (NOAELs); no calculation or
justification is required by the registrant.  If the study NOAEL is less
than that currently used by the Agency for regulation (i.e., used to
derive the acute and/or chronic reference dose), then Criterion No. 7 is
met and the flagging statement must reflect this (by the use of
Statement No. 2).  The Agency will then evaluate the regulatory impact
of the lower NOAEL.

COMMENT:	Commenter 124 indicated the proposed revisions to flagging
criteria could significantly increase the burden to registrants.

RESPONSE:  In the preamble to the proposed rule, the Agency acknowledged
the revisions could result in more flagging of studies, thus increasing
the burden.  This was the expected result because of the new types of
toxicity studies being proposed. 

 

	E.	Data Waivers

COMMENT:  Six commenters (119, 120, 123, 124, 125, and 133) expressed
their concerns about clarity, timelines for waiver requests, and the
organization of information.  Two commenters asked for more guidance on
when waiver requests would be considered.  Commenter 119 suggested a
transparent and clearly elucidated waiver-granting process and
recommended that EPA grant waivers only under the most stringent and
prescribed circumstances.  Commenter 120 felt that clarification of
table footnotes and use patterns would help knowing when and on what
basis waiver requests would be appropriate.  

RESPONSE:  The current 40 CFR part 158 states that “Because of the
wide variety of types and use patterns of pesticides, it is impossible
to spell out all of the circumstances which might serve as a basis for
waiving data requirements.”  Although this language was not carried
over into the proposed regulatory text, EPA tried to refine data
requirements and supply test notes that might help the registrant
determine if a waiver request is in order as Commenter 120 suggested. 
Applicants are encouraged to discuss the waiver request with the Agency
before developing and submitting supporting data, information, or other
materials.  

Once the discussion has been conducted, waiver requests must be
submitted in writing and include:

the data requirement(s) that the applicant believes should be waived

explanation(s) and supporting rationale(s) why the data requirement(s)
should be waived

any unsuccessful attempt(s) to generate the required data

any other information to support the request

alternative means of obtaining data to address the concern(s) underlying
the data requirement(s)

The Agency will review the waiver request and inform the applicant in
writing of its decision.  The decision will include a rationale for
determination of the waiver.  The Agency may send a notice to all
registrants or publish a notice in the Federal Register announcing its
decision if the decision applies to more than the requested product. 
The Agency decision to deny a waiver request is a final Agency action.

	

COMMENT:  Commenters 124, 125, and 133 were concerned about timelines
when waiver requests are denied; they suggested a decision be made well
in advance of application submission.  Commenter 119 also cautioned that
EPA must be diligent in assuring that the required tests be conducted by
the applicant and assessed by the Agency within a reasonable time
period. 

RESPONSE: While the Agency understands the concern about timelines, it
indicated in the proposed rule that consideration of waiver requests
must be done when Agency scientists review the application.  While not
intended as a disincentive to submit such requests as perceived by two
of the three commenters, the Agency is committed to timely decisions and
notification of the applicant with anticipated timelines in mind.

COMMENT:  The proposed organization of sections under “Waivers”
preserves the numbering from current 40 CFR part 158 and Commenter 123
suggested abandoning it and grouping closely-related sections instead. 
The commenter specifically proposed combining 158.30 (flexibility),
158.45 (waivers) and 158.75 (requirements for additional data) to remove
redundant material and shorten the information.  The commenter also
proposed a reference to FIFRA 3(c)(2)(E) and a definition of “minor
use” from FIFRA under “data waivers.”

RESPONSE:   The Agency proposed deleting 158.30 because it addressed
approval of registration actions and was more properly covered in part
152.  The Agency proposed to reformat the waiver process but retain its
provisions.  The Agency removed a redundant paragraph from the current
158.75 but retained the remaining paragraph.  The Agency proposed
removing redundant material as the commenter suggested but the Agency
believed that retaining the separation would be less confusing for
registrants accustomed to finding information in three separate
sections.  The Agency does not believe it is necessary to duplicate the
information from FIFRA regarding waivers for minor uses because
definitions and policies are largely covered by statutory mandates, not
regulations. 

COMMENT:  Commenter 124 suggested that EPA should reinstate language
previously found in §158.101 that directed the user to the data waiver
provisions.  

RESPONSE:  EPA accepts this comment and has included in the final rule
(§158.110) a reference to §158.45.   An applicant may avail himself of
the waiver provisions regardless of the designation of the study as R or
CR.

Formulators’ Exemption

	EPA chose to remove or revise provisions in part 158 that directly or
indirectly arise from the statutory formulators’ exemption of FIFRA
section 3(c)(2)(D).  First, EPA proposed to remove language in § 158.50
pertaining to the statutory formulators’ exemption.  Second, EPA
proposed removal of asterisks denoting the application of the
formulators’ exemption to product chemistry data.

COMMENT:  A number of commenters objected to the removal of
formulators’ exemption language, and others were confused by the
removal of the asterisks (which appeared in the product chemistry table
and toxicology table).  

RESPONSE:  Commenters appear to have been confused by the distinction
between the array of data that the Agency must have to determine whether
a pesticide may be registered (the data requirements of part 158), and
the means by which those data requirements are satisfied (the data
citation and compensation provisions of part 152, subpart E, including
the formulators’ exemption).  In a nutshell, part 158 specifies the
“what” and part 152 specifies the “how” with respect to some
aspects of addressing data requirements. The primary purpose of part 158
is to specify the data requirements pertaining to a product.  Part 158
was never intended to serve the broader purpose of specifying the
various means though which an individual applicant can legally satisfy
the data requirements; that is the purpose of the data compensation
provisions of part 152.  Part 152 lays out all of the ways of addressing
a data requirement specified in part 158 -- submitting new data, citing
existing data, citing to public literature, obtaining a waiver, or
claiming eligibility for the formulators’ exemption.  EPA believes
that it should reinforce this distinction by removing from part 158 what
is actually incomplete information about the formulators’ exemption.

	Eligibility for the formulators’ exemption is not a function of a
data requirement; eligibility depends on the purchase of a registered
product for incorporation into another product.  The 1984 regulations
erred in attempting to apply the formulators’ exemption to specific
product chemistry and acute toxicology requirements by means of the
asterisk notation.  First, the asterisks were displayed in a misleading
fashion so that it was not clear precisely when the formulators’
exemption did or did not excuse an applicant from the requirement to
submit data.  Furthermore, the asterisks were misleading because they
conveyed the notion that the data requirement need not be satisfied. 
The fact that certain data need not be submitted or cited by an
applicant eligible for the formulators’ exemption does not mean that
those data are not necessary to support the registration of his product.
 It means that the data requirement has been satisfied by another means,
usually the submission of data by the producer of the registered TGAI or
MP that the formulator purchases.

	In addition, maintaining information on the formulators’ exemption in
two locations in the Code of Federal Regulations is administratively
cumbersome.  As one commenter noted, the statute has been revised since
both of these regulations were issued, and neither § 152.85 nor 

§ 158.50 are accurate or complete.  For this reason, EPA believes it
important to consolidate the formulators’ exemption language in a
single location. 

	All commenters pointed out, correctly, that although EPA indicated in
the preamble that the formulators’ exemption text of § 158.50 was to
be relocated to part 152, no proposed regulatory language was included. 
EPA did not include in the proposal the actual regulatory text that
would be incorporated into part 152.  In the final rule EPA has included
the revised language, which would incorporate the provisions of §
158.50 into § 152.85 with needed conforming text changes.  EPA has also
corrected § 152.85 to reflect current FIFRA section 3(c)(2)(D), as
amended in 1988.  Except where required as a result of these statutory
amendments, EPA has made no substantive change to the exemption or
EPA’s interpretation of its applicability and it was therefore not
necessary to re-propose the changes discussed in the preamble to the
proposed rule.

	Although EPA believes that the formulators’ exemption should properly
be located in part 152 together with other provisions concerning
submission or citation of data, the Agency recognizes the value of
referring to the provisions of part 152 in part 158.   Accordingly, EPA
has revised § 158.70(a), by including a new paragraph (1) which
explains that the provisions of part 158 are to be read in conjunction
with those of part 152, subpart E.

Minor Uses 

	EPA proposed deleting the section on minor uses but, based on the
comments and subsequent review, the Agency retained portions of the
minor use section.

COMMENT:  Commenters 112, 120, 122, 123, 124, 125, 129, 133, and 134
expressed their concerns in various ways about the removal of current
§158.60 on minor use policy.  Five commenters recommended retaining the
section as is.  Three commenters recommended supplementing the current
information by:  adding a reference to FIFRA §3(c)2)(E) and a
definition of “minor use” from FIFRA; adding criteria regarding
minor use; codifying protections that exist outside of the regulations;
and collecting policy in one place in the regulations for Agency staff. 
Commenter 112 recommended retention of §158.60(a)(2) and (3).

RESPONSE:  The Agency continues to believe the non-regulatory policies
should not be retained in part 158 so supplementing what it retained
would not serve any useful purpose.  The paragraphs being deleted have
been superseded (the definition in paragraph (a)), are guidance only
(paragraphs (a)(1) and (b)), or are covered by regulations elsewhere
(paragraph (a)(4)).  EPA will in the final rule retain paragraphs (a)(2)
and (3), but has removed the remaining material and re-designated those
paragraphs.   

		Weight-of-Evidence Approach

	Some commenters requested clarification of the weight-of-evidence
approach, especially how it is applied for the developmental
neurotoxicity (DNT) data requirement.   It is discussed in detail with
DNT as an example in Unit V.H. of the preamble to the final rule.

Discussion of Comments on the Data Tables (Subpart B) 

Use Patterns

	In the preamble to the proposed rule, EPA proposed subdividing the
current nine major use patterns to fifteen use patterns to fully address
nonagricultural uses.  This proposal seemed to create some confusion
among commenters.

COMMENT:  Commenters 111 and 120 wondered why definitions of the
proposed use patterns were not included in the proposed rule for
comment.    Commenter 125 requested definition of “major use
patterns” and “pesticide use site groups.”  Commenters 123 and 125
identified inconsistencies in use patterns between the preamble
discussion and the tables of data requirements in the regulatory text. 
In addition, Commenter 114 recommended that EPA include a new category
of uses for “terrestrial nonfood non-crop uses” or “terrestrial
urban uses.”

RESPONSE:  In the proposed rule, EPA subdivided the existing use
patterns to assist registrants in focusing on data requirements for
their particular pesticide use.  EPA also included nonagricultural use
patterns not reflected in the current major use patterns and believed
that the resulting proposed 15 major use patterns were fairly
self-explanatory.  The major use patterns provide a convenient
organization in the data requirement tables to determine the likelihood
the data will be required.  The pesticide use site groups are more
specific to the registrant’s use site for a particular pesticide
product and can provide a starting point for determining which general
use pattern(s) is(are) most appropriate for the product in question.  

	The Agency appreciates commenters’ assistance in locating
inconsistencies between the preamble discussion and the regulatory text
and corrected them in the final rule.  One such inconsistency was the
“Indoor medical” general use pattern.  It was included when the rule
was intended to update all of part 158, including antimicrobial
pesticides.  When the proposed rule for antimicrobials was planned as a
separate entity, the “Indoor medical” use pattern was inadvertently
left in the original rule instead of being removed to accompany the
antimicrobial portion that was to be removed.  There were also five
Aquatic nonfood use patterns (Aquatic nonfood crop, Aquatic nonfood use,
Aquatic nonfood outdoor use, Aquatic nonfood residential, and Aquatic
nonfood industrial use) in the different disciplines.  The five were
consolidated into one major use pattern, Aquatic nonfood.  With the
removal of the “Indoor medical” use pattern and the reduction of
aquatic nonfood patterns to one, the final number of general use
patterns for conventional pesticides will be 12, rather than the 15 in
the proposed rule. The Agency appreciates one commenter’s
recommendation to include another major use pattern such as
“terrestrial urban uses” but believes that the patterns already
proposed are sufficient to cover some of the more specialized uses
without increasing the number of use patterns and adding to the
confusion.	

In addition, all the major use patterns will not appear in the data
table for each discipline.  Some of the use patterns have been collapsed
under a larger major use pattern for ease of use.  For example, the
major use patterns in the Toxicology Data Requirements table consist of
Food and Nonfood.  The discussion in §158.500 (b) explains that the
general use patterns of terrestrial food crop, terrestrial feed crop,
aquatic food, greenhouse food crop, and indoor food have been placed
under the major use pattern “Food.”  The “Nonfood” use patterns
include products classified under terrestrial nonfood crop, aquatic
nonfood, greenhouse nonfood crop, forestry, residential outdoor and
indoor, and indoor nonfood.  Therefore only two major use patterns
appear in the data requirement table for Toxicology.  Similar
adjustments have been made to other disciplines as appropriate.  

	B.  Appendix A 

	EPA proposed updating the current Appendix A, which contains a
compendium of pesticide use sites and major use patterns to help
registrants determine data requirements, and removing it from 40 CFR
part 158.  The Agency intends to issue the updated version on the OPP
website and update it periodically as the need arises; this would
provide EPA with the opportunity to correct and update the pesticide use
sites without a complicated and lengthy rulemaking.  Instead of
“Appendix A,” it will be entitled “Pesticide Use Site Index” and
function as a finding aid for those applicants needing help in
determining which major use pattern(s) would apply to their particular
product.

COMMENT:  Commenters 120 and 124 wanted the Agency to retain Appendix A
in 40 CFR part 158 to provide an opportunity to comment on the major use
patterns and the pesticide use sites.  Commenter 123 voiced the same
preference and requested a schedule for revising and republishing
Appendix A since it had not been revised since its original issue in
1984.  

RESPONSE:  EPA intended Appendix A to serve as reference for registrants
who could identify the pesticide use sites but not the general use
patterns to which the site would apply.  The use of Appendix A was not
intended to be a requirement for all registrants and thus not
appropriate for codification.  One of the major reasons for placing the
Appendix A information on the website was the ability to update the
index more frequently, as the need arises.  Commenters will still have
the opportunity to suggest changes to the index even though it now
resides on the website and the revisions should occur with more
timeliness.

COMMENT:  Commenter 122 supported the removal of outdated Appendix A
from the regulations and posting it on the EPA website for better
maintenance and frequent updates.  This commenter requested the Agency
establish a specific procedure for correction and revisions to the
index.

RESPONSE:   The Agency believes that providing the index in current
Appendix A in a more flexible format on the website will allow for more
frequent updates and revisions.  As new crops arise and pesticide use
sites evolve, the index will be updated to keep pace with new
terminology.

C.	Data Tables

	EPA proposed to continue its current system of identifying the
applicability of data requirements in the data tables, i.e. the
designations for required, conditionally required, and not required.  In
the proposed rule, EPA requested comment on its R/CR designation and
received no suggestions for alternative means of presenting the data
requirements.  Therefore, the final rule continues this longstanding
practice.

COMMENT:  Commenters 113, 124, 125, and 133 were confused by the
explanations of R and CR in the proposed rule and requested tighter
definitions and clarification of the test notes since the latter
provided insufficient guidance.

RESPONSE:  Some commenters were confused by the explanations of R and CR
in the proposed rule and requested tighter definitions and clarification
of the test notes since the latter provided insufficient guidance.  In
the proposed rule, EPA requested comment on its R/CR designation, and
received no suggestions for alternative means of presenting the data
requirements.  As described in the preamble to the proposed rule, the
R/CR terminology is a general presentation of the likelihood that a data
requirement will apply.    The use of R does not necessarily indicate
that a study is always required, but that it is more likely to be
required than not.  The use of CR means a study is less likely to be
required.   However, both R and CR designations must be read in the
context of the accompanying test notes to provide context for the R/CR
in the table.  An applicant may assume that a data requirement with R
will typically be required all the time.  The test notes accompanying
that R designation may provide supplementary information or identify
some condition(s) when the study is not required.   A CR designation
will generally include more extensive test notes describing the limited
conditionality of the requirement.  The final rule continues this
longstanding practice.  EPA revised some of the test notes to clarify
the conditions under which the data would be required.   

COMMENT:   Commenter 124 disagreed with EPA’s explanation of how the
required (R) and conditionally required (CR) designations were used in
the preamble and in proposed §158.110.  Stating that the statements
were contrary to their historical understanding and usage by companies,
the commenter urged EPA to be very clear about when data requirements
are actually required to provide certainty to companies initiating
studies.  

RESPONSE:  EPA notes that current part 158 has never been as certain as
the commenter suggests, i.e. that R means that the data are absolutely
required.  Current part 158 contains numerous examples of R-designated
data requirements that are tempered by test notes limiting their actual
applicability.  As EPA explained in the preamble to the proposed rule,
the R and CR designations are perhaps an imperfect means of presenting
complex data requirements with as much certainty as is possible.  The
test notes must be consulted in all cases.  Moreover, because of the
individual chemical and use patterns, even the test notes may not offer
the certainty that the commenter seeks.  In the final analysis,
applicants are encouraged to consult with the Agency.

COMMENT:  Commenter 120 questioned the availability of Pesticide
Assessment Guidelines from the sources in §158.70(c).

RESPONSE:  The Agency agrees with the commenter that it is not clear
that all the guidelines are available from NSCEP or NTIS.  Thus, the
Agency recommends that applicants access the OPP website (  HYPERLINK
"http://www.epa.gov/pesticides"  www.epa.gov/pesticides ) for the test
guidelines or consult their Product Manager.   As the guidelines are
revised, these are the two sources most likely to provide the latest
information.  The information in §158.70(c) will be revised to reflect
the best source.

 

COMMENT:  Commenter 120 inquired about the Agency’s basis for changing
“Reentry protection” to “Applicator and Post-Application
exposure.”

RESPONSE:   Although the Agency did not discuss the terminology change,
it did propose changing the subpart designation for Subpart D: 158.390
(Reentry protection) to Subpart K: 158.1050 (Post-Application exposure)
in Table 1 – Proposed Changes to Subpart Designations. The Worker
Protection Standard for Agricultural Chemicals (40 CFR parts 156 and
170) avoided the term “reentry” and sought to standardize the
terminology using the term “post-application exposure.”  In addition
the Worker Protection Standard broadened the scope of post-application
requirements for agricultural workers to include greenhouses, nurseries,
and forests.  The Agency is seeking to bring the Guidelines into line
with this key regulation.  In addition, incidental oral and other types
of residential exposures may occur from post-application oral (or
dermal) contact with individual ant, roach, or rodent baits, rather from
“reentering’ a treated area.  The term “post-application
exposure” is an inclusive and descriptive term for the types for
exposure being characterized.  “Application exposure,” on the other
hand, is new Subpart K: 158.1000 in the proposed rule and was not
combined with “Post-Application exposure.”  Both Applicator Exposure
and Post-Application Exposure appear under Subpart K: Human Exposure
Data Requirements.

COMMENT:  Commenter 123 believed that the proposed rule provided
insufficient information on how to obtain timely decisions from EPA on
data requirements and suggested that the rule should clearly state how
such decisions are to be obtained.  

RESPONSE:   The rule is intended to describe the types of data needed to
make regulatory decisions, and how to submit justifications for waivers
if the applicant does not believe that the data are needed.  The rule
describes with as much certainty as possible the criteria for data
determinations.  It is not possible for EPA to describe with certainty
on a case-by-case basis in the rule the precise data requirements that
might apply, as there are product and use pattern factors that may be
highly specific to an application.  EPA strongly encourages
pre-registration consultations to assist applicants in properly applying
the data requirements to their particular product and uses. 

Purposes of Registration Data Requirements

	As proposed, the material explaining the purposes of the registration
data requirements was removed from subpart D without revision and
relocated in subpart B.  There were no comments on relocating the
material from subpart D to subpart B.

III.      Discussion of Comments on Identifying Data for Experimental
Use Permits (EUPs) (Subpart C)

	EPA requested comment on a better way to identify data requirements for
EUPs besides the current use of brackets around R and CR designations to
make data tables simpler and more understandable.  The Agency suggested
separating EUP data requirements from the main data tables and placing
EUP requirements in a stand-alone data requirement table.    

COMMENT:  Commenters 120 and 122 supported the continued use of brackets
because they believed the designation was descriptive and clear. 
Commenter 124 believed that using brackets to distinguish EUPs was
adequate but encouraged the Agency to continue searching for
improvements.  In addition, this commenter suggested adding: brackets to
the product chemistry data requirement table to indicate all
requirements are necessary for EUPs; and a note for applicator exposure
and post-application exposure to indicate none of the studies are
required for EUPs. Commenter 125 suggested placing a EUP data
requirements table in part 172 instead of leaving EUP data requirements
in part 158. 

RESPONSE:    EPA had requested comment on this practice because it
wondered if the bracketing in the data requirement tables concentrated
too much information in the latter and made them harder to use.  In
§158.310(a)(3) of the proposed rule, there is a statement that all
product chemistry data must be submitted to support a request for a EUP.
 The sections on applicator exposure and post-application exposure in
the proposed rule relied on lack of brackets to indicate that none of
the studies were required for EUPs.  Because the information in part 172
was more procedural and part 158 is focused on data requirements, EPA
decided to keep the EUP data requirements in part 158.

	After examining alternate ways to indicate EUP requirements besides
using brackets, the Agency decided to designate a new subpart within
part 158 for EUPs.  That new subpart is Subpart C and it is placed early
in part 158 for applicants interested in EUPs so they can locate the
information they seek more efficiently.

IV.	Discussion of Comments on Product Chemistry Data Requirements
(Subpart D)

	EPA proposed two additional data requirements and other minor revisions
to clarify the applicability of existing requirements.  For example, the
Agency proposed to revise the definition of an active ingredient and
end-use product to include nitrogen stabilizers, which were added to the
definition of “pesticide” in 1996.

COMMENT:  EPA proposed only a few changes in product chemistry
requirements but the Agency received a number of comments on elements of
the product chemistry data requirements that EPA had not proposed to
change.  Topics included:  

1.  Certified limits [Commenter 113]

2.  Preliminary analysis [Commenters 122, 124]

3.  Submittal of samples [Commenter133]

4.  Definition of TGAI vs.  MP [Commenter 120]

5.  Statement of Formula [Commenter 124]

6.  Grouping of products to reduce or consolidate product chemistry
requirements [Commenter 124]

7.  Data on pesticide degradates [Commenter 114]

RESPONSE:  These comments are outside the scope of the Agency’s
proposal.  They may be considered for future revisions of part 158. 
Accordingly, EPA has not revised the final rule to address these
comments.  Except for the large number of comments on topics that were
not proposed, the remaining single comments were not considered key and
therefore not discussed in the preamble.  In the preamble, EPA indicated
that the former may be considered for future revisions of part 158.   

Test notes

COMMENT:  Commenter 124 suggested that instead of having the test notes
refer the reader to subsequent sections in the regulatory text that the
test notes be replaced with the subsequent paragraphs.  For example, for
“product chemistry and composition,” the last column of the table
would refer the reader directly to §158.320, rather than first to test
note 1 and then to §158.320.

RESPONSE:  EPA does not agree with this suggestion as it believes that
such a practice would create a mix of information in a column entitled
“Test Note No.” and possibly confuse the reader.  Therefore EPA has
not adopted this suggestion.

Disposition of §158.150  

COMMENT:  Commenter 120 noted that EPA did not include in its proposed
rule the text of current § 158.150, describing the purpose of various
product chemistry data.  That section contains no data requirements per
se, but describes how EPA uses product chemistry information in
evaluating a product for registration.  

RESPONSE:  EPA did include general information in proposed § 158.130 on
the purpose of other types of information.  Accordingly, in the final
rule, EPA has condensed the text of current § 158.150 and located it in
§158.130(b).

Data requirements for Color (830.6302) and Odor (830.6304)

COMMENT:  In the product chemistry table, EPA’s proposal stated that
the color and odor requirements for an EP were to be conducted with the
TGAI.  Commenter 28 pointed out that it makes little sense to use the
TGAI as the test substance for the EP.  

RESPONSE:  EPA agrees with the commenter and has changed the test
substance to the EP. 

UV/visible light absorption

COMMENT:  EPA proposed to add a new requirement for a UV/visible light
absorption range.  In the preamble, EPA identified this study as
defining the need for a photodegradation study in water if absorption
occurs within a certain range.  Commenters 122 and 124 suggested that
the study should be located within the environmental fate data
requirements, and that the nanometer range be included as a test note to
the study.  Commenter 120 suggested that the test substance (TGAI) is
inconsistent with EPA’s current practice for this requirement, and
should be revised to be the PAI.

RESPONSE:  With respect to the location of the requirement, EPA
disagrees that the requirement should be in the environmental fate data
requirements.  The light absorption study evaluates a basic property of
an ingredient, and thus properly belongs in subpart D together with
other basic physical and chemical properties.  Although identified as
being needed for the photodegradation in water study requirement, the
data may prove useful in other areas not yet identified and thus should
not be associated solely with the environmental fate data requirements. 
EPA is therefore retaining the UV/visible light data requirement in
product chemistry.

	With respect to the suggested test note revision, EPA also disagrees
with the commenter.  The study measures only the potential for an
ingredient or product to absorb light and identifies the range of that
absorption.  EPA uses this information to determine whether a
photodegradation study in water is needed: the criterion for the
photodegradation study is properly identified by a test note in the
photodegradation study requirement in subpart N.  The nanometer range
that triggers the photodegradation study is not relevant to the basic
physical property study.  Accordingly EPA has not adopted the
commenter’s suggestion.

	Finally, EPA agrees that the test substance should be the purest
substance generally resulting from the production process.  As a
practical matter, most production processes are not intended to produce
a pure active ingredient, but a high concentration TGAI that may contain
other ingredients present as a result of the production process.  The
PAI is primarily needed for residue chemistry analyses that measure a
pesticide chemical in extremely small amounts.  Nonetheless, if a PAI is
available, EPA believes the study should be conducted with that
ingredient, and has changed the test substance to be used to either the
PAI or the TGAI. 

Particle size, fiber length, and diameter distribution

COMMENT:  EPA proposed to add a new requirement for particle/fiber size
and distribution, applicable to the EP, but conducted using the TGAI or
PAI.  EPA identified its need for the data due to spray drift concerns. 
Commenters 28, 120, and 122 noted that data on the TGAI are not relevant
to spray drift, and suggested that the test should more appropriately be
conducted using the EP.

RESPONSE:  EPA agrees with the commenters that for spray drift purposes,
the appropriate test substance should be that actually applied (the EP),
and has revised the table accordingly.  In addition to providing
information for determining spray drift, this data requirement may also
contribute to determinations of inhalation toxicity.

0.1 μm).  The data would be useful for inhalation toxicity studies, as
well as for terrestrial exposure assessments.  The Agency believes that
the degree of specificity suggested by commenters need not be included
in the test note; the guideline and consultation with the Agency should
provide the necessary guidance.

  

Stability to normal and elevated temperatures, metals, and metal ions

COMMENT:  EPA proposed to require this information on a conditional
basis and to add a test note where previously there was none. 
Commenters 125 and 123 noted that although the new test note addressed
the conditionality of the requirement with respect to metal
interactions, it did not provide a description of the temperature
conditionality.  Commenters suggested that since all pesticides may be
exposed to “high temperature,” the data requirement was open-ended. 

RESPONSE:   EPA agrees with the commenters and has revised the test note
to include an upper limit criterion for a high temperature of >50( C
(>122( F).  

COMMENT:  Commenter 125 noted that the test note stated that the
potential metal interactions of concern were in storage, and the test
substance was limited to the TGAI.  He suggested that all products (EP,
MP, etc) could be destabilized by interaction with metals, and that it
could occur at points other than storage of the material.  

RESPONSE:  EPA notes that the test for stability to high temperature and
metal/metal ion interaction should be limited to the TGAI.  The purpose
of the testing is to determine the basic stability of the TGAI.  If the
TGAI breaks down at high temperature or because of instability to metals
before being formulated into an EP, potential breakdown products such as
impurities could be carried over into the formulation of subsequent
products.  The potential for formulated, packaged, and stored products
such as MPs and EUPs to break down is captured by the storage stability
test.

Explodability  

COMMENT:  Commenter 82 compared the U.S. data requirement with the
Canadian data requirement.  The Agency currently requires this data but
proposed to make it CR.  Canada currently requires the data but
applicants are usually provided with waivers.  Canada may reconsider the
conditionality of its data requirement in the future, pending the
outcome of part 158 final rule in the U.S.

 RESPONSE:  EPA will continue to work with Canada to harmonize data
requirements although U.S. data requirements are harmonized with
Canada’s to a high degree.

Partition coefficient (n-octanol/water)

COMMENT:  EPA proposed to change the requirement for the octanol/water
partition coefficient from CR to R, because the majority of pesticides
are organic and non-polar.  EPA did not intend to change the nature of
the requirement; however, in revising the test note associated with the
requirement, EPA described the requirement differently from its existing
note, which Commenters 122 and 124 found confusing.  

RESPONSE:  EPA believes that the current test note included in the
proposal adequately captures the requirement and has not revised the
test note.  The octanol/water partition coefficient is required for all
products that are organic and non-polar.

Density/relative density/bulk density

COMMENT:  EPA proposed to add a test note to this requirement,
clarifying when various density measurements were required.   EPA did
not intend to change the applicability or nature of this requirement
except to clarify how the requirement applies.  Commenter 28 raised
technical points about how density measurements might apply to various
types of products, and was confused by EPA’s proposed clarification.

RESPONSE:  EPA has had little difficulty in administering this
requirement, and believes that applicants understand the appropriate
measurement of density of various types of products.  Therefore, no test
note is actually required.  Accordingly EPA is deleting the confusing
test note in the final rule. 

	

Discussion of Data Requirements for Product Performance (Subpart E)

	The proposed rule did not apply to the data requirements for product
performance (efficacy).  The data requirements in current 40 CFR part
158 for product performance were relocated to Subpart E with no changes.
There were no comments on relocating product performance data
requirements to Subpart E.

	

Discussion of Comments on Toxicology Data Requirements (Subpart F)

	EPA proposed revisions that had been peer-reviewed by the FIFRA SAP and
retained data requirements from the current CFR.  The Agency proposed
to:  impose one new data requirement; codify four data requirements; and
revise six data requirements.

Tiered testing for nonfood pesticides

COMMENT:   Commenter 120 agreed that tiered testing based on exposure is
appropriate but wondered why the examples were so extreme.

RESPONSE:  The examples cited in the preamble to the proposed rule
(XI.B.2.i. and ii.) are intended to represent the extreme ends of the
spectrum: very high exposure which would require toxicity data similar
to that for a food use pesticide; and very low exposure requiring at
most only Tier 1 studies.  The Agency also believes that a tiered
testing approach based on the use pattern and expected exposure
scenario(s) is(are) appropriate for nonfood use pesticides.  The Agency
welcomes an open dialog with registrants and other stakeholders to
ensure clarity on its tiered approach to toxicity testing and specific
data requirements. 

COMMENT:   Commenters 125 and 133 wondered why a 90-day feeding study
would be required for a nonfood use product such as household
applications.   

RESPONSE:  When it has been determined that significant repeated
exposure could result from the use of a nonfood use pesticide, 90-day
feeding studies would only be required (Tier 2) to serve as
range-finding studies to determine dose levels for Tier 3 studies (e.g.,
carcinogenicity studies). 

Open literature

COMMENT:   Commenters 114 and 128 were concerned that the proposed data
requirements would require re-testing even if the information is already
publicly available from reliable sources and suggested that the Agency
require registrants to search the professional published literature
(i.e. scientific journals) and to provide copies of all relevant
publications to EPA.

RESPONSE:  Data from the open literature has been and is still
considered along with submitted data when appropriate and available. 
Section 158.32 (Format of data submissions), paragraph (c)(1)(vi) tells
the applicant how to submit a study if it is a reprint of a published
document.  

Immunotoxicity

  	EPA proposed requiring functional immunotoxicity testing to evaluate
the potential of a chemical to adversely affect the immune system since
immune system suppression has been associated with increased incidences
of infections and neoplasia.  Studies not specifically conducted to
assess immunotoxic endpoints are inadequate to characterize the
potential immunotoxicity of a pesticide, even if tissues likely to
suffer immunotoxic insult are examined. 

 

COMMENT:  Commenters 49, 116, and 128 strongly supported including the
immunotoxicity testing in the toxicology data requirements for all
pesticides.  Commenter 52 pointed out that the European Union includes
functional immunotoxicity testing and assessment of immune systems in
its 90-day rodent study and the U.S. did not address the use of combined
study in its proposed data requirement.  

RESPONSE:  The Agency agrees that the guideline did not specifically
address the issue of combining subchronic and immunotoxicity studies.
However, the studies can be combined as long as there are designated
groups of animals specifically for conducting a routine subchronic study
and an immunotoxicity testing, respectively.

COMMENT:  Commenters 125 and 133 requested clarification of when
immunotoxicity testing would be required.

RESPONSE:  Immunotoxicity testing (Guideline 870.7800) is required (R)
for all pesticides, food and nonfood use.

COMMENT:  Commenter 131 was opposed to codification of immunotoxicity
testing and detailed the reasons for its opposition.  One of the reasons
was the extensive divergence in immunological structure and response
between species that gives animal studies limited predictive power for
immunotoxicity in humans.  The commenter also cited the differences
between animal strains; artifacts in laboratory methodology; laboratory
conditions and stress that can negatively affect the immune system. 
Instead, the commenter recommended using the ILSI/HESI paradigm.

RESPONSE:  A discussion of details in the guideline is not appropriate
for inclusion in Part 158 but the commenter’s remarks will be
forwarded to the responsible division in OPP for review and
consideration.  While EPA agrees that the testing protocol needs further
work, discussions on other testing paradigms that may lead to guideline
revisions will continue through the International Life Sciences
Institute (ILSI) and Health and Environmental Sciences Institute (HESI)
cooperative effort as will consultation with stakeholders on the
development and validation of this test guideline.

COMMENT:  Commenters 112, 120, 52, 124, and 134 questioned the validity
of such a data requirement and suggested that the data from other
toxicity studies could be used as a trigger to ask for more information
on immunotoxic effects instead of requiring immunotoxic studies; they
also suggested changing the R to CR for food and nonfood uses.  

RESPONSE:  The Agency proposed requiring functional immunotoxicity
testing in response to the NRC review and FIFRA SAP recommendations.  As
explained in the preamble of the proposed rule (page 12293), this study
would be required for all pesticides since it would test endpoints not
identified in other studies.

	Immunotoxicity testing is necessary to evaluate the potential of a
chemical to produce adverse effects (i.e., suppression) on the immune
system. Immunosuppression has been associated with the loss in the
ability of the immune system to respond to a challenge such as HIV/AIDS
infections, tuberculosis (TB), Severe Acquired Respiratory Syndrome
(SARS), or neoplasia.  Because the immune system is highly complex,
current studies not specifically conducted to assess immunotoxic
endpoints are inadequate to characterize a pesticide’s potential
immunotoxicity.  While data from hematology, lymphoid organ weights, and
histopathology of routine chronic or subchronic toxicity studies may
offer useful information on potential immunotoxic effects, but these
endpoints alone are insufficient to predict immunotoxicity.  	Therefore
in the final rule, the Agency is requiring functional immunotoxicity
testing along with the data from endpoints in other studies to more
accurately assess the potential risk of pesticides on the immune system.

	

COMMENT:  Commenters 120 and 124 had several detailed suggestions on how
to update the guideline (870.7800) because they believed it was
inconsistent with current science and no adequately validated methods
existed for this work.  

RESPONSE:  A discussion of details in the guideline is not appropriate
for inclusion in Part 158 but the commenter’s remarks will be
forwarded to the responsible division in OPP for review and
consideration.  While EPA agrees that the testing protocol needs further
work, discussions on other testing paradigms that may lead to guideline
revisions will continue through the International Life Sciences
Institute (ILSI) and Health and Environmental Sciences Institute (HESI)
cooperative effort as will consultation with stakeholders on the
development and validation of this test guideline.

	 

COMMENT:  Commenters 116 and 128 suggested including studies using the
EP to provide useful data.

RESPONSE:  Regarding the issue of requiring studies other than those
included in the acute toxicity testing battery to be conducted with the
EP, it would be cost prohibitive and highly impractical for required
toxicity studies to be conducted with each formulated EP.  EPA is
mindful of the burden on the applicant to conduct studies which may not
yield additional useful information.  Only the studies included in the
acute toxicity test battery are required to be conducted with the EP for
labeling purposes.

COMMENT:  Commenter 134 had many suggestions, including adding
information in test notes and waiver information.  This commenter also
inquired about the details of the guideline. 

RESPONSE:  Immunotoxicity studies provide critical scientific
information needed to characterize potential hazard to the human
population on the immune system from pesticide exposure. The
immunotoxicity data can be the most sensitive endpoint and used to
select endpoints and doses for use in risk assessment; they are
considered a primary data source for reliable reference dose
calculation.

	The immunotoxicity test is a new requirement and part of the data
requirements for registration of a pesticide (food and nonfood uses). 
The Agency believes that no Test Note is required since the study is
discussed extensively in the preamble.  There are no criteria,
indicators, assay type, or other conditions to warrant a Test Note.  The
Agency will review waiver requests and make case-by case decisions.

	A discussion of details in the guideline is not appropriate for
inclusion in Part 158 but the commenter’s remarks will be forwarded to
the responsible division in OPP for review and consideration.

90-day oral – rodent 

COMMENT:   Commenter 52 compared the U.S. data requirement with the
draft data requirement of the European Union.  This commenter noted that
the EU requires only one 90-day rodent study, preferably the rat, while
the U.S. requests a 90-day mouse range-finding study besides the rat
study in case a carcinogenicity study is required.  

RESPONSE:  A 90-day range-finding study in both rats and mice is
required to determine dose levels when carcinogenicity studies are
required.  The 90-day mouse range-finding study would not be required if
the mouse carcinogenicity study is not required.

COMMENT:   Commenter 128 suggested including studies using the EP to
provide useful data.

RESPONSE:    It would be cost prohibitive and highly impractical to test
each formulated EP.  EPA is mindful of the burden on the applicant to
conduct studies that may not yield additional useful information.  The
Agency will notify the applicant when additional testing using the EP is
required.  EPA is committed to moving towards a more efficient and
reliable testing/risk assessment paradigm that: is more attuned to risk
assessment needs (i.e. hypothesis-driven); avoids requesting data not
used in risk assessment; and reduces and refines the use of laboratory
animals.

90-day inhalation – rat 

COMMENT:  Commenter 52 compared the U.S. data requirement with the draft
data requirement of the European Union and noticed that the EU
conditionally requires a 28-day inhalation rodent study while the U.S.
conditionally requires a 90-day inhalation study in the rat.

RESPONSE:  The 90-day inhalation study is conditionally required for
food and non-food use pesticides but studies of a shorter duration may
be considered as sufficient to satisfy this requirement based on the
frequency, magnitude and/or duration of use.  EPA encourages the
applicant to consult the Agency in such instances.  Inhalation waiver
criteria may be accessed on the EPA website at   HYPERLINK
"http://www.epa.gov/pesticides/ppdc/pria/september05/sept14minutes.pdf" 
www.epa.gov/pesticides/ppdc/pria/september05/sept14minutes.pdf .

COMMENT:   Commenters 108, 109, 110, 120, 122, and 124 suggested
shortening the 90-day study based on the magnitude and duration of human
exposure.  Commenter 134 mentioned a 28-day inhalation study and
requested specific guidance for waiver requests.

RESPONSE:  The 90-day inhalation study is conditionally required for
food and nonfood use pesticides.  There is currently no test guideline
for a 28-day inhalation study but studies of a shorter duration may be
considered as sufficient to satisfy this requirement based on the
frequency, magnitude and/or duration of use.  In addition, inhalation
waiver criteria are available on the EPA website (  HYPERLINK
"http://www.epa.gov/pesticides/ppdc/pria/september05/sept14minutes.pdf" 
http://www.epa.gov/pesticides/ppdc/pria/september05/sept14minutes.pdf ).

COMMENT:   Commenter 128 suggested including studies using the EP to
provide useful data.

RESPONSE:    It would be cost prohibitive and highly impractical to test
each formulated EP.  EPA is mindful of the burden on the applicant to
conduct studies that may not yield additional useful information.  The
Agency will notify the applicant when additional testing using the EP is
required.  EPA is committed to moving towards a more efficient and
reliable testing/risk assessment paradigm that: is more attuned to risk
assessment needs (i.e. hypothesis-driven); avoids requesting data not
used in risk assessment; and reduces and refines the use of laboratory
animals.

Prenatal developmental toxicity

COMMENT:  	Commenter 48 suggested the requirement be based on the likely
exposure pattern for nonfood uses, rather than a mandatory requirement.

RESPONSE:  Since there is much variety in pesticide chemistry, exposure,
and hazard, part 158 is designed to be flexible and data waivers will be
considered on a case-by-case basis for a pesticide.  The decision to
grant a waiver is based on consideration of the use pattern, exposure
pattern, and chemical characteristics.

COMMENT:	Commenter 48 also suggested that the second species requirement
be based on the likely exposure pattern and conducted a simple survey of
seven materials.  The commenter indicated the results of the survey
implied a two-generation study in the rat and a prenatal developmental
study in a second species might be sufficient for some nonfood
materials.  

RESPONSE:  The commenter provided a “simple survey” to suggest that
a rat reproduction study and a developmental study in a second species
would be sufficient to identify pre- and postnatal concerns for some
nonfood use pesticides.  This analysis is not adequate to make such a
conclusion for the Agency’s purposes.  Before considering regulatory
changes, the Agency will need to develop scientific position papers for
internal and external review (including review by the FIFRA SAP) and
public comment.

  

COMMENT:	Commenters 48, 82, 124, and 133 described the possible
technical and logistical challenges associated with combining the rat
developmental toxicity study with the two-generation reproductive
toxicity test.

RESPONSE:  These comments voice concern that various effects of some
test substances in a reproduction study protocol may interfere with
standard developmental observations if the reproduction study has an
added developmental toxicity component.  These are valid concerns and
laboratories are encouraged to consult with the Agency when developing a
protocol for a combined study.  It is additionally noted that the
combining of these studies is an option available to registrants to
consider and not a requirement by the Agency.

COMMENT:	Commenter 125 inquired about:  the cost increase resulting from
the combination of prenatal developmental toxicity study with the
two-generation reproduction study; the increase in the number of
animals; and whether the combination will provide the desired clarity
and economy.

RESPONSE:  Before a final decision is made to change any test protocol
to combine studies, a comprehensive investigation of costs and
effectiveness will be conducted to decide the feasibility of such a
change.

 	 

COMMENT:	Commenter 120 suggested the second prenatal developmental
toxicity study be conditionally required.  The study would be required
if the results of the first developmental toxicity study suggest
developmental effects in combination with evidence from other Tier 1
studies.

RESPONSE:  The Agency proposed requiring the prenatal developmental
study in a second species for nonfood use pesticides because the data
will provide some assurance that EPA is not basing an assessment on a
single species (e.g., rodent) which might be highly sensitive (or the
opposite) when compared to another (e.g., nonrodent).  Therefore, in
order to adequately characterize potential hazards to pregnant women and
their fetuses, the prenatal developmental study is required in two
species for all nonfood pesticides.

COMMENT:	Commenter 128, while approving of the data requirement name
change from “Teratogenicity” to “Prenatal Developmental
Toxicity,” pointed out that the test is not designed to assess effects
from exposures after birth or the postnatal effects of gestational
exposures.  This commenter suggested a test of postnatal developmental
toxicity be performed.

RESPONSE:   The suggestion is made that a postnatal developmental
toxicity study also be performed to assess the effects of gestational
exposures to developmental toxicants after birth.  This type of exposure
is currently routinely assessed in the reproduction and fertility
effects study (870.3800) and also in the developmental neurotoxicity
study (870.6300), when triggered.  The commenter also notes that
“male-mediated developmental effects on offspring are not considered
in the current guidelines for developmental toxicity testing,” which
is true but these effects would be detected and evaluated in the
guideline reproduction and fertility effects study and in the
developmental neurotoxicity study, when triggered. 

Neurotoxicity

COMMENT:	Commenters 124, 128, and 134 supported the elimination of the
90-day hen requirement and its replacement with the conditionally
required 28-day delayed neurotoxicity – hen study.   Commenter 124
agreed with the conditional requirement of the 28-day delayed
neurotoxicity study in hens, with the understanding that the requirement
would only apply to organophosphate compounds and recommended adding
Test Note 6 to the 28-day hen study. 

RESPONSE:  The Toxicology Data Requirements Table on page 12343 will be
revised to add Test Note 6 to the Test Note No. column for 870.6100 –
28-day Delayed neurotoxicity – Hen.  This data requirement will have
two test notes, Test Note 6 and Test Note 15.

 

COMMENT:	Commenters 124, 131, and 134 wanted the studies to be
conditionally required while Commenter 128 wanted them required.  Those
who supported the CR designation felt the studies should only be
required when neurotoxic effects are suggested in the standard battery
of acute, subchronic, and chronic toxicity tests.  Commenter 52
indicated the European Union conditionally requires neurotoxicity
studies in its draft proposal of data requirements and recommended the
U.S. also conditionally require this study.  Commenter 128 suggested
including studies using the EP to provide useful data.  

RESPONSE:  Since the acute and subchronic neurotoxicity studies in the
rat represent different types of exposure (i.e. a single exposure to the
pesticide versus repeated exposures), it is important to require both
studies to more completely understand the neurotoxic potential of the
pesticide and adequately characterize the potential risk to human
health.  The Agency believes that the existing toxicity testing would
not be sufficient as a condition for requiring further neurotoxicity
testing.  The acute and subchronic neurotoxicity studies include
specific neurotoxicity parameters such as motor activity assessment,
functional observation battery and neuropathy examination that are not
included in traditional toxicity studies but are needed for risk
assessment.  It would be cost prohibitive and highly impractical to test
each formulated EP in the neurotoxicity tests.  The Agency will notify
the applicant when additional testing using the EP is required.  EPA is
committed to moving towards a more efficient and reliable testing/risk
assessment paradigm that:  is more attuned to risk assessment needs
(i.e. hypothesis-driven); avoids requesting data not used in risk
assessment; and reduces and refines the use of laboratory animals. 

 

COMMENT:	Commenters 128 and 131 encouraged the substitution of the
neurotoxicity battery of tests with National Toxicology Program
Interagency Center for the Evaluation of Alternative Toxicological
Methods (NICEATM)-validated non-animal and in vitro tests as they became
available.    Commenter 131 cited information from the open literature
regarding the use of neuroblastoma cell lines and biochemical endpoints
and encouraged the Agency use the ILSI/HESI paradigm.

RESPONSE:  The Agency is committed to avoiding unnecessary animal
testing while taking into consideration principles of sound science and
the requirements of FIFRA to protect humans and   SEQ CHAPTER \h \r 1
the environment.  EPA is working closely with 15 other U.S. agencies to
advance the validation and adoption of alternative test methods through
the Federal Interagency Coordinating Committee on Validation of
Alternative Methods (ICCVAM) (    HYPERLINK
"(http://iccvam.niehs.nih.gov),"  http://iccvam.niehs.nih.gov), 
established by the National Institute of Environmental Health Sciences. 
EPA agrees that the ILSI/HESI paradigm represents the first
comprehensive effort to scientifically re-design the toxicology
animal-testing framework for agricultural chemicals.  The Agricultural
Chemical Safety Assessment (ACSA) proposal is consistent with EPA’s
direction and goals to develop a more efficient and reliable testing
paradigm.  However, ACSA is only one proposal that EPA needs to consider
in improving the risk assessment process of environmental chemicals.

 

COMMENT:	Commenters 125 and 133 wondered if the results of the acute and
subchronic neurotoxicity studies were intended to show adverse effects
in the central nervous system (CNS) affecting learning, memory or
performance, or adverse effects on visual, auditory, or somatosensory
senses.  

RESPONSE:  The Agency is routinely requiring the acute and subchronic
neurotoxicity studies in adult rats to more completely characterize the
potential for neurotoxicity resulting from single and repeated exposures
to pesticides. 

Developmental neurotoxicity (DNT)

COMMENT:	Commenters 120, 124, and 134 identified the requirement
inconsistency between the list of required first tier toxicity studies
and the requirements in the Table of Toxicology Data Requirements on p.
12344 of the proposed rule.

RESPONSE:  EPA received several comments alerting it to an error in the
list of required first tier toxicology studies for nonfood use
pesticides on page 12346; §158.510(b)(1)(iii).  The inclusion of the
developmental neurotoxicity study in the rat (guideline 870.6300) was an
error and this study will be removed from the list.  The developmental
neurotoxicity study in the rat (870.6300) is conditionally required (CR)
for food and nonfood use pesticides as indicated on the Table of
Toxicology Data Requirements on page 12344.

  

COMMENT:	Commenter 48 believed the discussion in the preamble appeared
to require DNT studies, although it was proposed as a conditional
requirement.  

RESPONSE:  The section of the preamble cited in this comment is
referring to the 1998 SAP recommendation to the Agency that the DNT
study be required for all food use pesticides.  However, based on the
experience gained with this study since 1998, EPA is now conditionally
requiring (CR) the DNT study for all food and nonfood use pesticides
based on a weight of approach (refer to Test Note 27, page 12345). 

COMMENT:	Commenter 49 appreciated EPA’s increased emphasis on DNT
testing because DNT data are essential to the aggregate and cumulative
risk assessments.  This commenter also supports EPA’s position that
harmonization of guidelines into a single set of OPPTS guidelines would
minimize variation among the testing produces but was concerned such
harmonization might lessen data requirements.  

RESPONSE:  The Agency recognizes the importance of the DNT study and
therefore is conditionally requiring this study in the rat (870.6300)
for all food and nonfood use pesticides.  For further information on
current risk assessment policies, please refer to Determination of the
Appropriate FQPA Safety Factor(s) in Tolerance Assessment (February 28,
2002; Docket # OPP-00757) and Application of the 10X Safety Factor in
Cumulative Risk Assessment (February 28, 2002; Docket # OPP-00759).

COMMENT:	Commenter 49 pointed out that the developing brain has been
shown to be the most sensitive health endpoint for many pesticides for
which the Agency has DNT data and found it contrary to have less
stringent requirements for this endpoint to protect children under FQPA.
 

RESPONSE:  While EPA agrees that effects on the developing brain can be
a sensitive endpoint for risk assessment, in a more recent retrospective
analysis of the DNT studies that have been received and reviewed by the
Agency to date, 8 out of 38 cases “resulted in the selection of a
lower regulatory endpoint for at least one exposure scenario” (Docket
ID OPP-2005-0190-0065).  For the remaining 30 cases, a study other than
the DNT study provided the most sensitive endpoint for human health risk
assessment.

COMMENT:	Commenter 49 believed that the source of developmental effects
to trigger a DNT test could only come from a DNT test and not standard
tests in developing animals.  This commenter also questioned whether the
inhibition of cholinesterase activity (ChEI) would be the most sensitive
effect for organophosphorus and N-methyl carbamate pesticides.

RESPONSE:  In the revised data requirements, the acute and subchronic
neurotoxicity studies are required for all food and nonfood use
pesticides, as are two prenatal developmental studies (in rodent and
nonrodent species) and a two-generation reproduction study in the rat. 
These studies provide key data in adult animals and in young animals
following pre- and postnatal exposure which can then be considered using
the criteria listed in Test Note 27 (page 12345) to determine the need
for the developmental neurotoxicity study.

	In response to the August 1999 Data Call-in Notice, OPP received and
completed the review of 20 developmental neurotoxicity studies conducted
with organophosphate pesticides.  In 13 out of 20 studies,
cholinesterase activity (ChEI) was measured in the pups; cholinesterase
was the most sensitive endpoint in these 13. 

	Only a limited number of developmental neurotoxicity studies are
available for carbamates (seven studies); for one chemical of the seven,
an endpoint from this study was used to assess acute dietary risk (not
chronic).

 

COMMENT:	A number of commenters were confused about when the DNT study
would be required and the weight-of-evidence approach and requested
clarification.  Commenters 125 and 133 found the criteria that would
suggest requiring a DNT study contradicted a later sentence indicating
that all neurotoxic pesticides would require a DNT study.

RESPONSE:  The text to which the comments refer reads “The Agency is
proposing to conditionally require developmental neurotoxicity studies
for all neurotoxic pesticides and/or when other criteria are met that
indicated a potential for toxicity to the developing nervous system,
based upon a weight-of-evidence evaluation of the toxicological
database.”  EPA has resolved the implied contradiction resulting from
a typographical error by changing “require” to “conditionally
required.”

COMMENT:  Commenter 116 favored including DNT testing but was concerned
that the criteria listed in the proposed rule for identifying
high-priority chemicals cannot identify every potential neurotoxicant.
This commenter also wondered why the same requirement was not proposed
for all pesticides used in and around homes, schools, and daycare
centers.  The commenter felt that a “knowledge-based” approach
should take account of both chemical-specific and exposure-specific
criteria.  

RESPONSE:   The developmental neurotoxicity study in the rat (870.6300)
is conditionally required (CR) for food and nonfood use pesticides as
indicated on the Table of Toxicology Data Requirements on page 12344. 
The decision to require this study (and any conditionally required
study) should be informed by both toxicological and exposure data.

COMMENT:	Commenters 125 and 133 both asked for clarification of triggers
for the conditionally required DNT study listed in Table 3 of the
proposed rule.

RESPONSE:  The table that you refer to in this comment (Table 3) is a
summary table of proposed changes to the Part 158 data requirements. 
The table that includes the test notes for the developmental
neurotoxicity study (and all other toxicology data requirements) is the
Toxicology Data Requirements Table on page 12343-12344.  Test Note 27
for this study contains the criteria to be considered in the weight of
evidence determination for requiring the study (i.e., “triggers”).

COMMENT:	In reference to §158.510 (Tiered testing options for nonfood
pesticides), Commenter 134 felt the DNT study should be conditional and
only be required when neurotoxic effects are suggested in the standard
battery of acute, subchronic and chronic toxicity tests and requested
clarification and well defined effects that would trigger the study.

RESPONSE:   The inclusion of the DNT study in the rat (870.6300) was an
error and this study will be removed from the list.  

COMMENT:	Commenters 49 and 82 were concerned that altered hormone
responses and/or effects on the thyroid seen from the two-generation
study as triggers for the DNT study were absent from Test Note 27.

RESPONSE:  Although thyroid effects were previously included as one of
the criteria considered in the weight of evidence for requiring a DNT
study, this criterion has since been removed based on the experience
gained with the study.  When thyroid effects of concern are observed,
the Agency will require a more specific special study to further
characterize the potential for a pesticide to adversely affect thyroid
hormones, thyroid structure, and/or thyroid hormone homeostasis during
development.

COMMENT:	Commenters 48, 113, and 120 agreed with EPA’s decision to
conditionally require this study based on a weight-of-evidence approach.
 They requested a clarification of Test Note 27 to indicate the effects
are part of the weight-of-evidence approach and not individual triggers.

RESPONSE:   To ensure clarity regarding the use of a weight of evidence
approach when conditionally requiring a DNT study, the first sentence of
Test Note 27 on page 12345 will be revised to read “A DNT would be
required using a weight-of-evidence approach considering...” instead
of “A DNT would be required using a weight-of-evidence approach
when….”  EPA provides additional information on the
weight-of-evidence approach and DNT in the preamble to the final rule.

	

COMMENT:	Commenter 124 agrees that the DNT study should be conditionally
required on a case-by-case basis and that the endpoints that could
trigger a DNT study not be used in isolation.

RESPONSE:  EPA agrees that the criteria used in the determination of the
need for a developmental neurotoxicity study listed in Test Note 27,
“should not be used individually in isolation”; rather all of the
available toxicology and exposure data would be considered together in a
weight-of-evidence determination.

COMMENT:	Commenter 124 requested further clarification of several terms
used in Test Note 27 to describe toxicity-related findings which could
be used as the basis for requiring a DNT study, specifically:
“functional or behavioral effects”; the differentiation between
“altered” and “adverse”; and the interpretation of “altered
neuroreceptor or neurotransmitter responses.”  

RESPONSE:  In interpreting these terms, it is important to emphasize the
context provided by Test Note 27 which is that the effects listed would
be considered as part of a weight-of-evidence approach.  EPA agrees that
weight-of-evidence considerations would include the factors listed by
the commenter (mechanistic data, dose-response information, route of
administration, and robustness of the data set).  In the context of Test
Note 27, the term “functional or behavioral effects” refers to
“neurological effects” in adult or developing animals [Test Note 27,
i and ii].  It is not practicable, in the context of test notes to part
158, to provide definitions for such terms as “altered” or
“adverse.” The terms are explained in greater detail in the document
referenced below. The Agency provides considerable discussion of these
issues in its published Risk Assessment Guidelines, including those on
Neurotoxicity (EPA/630/R-95/001F; April 1998) at
www.epa.gov/ncea/raf/pdfs/neurotox.pdf .  EPA provides additional
information on the weight-of-evidence approach and DNT in the preamble
to the final rule.

	

COMMENT:	Commenter 49 felt that making DNT testing conditional on
findings from other testing is a futile exercise because no other test
guideline provides information on endpoints relevant to significant
developmental outcomes such as learning disabilities and attention
deficit/hyperactivity disorder.

RESPONSE:   Based on the experience gained with this study, the Agency
stands behind the decision to conditionally require (CR) the DNT study
in the rat (870.6300) for food and nonfood use pesticides.  All
available toxicology data for the pesticide will be considered in the
weight-of-evidence determination of the need for the DNT using the
criteria cited in Test Note 27 on page 12345.  These criteria include
neurological effects seen in adult animal studies as well as
neurobehavioral effects following pre- and postnatal exposure to young
animals.

	  

COMMENT:	Commenter 123 referred to the interim summary table in EDocket
item OPP-2005-0190-0065 and pointed out it lacked a more complete
description of results of DNT tests.  Commenters could determine if the
tests were worthwhile depending on how results affected regulatory
outcomes.  

RESPONSE:  The document cited in this comment, OPP-2005-0190-0065,
included the preliminary findings in a more recent retrospective
analysis of DNT studies.  Since use of DNT studies in risk assessment
was relatively rare prior to the passage of FQPA, an assessment was
conducted to examine the outcomes of submitted DNT studies and to
determine the impact of DNT studies in OPP risk assessment decisions.  

The analysis demonstrated the utility of the DNT study in risk
assessments for pesticide chemicals.  

Results of available DNT studies demonstrated the absence of a single
“most sensitive” parameter, affirming the importance of conducting a
broad assessment of neurobehavioral and neuropathological endpoints,
representing a range of nervous system functions. 

Results also demonstrated the importance of conducting assessments at
multiple time points in offspring.

Sole findings (single effects at the LOAEL) occurred at both early and
late assessments

Treatment-related effects would have been missed by elimination of
either assessment time point

For the currently available chemicals, the early assessment was more
likely to detect a “sole finding” than was the late assessment

Several parameters were rarely identified as effects in offspring at the
LOAEL, although they may have been affected at higher doses;

Two parameters never identified effects at the LOAEL

Clinical signs

Qualitative neuropathological assessment  

Functional observations, as conducted in the DNT study, detected effects
at the LOAEL for only two chemicals

Changes in brain morphometric measures were seen at the LOAEL more
frequently than were changes in brain weight; simultaneous effects in
both these parameters were seen at the LOAEL for only five chemicals
(out of 22 having an effect on at least one of the two).

Mutagenicity	

COMMENT:	Commenter 128 suggested that EPA include studies using the EP
for all the mutagenicity tests (870.5100, 870.5300, 870.5375, 870.5385,
and 870.5395) to provide useful data.

RESPONSE:  It would be cost prohibitive and highly impractical to test
each formulated EP in the required mutagenicity tests.  EPA is mindful
of the burden on the applicant to conduct studies that may not yield
additional useful information.  The Agency will notify the applicant
when additional testing using the EP is required.  EPA is committed to
moving towards a more efficient and reliable testing/risk assessment
paradigm that:  is more attuned to risk assessment needs (i.e.
hypothesis-driven); avoids requesting data not used in risk assessment;
and reduces and refines the use of laboratory animals.

COMMENT:	Commenter 131 suggested OPP limit its data requirements for
genetic toxicity to in vitro studies and called attention to the draft
OECD TG 487 (In Vitro Micronucleus Test).

RESPONSE:  The commenter is directed to § 158.70(d)(2) of the
regulatory text in the proposed rule for the policy regarding OECD
protocols.  EPA will continue to work with OECD to harmonize data
requirements, testing protocols and methodologies.    SEQ CHAPTER \h \r
1 EPA is working closely with 15 other U.S. agencies to advance the
validation and adoption of alternative test methods through the Federal
Interagency Coordinating Committee on Validation of Alternative Methods
(ICCVAM).  As new tests and test batteries are validated, the Agency can
present them to the FIFRA SAP to review their applicability in meeting
regulatory needs and consider them for addition to the Agency’s test
guidelines.

COMMENT:	Commenter 124 asked the following questions about the
mutagenicity testing data requirement in the proposed rule:

(1)  What are the criteria for high or moderately prolonged exposure
that would trigger in vivo testing as part of the initial tier of
studies, if the three in vitro mutagenicity studies are negative, and
these studies are determined to have met the criteria for valid studies?

(2)  Is a second in vivo genotoxicity study (e.g. in vivo hepatocytes
UDS) necessary if the in vitro chromosome aberration study is the only
in vitro test producing a positive response and negative results are
obtained in an adequately conducted in vivo cytogenetics test?

(3)  In the event that the in vitro mammalian-cell gene-mutation assay
produces positive results, which in vivo study(s) does the Agency
consider appropriate?

RESPONSE:   As stated in the preamble to the proposed rule, EPA is
authorized to regulate pesticides under two federal statutes, the
Federal Insecticide, Fungicide, and Rodenticide Act (FIFRA) and the
Federal Food, Drug and Cosmetic Act (FFDCA).  

	EPA considers all food uses of pesticides to be high exposure (see Unit
XI. Toxicology Data Requirements; Subpart F).  For example, the criteria
for exposure-based testing from Toxic Substances Control Act (TSCA)
Section 5, provide examples.  TSCA is just one example of existing
criteria for requiring these types of study.  Accordingly, mutagenicity
testing, including an in vivo bone marrow assay for metaphase analysis
or a  micronucleus assay, is required for all general food and nonfood
use patterns of pesticides (e.g., terrestrial, aquatic, greenhouse,
forestry, and residential outdoor and indoor uses) (see Subpart F
-Toxicology, Table - Toxicology Data Requirements).

	Additional in vivo testing is evaluated on a case-by-case basis to
address uncertainties such as target tissue/organ specificity,
structural-activity relationships (SAR) or species differences in
metabolism or distribution.  On the other hand, if the only concern is
related to a positive result from an in vitro cytogenetic assay
indicating that the effect is secondary to clastogenicity, additional
testing may not be necessary. 

	In general, positive gene mutation assays (either Salmonella or in
vitro mammalian cell gene mutation assays or both) would trigger the
performance of an assay designed to detect the potential of the test
material to reach germ cells and interact with gonadal DNA.  However,
this decision would be influenced by the results from reproductive
toxicity studies, target tissue/organ specificity, structural-activity
relationship (SAR), exposure data, mechanism of action data,
pharmacokinetic and metabolism information, and subchronic and chronic
effects. As indicated by the statements above, the decision to require
additional testing proceeds on a case-by-case basis and takes into
account the overall weight of the evidence for a mutagenic concern.

Acute oral and dermal toxicity	

COMMENT:	Commenters 116 and 128 suggested including testing the EP in
addition to the TGAI to support applications for end-use products and
encouraged a transition to non-animal or in vitro testing as such
testing becomes available and validated.

RESPONSE:  As discussed in the proposed rule, the Agency determined that
studies using the EP provided the most useful data and would require
testing on the diluted form of the EP only if the product met the
conditions under §152.170(b) or §154.7(a)(1).  EPA is mindful of the
burden on the applicant to conduct studies that may not yield additional
useful information. The Agency will notify the applicant when additional
testing using the diluted product is required.  EPA is committed to
moving towards a more efficient and reliable testing/risk assessment
paradigm that:  is more attuned to risk assessment needs (i.e.
hypothesis-driven); avoids requesting data not used in risk assessment;
and reduces and refines the use of laboratory animals.

COMMENT:	Commenter 52 compared the data requirements from the European
Union with those of the U.S.  The EU conditionally requires these
studies; the U.S. requires the studies unless the test material is a gas
or a highly volatile liquid or if the material is corrosive to skin or
has a pH of less than 2 or greater than 11.5.

RESPONSE:  The draft EU requirement is conditional when the applicant
can justify to the satisfaction of the competent authority that Council
Directive 99/45/EEC can be invoked.  The test note to the U.S. data
requirement has three possibilities when the test would not be required.
 There are conditionalities attached to both the U.S. and the EU data
requirements, but only a comparison of the final versions of both data
requirements will supply a definitive answer.

COMMENT:	Commenter 28 pointed out that the asterisk used in current part
158 to designate the EP is needed to support an application under the
formulator’s exemption is missing from the proposed rule.

RESPONSE:   Some commenters were confused by the removal of asterisks in
the proposed rule for the toxicology data requirements table.  By
relocating the formulators’ exemption language to part 152, EPA
believes the consolidation of information in a single location
eliminates the need to consult two different parts in 40 CFR, i.e. parts
152 and 158 for information regarding the formulators’ exemption.  The
relocation rendered the use of asterisks in part 158 unnecessary without
removing the exemption. 

Primary eye irritation, primary dermal irritation, and dermal
sensitization

COMMENT:	Commenters 28 and 112  pointed out that the asterisk used in
current part 158 to designate the EP is needed to support an application
under the formulator’s exemption is missing from the proposed rule. 
They believed this contravention of the formulator’s exemption was not
intentional and requested clarification to ensure that needless testing
would not be conducted.   RESPONSE:  Some commenters were confused by
the removal of asterisks in the proposed rule for the toxicology data
requirements table.  By relocating the formulators’ exemption language
to part 152, EPA believes the consolidation of information in a single
location eliminates the need to consult two different parts in 40 CFR
for information regarding the formulators’ exemption.  The relocation
rendered the use of asterisks in part 158 unnecessary without removing
the exemption. 

	

COMMENT:	Commenter 52 compared the U.S. data requirements with those of
the European Union.  The data requirements are conditionally required
for the EU if the applicant can justify not conducting this study to the
satisfaction of the competent authority; this data is required in the
U.S. but with conditionalities in the test notes.  

RESPONSE:  There are conditionalities attached to both the U.S. and the
EU data requirements, but only a comparison of the final versions of
both data requirements will supply a definitive answer as to the extent
of the differences between the two.

COMMENT:	Commenter 28 wondered if adding a test on the TGAI to support
an end-use application is really necessary or appropriate, especially if
the EP is not produced by an integrated process.  The material coming
into contact with the eye or skin of those handling the formulated
product would not in general be the TGAI alone, but rather the entire
formulated product.  In many cases the “inert” ingredients may have
more of an effect on eye and skin irritation than the “active”
ingredients.  Commenters 125 and 133 believed TGAI data should not be
required to support an EP registration and wondered if the study on the
EP would be used to generate the signal word and precautionary
statements on the label.

RESPONSE:  These are the same data requirements as in the current §
158.340 for the six acute toxicity tests for either a TGAI/MP or EP. 
There has been no change to the data requirements, and there are various
methods of data compensation available to registrants, with the
formulators’ exemption as one example.  The Agency is not requiring
any additional data to be performed on the TGAI/MP in order to register
an EP compared to the current requirement.  It has always been a
requirement that studies be performed on the TGAI for the six acute
toxicity tests as part of the overall registration decision for a new
active ingredient. Any EPs will be considered for registration only
after the Agency makes the TGAI registration decision.  The front panel
of every EP pesticide label is developed from the data on the six acute
toxicity tests (i.e., signal word, hazard precautionary statements).  

COMMENT:  Commenter 128 supported the additional testing but urged
substitution of the acute toxicity battery of tests with validated
non-animal and in vitro tests as they become available while Commenter
131 opposed the expansion of the testing.

RESPONSE:   EPA is committed to moving towards a more efficient and
reliable testing/risk assessment paradigm that:  is more attuned to risk
assessment needs (i.e. hypothesis-driven); avoids requesting data not
used in risk assessment; and reduces and refines the use of laboratory
animals.  

21-day dermal and 90-day dermal

COMMENT:	Commenters 108, 109, and 110 summarized the proposed 21- to
28-day subchronic dermal toxicity test for food uses from CR to R
because of worker risk assessments.  Since not all food use applications
pose worker risk, the requirement will be tailored to the potential for
worker exposure.  If the dermal route is the major route of exposure for
nonfood uses, the 90-day study would be conditionally required instead
of the 21- to 28-day subchronic study.  The latter test would be
insufficient to identify potential hazards.  

RESPONSE:  This is an accurate summary of the proposed changes to the
dermal data requirements for food and nonfood use pesticides.

COMMENT:	Commenters 108, 109, 110, 122 and 125 believed that the food
and nonfood differentiations for these tests are not relevant.  They
also believed the use patterns pertaining to the frequency and duration
of exposure are more relevant than whether the product is applied to a
food or nonfood crop.  They proposed placing these requirements along
with the inhalation toxicity requirements in a separate table based on
occupational and residential use patterns. 

RESPONSE:  The Agency realizes that the categories for toxicology data
requirements are broad but believes they reflect the reality that much
more toxicity data are necessary for evaluating potential widespread
dietary exposure resulting from a food-use pesticide than for exposure
resulting from a nonfood use pesticide.  Therefore, the food and nonfood
use categories best serve the Agency in requiring toxicology data to
support pesticide registration and re-registration. Section 158.500(b)
lists the general use patterns, occupational and residential, under the
food and nonfood use patterns.  EPA proposed an increased number of
major use patterns but many commenters found the increase more confusing
than useful.  

COMMENT:	Commenters 108, 109, 110, 122, 124, 125, 133, and 134
questioned the relevance of a 90-day study when exposures rarely exceed
45 days; considering the low dermal absorption of many active
ingredients, only minimal toxicity is typically seen in repeated dermal
exposure studies.  One of the commenters proposed that the basic
requirement be a conditional 21/28 day dermal study and waive it if the
toxicity endpoint selected for risk assessment is not an endpoint
determinable by the data requirement. 

RESPONSE: The Agency considers the 21/28-day dermal study insufficient
for nonfood use pesticide assessment because higher tiered studies
(i.e., chronic or cancer studies) are generally not required for nonfood
use pesticides.  While 45-day exposures are common, EPA believes that
they are not the maximum duration.  For example, professional
applicators may be subjected to repeated exposures during the 3 months
of peak summer infestations.  Since for many pesticides there is
increased toxicity with increased exposure, professional applicators may
not be adequately protected with 45-day studies.  Existing regulations
provide the flexibility to implement alternative studies, on a
case-by-case basis, as appropriate.  Registrants should consult with the
Agency if there is any question regarding the appropriate duration of
the study.  The highest level of hazard evaluation available for a
nonfood use pesticide is satisfied through a subchronic toxicity test,
i.e., a 90-day repeated exposure to the nonfood pesticide.  Therefore,
the final rule will require the 90-day dermal toxicity study for nonfood
uses. 

COMMENT:	Commenters 108, 109, 110, and 124 suggested that the
requirement be based on the Tier 1 risk assessment.  If dermal exposure
is low, additional studies and data requirements would not be warranted;
dermal studies for EPs should only be required if the attributes of the
“additives” are known or the attributes are known vehicles for
enhanced dermal penetration.  

RESPONSE:  In cases where the potential for dermal exposure is very
limited, in terms of the frequency, magnitude and/or duration of
exposure, the registrant may request a data waiver and perhaps a shorter
duration study could meet this requirement.  Applicants are encouraged
to discuss the request with the Agency before developing and submitting
supporting data, information or other materials.

COMMENT:	Commenters 124, 125, 133, and 134 wondered what the criteria
were for testing on the EP due to toxic effects or increased dermal
absorption.  One commenter requested additional guidance to define
co-formulants and their contents in the EP that are likely to increase
dermal absorption of the active ingredient.  Another commenter suggested
global harmonization of the guideline was highly desirable based on past
experience.

RESPONSE:  Test note 11 (page 12345) explains that a dermal study may be
conditionally required for an end-use product (EP) if the product, or
any component in it, could lead to potentially toxic effects to the user
(handler, applicator, etc.) or if the other components of the product
could increase dermal absorption of the active ingredient.  The
determination whether such a study would be required is the
responsibility of the manufacturer in consultation with the Agency.  
EPA will continue to work with Canada and the European Union through
OECD to harmonize data requirements, testing protocols and methodologies
and to promote work-sharing opportunities.  EPA provides additional
guidance to fulfill unique U.S. regulatory requirements.

COMMENT:	Commenter 128 recommended that the 90-day dermal study be
extended to R for food and nonfood uses since worker exposure must be
evaluated in both cases.  

RESPONSE:  Since the data requirements for a food use pesticide are
generally more extensive than for a nonfood use pesticide, the 21-day
dermal study is adequate for food use because higher tiered toxicity
studies are routinely received.  The Agency simply needs to determine
whether the dermal route of exposure reveals a different toxicity
profile than the oral route.  The Agency believes 21 days is sufficient
to confirm that unforeseen toxic effects are not expressed via the
dermal route of exposure.

COMMENT:	Commenter 134 recommended accepting the 90-day oral study plus
a dermal penetration study to satisfy the requirement for a 90-day
dermal toxicity study, especially in light of the 21/28-day dermal
requirement.

RESPONSE:   A dermal penetration study in addition to a 90-day oral
study could be acceptable in appropriate cases to support waiving the
90-day dermal study requirement for a nonfood use pesticide.  As
previously stated, part 158 is designed to be flexible and data waivers
will be considered on a case-by-case basis for a pesticide.  The
decision to grant a waiver is based on consideration of the use pattern,
exposure pattern, chemical characteristics, etc.

Carcinogenicity

COMMENT:	Commenter 23 advocated adding more studies, especially
long-term ones, to protect the public from cancer.  Commenter 128
suggested including additional studies using the EP to provide useful
data.

RESPONSE:  EPA requires long-term carcinogenicity studies for all food
use pesticides and other pesticides if the use pattern indicates
significant exposure.  It would be cost prohibitive and highly
impractical to test each formulated EP in the required mutagenicity
tests.  The Agency will notify the applicant when additional testing
using the EP is required.  EPA is committed to moving towards a more
efficient and reliable testing/risk assessment paradigm that:  is more
attuned to risk assessment needs (i.e. hypothesis-driven); avoids
requesting data not used in risk assessment; and reduces and refines the
use of laboratory animals. 

 

COMMENT:	Commenter 52 compared U.S. data requirements with those of the
European Union and pointed out that the latter requires toxicokinetic
data while the U.S. does not.  The EU also allows the use of transgenic
animals as a second rodent species.

RESPONSE:  EPA is aware that toxicokinetic data is useful for dose
selection in long-term studies and the Agency currently uses such data
when available.  Currently, transgenic animals are not required in
Agency testing.  However, if studies using transgenic animals were
submitted, they would be considered along with the standard studies.

COMMENT:  Commenter 82 wondered why the durations in Test Note 19 for
the chronic rodent feeding study (food use) and the chronic rodent
feeding study (nonfood) are different for the same endpoint.

RESPONSE:  Test Note 19 refers to the case when, for a food use, the
registrant opts to combine the required chronic oral toxicity study with
the required carcinogenicity study to simultaneously fulfill the
requirements for both (870.4300).  In this case, the study duration for
the combined chronic oral/carcinogenicity study would be 24 months.   

COMMENT:  Commenter 82 did not find it easy to discern from the test
notes that accompany the table in Section 158.500 what conditions are
needed to trigger cancer studies for non-food uses.  

RESPONSE:  The conditions needed to trigger the requirement of a cancer
study for a non-food use are described in Test Note 20.  The difference
in the study duration for the chronic oral toxicity study conducted for
a food versus nonfood use are due to the difference in typical exposure
pattern for these uses (i.e. exposure resulting from a food use is
expected to be possible over the span of a lifetime while exposure
resulting from a non-food food use is expected to be of a lesser
duration).

COMMENT:  Commenter 124 thought “Oncogenicity” should be retained
instead of changing the data requirement name to “Carcinogenicity”
because the former refers to benign and malignant tumors while the
latter refers only to malignant tumors—and the EPA guidelines are
designed to detect both types of tumors.

RESPONSE:   The name change for the data requirement from
“Oncogenicity” to “Carcinogenicity,” reflects a harmonization
effort with other Agency carcinogenicity documents (e.g., the new
Guidelines for Carcinogen Risk Assessment; EPA/630/P-03/001F; March
2005).

The title of test guideline 870.4200 is “Carcinogenicity.” 
Additionally, the term carcinogenicity is associated with animal testing
as opposed to the human condition.  Although the guideline title change
from "Oncogenicity" to "Carcinogenicity" might lead to the assumption
that only cancerous tumors are being evaluated, it is clear from the
discussion within the guideline that the Agency will evaluate both
benign and malignant tumors in their review.

COMMENT:  Commenter 131, citing from the literature, contended that
results indicated that rodent carcinogenicity assays are much less
reproducible than previously expected and have serious limitations.

RESPONSE:   EPA is participating in efforts by ILSI/HESI, ICCVAM, and
the FDA to improve and refine cancer studies.  In the interim, the
Agency will continue to use them in cancer consideration until more
refined studies are validated for use.  Data from these cancer studies
have other applications.  The two-year study in the rat is a combined
cancer and chronic study that provides critical non-cancer data
applicable to regulatory end-point selection, especially the chronic
reference dose.  The cancer study in the mouse also provides non-cancer
toxicity data that is useful in hazard characterization and some
end-point selection.

Reproduction and fertility effects

COMMENT:	Commenters 48, 125, and 133 requested clarification that the
study will be required for an active ingredient used to formulate
products with significant human exposure through food use. 

RESPONSE:  The proposed requirement of a reproduction study for nonfood
use pesticides would be based on a weight-of-evidence consideration of
the toxicology data and potential exposure in terms of the frequency,
magnitude and/or duration.  This is an exposure-based data requirement
and may not always be necessary.

	OPP is currently working with EPA's National Center for Computational
Toxicology (NCCT) to populate a Toxicological Reference Database
(ToxRef). The current priority is to populate ToxRef with data from the
rat 2-generation reproductive study, prenatal toxicity, and systemic
toxicity studies on hundreds of pesticides that represent different
classes, modes of action, and toxicity profiles. EPA will use this
relational database to determine the value of endpoints currently
evaluated in risk assessment (i.e., the F1 versus F2 responses).

COMMENT:	Commenter 52 compared U.S. data requirements with those of the
European Union.  The EU is now proposing to require measurement of TGAI
or metabolites in milk while the U.S. does not.

RESPONSE:  EPA does use toxicokinetic data when it is available. 
Although it is not routinely required, the Agency will ask for this data
on a case-by-case basis.  The Agency does not currently require TGAI or
metabolite data in milk.  However, this is an option in the
developmental neurotoxicity study protocol to confirm adequate dosing of
the pups.

COMMENT:	Commenters 125 and 133 wondered if there were any studies that
are predictive or structural relationships that may be indicative of
reproductive effects.  They also wondered whether “constant-release
aerosols” were total release foggers or metered release aerosols.

RESPONSE:   The examples cited in the preamble on page 12297 (section XI
C 3 v) represent types of nonfood use pesticides which require
reproduction studies based on exposure.  The term “constant release
aerosols” refers to those pesticides formulated for uses that may
result in repeated exposure over several months (e.g., metered release
aerosols).

COMMENT:	Commenters 125 and 133 noticed the study in the table is not
indicated to be a two-generation study, as it appears in the current
part 158 table.

RESPONSE:   The text in the Data Requirements column of the Toxicology
Data Requirements table on page 12343 will be revised for 870.3800 to
read “Reproduction and Fertility Effects.”  This change will reflect
the test guideline, which is for a two-generation reproduction study.

Scheduled-controlled operant behavior, Peripheral nerve function, and
Neurophysiology – Sensory evoked potentials

COMMENT:	Commenters 113, 124, 125, 133 and 134 felt the inclusion of
three specialized studies (Scheduled-Controlled Operant Behavior –
Guideline 870.6500, Peripheral Nerve Function – Guideline 870.6850,
and Neurophysiology-Sensory Evoked Potentials – Guideline 870.6855)
was premature.  They questioned whether these studies had undergone
inter-laboratory validation and recommended that EPA provide specific
and scientifically-justifiable triggers for any of the studies. 
Commenter 133 wondered if this testing would be commonly required.

RESPONSE:  EPA agrees that these three studies have not undergone
inter-laboratory validation. EPA discovered upon review that these
studies were seldom required during the Reregistration process and were
therefore not likely to be required often in the future.  Thus the
Agency has determined that these studies could be removed from the
toxicology data requirements table of commonly required studies in part
158.  If the need ever arises in the future, the Agency may require any
of these studies on a case-by-case basis since there are validated OPPTS
guidelines in place.

COMMENT:   Commenter 128 suggested including studies using the EP to
provide useful data.

RESPONSE:    It would be cost prohibitive and highly impractical to test
each formulated EP. EPA is mindful of the burden on the applicant to
conduct studies which may not yield additional useful information. The
Agency will notify the applicant when additional testing using the EP is
required.  EPA is committed to moving towards a more efficient and
reliable testing/risk assessment paradigm that: is more attuned to risk
assessment needs (i.e. hypothesis-driven); avoids requesting data not
used in risk assessment; and reduces and refines the use of laboratory
animals.

Dermal penetration

COMMENT:   Commenters 120 and 124 wondered why EPA did not incorporate
the best available science in its OPPTS harmonized test guideline
(870.7600).  They observed the OECD test guideline for in vitro testing
has been developed. 

RESPONSE:  OPP does not currently accept in vitro dermal penetration
studies since this methodology has not yet been validated as a
replacement for in vivo dermal penetration studies.  Currently the
Agency prefers to have chemical-specific dermal absorption study data
for risk assessment.  However, in the absence of chemical-specific
dermal absorption data, it is possible that a value for risk assessment
could be calculated from available oral and dermal studies.  Once the in
vitro dermal penetration methodology has been validated, OPP will accept
this as an alternative to in vivo dermal penetration studies.

COMMENT:  Commenters 52 and 124 requested clarification of Test Note 34.

RESPONSE:  Test Note no. 34 in the Toxicology Data Requirements table on
page 12345 has been revised for further clarification.  The revised
note, now re-numbered as Test Note 35, reads as follows:  “A risk
assessment, assuming that dermal absorption is equal to oral absorption,
must be performed to determine if the study is required, and to identify
the doses and duration of exposure for which dermal absorption is to be
quantified.”  This risk assessment should consider all available oral
studies.  If this “worst case” assessment indicates that there is no
risk concern, then the study would not be required.

COMMENT:   Commenter 128 suggested including studies using the EP to
provide useful data.

RESPONSE:    It would be cost prohibitive and highly impractical to test
each formulated EP.  EPA is mindful of the burden on the applicant to
conduct studies which may not yield additional useful information.  The
Agency will notify the applicant when additional testing using the EP is
required.  EPA is committed to moving towards a more efficient and
reliable testing/risk assessment paradigm that: is more attuned to risk
assessment needs (i.e. hypothesis-driven); avoids requesting data not
used in risk assessment; and reduces and refines the use of laboratory
animals.

Metabolism and pharmacokinetics

COMMENT:  Commenter 52 requested clarification whether Test Note 32
applies to both food and nonfood use or only to nonfood use.

RESPONSE:  The test notes included in the Toxicology Data Requirements
table on page 12343-12344 are applicable to those data requirements
which are required (R) and those which are conditionally required (CR). 
For example, in the case of guideline 870.7485, Test Note 32 would be
applicable to both the nonfood use as well as to the food use.  In the
case of the food use, this study would be required. In the case of the
nonfood use, this study requirement would only be considered if the
long-term studies had been required.  Additionally, as stated in the
Test Note, it may be required if significant adverse effects are seen in
other studies which could be elucidated by these studies.

Companion animal safety

COMMENT:   Commenter 128 suggested including studies using the EP to
provide useful data.

RESPONSE:    It would be cost prohibitive and highly impractical to test
each formulated EP. EPA is mindful of the burden on the applicant to
conduct studies which may not yield additional useful information.  The
Agency will notify the applicant when additional testing using the EP is
required.  EPA is committed to moving towards a more efficient and
reliable testing/risk assessment paradigm that: is more attuned to risk
assessment needs (i.e. hypothesis-driven); avoids requesting data not
used in risk assessment; and reduces and refines the use of laboratory
animals.

Non-rodent chronic studies (one-year dog study)

	EPA currently requires a 90-day dog study and a one-year dog study for
all food and nonfood uses to fulfill the non-rodent data requirements. 
EPA referenced published literature that suggested that the one-year dog
study may not be necessary.  Based on analysis of a large body of
one-year dog studies in its toxicology database, EPA proposed to
eliminate the one-year dog study but retain the 90-day study.  EPA
solicited review and comment by the FIFRA SAP on the results of the
preliminary analysis for RfD derivation on May 5-6, 2005.

COMMENT:	Ten commenters addressed the elimination of the one-year dog
study.  Commenter 52, in comparing European Union and U.S. data
requirements, indicated the EU requires a one-year dog study but not a
90-day study; the commenter also correctly pointed out that the one-year
study should be considered a subchronic study since 1 year does not
cover the majority of the lifespan of the species.  The EU also requires
toxicokinetic and mechanistic data, which the U.S. does not.  Commenters
113, 124, 125, 130, 131, 133, and 134 strongly supported elimination of
the one-year dog study.  

RESPONSE:	The FIFRA SAP reviewed the Agency’s retrospective analysis
of the toxicity studies and encouraged the Agency to continue its
analyses with a larger database.  The FIFRA SAP made the following
recommendations:  (1) increase the robustness of data analysis by
including dog study datasets that were not used for the RfD
determination; (2) conduct an analysis more representative of a
prospective comparison through delineating the 13-week No Observed
Adverse Effect Levels (NOAELs) and Lowest Observed Adverse Effect Levels
(LOAELs) independent of the one-year study and establish data review
criteria; (3) consider data analysis for separate classes of pesticides;
(4) include additional background information on RfD that provides
better perspectives for reviewing the Agency position paper; and (5)
revise the title of the Agency position paper to reflect the purpose of
the data analysis.  The FIFRA SAP specified that “if the results of
the analyses continue to indicate little added value from the one-year
studies, the Agency could move toward eliminating them on a stronger
basis.”

EPA has completed a more extensive analysis of dog toxicity studies on
110 chemicals representing over 50 different classes of pesticides
(USEPA 2006).  EPA concluded from this analysis that extending a dog
toxicity study beyond a thirteen-week duration does not provide
additional essential toxicity information and eliminating the one-year
dog toxicity study does not compromise the data needed for the
determination of chronic RfDs and margins of exposure (MOE).  Thus,
reliance on the required chronic rodent studies, two-generation rat
reproductive study, and the thirteen-week dog toxicity study is
generally expected to provide an adequate basis for chronic RfD
derivation in pesticide risk assessment.  

	EPA acknowledges that there may be situations where a longer duration
dog toxicity study may be warranted when a pesticide chemical is highly
bioaccumulating (e.g. builds up in body fat) and is eliminated so slowly
that it does not achieve steady state or sufficient tissue
concentrations to elicit an effect during a 90-day study.  EPA
anticipates that this situation will be infrequent since current
pesticides are not usually designed to be highly persistent and
bioaccumulating.  If such a chemical is encountered, EP would require
the appropriate tier 2 metabolism and pharmacokinetic studies to more
precisely evaluate bioavailability, half life, and steady state and
determine if a longer duration dog toxicity study is needed.

Endocrine disruptors

COMMENT:	Commenters 116, 119, and 128 introduced the Endocrine Disruptor
Screening Program (EDSP) in the context of the thyroid testing protocols
(p. 12296).  They acknowledged that developing protocols to screen
endocrine disruptors has taken more time than initially expected and
that the required testing cannot yet be specified.  Nevertheless,
Commenter 119 felt EPA should include endocrine disruptor effects
testing in the data requirements to allow registrants to plan for the
future and EPA could avoid another rulemaking by doing this.  This
commenter also recommended EPA consider requiring registrants to conduct
the testing.  Commenter 128 expressed concerns about the activity of
endocrine disrupting chemicals at concentrations far below those being
tested in toxicity studies and referenced several studies from the
literature.  

RESPONSE:  EPA does not agree with the recommendation to include a data
requirement for endocrine disruptor screening in the final part 158
rule.  As the comment notes, because of the state of scientific
understanding of endocrine disruptor testing, such a provision would
need to indicate that currently such testing is "not required," except
on a case by case basis.  In fact, EPA is still working to identify and
validate appropriate assays to include in an endocrine disruptor
screening battery
(www.epa.gov/scipoly/oscpendo/pubs/assayvalidation/index.htm).  Thus, a
"requirement" for endocrine disruptor testing in the final rule would
not only fail to identify any criteria for requiring endocrine disruptor
testing, but also could not specify the types of studies that might
potentially be required.  Such a "requirement" would provide no
meaningful guidance for pesticide applicants or registrants.  Since EPA
in general intended its proposed and final versions of part 158 to
codify current data requirements, the Agency has decided not to accept
the commenter's recommendation.

	EPA, however, does agree with the comment that pesticide companies, not
EPA, should conduct any studies required by the endocrine disruptor
screening program.  Accordingly, EPA notes that, when the endocrine
disruptor program reaches the stage of full implementation, the Agency
will use its authority to impose testing requirements on pesticide
companies and others who produce pesticide chemicals to generate data to
assess endocrine disrupting effects.  There is no need to modify the
proposed rule to reflect this position.

B.	Test Guidelines Under Development

	EPA listed six studies for which guidelines are under development; they
may be required on a case-by-case basis to support the registration of
particular pesticide products.  As the Agency’s experience with these
studies increases and if the studies are imposed with regularity, EPA
may propose to include them in future revisions to part 158.  

COMMENT:	Commenters 133 and 125 pointed out a mistake in the wording of
one of the studies listed:  direct dosing of neonates prior to weaning
for exposure through the maternal route.  This mistake led to some
confusion.  Both commenters had technical and cost concerns with the
wording as it was proposed and pointed out that neonates were already
exposed through the maternal route in the two-generation reproduction
and chronic feeding studies.

RESPONSE:  EPA agrees that the wording should read:  “direct dosing of
neonates prior to weaning rather than exposure through the maternal
route.”  Neonates are routinely exposed through the maternal route (as
opposed to directly dosed) in the current guidelines for developmental
and reproduction studies.

COMMENT:	Commenter 48 said it seemed reasonable to request additional
studies where the results might help assess safe exposure levels but be
individually designed to answer the necessary end-points.  They should
not be routinely required but when knowledge has advanced, a guideline
for these studies would then be appropriate. 

RESPONSE:  EPA appreciates this comment on the circumstances under which
such data should be required and will integrate these comments in the
Agency’s continuing discussions on other testing paradigms that may
lead to guideline revisions.

C.	Alternative Testing Paradigms

ILSI/HESI and the ACSA testing paradigm

COMMENT:  Eleven commenters commented on the tiered-testing approach
discussed in the preamble to the proposed rule.  Six commenters
(Commenters 83, 86, 87, 88, 101, and 104) commented on the Health and
Environmental Sciences Institute (HESI)/International Life Sciences
Institute (ILSI) project, “Agricultural Chemical Safety Assessment
(ACSA): a Tiered Approach” and urged EPA to consider the
tiered-testing approach.

Five commenters (120, 124, 128, 130/131, and 134) also suggested that
EPA incorporate the ACSA into the final rule.  Commenter 120 pointed out
that the use of structure-activity relationships (SAR) and predictive
modeling has developed exponentially over the last decade and that
modeling for nontarget organisms and environmental exposure should be
incorporated whenever possible.  Commenter 124 commended EPA for its
significant participation in ACSA and felt that a number of the concepts
developed in ACSA were ripe for incorporation into pesticide testing
requirements at this time and thus requested a delay in finalizing the
rule to allow this to happen.  Commenter 128 called for termination of
EPA’s role in ACSA because of an absence of public interest
representation in the ACSA project; this commenter also asked for
“transparency that has formed the focus for discussion on the
Scientific Advisory Panels (SAP) and Pesticide Policy Dialogue Committee
(PPDC).”  Commenter 130/131 felt that a number of ACSA recommendations
could be incorporated into part 158 to eliminate wasteful redundancies. 
Commenter 134 also recommended incorporation of the ACSA paradigm; this
commenter also offered more detailed comments on toxicity studies.

RESPONSE:  ACSA represents the first comprehensive effort to
scientifically redesign the toxicology animal-testing framework for
agricultural chemicals. The ACSA proposal is consistent with EPA's
direction and goals to develop a more efficient and reliable testing
paradigm. Under the ACSA scheme, some studies would be eliminated while
endpoint coverage would be increased in redesigned studies based on
responses observed in a core set of toxicity tests. The value of the
scheme is that animals are more fully utilized and the need for some
tests can be eliminated if the core set of tests or existing knowledge
does not indicate a concern. Decisions on next steps must be made
throughout the course of the study as a thorough evaluation of all
available information, including data on the pharmacokinetics and mode
of action of the pesticide (if such data exist), could lead to different
conclusions regarding the appropriate way to approach testing.

EPA has multiple activities underway to address the remaining science
and policy issues associated with the ASCA proposal.  One essential step
towards adopting the ASCA proposal will be conducting retrospective and
prospective data analyses to determine whether this new testing paradigm
will meet EPA's risk assessment needs as defined by statute.  To this
end, the Office of Pesticide Programs is currently working with EPA's
National Center for Computational Toxicology (NCCT) to populate a
Toxicological Reference Database (ToxRef). The current priority is to
populate ToxRef with data from the rat 2-generation reproductive study,
prenatal toxicity, and systemic toxicity studies on hundreds of
pesticides that represent different classes, modes of action, and
toxicity profiles. EPA will use this relational database to determine
the value of endpoints currently evaluated in risk assessment (i.e., the
F1 versus F2 responses). This analysis will provide scientific support
for EPA's adoption of the proposal as the analysis will subject the ASCA
proposal to a much broader set of chemicals than that used to develop
the proposal. 	

Another critical step is gaining scientific consensus on the triggers
(i.e., the points at which a concern is indicated and a higher level of
testing is needed). The retrospective analyses will also be used to
refine or confirm the ASCA proposed triggers for test decisions.  Once
the analysis is complete, EPA will be able to complete draft guidance on
testing.  The analyses and guidance are planned to be subject to SAP
review and public comment in 2008. 

Another essential step is testing how the ASCA scheme works in practice.
There are plans to conduct several case studies using the ASCA tiered
testing proposal.  From these case studies, EPA will be able to assess
the laboratory testing feasibility of such a complex study and to
evaluate the ability of the approach and its parameters to characterize
known toxicants and address risk assessment needs. Based on early
scientific reviews, EPA scientists are already working on improvement of
the ASCA tiered testing approach.  EPA will consider the results of the
SAP review of the retrospective analyses and draft guidance, issues
raised by stakeholders, and the case studies, in determining what
revisions to current data requirements and testing guidelines may be
appropriate.  As the science issues are adequately vetted and crucial
questions resolved, EPA intends to promulgate the appropriate regulatory
changes on a timely basis.  In the meantime, the existing regulations
provide flexibility to implement any updated, new or novel testing
schemes, on a case-by-case basis, as appropriate, until the changes are
codified.  Case-by-case determinations would be made in consultations
with the Agency without the necessity of the waiver process.  It should
be noted that ACSA is only one proposal that EPA will consider in
improving the risk assessment process of environmental chemicals. 

	Other relevant activities to consider include the  National Academy of
Sciences (NAS) recommendations on Toxicity Testing and Assessment of
Environmental Agents (expected in 2007; Project ID BEST-U-03-08-A),
OECD’s Integrated Approach to Testing and Assessment, as well as
predictive toxicity tools (QSAR, “-omics,” etc.) developed by
EPA’s Office of Research and Development’s (ORD) Computational
Toxicology Program (www.epa.gov/comptox). 

	Before considering regulatory changes to reflect the results of
EPA’s consideration of ACSA, NAS, and other recommendations, the
Agency will develop scientific position papers on the new approach and
recommendations for internal and external review; the latter includes
review by the FIFRA Science Advisory Panel and opportunities for public
comment.  External peer review and acceptability by other national and
international regulatory authorities are crucial before implementation
of any new testing paradigm and data requirements. Harmonization with
the data requirements of these same authorities is also an important
factor.  Other countries currently require studies that were omitted in
ACSA; this could pose significant problems for registrants if a
harmonized approach is not adopted world-wide.  The proposed rule was
concerned with codifying the data requirements in 40 CFR part 158.  Data
requirements identify the kinds of questions registrants must address
about the potential hazards and levels of exposure.  Test guidelines
describe test methods that may be used to perform a study to answer the
questions the registrants must address.  Test guidelines are developed
and updated during a process separate from updating data requirements. 
Therefore, the commenters’ suggested changes to test guidelines will
be forwarded to the respective divisions for review.  Any possible
changes in test guidelines will be presented to the FIFRA SAP and open
to public comment before adoption. 

	At the PPDC meeting held November 8-9, 2006, the EPA/PPDC Alternative
Testing Project reported on the adoption of non-animal methods to
replace the Draize methods for acute eye and skin irritation for
antimicrobial cleaning projects only.  The purpose of the project is to
allow EPA reviewers to make Toxicity Category and Product Labeling
decisions based on these alternative assays.  Eight companies have
submitted data and will assist the project in various ways.  The
Background Review Document is expected to be submitted to ICCVAM in
Spring 2007 with EPA consideration of the Interim Science Policy for
non-animal assays in Summer/Fall 2007.

		

Discussion of Comments on Ecological Effects Data Requirements (Subpart
G)

A.  Terrestrial Wildlife

1.  Acute Oral Toxicity Test with a Passerine Species

The Agency proposed a requirement for an additional avian acute oral
toxicity study.  The second acute oral study is to be conducted on a
passerine species (i.e. red-winged blackbird) as a requirement to
support all outdoor uses, including residential outdoor uses.  The other
avian acute oral study is to be conducted on either the mallard duck or
the bobwhite quail, which has been standard policy.  This revision of
the avian acute toxicity data requirement elicited a significant number
of comments, as compared to comments about other proposed changes in the
data requirements for terrestrial organisms.  The comments not only
concerned the addition of a passerine species to the avian acute oral
data requirement, but also test note number 4 which specifically named
the red-winged blackbird (Agelaius phoeniceus) as the preferred
passerine species. 

COMMENT   Four commenters (# 112,  # 113, # 120  and # 125) questioned
the need for another avian acute oral toxicity study, as the accepted
policy has historically been to require only one avian acute oral study.
 Commenters #113 and # 146 also indicated that there was confusion about
the addition of the passerine test, and interpreted the requirement as
either testing three species or requiring a passerine test in lieu of
the commonly required bobwhite or mallard tests.

RESPONSE   The Agency has always required testing on either bobwhite or
mallard (one species is required for LD50 testing).  The new requirement
calls for testing on either bobwhite or mallard plus the passerine.  
There has been no proposal for requiring testing for three species.   
SEQ CHAPTER \h \r 1 The Agency, in 1993, consulted the Science Advisory
Panel (SAP) on the subject of acute toxicity testing of birds.  The SAP
indicated that the lack of testing of passerines represented a
potentially significant data gap.

COMMENT   One commenter (#128) stated that two bird species should
always be tested for acute oral effects and expanded to 3 species for
compounds with acute oral LD50s of 500 mg/kg or less.

RESPONSE   The Agency can see the utility for expanding the number of
tests to three species to address uncertainty about intraspecies
sensitivity.  However, the Agency believes that such an expansion should
be based on the results of appropriate ecological risk assessment
results and any need for addressing uncertainties that limit risk
management decision-making.  The Agency is keeping the number of tested
species for the avian acute oral data requirement to two species in this
rulemaking.

COMMENT   Three commenters (#122, # 113,  #112) requested that the
Agency consider other passerine species and provide a list of
recommended species to the regulatory community.  One concern raised by
two commenters (#142 and #112) was the protection of the red-winged
blackbird under the Migratory Bird Treaty Act and the requirement to
obtain permits from the FWS to collect live red-winged blackbirds. 
Additionally commenter142 indicated that state agencies may also require
state permits in addition to the federal ones.  Their research
experience showed that the permit issue caused significant logistical
problems.

COMMENT   Commenter 142 also cited human health and ethical reasons for
not using the red-winged blackbird in a laboratory setting.  The human
health issue relates to the possible transmission of avian-borne
diseases from wild-caught birds to their lab-reared birds and to the
people who must handle the birds on a daily basis.  They recommend that
commercially available species as the zebra finch be used for passerine
tests, and the tests should be designed on a case-by-case basis.

COMMENT   Commenters #124 and #137 also asked for increased flexibility
in their choice of the test species, by citing the difficulty in
obtaining sufficient numbers of the birds for a toxicity study and the
difficulty in maintaining this species in a laboratory facility.  Both
commenters cited the USGS Breeding Bird Survey,
http://www.mbr.pwrc.usgs.gov/bbs/htm03/trn2003/tr04980.htm which
presents data that populations are declining in North America.  Both
commenters stated that they preferred that the Agency continue its
policy of extrapolating the data from the mallard and bobwhite acute
studies to passerine species in its risk assessments.  They both
continued that wild species should only serve as laboratory test animals
“when absolutely necessary”, when extrapolation does not
significantly reduce uncertainty.  Commenter #124 proposed an alternate
version of proposed test note 4:

Data are preferred on mallard or bobwhite quail for all uses. 
Additional species may be tested on a case by case basis to reduce
uncertainty about the toxicity of the chemical to wild species.

RESPONSE   The Agency selected the red-winged blackbird as a test
species because of (1) its prevalence in agroecosystems, (2) its
demonstrated use in avian toxicity testing with pesticides, and (3) the
availability of an existing data set to compare its sensitivity with
other species and provide a starting database for comparison of toxicity
across pesticides.  The guidelines will be modified to include the need
for a passerine species, with the red-winged blackbird listed as one of
the preferred species, rather than an explicit requirement for
red-winged blackbird testing.  Therefore, if the red-wing blackbird is
not available, a different species is to be proposed for use.  The
Agency will revisit the issue of an acceptable species list with this
goal in mind.  Testing protocols may list other species upon
reconsideration of this issue.

The Agency’s risk assessment process makes use of the most sensitive
species tested.  In addition, refinements of the risk assessment may
also consider the distribution of interspecies sensitivity.  More than
one tested species allows for consideration of interspecies sensitivity
and testing of a passerine addresses concerns that broad, untested avian
taxa may be more sensitive that previously required mallards and
bobwhites.

COMMENT   The Agency received two comments that the requirement for an
acute toxicity test with a passerine species should be based on the
results of the acute oral data from the mallard or the bobwhite,
whichever was tested.  One commenter (#113) stated their position that
an additional test with a passerine species could be justified if the
test substance were significantly toxic to either of the other test
species; but the requirement should be conditional at most. 
Alternatively, the other commenter (#82) stated that the passerine study
may not be needed if the test substance were practically non-toxic to
the other test species.  This second commenter also recognized that
passerines are frequently more sensitive than the bobwhite and mallard,
and stated that they could support the requirement for outdoor use.  The
requirement could be aligned with the toxicity level from the acute
study with either bobwhite or mallard.  (They proposed an LD50 range of
<500 to 1000 mg/kg-bw).

RESPONSE   The Agency acknowledges that passerines can often be more
sensitive than the mallard or bobwhite and so has not established
conditions for requiring the testing on the basis of toxicity in either
mallards or bobwhite.  As noted previously, currently testing occurs on
either bobwhite or mallard (one species is required for LD50 testing). 
The new proposal requires testing on either bobwhite or mallard and the
passerine (two species are required for testing).  There has been no
proposal for requiring testing for three species. 

COMMENT   Two commenters (# 125, # 133) asked what data the Agency used
to support the contention that passerine species are less tolerant to
pesticides than larger species.  They also asked what data the Agency
will gain from the passerine test.

RESPONSE  The Agency’s concern is not necessarily that passerines are
more sensitive than larger species, but that passerines represent a
large number of North American species and, when tested, have proven to
be often, though not exclusively, more sensitive than non-passerines. 
The Agency, in 1993, consulted the SAP on the subject of acute toxicity
testing of birds.  The SAP indicated that the lack of testing of
passerines represented a potentially significant data gap.

Schafer and Brunton (1979) published a summary of comparisons between
species.  In ranking the LD50 values for six species tested (4
Passeriformes, 1 Columbiformes, and 1 Galliformes) with 36 pesticides,
the red-winged blackbird was often the most sensitive species tested. 
For the average LD50 over all chemicals tested, red-winged blackbird was
the most sensitive of the species tested.  Reviewing the available
literature and their own test results, the authors concluded that
sufficient data exist to suggest that mallards and bobwhite quail are
poor indicators of acute and subacute sensitivity and are poor
indicators of the sensitivity of most North American bird species.   

In comparing the results of individual species (3 Passeriformes, 4
Galliformes, and 1 Anseriformes) testing with extrapolated lower bound
limits to intraspecies sensitivity distributions for up to 67 chemicals,
the red-winged blackbird acute effects endpoints more consistently were
ranked near the 5th percentile than any other species tested.

Schafer, E.W. and R.B Brunton.  1979.  Indicator species for toxicity
determinations: Is the Technique usable in test method Development?  In:
Vertebrate Pest Control and Management Materials, ASTM STP 680, J.R.
Beck, Ed., ASTM, 1979, pp. 157-168

Mineau, P., A. Baril, B.T. Collins, J. Duffe, G. Joerman, and R. Luttik.
 2001.  Pesticide acute toxicity reference values for birds.  Rev.
Environ. Contam. Toxicol.  170:13-74. 

COMMENT  The Agency also received a series of comments from the EU (#56)
about the passerine data requirement.   The EU stated that assurance
that EPA will not base a risk assessment on a single species which might
be more sensitive or less sensitive as compared to other species is not
sufficient reason to require this additional test.  They contended that
the use of scientifically sound extrapolation factors in the risk
assessment process can account for this type of uncertainty.

RESPONSE   The Agency agrees that it should consider scientifically
valid extrapolation factors, where data are available to support their
development.  However, given the extremely limited number of species
usually tested within given taxonomic groups, the total lack of test
data in other taxonomic groups, and the recognition that such data
limitations are further compounded by the likelihood that extrapolations
are unstable across pesticide mechanisms of action, the Agency is
concerned that existing data may only be suitable for establishing
extremely conservative extrapolations at the screening level.  The
Agency believes that adding the passerine test to its suite of avian
toxicity studies will provide a more robust risk assessment than using
conservative extrapolation factors.  Additional testing in the future
will serve as a basis for a scientifically more robust evaluation of
potential extrapolation factors. 

Four additional comments submitted by the EU and the Agency responses to
each comment are:

COMMENT 1.  Delete additional passerine test and use a science-based
assessment factor.

RESPONSE   In 1996 the SAP recommended inclusion of passerine species
because of the recognition that such birds may be more sensitive than
other tested species. Though passerines have been shown to be more
sensitive than other tested species, the sensitivity relationship is
variable across pesticides.  To date, OPP does not have a
screening-level assessment factor to account for this uncertainty.  The
subsequent issue is, if application of some generic uncertainty factor
were applied and screening risk assessments “fail”, what additional
course of refinement on the effects is possible without additional data?

COMMENT 2. Testing on a passerine species (i.e., redwing blackbird)
from a world wide perspective is a strange species to choose as it is
only found in northern America and difficult to raise in captivity.

RESPONSE   The red-winged blackbird is found in a variety of North
American agroecosystems, and there exists background toxicity data for a
variety of pesticides.  This allows for any comparisons with existing
tested pesticides (if needed) and allows for an ecologically relevant
risk assessment effects endpoint for the area in which most Agency
pesticide risk assessments are conducted.  However, the Agency is open
to consideration of additional passerine species as alternatives to the
red-winged blackbird.

COMMENT 3. The document is not clear how much additional avian
effects’ testing is needed.

RESPONSE   The preamble in the final rule clarifies issues raised by
several commenters regarding other avian testing requirements, such as
the reproduction studies and the field testing.  Additionally, the test
notes for the avian data requirements in Subpart G of the final rule
were rewritten for clarity.

COMMENT 4. The international community is aiming to withdraw the acute
avian oral toxicity study.  Why propose additional testing with an
obsolete test guideline?

RESPONSE   Current risk assessment procedures for the evaluation of
listed species require knowledge of the dose/response relationship.  In
addition, advancement of risk assessment to Level 2 techniques uses the
dose - response relationship for acute oral toxicity studies to
establish acute tolerance values for modeled individual birds. 
Alternatives to the acute oral dose study have, to date, not empirically
demonstrated an ability to establish dose - response relationship
parameters equivalent to those established using the current toxicity
protocol.

COMMENT   One commenter (#120) stated that a laboratory study with
passerine birds is not technically feasible.

RESPONSE   The Agency does not agree with the comment.  Canaries have
successfully been used as test animals in acute toxicity testing.  Refer
to EXTOXNET Pesticide Information Profile for Triadimefon in which
canary LD50 values from Kidd, H. and James, D. R., Eds. The
Agrochemicals Handbook, Third Edition. Royal Society of Chemistry
Information Services, Cambridge, UK, 1991 (as updated) are provided. 
The website for this document is:

http://ace.orst.edu/cgi-bin/mfs/01/pips/reflist8.htm

To summarize, based on the comments, the Agency deleted the red-winged
blackbird as the only acceptable passerine species for an additional
avian acute oral toxicity study.  However, the passerine acute oral
study is still required, in addition to one with either an upland game
bird or a waterfowl species.  The Agency will consider alternative
species submitted by the public or a registrant, as long as the
alternative species meets the criteria in the acute oral toxicity
guideline.

2.  Avian Dietary Study

COMMENT   Commenter #56 questioned the value of continuing to require
the avian dietary study.

RESPONSE   The Agency wants to maintain this study to determine the role
dietary intake plays in the sensitivity of birds exposed over several
days to a pesticide-contaminated diet.  We note that the EU continues to
work on the design of the avian dietary study with the US and other
countries through OECD.

 

3.  Japanese quail

COMMENT   The Agency received two comments regarding the use of the
Japanese quail as a test species in the acute toxicity test and in the
reproduction test.  

COMMENT   One commenter (#56) stated the Japanese quail should be
accepted for acute toxicity testing.

RESPONSE   The Agency addressed the issue of Japanese quail when it
submitted the following to OECD on March 24, 2003.  

"The Japanese quail should not be listed as a preferred test species. 
Many years of domestication and artificial selection in this species may
have affected the response of this species to chemicals.  Also, a
species comparison of species sensitivity done for the 1994 Pensacola
meeting showed that the Japanese quail was significantly less sensitive
than the northern bobwhite in the dietary test.  Although this
difference was not found for the acute oral LD50's, it still indicates
that these two species respond differently to toxicants.  In addition,
the EPA has a long history of testing with the bobwhite and has
accumulated a large database of acute toxicity results for this species.
 Using another test species would increase uncertainty of comparison of
toxicity and risk among chemicals."

COMMENT   Another commenter (#128) wants the Agency to harmonize with
OECD regarding using the Japanese quail as an alternate for the bobwhite
quail in reproduction testing.

RESPONSE   At this time, the Agency has not harmonized with OECD on the
use of Japanese quail for reproduction testing because of concerns over
the high degree of domestication of the species and the extremely high
rate of reproduction that is poorly representative of North American
species.  However, the Agency is still actively considering the species
use in multiple generation reproduction testing because of laboratory
logistical issues associated with such long-term tests and lengthy
intergenerational times for other species.

4.  Avian toxicity endpoints

COMMENT   The FWS, (#146) continues to encourage the Agency to continue
to expand the endpoints evaluated in avian toxicity studies to include
behavior, enzyme levels, and other physiological, biochemical, and
morphological characteristics.

RESPONSE   The Agency has committed to considering an expanded suite of
sublethal effects.  However, there should be clear and reasonable
relationships between such measurement endpoints and Agency risk
assessment endpoints related to survival and fecundity of individuals.

5.  Avian reproduction 

COMMENT   The Agency received two comments from one correspondent (#120)
stating that the need for an avian reproduction test should be based on
the pesticide’s properties.  The first comment stated that the testing
should be waived when there is neither evidence of toxicity from oral or
dietary routes nor evidence suggesting that such effects are of concern.
 The second comment stated that reproduction testing should not be
required for compounds that break down rapidly, partition rapidly in
aquatic systems, or do not bioaccumulate in aquatic species that are
potential food sources for some avian species.

RESPONSE   The Agency does not agree with the first comment.  Adverse
effects on avian reproduction can occur at levels of exposure several
magnitudes lower than those that can cause acutely toxic effects.  With
regard to the second comment, existing avian reproduction testing
involves a study that is some 21-weeks in duration.  The design of this
study, drafted in an era of organochlorine pesticides, reflects a
concern at the time for allowing exposure periods long enough to reach
test animal tissue saturations.  However, this prolonged exposure period
may not be necessary for less bioaccumulative compounds.  Therefore, for
some chemicals the actual length of the exposure window may be
considerably shorter to elicit effects than the study would suggest. 
This raises considerable uncertainty as to just what would be the
appropriate environmental persistence criteria that would be suitable to
evaluate whether a specific pesticide might pose a risk for reproduction
impairment.  Rapid partitioning in aquatic systems has little bearing on
whether a pesticide will pose a risk in terrestrial agroecosystems for
species not consuming aquatic organisms. Bioaccumulation is a concern
to the Agency; however, the Agency’s risk assessment also considers
dietary exposures from pesticide directly applied to vegetation and
invertebrates in the treated field or off-field through spray drift. 
These exposures, at the very least, involve consumption of food items
impinging pesticide at the time of application, a situation where
bioaccumulation is not a critical factor.

COMMENT   Two commenters (#125, #133) questioned why organophosphate
(OP) insecticides are cited as the reason for requiring measurement of
effects on the egg.  They questioned if other pesticides that are now
used have also been linked with eggshell effects.

RESPONSE   The Agency maintains that reproduction studies involving both
bobwhite and mallard test species have shown eggshell effects in a
variety of pesticide classes including some OPs.  However, this endpoint
is not consistently the most or least sensitive of all endpoints
measured.

COMMENT   One commenter (#128) advocated the development of reproduction
tests with passerine species.  Their interest was based on the fact that
the current species used in this test, the mallard and the bobwhite, are
precocial species (birds that are born covered with feathers, able to
see and leave the nest soon after hatching).  Passerine species, which
are altricial (birds that are born naked and blind and depend on their
parents for food), may have significant behavioral responses to
pesticides different than those of the currently tested species.  These
responses could affect reproduction through factors as incubation
behavior and care of young.  They acknowledge that there presently are
no testing protocols for passerine species, but they encourage the EPA
to support the development of passerine reproduction testing with
species like the zebra finch or the house finch.

RESPONSE   The Agency believes that addressing the potential differences
in reproduction between passerines and other birds is scientifically
appropriate.  However, at this time, no protocols have been made
available to the Agency for such testing.  Given the challenges testing
labs are faced with for existing reproduction tests, protocols for
passerines will not be available for this edition of Part 158.  

6.  Wild Mammal Testing

COMMENT   The Agency received three comments regarding the wild mammal
toxicity test and test note 7.  The first comment (#120) stated that
test note 7 was unclear, and they asked for more specific guidance as to
what avian or mammalian acute and subacute testing, fate characteristics
and use patterns could trigger this data requirement.

RESPONSE   The Agency evaluates the need for wild mammal toxicity on a
case-by-case basis.  The results of effects testing or fate testing
alone are not the causal factor in such a determination.  Rather, such
study requirements are based on whether, given the use pattern, effects
and fate profile, benefits, and current risk assessment, there is
sufficient uncertainty to preclude a determination of the risk/benefit
relationship.

COMMENT   The second commenter, # 124, stated that wild mammal studies
should only be triggered when the terrestrial risk assessment triggers a
potential concern based on mammalian endpoints generated in the
toxicology data package.  They proposed the following changes to test
note 7:

Data on wild mammal species may be required when a refined terrestrial
risk assessment triggers a potential concern for a given use pattern
based on laboratory toxicity endpoints and a refined exposure
assessment.  Consideration needs to be given to the potential for
exposure and the potential assessment endpoints that could be impacted.

COMMENT  Commenter # 137 proposed that test note 7 be revised to state
that data on a wild mammal species may be required when the terrestrial
risk assessment triggers a potential concern (acute RQ > 0.5; chronic RQ
> 1.0) for a given use pattern based on laboratory toxicity endpoints
and a refined exposure assessment.

RESPONSE   The Agency reiterates that there may be case-specific
information that would trigger the need for additional testing.  This
might include lines of information that suggest that available toxicity
data provide unsuitable surrogacy for a particular non-target species. 
While the Agency will not be changing part 158 from what was proposed in
this regard, we will continue to consider more specific criteria over
time, and include those in later revisions to part 158 as appropriate.

7.  Acute Toxicity Studies with Reptiles

COMMENT   The Agency received one comment (#146) stating that effects on
reptiles still are inadequately addressed in this new regulation. 
Continuing to use avian species, even with the addition of a passerine,
test is not adequate to assess risks to reptiles.

RESPONSE   The Agency will consider any peer-reviewed reptile testing
protocols for possible future addition in required testing.  Information
demonstrating a biologically significant difference in sensitivity or
exposure between birds and reptiles, which would suggest that bird risk
assessment is not adequately protective, can still be considered in
individual risk assessments.

8.  Field testing

The Agency received four comments regarding the data requirement for
simulated or actual field testing with terrestrial animals.  

COMMENT   One commenter (#120) stated that the information provided in
the test note for this data requirement (proposed test note 8) was
nebulous and asked for clarification. 

 RESPONSE   The Agency evaluates the need for field testing on a
case-by-case basis.  The results of effects testing or fate testing
alone are not the causal factor in such a determination.  Rather, such
study requirements are based on whether, given the use pattern, effects
and fate profile, benefits, and current risk assessment, there is
sufficient uncertainty to preclude a determination of the risk/benefit
relationship.

COMMENT   Two commenters (# 124 and # 137) stated that additional
testing, particularly with wild species in the natural environment,
should only be conducted when refined risk assessments indicate a
potential concern.  Risk based triggers ensure that these studies are
only performed when other tools and process have indicated that field
data is required to resolve uncertainties. 

COMMENT   Commenter # 137 suggests that additional testing, particularly
with wild species in the natural environment, should only be done when
the refined terrestrial risk assessment indicates a potential concern
which they described as an acute RQ > 0.5 or RQ >> 1.0.  They believe
that using a risk-based trigger ensures that field studies are only
conducted when all other ecotoxicological tools and processes have still
left uncertainties that need to be resolved by a field study.

RESPONSE   The Agency concurs in part.  Field studies have traditionally
been performed to address uncertainties in risk assessments, especially
those risk assessments predicting environmental effects of concern. 
However, setting a conditional requirement that triggers such studies
only when risk assessment tools predict adverse effects ignores the
possibility that lines of information may conversely point out
inadequacies of the existing tool to provide adequate protection.  In
such cases a prediction of no concern for environmental effects, with
attendant uncertainties, may trigger additional data development before
a risk management decision is reached.

COMMENT   Commenter # 124 proposed the following change to proposed test
note 8:

Higher tier testing may be required for a specific use pattern when a
refined risk assessment indicates a concern based on laboratory toxicity
endpoints and refined exposure assessments.

RESPONSE   The Agency concurred and changed test note 6 in the final
rule to the language submitted by commenter #124.

COMMENT   Commenter #146 stated that field testing can provide a more
realistic assessment of potential impacts to nontarget species that may
act in consort to affect an organism’s fitness and should remain a
data requirement.

RESPONSE   The Agency agrees with this comment that field testing can be
useful, if conducted with the requisite scientific rigor.  To this end,
the Agency has retained the existing field testing data requirements in
Part 158.

9.  TEP testing 

A significant number of the comments the Agency received concerned the
confusion in the data table regarding the use patterns that would need
to be supported by TEP testing, in addition to testing with the active
ingredient.

COMMENT   Two commenters (#113 and # 146) stated that the proposed rule
did not clearly state when testing with end-use products would be
required.  Commenter #146 recommended TEP testing for all products with
potential aquatic or terrestrial nontarget exposure.

RESPONSE   The Agency evaluates the need for testing of TEPs on a
case-by-case basis.  In such evaluations, the Agency relies on available
lines of evidence such as published literature, 6(a)(2) data
submissions, European regulatory testing, and confidential statements of
formula.  The potential for non-target organism exposure to TEP would
naturally be a consideration as well.  

COMMENT   Another commenter (#82) stated that a different protocol or
type of study (other than gavage) may be required to assess avian oral
toxicity of an end-use product, particularly a granular.

RESPONSE   The Agency acknowledges this, and on a case-by case basis,
requests for such testing are accompanied by discussions of appropriate
protocol adjustments.

COMMENT   A fourth commenter (#120) stated that the table in the
proposed rule for avian toxicity studies with TEP indicated that the
studies are required for all uses except greenhouse and indoor which are
conditionally required.  However propose footnote 3 indicates that
testing with TEP is conditional based of results of acute and dietary
studies.  Specific triggers are not identified and should be.  TGAI and
TEP should be separated indicating conditional requirements for TEP
testing.

COMMENT   Commenters # 124 and # 137 stated that TEP testing for avian
species should only be triggered when the nontarget terrestrial organism
is expected to encounter the intact end-use formulation or is expected
to use the formulation itself as a food source, and the risk of adverse
effects in such a situation is potentially high (RQ>0.5) based on
calculations using the toxicity of the TGAI.  Commenter # 124 proposed
that proposed test note 3 state that data using the TEP should be
conditionally required based on the results of the testing with the
TGAI, the potential for oral ingestion of the end use formulation, and
an acute RQ>0.5, based on the TGAI data.

COMMENT   Two commenters (#125, #133) stated that testing of TEP for
passerine effects will become burdensome and costly.  They asked who
will decide which product to test, and who will then monitor to see if
additional formulas need to be investigated?

RESPONSE   In light of the number of comments received on this issue,
and past experience that shows TEP testing has mainly been required for
granular formulations or other special situations, the conditional
requirement for formulation testing was removed from the data
requirements in the final rule.  It remains consistent with past policy
and may be required on a case-by-case basis.

10.  Use Patterns

Several comments indicated that there was confusion as to the
relationship between specific use patterns and the data needed to
support that use pattern.  

COMMENT   One commenter (#124) stated that the dietary TGAI testing for
aquatic non-food residential uses should only be triggered when the
nontarget terrestrial organism is expected to be exposed in the
environment and the terrestrial acute risk assessment triggers a
potential concern based on acute oral test with the TGAI.  They proposed
the following change to proposed test note number 6:

For aquatic nonfood residential uses, if the TGAI acute avian risk
assessment indicates a significant concern for a given use, and there is
a potential for exposure, then an additional acute dietary test with
TGAI may be conducted using either bobwhite quail or mallards.

RESPONSE   The Agency removed use patterns such as aquatic residential
and consolidated all subdivisions under aquatic to simply “aquatic use
patterns” in the final rule.  The Agency did not change the number or
types of birds that must be tested for the dietary toxicity test.  All
aquatic uses require the dietary test with both the upland game bird and
waterfowl species. 

COMMENT Commenter 146 asked that the Agency clarify the use of avian
testing for the aquatic non-food residential uses 

RESPONSE   The Agency’s position is that avian exposure from labeled
uses is expected to be limited for aquatic non-food residential uses. 
However, when data are required, these data will be used in development
of the avian risk assessment.

COMMENT  Two commenters (#125, #133) stated that presently a subacute
avian dietary study is required for domestic (residential) outdoors and
is conditionally required (CR) for indoor or greenhouse use patterns. 
However, the proposed 158 rule shows that the dietary study is being
eliminated in favor of the acute oral study.  They do not understand
which of the two avian studies better portrays field situations.

RESPONSE   The Agency made the switch to requiring the avian acute oral
study for indoor uses and greenhouse uses based on the expectation that
acute oral toxicity studies may be more representative of conditions
involving any accidental environmental release associated with these
uses.

COMMENT   Commenter # 125 questioned why the avian reproduction study
is now required for residential outdoor and terrestrial uses.

RESPONSE   Birds can be exposed to pesticides on these sites during the
times when exposure may potentially affect a bird’s ability to
reproduce successfully.  The exposure period can occur prior to
egg-laying, when the adult is physiologically preparing to reproduce, or
during the actual egg-laying or nesting stages when the adult, eggs or
juveniles can be exposed.  Therefore, the avian reproduction study
provides data essential to determining risks to birds during this stage
of their life.

11.  Guidelines Not Finished 

COMMENT   The Agency received seven comments from five commenters (#112,
#120, #123, #124, #137) that the 850 series of OPPTS guidelines for
ecological data, cited in proposed subpart E, only exist in draft form
and have never been established as final guidance documents.  The
general opinion was that EPA should not propose data requirements in the
absence of formal, established guidance.  Commenters # 112 and #120 also
stated that the lack of finalized guidelines would place an unfair
burden (cost) on the regulated community due to the lack of access to
the substance of the data requirements and potential revisions to the
ongoing drafts.  Commenter #56, the EU, stated that the Agency should
place more effort towards the development of a common approach based on
use of internationally agreed and validated test guidelines.  Commenters
#124 and #137 stated that the draft 850 guidelines do not meet “the
expectations of the USEPA Environmental Fate and Effects Division (EFED)
for the terrestrial and aquatic nontarget organism data packages.” 
This statement is based on their reviews of EFED risk assessments. 
Commenter #124 proposed that both guidance documents (850 series and 71
series) be noted in the data requirement tables until such time “that
the 850 series guidance is revised to reflect the EFED reviewers’
requirements for these toxicity studies.”

RESPONSE   The 850 series of guidelines is scheduled to be completed and
available to the public by late 2007.  Nonetheless, guidelines are
guidance documents only, and the promulgation of data requirements does
not depend on the availability of guidance documents.

Insects

COMMENT  The Agency received four comments (# 124, #125, #133 and #137)
stating that the conditions in proposed test note 26 of the proposed
rule for the field study requirement are too broad and that the
guideline for this study is vague. 

RESPONSE   The Agency agrees that the definition for the term “field
testing” and the test criteria need to be clarified.  The intent is to
allow for additional testing to address a specific concern based on
effects noted in testing with bees or other terrestrial arthropods. 
Field testing, in this context, would most likely be the type of testing
identified in the comment as “semi-field”, for example a tent or a
tunnel.  We also note that under item iii for proposed test note 26, the
word “terrestrial” was inadvertently omitted before the word
“arthropod”.  This was corrected in the final rule, so the sentence
in finalized test note 25 states “...studies with terrestrial
arthropods other than bees...”.

COMMENT   One commenter (#120) stated their belief that acute contact
toxicity study should be designated as CR for the aquatic uses. 
Specific application methods could be indicated for further testing in a
footnote, while others such as directed applications or incorporation
into water, or formulation types such as granulars could be specifically
cited as examples of restricted exposure scenarios.

RESPONSE   The Agency agrees with the CR designation for the acute
contact toxicity test for aquatic uses. It was changed in the final
rule.  The acute contact toxicity study is a basic test designed to
provide hazard data on the intrinsic nature of the chemical. 
Application methods or type of formulation are not determining factors
for the data requirement.  Therefore, these factors are not taken into
consideration with regard to requiring this study.

COMMENT   One commenter (#125) asked what residential uses are likely to
trigger the field test. 

RESPONSE   The requirement for a field study with pollinators is
determined by weight of evidence information, and not so much by the use
pattern.  The field study can be required if other insect studies,
including any incident data, show an effect that cannot be further
investigated in additional laboratory testing.  Test note 25 in the data
table in the final rule provides the conditions under which this test
may be required.  As with other ecological effects field testing, the
registrants are strongly urged to contact the Agency prior to initiating
any field testing.

Aquatic Organisms

  SEQ CHAPTER \h \r 1 1.  Sediments   

	The Agency received forty-three comments about the newly codified acute
and chronic sediment toxicity data requirements.  Most of the comments
concerned the conditions for requiring these tests (primarily proposed
test notes 23 and 24).  Some of the comments discussed risk assessment
issues.  As mentioned above the majority of the comments the Agency
received about the sediment toxicity data requirement concerned the
language of the test notes for the data requirements.  The commenters
cited not only the test notes, but also the sections of the Preamble
where the sediment data requirements were discussed in detail. More than
half of the comments focused on the triggers based on the Kd value and
the half-life value.  

COMMENT  Two commenters (#124, #137) asked the Agency to justify a
statement in the Preamble regarding the  ability to assess risks from
sediment bound pesticides using only the water column data [
“…effects of sediment bound pesticides … on aquatic environments
cannot be accurately assessed from bioassays on compounds suspended in
the water column alone…” (X.B.2)]. The commenters referred the
Agency to use of the Equilibrium Partitioning Theory (EqP) that was
published by EPA (DiToro, et. al. 1991, Environ. Toxicol. Chem.
10:1541-1583) to estimate risks from sediment bound contaminants on
aquatic ecosystems.  They pointed out that EqP theory links water column
concentrations to sediment concentrations to allow the assessment of the
impact of bound pesticides.  They emphasized that the agency needs to
recognize that sediments are complex environments, and that it is often
difficult to characterize exposure in terms of the bioavailable
fraction; uncertainty is not necessarily reduced by performing sediment
toxicity studies.

RESPONSE   The Agency reiterates from the Preamble that lipophilic
compounds or hydrophobic chemicals can dissipate from the water column
but may still remain in the aquatic environment adsorbed to sediments. 
Effects in the water column may be of short duration constituting acute
toxicity, while effects from the sediment/ pore water may show morbidity
and growth or emergence effects (e.g., Chironomus).  Sediment bound
compounds can differ significantly from compounds in solution, showing
different physical, chemical, and biological properties, chemical
partitioning, bioavailability, etc.  While the Agency can extrapolate
sediment toxicity by using EqP and water column toxicity values, this
cannot account for the complexity of sediment and pesticide
interactions.  Actual testing of spiked sediments will present a more
accurate depiction of possible risk to benthic invertebrates.

COMMENT   The same two commenters (#124, #137) also stated that sediment
toxicity studies should only be required when the Agency’s risk
assessment based on the water column toxicity data and the environmental
fate data indicate there is substantial uncertainty regarding potential
risks of the pesticide in the sediment layer of aquatic ecosystems.

RESPONSE   The Agency does perform an aquatic risk assessment that
includes a sediment component prior to requiring sediment testing.  The
Agency applies the EqP approach by using available water column toxicity
data and model derived sediment/pore water exposure values to estimate
risk.  With this approach the Agency extrapolates potential risk to
benthic, as well as other aquatic organisms.  Although laboratory
sediment testing may not remove all of the uncertainties regarding a
pesticide and its interactions in the environment, these test can help
to reduce this uncertainty.

	It is the Agency’s position that the requirement for whole sediment
toxicity testing is not levied exclusively to remove or reduce
uncertainty of potential risk in sediment versus water column matrices.
 The conduct of sediment toxicity tests considers multiple routes of
exposure. Even assuming good correlation between water column and
sediment toxicity vis-à-vis EqP considerations, the comparison is most
likely limited to exposure pathways associated with sediment pore water.
The Agency believes that additional pathways should be considered (e.g.
ingestion, dermal, etc.), as would be the case for spiked sediment
toxicity tests, which we believe provides a better overall assessment of
potential risk in the sediment compartment than a water column study
alone. The use of sediment toxicity studies is already limited primarily
because they are generally only considered after vigorous problem
formulation.

COMMENT   Two commenters (#120, #122) questioned the data requirement
for the whole sediment chronic invertebrate study as no guideline was
listed for this requirement.  They suggested that EPA harmonize with
OECD and cite OECD Method 218 for the chronic study.

RESPONSE   The Agency is harmonized with OECD with respect to this data
requirement.  OECD Guideline 218 (Sediment-Water Chironomid Toxicity
Test Using Spiked Sediments) was drafted to take into consideration
“all potential routes of exposure” and is focused on long-term
exposure (C. tentans 28 – 65 day exposure). This coincides with the
Agency’s needs and protocol for chronic sediment testing.

COMMENT   There were three comments (#120, #124, #133) that asked for
clarification of the Agency’s definitions of acute and chronic
sediment toxicity studies as described in the preamble.  One of the
comments stated that the acute sediment testing guidelines most commonly
used in the USA are more analogous to a chronic fish early life stage
study (ELS) in which mortality and growth are measured, than to acute
fish or Daphnia studies.  Another commenter thought that the typical
duration of greater than 10 days for most sediment toxicity studies was
more representative of chronic effects, not acute effects, as this time
period represents a significant portion of the typical test organism
life span.

RESPONSE   The Agency does not consider the ELS to be a chronic test
because reproduction is not a component of the testing.  Study duration
of 10 days covers early instar growth for chironomids.  The life cycle
of a chironomid is about 28 days (egg to egg).  The 10 day study is very
appropriate for acute toxicity evaluation, but not for a chronic
assessment.  The 10 day acute sediment testing covers morbidity and
growth, whereas the 48 hr EC50 invertebrate acute study only addresses
morbidity.  Neither study evaluates reproduction.  This is measured in
the chronic 65 day sediment study, as well as the invertebrate full life
cycle study.

	The chronic sediment study continues through emergence, which is a
measure of reproductive success.  The guideline, EPA/600/R-99-064,
provides the methodology for the 50 to 65 day Chironomus tentans
life-cycle sediment toxicity study.  The endpoints include 20 day larval
survival and weight, female and male emergence, number of egg cases
oviposited, number of eggs produced, and the number of hatched eggs. 
The guideline also contains the 42 day Hyalella azteca which, likewise,
measures reproduction endpoints.  Guideline EPA 600/R-01-020 provides
the methodology for the 28 day marine/estuarine sediment toxicity test
with Leptocheirus plumulosus, another chronic test which contains
reproduction endpoints.  The OECD 218 guideline, mentioned above, is 20
to 28 days in duration for C. riparius and C. yoshimatsui and 28 to 65
days for C. tentans. The endpoints in this guideline include development
time, total number of fully emerged male and female midges, with
optional 10-day larval survival and growth. 

COMMENT   Six commenters (# 113, #120, #122, #124, #125, #133) expressed
concern about the numerical values for the Kd and the half-life factors
for the acute and chronic sediment tests.  One comment asked for
justification to support the selection of the Kd value of 50 as the
criterion.  They also asked the Agency to clarify if the Kd value is the
mean, the maximum or 90%tile upper confidence limit of the mean value
observed in the soil adsorption studies.  This commenter proposed
alternative criteria for the acute study:  the study is required if the
soil Kd (specify mean, maximum or 90% tile) > 50, and; if the half-life
in soil or sediment is > 1 day (as indicated by aerobic soil, anaerobic
soil or aquatic metabolism sediment-phase degradation studies). These
criteria would lead to the following conclusions: the study is not
triggered if the material degrades rapidly in soil and sediment
(half-life < 1 day), or if the material is sorbed weakly to soil or
sediment (Kd < 50).

RESPONSE   The Kd criterion represents the mean value observed in the
soil adsorption studies.  The Agency’s justification in the proposed
rule for selecting Kd > 50 L/kg as a criterion for requiring the study
was that this value would capture those chemicals with about 80%
adsorption to sediments (relative to organic carbon).  In the 1980s the
Agency considered selecting a Kd value lower than 50 L/kg, in the range
of 3 to 10 L\/kg; however, at the time the proposed rule was drafted,
EPA believed a Kd > 50 was sufficiently conservative. 

COMMENT   The Agency received a comment from Canada’s PMRA (#82) that
questioned the appropriateness of using the Kd value as a trigger for
sediment testing.  They stated that their experience indicated that
pesticides with relatively low Kd values (less than 50) may readily
partition to the sediment.  They suggested that the trigger should be
based on the results of the aquatic transformation studies, particularly
the mass balance results and the half lives in sediments.  They
discussed data that showed significant binding of the chemical, as
determined by unextractable residues, when the Kd value ranged from ∼2
to 14, much less than the value of 50 L/kg used by EPA.  

RESPONSE   Based on the comment from PMRA, Agency scientists re-analyzed
the  value for the Kd criterion with data from the US Geological Survey
(USGS).  [U.S. Geological Survey.  2000.  Pesticides in Stream Sediment
and Aquatic Biota.  Current understanding of distribution and major
influences.  FS 092-00 (8-24-00).  4 pages.] [ url = 

     HYPERLINK "http://ca.water.usgs.gov/pnsp/rep/fs09200/fs09200.pdf" 
http://ca.water.usgs.gov/pnsp/rep/fs09200/fs09200.pdf  ).]  The Kd
values for pesticides commonly detected in sediment ranged from 1.6 to
2,095 with a mean value of 86 and a median value of 59.  This analysis
provided EPA with an important new perspective on Kd values, and the
Agency considered lowering the value of the criterion. However, EPA
decided not to change

the Kd value from that in the proposed rule based on science and policy
considerations. First, the Kd value, which indicates binding potential
of the pesticide (unadjusted for dependency upon organic carbon) is not
the primary factor in determining the need for sediment testing (i.e.

persistence, toxicity and exposure are the main factors). More
importantly, the Agency believes that such a change warrants input from
the scientific community along with broader public input on the Kd
trigger. The Agency may consider changing the Kd value in future updates
to part 158 requirements.

COMMENT   One commenter (#122) appeared to question which environmental
fate metabolism studies are used to determine the persistence criteria
that may trigger the acute sediment study.  They stated that the study
is required if the Kd > 50L/kg in either aerobic soil or aerobic aquatic
metabolism studies.  They wondered if the anaerobic soil half-life value
could also be used as an additional predictor of sediment persistence. 

COMMENT   One commenter (#122) stated that it does not make much sense
to require the acute study if the half-life is moderately short (i.e.
<10 days), because acute toxicity would still be a concern if the
half-life were longer.  They wondered if this was a typo.  They
proposed, instead, that a very short soil or sediment half-life could be
a criterion for not requiring the study; e.g. if the half-life is <1
day, the study should not be required because residues would likely not
reach a water body in significant concentrations regardless of the
adsorption potential of the material.  Another commenter stated that
short half-life has less potential for invertebrate effects than a
chemical with a half-life greater than 10 days.   

COMMENT   Five commenters (#120, #122, #124, #125, #137) stated that it
is difficult to assess EPA’s triggers for sediment toxicity testing
due to inconsistencies in the document.  The triggers to which they are
referring are reported in Unit X.B.2.i and ii (p. 12289d) and
§158.400(e), test notes 23 and 24 (p. 12345c) in the proposed rule. 
The trigger for acute testing is reported to be a Kd  > 50 mg/L and a
half life of < 10 days. The commenters believe that using the symbol for
“less than” in reference to the half life value in the acute test is
a typographical error and should have read > 10 days.  For chronic
testing the trigger is a half-life > 10 days, along with Kd > 50 mg/L,
and a reference to the acute sediment studies (EEC > “acute”
sediment EC50/LC50 ), implying, in their view, that an acute study must
be done prior to conducting the chronic.  They requested that the Agency
clearly specify the conditions for both acute and chronic testing. They
stated that three factors, adsorption, persistence, and toxicity, are
important in determining whether a compound is of potential concern in
the sediment.  In their opinion, all three factors should be considered
when setting triggers for sediment toxicity testing.

RESPONSE   It appears from the above comments that the commenters
misunderstand the purpose of the triggers cited above.  The Agency
affirms that the intent of the triggers for the acute and chronic
sediment tests is not to determine length of test.  They were designed
to determine if the sediment compartment should be considered for
testing.  Once that determination is made, then problem formulation will
determine the specifics of the data required.  The Agency strongly
advises that the registrant consult with the biologists concerning type
of study and test organism selection.  The Kd trigger, which is the
partition coefficient used as an expression of binding capability of the
chemical, will be the same for either the acute or chronic sediment
test.  It is the persistence (i.e. half-life) that drives the decision
of which length of study to require.  For example, if the soil or
aquatic aerobic/anaerobic half-lives are less than 10 days (Agency
policy is to use the most conservative value, unless evidence is
provided to support the use of an alternative value), then the Agency
would accept the10 day sediment study, unless there are clear
reproductive issues a priori.  For half lives greater than 10 days, a 28
to 65 day study would be more appropriate. 

	The Agency must determine if the proposed use pattern will result in
the compound reaching an aquatic system via drift and/or runoff at
levels that could result in risk to aquatic organisms. This potential
for exposure to an aquatic system is determined through appropriate
modeling or monitoring data. Once the Agency determines or extrapolates
that the use pattern has the likelihood for chemical exposure to an
aquatic system the triggers for persistence and adsorption are reviewed
(previously discussed). Toxicity will be taken into consideration
relative to potential exposure.  Consultation with the Agency is needed
if the registrant is uncertain as to which length of study is
appropriate. 								

COMMENT   Two commenters (#124, #137) proposed that a value of log Kow >
3 is a more commonly used value with which to judge whether a compound
might have adsorptive potential.

RESPONSE   The agency agrees that the Kow (octanol-water partition
coefficient), along with the Koc (soil organic carbon-water partition
coefficient), are valid environmental fate values to use as criteria for
these studies.  Both values are frequently more available than either
the Kd or half-life values.  The log Kow > 3, which is equivalent to Koc
> 1000) is a more conservative value.  Subsequently, a pesticide’s
requirement for submission of sediment studies can also be determined by
either of these two values.  The test notes in the final rule were
revised to include the Kow and Koc.

COMMENT   The Agency received five comments (#120, #122, #124, #125,
#137) regarding the statement in the Preamble which states that the
sediment testing requirement “would not be commonly required.”  They
contended that this statement is misleading because they view the
proposed trigger levels as quite liberal, such that a large number of
compounds, including those where no sediment concern has been
identified, would trigger testing.  According to them, the trigger Kd >
50 L/kg is quite low, and inconsistent with current scientific
knowledge.  

RESPONSE   The Agency acknowledges that the statement would not be
commonly required” was misleading.  The Kd criterion represents the
mean value observed in the soil adsorption studies.  The Agency’s
justification in the proposed rule for selecting Kd > 50 L/kg as a
criterion for requiring the study was that this value would capture
those chemicals with about 80% adsorption to sediments (relative to
organic carbon).  In the 1980s the Agency considered selecting a Kd
value lower than 50 L/kg, in the range of 3 to 10 L\/kg; however, at the
time the proposed rule was drafted, EPA believed a Kd > 50 was
sufficiently conservative.  Based upon the analysis of the USGS data and
USGS report, the Agency is confident in the selection of a Kd value > 50
L/kg as one of the triggers for requiring sediment toxicity testing.

COMMENT   Commenter #122 questioned the use of an EEC (estimated
environmental concentration) to trigger the chronic toxicity study as
this value is prone to considerable variation and non-uniformity.  Each
EEC calculation is a function of a large number of assumptions in the
modeling including the very wide range of environmental characteristics
of the potential target sites.  For purposes of simplification and
uniformity, they proposed alternate criteria, based on persistence and
toxicity, without calculation of an EEC.   Their proposal is:  1) the
chronic study is required if the acute toxicity is <100 mg/kg sediment
(or some other suitable limit indicating a ‘practically non-toxic’
classification) or the soil Kd (specify mean, maximum or 90% tile) > 50,
and; 2) the sediment half-life is >X days in aerobic soil or aquatic
metabolism studies; otherwise, the chronic study is not required.  These
criteria trigger a chronic study if the material is persistent and sorbs
to soil/sediment, or is acutely toxic to sediment organisms and is
persistent.

RESPONSE   It appears that the question is really the appropriateness of
EEC versus toxicity for requiring a chronic sediment toxicity test.
 One advantage of using the EEC is the fact that its determination is
based on the modeling of variables unique to the respective chemical,
therefore any uncertainty would be due to the limitations of the model,
and certain spatially explicit deviations. The major weakness of using a
toxicity threshold as a trigger for this test is the fact that the data
base of laboratory sediment toxicity studies is not yet robust enough to
exact any meaningful correlations of intrinsic toxicity in the sediment
to a specific threshold of water column toxicity.  A level of 100 mg/kg
may be adequate for water column, but whether it is an appropriate
threshold for sediment still needs to be determined. Furthermore, in
these early stages of sediment toxicity testing and sediment risk
assessment, perhaps adsorption and persistence should be the key
criteria for triggering a sediment toxicity test. 

COMMENT   One comment (#122) stated that the criterion for persistence
in soil/sediment should probably be less than 10 days. They continued
that a material with a 10 day half-life will degrade by a little less
than 75% in a 28-day midge life-cycle study, indicating that a
significant fraction of material could be present over the life-span of
a sediment-dwelling organism.  They proposed that a more suitable cutoff
would ensure degradation of material to an insignificant level well
before the life-span of an indicator organism elapsed.  For example, a 2
day half-life criterion would allow 14 half-lives to elapse in 28 days,
and would ensure the degradation of material to insignificant levels
(>99.9% degradation).

RESPONSE   The Agency reiterates that the use of a half-life value of
less than 10 days for the persistence trigger can be evaluated for a
future update of this rule, based on the sediment toxicity studies
submitted following publication of this rule.  

COMMENT   This commenter (#122) stated that the half-life criterion
should be based on the degradation of the analytically-identifiable
parent material, and not on the dissipation of the non-extractable
residue which cannot be analytically identified as the parent material.
They continued in their statement that the non-extractable residue is,
by definition, not extractable, and therefore, also not biologically
available to sediment dwelling organisms.

RESPONSE   The Agency has not yet determined specifically which
half-life correlates best with greatest sediment adsorption and
exposure.  Therefore, we generally use the “worst-case” half-life of
the soil or aquatic aerobic or anaerobic half-life.  However, through
problem formulation and conceptual modeling, it would be determined a
priori whether residual pesticide concentrations are likely to occur in
water and sediment, and only in cases where exposure is likely would
testing be required. 

COMMENT   The Agency received one comment (#56) that questioned why the
LC50/EC50 values are triggers for the chronic whole sediment toxicity
test.  They stated that chronic toxicity is often exhibited at
concentrations lower than the LC50/EC50 values.  They suggested that a
more appropriate trigger would be that sediment concentrations exceed
the NOAEC (no adverse effect concentration) or 0.1 * LC50/EC50 values.

RESPONSE   The Agency reiterates that the triggers are principally for
determining which chemicals warrant a sediment toxicity study at all. 
However, the Agency agrees that the condition in test note 22 regarding
the LC50/EC50 values is unclear and revised the statement to read 

	“The estimated environmental concentration in sediment is greater
than 0.1 of the acute LC50/EC50 values.”

	COMMENT   One commenter (#120) expressed concern that testing would be
required, regardless of the low risk for aquatic contamination, if the
triggers listed in these two test notes applied to the chemical under
review.  They asked the Agency to identify specific use patterns (seed
treatments and soil-incorporated pesticides, for example) that would not
require sediment testing based on low leaching potential and strong
adsorption properties.  

	RESPONSE   The response to this comment lies in the Agency’s decision
that problem formulation will determine the specifics of the data
required.  The Agency assesses these chemical properties in conjunction
with available toxicity data in order to assess risk and whether
sediment testing is warranted.  With regard to the Agency predefining
use patterns that will not require sediment testing, this is not an easy
effort.  The argument that compounds with strong adsorption properties
and low leaching potential should not reach streams and lakes especially
if they are soil incorporated is a position that the Agency has usually
followed.  However, the Agency has recently been presented with
monitoring data showing that synthetic pyrethroids (family of compounds
that are highly adsorptive to organic matter) used in residential
settings (lawn care, building perimeter use, crack and crevice use,
etc.) can result in runoff to storm drains that empty into nearby
streams (Weston, D.P., J.C. You, M.J. Lydy.  2004.  Distribution and
toxicity of sediment -associated pesticides in agricultural-dominated
water bodies of California’s Central Valley.  Environmental Science
and Technology.  38:10:2752 - 2759).  For this reason, we cannot define
specific use patterns or applications that will not automatically
require sediment testing.

COMMENT   One commenter (#120) wanted EPA to specify in the test notes
when freshwater or marine organisms must be tested for sediment
toxicity.

RESPONSE   Nearly all chemical contaminants entering coastal waters are
likely to accumulate in estuarine or marine sediments.  Therefore,
sediment toxicity data are required for marine/estuarine test species if
the product is intended for direct application to the estuarine or
marine environments, or the product is expected to enter this
environment in concentrations which the Agency believes to be
significant, either by runoff or erosion, because of its expected use or
mobility pattern.  Refer to test note 23 in the final rule for the
specific wording.

COMMENT   The Agency received three comments (#113, #124, #137)
regarding the Agency’s requirement for using spiked sediment in the
studies as opposed to the EU’s requirement for using spiked water. 
They believe that this difference results in less harmonization and
additional studies to address the same basic risk question.  They
proposed that the Agency should adopt the spiked water procedure
currently in use instead of imposing a new study design.

RESPONSE   The Agency requires spiked sediment testing to better
understand the potential effect of sediment bound pesticide to benthic
organisms. Test methods to address this information need are also
covered in the OECD Guidelines 218. The OECD Guideline 219 study relies
on spiked water as opposed to spiked sediment.  Although the Agency
usually accepts the 219 study as supplemental information, the study
does not address the Agency’s concerns regarding the prolonged
exposure of sediment bound pesticides to sediment-dwelling organisms.
The OECD Guideline 219 spiked water study does not include equilibration
of pesticide bound sediment with pore water, which can affect the
bioavailability of the compound in this compartment.  

 

COMMENT    The Agency received one comment (#82) regarding an acute pore
water test as part of the sediment testing scheme.  The commenter
questioned the utility of an acute pore water test for regulatory
purposes because many benthic species aerate their immediate environment
by actively circulating overlying water through their burrows and thus
the toxic effect may be more closely associated with water column
concentrations than with pore water concentrations.  They recommended
that a whole sediment toxicity test is more appropriate because toxicity
will be captured from all routes of exposure.

RESPONSE   Whole sediment toxicity testing captures all routes of
exposure and consists of the sediment and associated pore water. The
Agency does not require separate pore water testing.  Pore water
toxicity is an important part of these tests as these data provide
additional information on toxic exposure to benthic organisms other than
through direct contact or ingestion of sediment particles. 
Concentrations of chemicals in pore water can be calculated from the
corresponding sediment concentration if they are not measured directly. 
The registrant must address pore water issues when they design the
study. [Guide for planning and conducting sediment pore water toxicity
identification evaluations (TIE) to determine causes of acute toxicity
at Navy aquatic sites.  Naval Facilities Engineering Service Center. 
User’s Guide UG-2052-ENV.  Prepared by Science Applications
International Corporation.  Newport, Rhode Island 02840.  March 2003. 
http://web.ead.anl.gov/ecorisk/methtool/pdf/ug-2052-tie.pdf]

2.  Fish Acute

COMMENT   The Agency received three comments, from #124, #125 and #133,
regarding the fish acute data requirement.  The comment asked for
clarification regarding the number of freshwater fish studies that are
now required.  According to their interpretation, the new rule seems to
suggest that a second fish species would be required to support
greenhouse and indoor uses. This is clearly supported in Table 3 of the
proposed rule, however EPA should review the text description for
clarity.  Currently, Part 158 requires two freshwater fish studies with
the TGAI to support terrestrial and aquatic (food crop and nonfood),
forestry, and domestic outdoor uses and conditionally requires one of
these studies for greenhouse (food crop and nonfood) and indoor uses.

RESPONSE   With regard to greenhouse use, the Agency requires the
testing of one fish species for labeling purposes.  If the LC50 < 1 ppm
no other fish species testing is required. However, if the LC50 is
between 1 and 100 ppm a second species will be required.  Although this
appears counterintuitive, the rationale reflects the need for labeling
for greenhouse use since the Agency does not conduct quantitative risk
assessments on this use.  If the LC50 is < 1 ppm, the label statement
(toxic to aquatic organisms, etc) is used.  If the LC50 is between 1 and
100 ppm a second fish acute test would be required to substantiate the
potential for hazard to aquatic organisms and to ensure the appropriate
labeling (e.g., if the second fish study produces an LC50 < 1 ppm).   
SEQ CHAPTER \h \r 1 [Note– EPA guidance documents for the fish acute
toxicity study indicate that testing above 100 ppm would not be needed
as the toxicity category for test concentrations > 100 ppm is
“practically nontoxic”.   This ecotoxicological category of toxicity
is adapted from Insecticides, Brooks, H.L. et al. (1973) Cooperative
Extension, Kansas State University, Manhattan, Kansas.  Refer to
Pesticide Reregistration Rejection Rate Analysis: Ecological Effects. 
EPA 738-R-94-035.  December 1994; and the Agency’s Technical Overview
of Ecological Risk Assessment

Analysis Phase: Ecological Effects Characterization.  (  HYPERLINK
"http://www.epa.gov/oppefed1/ecorisk_ders/toera_analysis_eco.htm" 
http://www.epa.gov/oppefed1/ecorisk_ders/toera_analysis_eco.htm )  which
lists the Program’s ecotoxicity categories for terrestrial and aquatic
organisms.]

3.  Fish Chronic

COMMENT   The Agency received one comment (#124) regarding the
description of chronic testing with saltwater organisms.  In Section
X.3.vii of the draft preamble, the Agency discussed the needs for the
fish early life stage test and the invertebrate life cycle test for
freshwater species, but did not discuss these studies for saltwater
species.

RESPONSE   Although discussion of chronic tests with saltwater species
was missing from the preamble, the draft test notes in the proposed
regulatory text adequately indicated the conditions and use categories
for requiring these tests with saltwater species.

COMMENT   One commenter (#122) suggested that the Agency take into
consideration the difficulties of using EEC - based triggers for the
chronic studies.  They also stated that there is no justification to
limit chronic studies to those products with high acute toxicity.

RESPONSE   The Agency affirms that chronic studies are required to
support registration of an end-use pesticide product that is applied
directly to water or is expected to be transported to water from the
intended use site. These study requirements reflect the uncertainty that
surrounds pesticide exposure and their potential for impact to aquatic
organisms. Since exposure is a major driving parameter is assessing
acute and/or chronic risk, this factor must be defined and addressed.
However, when this information is lacking, the Agency generally
evaluates the need for chronic testing by assessing the likelihood of
risk occurring and if any of the following conditions apply: 1)
pesticide is persistent in the aquatic environment and is expected to be
present in water in a continuous or recurrent manner; 2) the chemical
accumulates; 3) EEC or actual water concentrations are < 0.01 of the
acute toxicity values; 4) pesticide mode of action or other studies show
that reproductive physiology may be affected from exposure.

COMMENT   The Agency received one comment (#122) that questioned why the
fish life cycle study can be required based on the relationship between
the EEC and the no-observed-effect level in the invertebrate life cycle
study.

RESPONSE   The Agency uses the data from the fish life-cycle study to
evaluate risk from chronic pesticide exposure to fish reproduction and
other life stages.  The Agency can use the results of reproduction
studies from any other organism, including invertebrates, if the data
suggest that the reproductive physiology of fish can also be impacted.

4.  Testing of Degradates

COMMENT   The Agency received a comment (#114) that the data
requirements should include toxicity testing with degradates of
pesticides as they can present significant environmental risks. 

RESPONSE   The Agency evaluates degradates in relation to their
potential toxicity and does require appropriate testing on a
case-by-case basis if the degradate appears toxic.  If the environmental
fate data show the degradates can potentially persist, and Subpart F
toxicology data show they are toxic, then aquatic toxicity testing is
required.

5.  Sublethal Endpoints

COMMENT   One commenter (#127) stated that toxicity test results for
sub-lethal endpoints other than growth and reproduction are also
necessary.  For example, effects on behavior, swimming performance, and
reproduction can be critical to the survival of a species

RESPONSE   The Agency does summarize sublethal endpoints in the risk
assessment process when this information is available. Acute and chronic
study guidelines require that the study authors report sub-lethal
effects if there is an occurrence (swimming performance, lethargy, etc);
the extent to which behavioral or swimming performance data is used in a
quantitative fashion is limited by uncertainty in relating these
responses to quantitative responses in demographic rates (e.g.,
mortality, reproductive fitness) that underlie population responses.

 

6.  Bioaccumulation Testing

COMMENT   Three commenters (#120, #124, #137) stated that the test notes
for the bioaccumulation and bioavailability studies were unclear and did
not adequately describe the conditions under which the studies would be
required.

RESPONSE   The Agency also received several comments about these studies
under the environmental fate data requirements.  This suite of studies
was included in not only the aquatic organisms data requirements, but
also in the environmental fate data requirements.  Those who commented
about the studies in both tables stated that test note 10 in the draft
fate table was well-written and descriptive of the conditions for
requiring these studies.  They recommended that test note 10 should
replace the test note for these studies in the aquatic organisms table. 
For the sake of clarity, the bioaccumulation/bioavailability data
requirement was deleted from the environmental fate data requirements
table in the final rule, Subpart N, and test note 10 from the draft fate
table (Not required when the octanol/water partition coefficients of the
pesticide and its major degradates are less than 1,000; or there are no
potential exposures to fish and other nontarget aquatic organisms; or
the hydrolytic half-life is less than 5days at pH 5, 7, and 9) is now
test note number 19 for these studies in the Subpart G in the final
rule.

7.  TEP testing  

COMMENT   EPA proposed to require acute testing with the TEP for
freshwater and estuarine organisms based on either the introduction of
the TEP directly into an aquatic environment or the estimated
environmental concentration of pesticide equaled or exceeded one-half
the LC50 of the TGAI when the end product was used as directed or an
ingredient in the formulation was expected to enhance the toxicity of
the active ingredient or to directly cause toxicity to aquatic
organisms. One comment (#137) recommended that TEP testing with
estuarine organisms should be conditional based on the results of TEP
testing with freshwater organisms, or if estuarine organisms were more
sensitive to the TGAI than were freshwater organisms.  

RESPONSE   The Agency requires TEP testing of freshwater and estuarine
organisms for all outdoor uses. As the environments of the estuarine and
freshwater organisms are different, how the chemical ingredients that
comprise a formulated product will react in the different aquatic
systems cannot be readily predicted. Therefore, the responses of each
group of organisms are independent of each other, necessitating testing
of both freshwater and estuarine organisms with the EP in addition to
the TGAI, if the triggers in the test note (9) are met.

Plants

1.  Nontarget Plant Guidelines and Harmonization

COMMENT  The Agency received six comments (#112, #122, #123, #124, #137,
#139) stating that the data requirements for nontarget plant testing
should not be promulgated if the test guidelines upon which the data
requirements rely are not finalized. 

RESPONSE   While the final rule deals solely with data requirements for
conventional pesticides, the Agency recognizes the importance of the
connection between these final data requirements and the guidance
documents that provide information on how the data requirements may be
satisfied.  The Agency is in the process of updating its nontarget plant
test guidelines with the OPPTS and the OECD.  Guidelines are scheduled
to be completed and available to the public by late 2007.  Nonetheless,
guidelines are guidance documents only, and the promulgation of data
requirements does not depend on the availability of guidance documents.

COMMENT   Two additional comments (#122, #124) also encouraged the
Agency to harmonize the respective guidelines for these studies. Two
comments mentioned that OECD is currently considering draft guidelines
for seedling emergence and vegetative vigor studies.  They encouraged
the Agency to harmonize the respective guidelines for these studies.  

RESPONSE   The comment in this section speaks more towards guidance that
is being proposed by OECD regarding individual non-target plant data
requirements and the specifics on how to conduct the individual studies.
 The Agency is a participating member of OECD and will harmonize with
these plant guidelines when they are completed.

2.  TGAI vs. TEP as the Test Material

COMMENT   Six commenters (#113, #122, #124, #125, #133, #137) expressed
concerns about the requirement that the TEP is the test material for the
terrestrial plant studies.  The stated preference was that use of the
TEP as the test material be changed from a requirement to a
recommendation, with the TEP considered the preferred or standard test
substance.  An alternative to the Agency’s proposal was that the test
substance may alternatively be applied as either a formulation other
than the TEP or as the Technical Grade Active Ingredient (TGAI) if there
are issues or difficulties related to the use of the TEP for these
studies. 

COMMENT   The most common concern expressed by the commenters was the
issue that during the development of a new product containing a new
active ingredient (AI), the final formula for the end use product may
differ from what was used in the testing.  Furthermore, the company that
develops the active ingredient and conducts the Tier I seedling
emergence and vegetative vigor studies and the Tier I aquatic plant
growth studies does not necessarily formulate the end products for that
active.  The developer of the AI may not necessarily know what use
patterns and TEP(s) the formulators may produce.  One of the commenters
raised the issue that this will create data compensation issues if a
formulator develops uses unknown at the time the AI is being developed.
The formulator appears to be required to generate data with TEP.  They
also stated that it is unclear whether the Agency expects new data each
time the composition of an existing TEP is changed.  In many cases,
these changes would not be expected to significantly change the results
of the test.  The Agency should be cognizant of this and require testing
of a formulation representative of the TEP.

RESPONSE   The Agency recognizes that new AIs in the early stage of
development may not have the final formula(s) for end-use products with
the new AI. The Agency expects that the adjuvants that enable the new AI
to penetrate the plant cuticle or be translocated to a plant’s site of
action effectively, to be used at the maximum percentage as it is
anticipated when the AI is marketed.  The Agency may require additional
testing if the final formulation appreciably differs from that tested. 
Data generated with TEP is usually done by the registrant, that is, the
company submitting the application for the registration of the proposed
use.  As new uses are proposed, the Agency makes a brief determination
if additional data are needed based on the use pattern, toxicity of the
chemical to the organisms and the persistence of the chemical to the
environment.  The Agency also wishes to point out that the regulations
specify that the aquatic plant (Tier I and II) be tested with either the
TGAI or the TEP.  The terrestrial plants (Tier I and II) must be tested
with the TEP.  

COMMENT   Other comments (#113, #122, #124, #137) concerned the
possibility that the TEP may be composed of a mixture of two or more
active ingredients.  They expressed the concern that as adverse effects
on plants are based on exposure to a single AI, it would be necessary to
modify the TEP to include only a single AI, or use the TGAI rather than
the TEP in order to obtain data on a single AI.  In this case, for
products that are in development at the time plant testing is conducted,
it is possible that some minor refinement to the formulation may be made
between the time testing is initiated and the product formulation is
finalized.  In this case, the plant tests may have been conducted on a
formulation that is similar to the TEP, but is not an exact match to the
TEP that is commercialized. Under these circumstances, testing of a
formulation that is representative of the TEP rather than testing
required to be of the TEP may be more appropriate.

RESPONSE   The Agency’s response is that mixtures of active
ingredients, if required to be tested, will be with TEP.  As to whether
mixtures are tested, this will be determined on a case by case basis. 
Rarely does the Agency require testing of mixtures.	

3.  Expansion of Data Requirements     

COMMENT  The Agency received one comment (#133) regarding the statement
in the draft Preamble that  "EPA is not proposing any major changes to
the plant protection data requirements from those currently listed in
Part 158."  The commenter believes that this statement appears to
overlook the fact that EPA has in fact expanded the data requirements to
include outdoor residential uses, which were never subject to these
requirements, and expands the product testing to include not only TGAIs
but TEPs as well.  According to the commenter, EPA does not provide any
explanation as to why this increase in the scope of the requirements to
include end-use products as well as TGAIs is necessary.  They suggest
that these requirements be removed.

RESPONSE   The Agency has been requesting non-target terrestrial plant
tests with TEP for a number of years.  Commenter # 124 understands that
the change is bringing 158 into agreement with current policies and
guidelines, and they acknowledge this in their statement “This
revision is in line with current OPPTS guidelines and current Agency
practices.”  Many of the herbicide active ingredients cannot
significantly harm plants unless there are adjuvants available to help
the chemical penetrate the plant defenses (i.e. surfactants, etc.). 
Outdoor residential uses are now included among the sites requiring
plant testing because data indicate that herbicide uses on these sites
such as turf can harm nontarget plants through runoff.  Turf is
classified an outdoor residential terrestrial use, and therefore
requires nontarget plant testing.

4.  Nontarget Plant Testing for Indoor Uses 

COMMENT   One commenter (#120) asked for an explanation as to why the
Agency included indoor uses among those requiring nontarget plant
testing.

RESPONSE   The Agency acknowledges that including indoor uses among
those requiring plant testing was an error.  The table in the final rule
is corrected.  Non-target plant testing is not required for indoor use. 
Additionally, in response to this comment, testing for aquatic non-food
residential use is also eliminated.

5.  Species Testing

COMMENT   The Agency received three comments with differing opinions
regarding the numbers and types of plant species that Agency requires to
be tested.  One commenter (#124) recommended that testing of five
aquatic species should not be required for pesticides that are not
herbicides.  The need for testing of other species should be based on
the EC50 values of the two species tested and the EEC.

RESPONSE   The Agency found that a survey of the herbicides and
insecticides for which aquatic plant data were submitted under FIFRA
showed that the most sensitive aquatic species can be any one of the
five species tested for herbicides and insecticides.  The Agency,
therefore, requires five aquatic plant species for non-herbicidal
pesticides.

COMMENT   Two commenters (#82, #128) stated that EPA should increase
the range of species tested in nontarget plant protection studies.  The
proposed data requirements leave unchanged EPA’s current practice of
requiring terrestrial plant testing on only ten species.  All of these
species are annual agricultural or vegetable plant species.  These ten
species are considered by the Agency to be surrogates for the 16,000
native plant species in the U.S.  One of the commenters would like to
see a movement away from the typical 10 crop species and a movement
towards inclusion of non-crops to represent more ‘ecologically
relevant’ species.  For example, hardwood trees, native shrubs,
conifers, native grasses, and ferns are all completely ignored.  One
commenter indicated that there is a list of suitable non-crop species
for testing in Annex 3 of the newly revised OECD Guidelines 208
(Seedling Emergence and Seedling Growth) and 227 (Vegetative Vigour,
March 21, 2006).  They recommended that this list should be included in
the EPA Guidelines since the EPA supported the OECD recommendation for
inclusion of non-crop species.

RESPONSE   The Agency agrees that some of the uncertainty inherent in
the use of crop species would be alleviated by the use of non-crop
species in toxicity testing.  To that end, the OECD Annex 3 table of
acceptable non-crop species will be incorporated into the 850.4100 and
850.4150 testing guidelines for Seedling Emergence and Vegetative Vigor
studies, respectively, to be harmonized with NAFTA and OECD.

6.  Additional Endpoints

COMMENT   One commenter (#128) stated that EPA should increase the
duration of nontarget plant protection tests and include reproductive
endpoints (endpoints that measure yield of fruit and seed).  Low dose,
high potency herbicides such as acetolactate synthase inhibitors have
been the subject of research over the last two decades because they move
away from target sites in water, on soil particles, and as spray drift,
and have caused reproductive injury to plants at herbicide
concentrations so low that did not produce visible leaf injury.  This
kind of effect can have ecosystem-level effects, but is currently
ignored by plant protection data requirements, in which the maximum test
length is 28 days, too short to capture the reproductive phase of most
species.

RESPONSE   The Agency acknowledges that having these additional
endpoints would significantly enhance the risk assessment analysis for
nontarget plants.  However, methodologies to measure these endpoints are
still under development.   Laboratory protocols are currently under
development for plant reproductive testing using various species. 
Following the development of plant reproductive effects testing
protocols, we will submit these protocols, and how they would be used in
risk characterization, to appropriate Agency, stakeholder and public
peer review. Then we will make efforts to incorporate these studies into
our risk assessment paradigm via appropriate processes. 

7.  TIER III Guidelines

COMMENT   The Agency received three comments (#122, #124, #137)
regarding the Tier III (field testing) study guidelines and the process
of problem formulation and refinement of the ecological risk
assessments.  They recommended that the field studies be conducted
within the context of problem formulation to characterize risks to
plants under actual use conditions.  Therefore, they believe that the
Tier III study guidelines should be revised as needed, to ensure the
studies provide useful information to refine the risk assessment and to
provide guidance on practical, manageable approaches to conducting these
studies.

RESPONSE   The Agency states that the comments in this section speak
more towards guidance for how to address individual non-target plant
data requirements and provide information that meets the needs of the
regulatory bodies. The problem formulation, relevant endpoints, and
approaches to conducting these studies are covered in the 850.4300
testing guidance as well as specifics on how to conduct the individual
studies.   Tier III non-target plant toxicity studies are conditionally
required.  These studies are required on case-by-case basis following
discussions with the registrant of the chemical(s) of concern.

8.  Proposed Test Note 3

COMMENT   The Agency received one comment (#122) regarding the placement
of proposed test note 3 for the Tier I and Tier II seedling emergence
studies.  The data table indicates that seedling emergence studies are
generally not required for granular formulations.  They indicated that
this is an error since the exemption for testing granular formulations
was previously directed at vegetative vigor studies rather than seedling
emergence studies. Additionally, the preamble indicated that vegetative
vigor studies are not required for baits as well as granular
formulations.  The test note should be corrected.

RESPONSE   The Agency acknowledges that proposed test note 3 was
inaccurately placed next to the seedling emergence studies.  This has
been corrected, and this test note now refers to the Tier I and Tier II
vegetative vigor studies in the final rule.

9.  Test Notes 5 and 6: The Conditions for Moving from Tier I to Tier II
Studies 

COMMENT   The Agency received one comment (122) asking for clarification
of test notes 5 and 6 which state that “if a terrestrial species
exhibits a 25 percent or greater detrimental effect” and “if an
aquatic species exhibits a 50 percent or greater detrimental effect”,
respectively.

RESPONSE   The Agency agrees that the wording of both test notes is
ambiguous.  

The new wording for test note 5 is, “Required if a tested terrestrial
species exhibits a 25 percent or greater detrimental effect in the Tier
1 study.  When Tier II testing is required, the test species must be the
species that showed detrimental effects in the Tier I testing.”

The new wording for test note 6 is, “Required if a tested aquatic
species exhibits a 50 percent or greater detrimental effect in the Tier
1 study.  When Tier II testing is required, the test species must be the
species that showed detrimental effects in the Tier I testing.”

COMMENT   Another commenter (#82) referred to the findings of the FIFRA
Scientific Advisory Panel (SAP) in 2001 when it convened to discuss the
proposed NAFTA Non-Target Plant Toxicity Tests.  The SAP indicated that,
progression from Tier I to Tier II should be based on a statistically
significant effect >10% relative to the control for aquatic plants and
between 50% to 25% for terrestrial plants.  This commenter recommended
that, as a conservative approach, however, to use the 25% for
progression from Tier I to Tier II for terrestrial plant studies.

RESPONSE   For terrestrial plants, the Agency agrees in that the
progression from Tier I to Tier II testing will remain 25% inhibition or
greater.  However, effects seen at less than 25% may raise concerns for
federally listed endangered and threatened species, and additional
testing at Tier II may be needed to mitigate the presumption of risk to
listed species.

10.  Requirement for ILV Testing in the Field Studies

COMMENT Five commenters (# 113, #122, #124, #125, #133) stated that the
proposed rule would "require independent laboratory validation [ILV] of
the environmental chemistry methods used to generate data associated
with [Tier III] studies".  According to them, the ILV requirement is
currently limited to methods for quantifying residues in food, soil,
water and air.  The proposed revision does not state which additional
matrices are to be addressed nor how the ILV would be used. The
requirement for ILVs would add an additional burden to the registrants
if ILVs are required for the spray mixture or other matrices for which
there are no current ILV requirements. They recommend that the proposed
requirement be clarified to accept ILV conducted to meet similar
requirements under Subparts N or O for residue chemistry and
environmental fate.  In their opinion, the need for additional ILV of
methods for these Tier III studies should be rare.

RESPONSE   An independent laboratory validation verifies that the
analytical method, as written by the study director, can be performed by
a second laboratory and that laboratory can achieve similar performance
results.  This ensures that other stakeholders interested in monitoring
for the pesticide will have an acceptable method to do so.  Tier III
plant studies are usually very rare and are requested only when
significant concerns for non-target plant risk are expressed.

	GLP standards in 40 CFR part 160 do not require ILV.  Use of ILV is
specified in the Ecological Effects Test Guidelines, OPPTS 850.7100 Data
Reporting for Environmental Chemistry Methods (ECMs).  This is a
harmonized guideline which has been in effect since the mid-1990s, and,
as such, is a codification of current practice.  Guideline 850.7100
states that all methods, including ILV, should be conducted under GLP. 

Discussion of Comments on Human Exposure Data Requirements (Subpart K)

	The current data requirements in part 158 do not contain studies to
determine applicator exposure from pesticide use.  Since EPA believes
these data are essential for fulfilling its mandate to protect human
health from pesticide risk, including aggregated and cumulative risks,
it proposed to make to make applicator exposure studies a standard part
of its regulatory requirements.  EPA proposed to codify applicator
exposure data requirements in a new subpart to cover agricultural
applicators, occupational applicators, and residential applicators.

Data Requirements for Applicator Exposure

COMMENT:	Commenter 82 compared the U.S. data requirements with those of
Canada and concluded that in general, the U.S. data requirements
outlined in the proposed rule are now more harmonized with the Canadian
data requirements.  

RESPONSE:  The U.S. has added data requirements for applicator exposure
and more specific data requirements for post-application exposure,
particularly for residential sites and some occupational sites such as
greenhouses.  The conditions under which data are required are very
similar to Canadian conditions.  Comparisons of proposed U.S. and
Canadian data requirements are somewhat complicated; data requirements
are based on use site categories that are classified slightly
differently between the two countries and the types of studies required,
while being essentially the same, are named differently.  However, in
the final analysis the data requirements are now very similar.

	 

COMMENT:  Commenter 120 believed the exposure criteria that would
trigger applicator exposure studies were “so broad as to be
meaningless.”  This commenter believed that it would be preferable
“to state that these data requirements always apply except where
pesticides are applied via a completely closed system with no potential
for exposure during mixing, loading, or application, if that is the
Agency’s intent.  Otherwise, the Agency should clearly define the
conditions under which these data requirements are applicable.”

RESPONSE:  The Agency considers various factors such as:  hazard
(toxicity) of the active ingredient; incident report; information on
types of exposure; levels of exposure, duration of exposure; and methods
of application in considering whether to require chemical-specific
exposure data.  In making a judgment, the Agency also considers the
availability of surrogate data.  The Agency data based on exposure
assessment of individuals performing mixing/loading activities using
closed systems indicate that the individuals are indeed exposed,
although at rates lower than rates using open systems.  For very toxic
chemicals, estimates of exposure using closed systems can still result
in exposures of concern.  Furthermore, there are many types of closed
systems for which the Agency does not have data.  Therefore, the Agency
will retain the approach discussed above and believes it is more
flexible than “broad.”

COMMENT:	Commenter 120 strongly recommended that EPA rely on
determinations and/or surrogate data estimates for exposure from other
agencies such as the Occupational Safety and Health Administration
(OSHA) and recommended “that the Agency accept OSHA workplace exposure
limits in lieu of a requirement to conduct a specific study” and
“strongly recommends the Agency use surrogate data where
appropriate.”

RESPONSE:   The Agency does consider OSHA standards.  It must be noted
though that OSHA standards are developed for industrial workplace
exposures, which are likely to be enclosed workplaces.  Conventional
agricultural pesticide chemicals that are applied outdoors can present a
very different use scenario.  OSHA standards may not be based on a
toxicity database as robust as that generated by registrants to support
their products.   The Agency will rely on the most dependable database. 

	The Agency has a long history of relying on surrogate exposure data and
databases.  To estimate occupational and residential exposures, the
Agency uses databases containing large numbers of measured values of
dermal and inhalation exposure for pesticide workers.  Using these
measured data from one study/scenario as surrogate or generic data for
another study/scenario is appropriate since it is generally believed
that the physical parameters of the handling and application process
(e.g. the type of formulations, the method of application, and the type
of clothing), not the chemical properties of the pesticide, control the
amount of dermal and inhalation exposure.  

	However, for certain types of pesticide formulations or use scenarios,
there is no exposure data, and therefore, it is not possible to perform
an occupational/residential risk assessment.  This is particularly one
of the types of situations in which the Agency would require
chemical-specific exposure data.

 

COMMENT:	Commenters 125 and 133 asked “What will the criteria actually
be for each of the noted categories? Will the Agency publish the
threshold adverse effect levels for each category? Would generic data be
acceptable to fill the data requirements?”

RESPONSE: The proposed criteria in the rule were the toxicity data
requirements to be considered rather than specific values.  EPA can be
more transparent about the basic risk assessment process but further
transparency is difficult when the detailed process for an individual
pesticide is contingent on the data from multiple studies in the
database.  When assessing exposure and risk, EPA considers the toxicity
data in its database together with the exposure data for the pesticide. 
Depending on the nature of the pesticide being evaluated, any number of
toxic effects may be selected for the risk assessment.  These toxic
effects may be found from any of the following studies in the toxicity
database.  

870.3100    90-day Oral -- rodent	

870.3150    90-day Oral – non-rodent	

870.3200    21/28-day dermal	

870.3250    90-day dermal	

870.3465    90-day inhalation -- rat	

870.3700  Prenatal developmental toxicity – rat and rabbit preferred

870.3800    Reproduction and fertility effects	

870.4100  Chronic oral toxicity -- rodent	

870.4200  Carcinogenicity – rat and mouse preferred	

870.6100  28-day delayed neurotoxicity -- hen

870.6200  90-day neurotoxicity -- rat	

870.6300    Developmental neurotoxicity	

870.7485    Metabolism and pharmacokinetics

870.7600    Dermal penetration	

	EPA then identifies any adverse effects in the toxicity database that
are relevant to the type of exposure for the pesticide.  It is not
possible to predict beforehand which adverse effects will be relevant to
a type of exposure.  The exposure data may be surrogate data from an
exposure database or chemical-specific exposure data.  The relevant
adverse toxicity data and the exposure data are then considered together
in the risk assessment.

	The Agency has a long history of relying on surrogate exposure data and
databases. However, for certain types of pesticide formulations or use
scenarios, there is no exposure data, and therefore, it is not possible
to perform a risk assessment.  This is the type of situation when the
Agency would require chemical-specific exposure data.  

Dermal exposure studies

COMMENT:	Commenters 108, 110, 124 and 134 said that the Agency proposes
to add data requirements for both outdoor and indoor dermal exposure
studies (Guidelines 875.1100 and 875.1200). Guidelines 875.1100 and
875.1200 were developed utilizing OPP guidelines 230 and 231 as source
material. However, few changes were made in updating from 230, 231 to
875.1100 and 875.1200. Because of this the methodology described in the
guidelines is not current and inconsistent with the methodology being
used in studies.

RESPONSE:  See response under Inhalation exposure studies.

Inhalation exposure studies

COMMENT:	Commenters 108, 110, 124, and 134 pointed out that Guidelines
875.1300 and 875.1400 were developed using OPP guidelines 230 and 232 as
source material but few changes were made in updating from 230 and 232. 
Because of this the methodology described in the guidelines is not
current with the methodology used in studies.  

RESPONSE:   EPA acknowledges that these four guidelines were finalized
in 1996 and that scientific knowledge has progressed in the
approximately 10 years.  The Agency has reviewed and accepted for use in
various risk assessments many studies that are categorized as
non-guideline.  As the commenters have stated above, other methodologies
are being used in studies that are being reviewed by the Agency.  The
Agency will consider these comments as its scientists work to
revise/update the guidelines.

Biological monitoring

COMMENT:	While Commenters 110 and 124 supported including biological
monitoring as a conditional data requirement, they wondered if the
Agency would be permitted to evaluate such studies because of the Boxer
amendment imposing a one-year moratorium on such evaluations.  They were
joined by Commenters 113, 133, and 134 in recommending revision of the
requirement to permit the use of rodent or primate pharmacokinetic data
with supporting rationale regarding the applicability of the use of data
from a non-human species.

RESPONSE:  EPA will comply with any statutory or regulatory requirements
concerning human research and will modify its data requirements if
necessary.  EPA promulgated a final human studies rule on April 7, 2006
(71 FR 6137, February 6, 2006) covering types of human research.  In
many, if not most or all cases, biomonitoring studies conducted on
pesticides will be subject to the new requirements of the final rule. 
The Agency believes that the use of rodent or primate pharmacokinetic
data in conjunction with human biomonitoring studies would significantly
increase the uncertainties of the exposure data, and the resulting risk
assessment.  

Data reporting and calculation information

COMMENT:	Commenters 108, 110, 124, and 134 addressed Guideline 875.1600
by indicating that there is no mention of Good Laboratory Practices
(GLP) report requirements or PR 86-5 report-writing guidelines.  They
wondered if the Pesticide Handlers Exposure Database (PHED) remain a
viable option for new surrogate data since the proposed rule mentions
submitting data in a format for submission into PHED.

RESPONSE:  Guideline 875.1600:  Application Exposure Monitoring Data
Reporting specifies the data needed by Agency scientists for an
appropriate level of review and evaluation, and offers a format that the
Agency has found useful.  The guideline was written by science reviewers
for the scientists actually generating the data in a performing
laboratory.  The studies are eventually sent to the Agency, not by the
performing laboratory, but by the “person” who paid for the study. 
The GLP statement and the other PRN 86-5 specifications are
administrative elements for inputting the study into the Agency’s
Master Record Identification (MRID) system.  Such formatting is
considered to be the responsibility of the submitter, not the performing
laboratory.  

	The guideline currently contains a statement about submitting a
diskette for entry into PHED and reflects the electronic format
available when the guideline was finalized in 1966.  The next revision
of PR 86-5 will reflect the preferred format(s).  The Agency does not
plan to add new surrogate data into PHED but will continue to consider
the data already in PHED.  The fate of PHED and the generation of new
data are dependent on Agency efforts to take AHETF study designs to the
Human Subjects Review Board (HSRB).  The Agency approach for evaluating
data in PHED was the subject of a recent FIFRA Scientific Advisory Panel
(SAP) in January 9-12, 2007.   The Agency’s analysis will continue
throughout this year.  

Product use information

COMMENT:	Commenters 108, 110, 124, and 134 were concerned that Guideline
875.1700 does not appear in the official final form of the OPPTS
Harmonized Test Guidelines for Occupational and Residential exposure. 
They questioned the imposition or codification of a “data requirement
that relies upon or references a guideline that does not officially
exist” and recommends the Agency finalize and issue revisions to the
875 series of guidelines before imposing data requirements.

RESPONSE:  The Agency agrees that not all of the 875 Guideline Series
for Occupational and Residential Exposure have been finalized.  However,
the language for 875.1700 will be similar to 875.2700. The latter
guideline is one of the draft Guidelines that were presented to the
FIFRA Science Advisory Panel (SAP) in March 1998 appear on the
Agency’s website at   HYPERLINK
"http://www.epa.gov/scipoly/sap/meetings/1998/march/contents.htm" 
http://www.epa.gov/scipoly/sap/meetings/1998/march/contents.htm .  The
Agency will be able to devote resources to finalization of the test
guidelines after meeting some more pressing deadlines and believes the
test guidelines will be finalized at the end of 2008.  In addition, the
Agency’s scientists can provide guidance to registrants or task forces
on aspects of study design and are always willing to work with
individual registrants to develop study designs for fulfilling data
requirements.

  

COMMENT:	Commenter 133 asked if product use information is simply the
label.  This commenter also wondered if recently submitted general task
force data provide such information.

RESPONSE:  Often the label is not descriptive enough of the exposure
scenarios, in particular, timing of applications and frequency of use.  
Data such as those data that are available in the Residential Exposure
Joint Venture (REJV) survey can be acceptable.  The Agency will consider
these comments as its scientists work to finalize the guidelines at the
end of 2008. 

Use of surrogate data

COMMENT:	Commenters 125 and 133 noted the discussion of the PHED
database, the mention of the Outdoor Residential Exposure Task Force
(ORETF) but no mention of Residential Exposure Joint Venture (REJV).
They said the Agency should not be singling one particular task force
for mention but should discuss all of the task forces that have
developed data.

RESPONSE:	 The commenters are correct in that the proposed rule on page
12309 state “[s]urrogate data may be obtained from several reliable
sources,” and then only discussed the use of PHED and ORETF surrogate
data.  Some of the other task forces that have generated exposure data
are the Indoor Residential Exposure Joint Task Force, the Agricultural
Handlers Exposure Task Force, and the Agricultural Reentry Task Force.  

Data Requirements for Post-Application Exposure

	The re-entry protection data requirements in the current CFR are being
revised because they no longer meet the needs of the Agency in all
post-application settings.  The 1984 data requirements were developed to
assess the risks to agricultural workers and others who must enter a
treated field.  EPA has been concerned about exposure to pesticides in
occupational and residential settings and the proposed codification of
data requirements reflects this concern.  The proposed data requirements
would allow EPA to assess aggregated and cumulative risks with special
emphasis on children. 

COMMENT:  Commenter 128 believes that for some pesticides, inhalation
exposures may comprise a substantial fraction of the total exposure that
EPA currently does not evaluate for non-fumigant pesticides.  This
commenter urged EPA to use the existing information collected by the
California Air Resources Board (CARB) and referenced several articles in
open literature.  Commenter 128 also supported changing the data
requirement for inhalation exposure (875.2500) from conditionally
required to required and recommended that vapor pressure and half-life
be used as a guide to potentially problematic chemicals early in the
risk assessment process.  

RESPONSE:  The commenter supports the Agency’s proposal to require
post-application exposure data, in particular, for the inhalation route.
 As part of their comment, they cited data available from CARB
indicating off-site migration of volatile pesticides from agricultural
sprays having vapor pressures of greater than 1 x 10-6.   The Agency
acknowledges that there is a potential for exposure from this pathway
and will consider such factors such as vapor pressure and the half-life
of semi-volatile compounds when identifying chemical-specific data
requirements.

COMMENT:	Commenter 133 was concerned that the preamble indicated that
post-application exposures have been associated with a significant
proportion of reported incidents in the record and felt such conclusions
were inappropriate in the absence of any substantiation.  This commenter
stated that in many cases incidents reported to PCCs (poison control
centers) cannot be conclusively linked to pesticide use. 

RESPONSE:  The Agency relies on a number of sources for incident data,
including poison control centers.  The reliability of the information is
evaluated on a chemical-by-chemical basis.

COMMENT:	Commenter 133 requested a better definition as to when soil
dissipation would be required for residential settings.

 RESPONSE:   Soil residue dissipation (Guideline No. 875.2200) is CR for
residential use patterns.  Test Note 7 for this data requirement states
that data are required for residential sites if the pesticide is applied
to or around soil or other planting media both outdoors and indoors,
e.g., residential greenhouse or houseplant uses.

COMMENT:	Commenter 133 believed that requiring Dermal exposure and
Inhalation exposure studies (guidelines 133-3 and 133-4) for residential
use will create problems for formulators and wondered whether modeling
or other generic task force data would be acceptable.

RESPONSE:  The commenter had not indicated the types of problems that
could be created as a result of requiring these data in residential use
patterns.  In the absence of the specific problems, the Agency can only
state that modeling or other generic data may be acceptable.  Applicants
are encouraged to discuss their considerations in those areas with the
Agency.

COMMENT:	Commenter 133 believed that the post-application exposure
requirements were newly imposed, contrary to the discussion in the
preamble, and that a great deal more data is actually being proposed for
collection than is necessary or reasonable.

RESPONSE:  Post-application exposure data have been required for
agricultural uses since a DCI was issued in 1995.  Since FQPA in 1996,
the Agency has routinely conducted residential exposure assessments for
all active ingredients that have use patterns indicating the potential
for residential exposures if the screening-level risk assessments
identify risks of concern.   For residential exposure assessments, the
Agency’s Standard Operating Procedures (SOPs) for Residential
Exposures can be used by Agency assessors.  	

Criteria for testing

COMMENT:	Commenter 133 pointed out that the two criteria for requiring
post-application exposure data were retrospective, not prospective.  The
commenter wondered how an applicant would know how to apply the criteria
if the active ingredient is new and no incident data or use history was
available.

RESPONSE:  	The Agency does not expect incident data for new products
with new active ingredients. 

Biological monitoring

COMMENT:	Commenters 125 and 133 wondered what alternative studies were
possible if Congress banned human testing.  

RESPONSE:    EPA will comply with any statutory or regulatory
requirements concerning human research and will modify its data
requirements if necessary.  EPA promulgated a final human studies rule
on April 7, 2006 (71 FR 6137, February 6, 2006) covering types of human
research.  In many, if not most or all cases, biomonitoring studies
conducted on pesticides will be subject to the new requirements of the
final rule.  

COMMENT:	Commenter 133 asked for options when the Agency requires a
biological monitoring study where swimmers are exposed and passive
dosimetry methods are not feasible. 

 RESPONSE:  When swimmers are exposed and passive dosimetry methods are
not feasible, the Agency relies on a swim model that that can also be
used in place of biological monitoring. 

COMMENT:	Commenters 125 and 133 indicated that the biological monitoring
data requirement (875.2600) will place additional testing requirements
on formulators unless other generic task force data are acceptable.  

RESPONSE:  The Agency believes that the development of generic task
force data could be possible for almost all active ingredients. 
However, for certain pesticide formulations or use scenarios, there is
no exposure data.  In this type of situation, the Agency would require
chemical-specific exposure data.

COMMENT:	Commenters 109, 110, 122, 124 and 134 supported using human
studies conducted under proper ethical guidelines, but were concerned
whether the Agency would be permitted to evaluate such studies because
of the Boxer amendment to the FY2006 appropriations.  These commenters
recommended that the Agency provide flexibility in the development of
the supporting pharmacokinetic data; the commenters also recommended
revising the data requirement to permit use of rodent or primate
pharmacokinetic data with supporting rationale for using data from a
non-human species.

RESPONSE:   EPA will comply with any statutory or regulatory
requirements concerning human research and will modify its data
requirements if necessary.  EPA promulgated a final human studies rule
on April 7, 2006 (71 FR 6137, February 6, 2006) covering types of human
research.  In many, if not most or all cases, biomonitoring studies
conducted on pesticides will be subject to the new requirements of the
final rule.  The Agency believes that the use of rodent or primate
pharmacokinetic data in conjunction with human biomonitoring studies
would significantly increase the uncertainties of the exposure data, and
the resulting risk assessment.

Product use information	 

COMMENT:	Commenter 133 suggested that product use information should be
covered by recently submitted generic task force data while Commenter
125 suggested that such information should be covered by the Non-Dietary
Exposure Task Force (NDETF) and Residential Exposure Joint Venture
(REJV) data.

RESPONSE:   The Agency agrees that recently submitted generic task force
data should cover most currently registered products.  However,
additional chemical-specific data for other products (different active
ingredients) not covered by NDETF may be required in the future.

Description of human activity

 COMMENT:	Commenters 109, 110, 122, 124 and 134 agreed with the Agency
that information describing the possible activities in which people may
be engaged after a site has been treated (Guideline 875.2800) is
essential for accurate assessment of post-application exposure. The same
commenters believe that there are several aspects of the proposed
requirement that are problematic. They believe that these needs may be
adequately fulfilled through the Agricultural Reentry Task Force (ARTF)
Survey.  The commenters go on to state that ARTF has generated and
submitted by far the most extensive and comprehensive survey of North
American agricultural post-application  exposure activities that has
been performed to date, or is likely to be performed for some time to
come, and should be cited as a comprehensive source of information
available to satisfy this data requirement.  

	Commenters 125 and 133 were pleased that human activity information
will become required information, including differences between adults
and children since these data have been generated by Outdoor Residential
Exposure Task Force (ORETF) and other task forces.

RESPONSE:   The Agency agrees that recently submitted generic task force
data should cover most currently registered pesticides.  However,
additional chemical-specific data for other products (different active
ingredients) not covered by task force data may be required, such as the
timing and frequency of use.

 

Data reporting and calculation information

	There were no comments regarding data reporting and calculation
information.

Nondietary ingestion exposure

COMMENT:	Commenter 133 believed the conditionally-required study to
evaluate potential oral exposure and the mention of “residue in the
rinsate from hand-washing” appears to imply intentional human dosing
and asked for an alternative if Congress bans human dosing.

RESPONSE:  First, Congress has not banned human dosing.  Consistent with
the Congressional direction to EPA in its 2006 Appropriations Act, on
February 6, 2006 EPA issued a final rule extending Common Rule
protections to non-pregnant, non-nursing adult human subjects of third
party research involving intentional exposure to pesticides (71 FR
6137).  The rule also forbids any new EPA or third-party research
involving intentional exposure of children or pregnant or nursing women,
and forbids EPA to consider in actions it takes under the pesticide laws
any research involving intentional exposure of children or pregnant or
nursing women, except under very narrowly defined circumstances when to
consider it would be more protective of public health than not to
consider it.

	The Agency's concern for potential non-dietary oral exposure of
children can be addressed in a way that is entirely consistent with
these new rules.  Several types of studies have been conducted in the
past and could be conducted in future under the new rules to explore
surface-to-hand transfers of residues from, e.g., lawns, other
plantings, decks, play structures, fabrics, indoor hard surfaces, etc. 
These studies use adult volunteers to determine how much residue per
unit area transfers to a hand in contact with a pesticide-treated
surface.  One method for measuring this transferred residue is by
washing and rinsing the hand and capturing the rinsate for analysis.  

	Results from this kind of study about how much residue transfers to an
intentionally exposed adult's hand can then be combined with data about
hand-to-mouth behavior of young children (from strictly observational
research) to estimate non-dietary oral exposures of children.  With
these estimates and other knowledge about the hazard of a pesticide the
Agency can assess the safety of the likely exposures of young children
without exposing them directly to the pesticide in question. 

COMMENT:	Commenter 133 believes the Nondietary ingestion exposure data
requirement (Guideline 875.3000) should be addressed by generic task
force data bases.

RESPONSE:   The Agency believes that the development of generic task
force data could be possible for almost all active ingredients. 
However, for certain pesticide formulations or use scenarios, there is
no exposure data.  In this type of situation, the Agency would require
chemical-specific exposure data.

Dislodgeable foliar residue dissipation and turf transferable residues

 COMMENT:	Commenters 109, 110, 122, 124 and 134 thought the application
of default factors for estimating these residues in current assessment
was sensible and encouraged the Agency to maintain the current default
policy to encourage sensible allocation of resources and include the
policy in the data requirement.  If the policy is maintained, the
commenters wondered whether is should be R as proposed.  As a member of
ORETF, Commenter 125 was pleased to see this data requirement proposed
as R.

RESPONSE:  The Agency encourages registrants to conduct
chemical-specific turf residue studies and concurrent dermal exposure
measurements.   The use of screening-level exposure assessments that
include the use of default factors remains an option for fulfilling this
data requirement provided that the screening-level risk is less than the
Agency’s level of concern.  

The Agency believes that the requirement should remain required rather
than conditionally required because it believes the data collected is
important in assessing this important exposure pathway.

COMMENT:	Commenters 125 and 133 wondered what alternatives are proposed
if Congress bans human dosing experiments since these residues are
typically measured by hand presses and do involve human exposures.

RESPONSE:  EPA will comply with any statutory or regulatory requirements
concerning human research and will modify its data requirements if
necessary.  EPA promulgated a final human studies rule on April 7, 2006
(71 FR 6137, February 6, 2006) covering types of human research.  In
many, if not most or all cases, biomonitoring studies conducted on
pesticides will be subject to the new requirements of the final rule.  

Soil residue dissipation	

COMMENT:	For this requirement, occupational is R, but residential is CR.
 Commenter 133 wondered what residential scenarios would trigger this
requirement.

RESPONSE:  The commenter should refer to Test Note 7, which is linked to
that data requirement, which states:  “Data are required for
residential sites if the pesticide is applied to or around soil or other
planting media both outdoors and indoors, e.g., residential greenhouse
or houseplant uses.”

COMMENT:	Commenters 109, 122, 124, and 134 requested clarification of a
trigger for this data requirement since there is available data on
chemical release from soil in other parts of the data package (i.e.,
potential exposure to treated soil does not directly relate to exposure
to the pesticide).  This commenter points out that uses exist in which
most of the material applied ends up in the soil, but for the vast
majority of agricultural and residential use scenarios, there is
currently no reason to believe that post-application contact with
treated soil is more than a negligible contributor to exposure.

RESPONSE:  The Agency proposed to expand the Soil Residue Dissipation
study to include broader agricultural, greenhouse, nursery, forest, and
residential settings.  This study will be required for occupational use
sites involving substantial exposure to treated soil and conditionally
required for residential use sites when there is information suggesting
that the pesticide is persistent.  

Dermal and inhalation exposure

COMMENT:	Commenters 109, 110, 122,  124 and 134 indicated that both ARTF
and ORETF have supplied comprehensive post-application exposure
databases to the Agency; ARTF and ORETF were primary suppliers of dermal
and inhalation exposure data for agricultural chemicals and lawns in
response to two major data call-ins.

RESPONSE:   The Agency agrees that the two task forces have submitted
dermal and inhalation exposure data to the Agency.  All of the submitted
data has not yet been completely reviewed and therefore cannot be
included in the Agency database at this time.   The Agency believes that
there may still be post-application exposure scenarios in
non-agricultural settings for which dermal and inhalation exposure data
could be needed for residential risk assessments.  Additionally,
registrants who are not members of the two task forces need to submit
their own data or find some other way to satisfy the data requirements.

COMMENT:	Commenter 125 believed that requiring data on dermal and
inhalation exposure in residential uses would create problems for
formulators and asked if modeling from ORETF data would be acceptable.

RESPONSE:  Since the commenter did not indicate what specific types of
problems would be created for formulators, the Agency did not find it
possible respond with any specificity.

Use of surrogate data

COMMENT:	Commenters 109, 110, 122, 124, and 134 believed that the
discussion in the preamble about generally not using surrogate data for
any of the post-application residue data requirements may be misleading
because:

EPA has commonly applied default dislodgeable foliar residue/ turf
transferable residue (DFR/TTR) estimates in its assessments;

Within dislodgeable foliar residue (DFR) and turf transferable residue
(TTR) research, only representative formulations are selected for field
studies;

Two distinct active ingredients may have chemical and formulation
properties so similar that one active ingredient may stand as a
surrogate for the other.

RESPONSE:

The commenter correctly points out that the Agency relies on standard
values for time zero residues based on our review of a large database of
pesticide data.  At issue with the requirement of chemical-specific
residue dissipation data is that the dissipation of a pesticide is
likely to be chemical-specific and formulation-specific.   It is
unlikely that the Agency will accept surrogate dissipation data unless
there are convincingly similar properties as discussed in item three.

Given the few data generally submitted to the Agency for a given
pesticide active ingredient, it is important that they be
chemical/formulation specific and that they represent the higher
exposure scenarios.

The Agency will consider chemical properties for a given active
ingredient on a chemical- by-chemical basis.   The Agency agrees that
this approach will be less common.

COMMENT:	Commenter 120 encouraged the Agency to use surrogate data in
instances when generic data can be broadly applied because it may be an
unreasonable burden to the registrant to generate such data on a
product-by-product basis. This commenter mentioned a number of task
forces generating data for Agency purposes and suggested administrative
relief for the task forces by Agency support for data generation, data
compensation for submitted and cited data, and data formatting.

 RESPONSE:  The Agency believes that the development of generic task
force data could be possible for almost all active ingredients. 
However, for certain pesticide formulations or use scenarios, there is
no exposure data.  In this type of situation, the Agency would require
chemical-specific exposure data.  The Agency does not believe that the
administrative reliefs requested by the commenter fall within the
purview of this rule. 

Test guidelines.

COMMENT:	Commenters 120, 122, 124 and 134 pointed out that the OPPTS
Harmonized Test Guidelines for Occupational and Residential Exposure in
their official form do not contain Guideline 875.2300, the Indoor
Surface Residue Dissipation Study, and recommended that EPA revise and
finalize the guideline before imposing the data requirement. 

Commenters 109, 110, 122 and 134 indicated that Guideline 875.2700 is
not available in the final OPPTS Harmonized Test Guidelines for
Occupational and Residential Exposure and this data requirement should
not be imposed until proper guidance is available.

Commenter 134 believes the Agency should address the issues raised by
the 1998 SAP on the proposed 875 Part B guidelines.  This commenter also
indicated that final guideline for this data requirement is absent from
the OPPTS harmonized guidelines and requested additional details on
developing the science-based models and formulas that are referenced in
this section.  

RESPONSE: The Agency agrees that not all of the 875 Guideline Series for
Occupational and Residential Exposure have been finalized.  However, the
draft Guidelines that were presented to the FIFRA Science Advisory Panel
(SAP) in March 1998 can be found on the Agency’s website at  
HYPERLINK
"http://www.epa.gov/scipoly/sap/meetings/1998/march/contents.htm" 
http://www.epa.gov/scipoly/sap/meetings/1998/march/contents.htm .  

	In September 1999 the Agency returned to the SAP to discuss residential
exposure data requirements, including variables impacting non-dietary
ingestion   (  HYPERLINK
"http://www.epa.gov/scipoly/sap/meetings/1999/september/resid.pdf" 
http://www.epa.gov/scipoly/sap/meetings/1999/september/resid.pdf .). 
The Agency then adopted revisions to several exposure algorithms,
including wet hand transfer. 

	An examination of the FIFRA SAP website since 1998 to the present will
show many presentations to the SAP on assessing occupational and
residential exposures.  The presentations on aggregating exposures for
cumulative assessments and the review of newer modeling techniques are
of primary importance.  Science has evolved in this area as the Agency
“learned by doing.” The Agency agrees that it should complete and/or
revise its guidelines, but also believes that whether in draft or in
final form, that information is available to the public.  The Agency
expects to be able to devote resources to finalize the test guidelines
at the end of 2008.  In addition, the Agency’s scientists can provide
guidance to registrants or task forces on aspects of study design and
are always willing to work with individual registrants to develop study
designs to fulfill data requirements.  The methods are also described in
the published literature and documents generated by the Agency’s
Office of Research and Development.

	

Discussion of Comments on Environmental Fate Data Requirements (Subpart
N)

1.  Guideline Harmonization and Numbering of Fate Guidelines 

COMMENT  We received nine comments (# 112, 113, 120, 122, 123, 124, 125,
134, 137) stating that the proposed data requirements for environmental
fate data should not be promulgated if the test guidelines upon which
the data requirements rely are not finalized or not available to the
public that will be using them.  Commenters stated that these test
guidelines should be harmonized with OECD to avoid duplication.  The
guideline numbers in the proposed rule are new (835 Series) and replace
the current 161 - 166 Series.  However, it was unclear to some
commenters if the new numbers simply reflect a new numbering system or
reflect revisions of the test guidelines.  They recommended that the
Agency should post the new numbers and their respective guidelines on
the EPA website so the numbering system is clarified.  The website
should also include a cross-reference to the old numbering system and to
the OECD guidelines.

RESPONSE   While the proposed rule deals solely with data requirements
for conventional pesticides, we recognize the importance of the
connection between these proposed data requirements and the guidance
documents that provide information on how the data requirements may be
satisfied.  Nonetheless, guidelines are guidance documents only, and the
promulgation of data requirements does not depend on the availability of
guidance documents.  The Agency is in the process of updating its
environmental fate test guidelines in accordance with its harmonization
efforts with the PMRA and the OECD.  The guidelines are scheduled for
release to the public by late 2007.  For example, the Agency is in the
final stages of making available to the public a joint NAFTA terrestrial
field dissipation guidance document that has, in fact, been through
several rounds of public participation and comment over the past decade.
 The guidance was posted in April 2006, and the FR notice announcing the
availability of the guidance and the response to comments for the
document was posted shortly afterwards.

In addition, we are currently updating many of the laboratory fate test
guidelines with guidance now available in final form from the OECD test
guidelines program.  Where a final OECD test guideline is not yet
available, guidance presented in Subdivision N of the Pesticide
Assessment Guidelines can still be used to address data requirements
proposed in this rule.  We are also working toward updating the EPA
website and clarifying which guidelines are OPP-specific versus
OPPT-specific.  In addition, the Agency will clarify which guideline
within Subdivision N is appropriate for use for each of the 835 series
data requirements.  Also, new guidance based on final OECD test
guidelines will also be cross-referenced.

2.  Terrestrial Field Dissipation Data Requirement

COMMENTS   We received 15 comments from six commenters (#52, 113, 120,
122, 124, 134) that expressed concern about clarifications to the
terrestrial field dissipation data requirement as expressed in the
preamble as well as the regulatory data requirement table.  

Most of the comments regarding the terrestrial field dissipation data
requirement concerned the expansion of the conditional requirement for
aquatic food crops and aquatic nonfood uses when the pesticide is
applied to aquatic sites that are intermittently dry. Such crops as rice
paddies and cranberry bogs which are cultivated in floods may require a
terrestrial field dissipation study in addition to an aquatic
dissipation study.  

Several commenters stated that conducting both field studies is not
warranted simply based upon the agricultural practices for the crop. 
The terrestrial field dissipation data should only be required when the
laboratory tests indicate relative persistence of the pesticide.  They
pointed out that this study would be technically very difficult to
conduct.  The test also increases the complexity of already complex
tests, and the usefulness of this data to a regulatory decision was
unclear.

RESPONSE   The Agency submits that field dissipation data have always
been required to support registration of pesticide use on rice.  Use on
rice has generally been categorized as an aquatic use; however, as
several commenters correctly pointed out, there are wet and dry phases
to rice production.  In some types of rice production such as dry-seeded
rice, the fields are flooded for only a short period of time.  Rice
grown under these conditions is more characteristic of a terrestrial
crop than an aquatic crop.  Therefore, in the final rule, the Agency
made the terrestrial field dissipation a conditional requirement for
aquatic use patterns such as dry-seeded rice in order that the fate and
transport under actual use conditions  may be understood.  The Agency
believes, and the SAP concurred, that aquatic use pesticides applied to
sites that are intermittently dry may be better suited for testing under
the terrestrial field dissipation guidance. 

COMMENTS   Some commenters were also concerned that the Agency was not
considering several important factors in requiring terrestrial field
studies for aquatic sites.  Two comments stated that including sites
such as cranberry bogs and rice paddies could expand the number of sites
needed for a typical dissipation study and involve soil types that could
cause analytical challenges.  The aquatic crop uses identified are often
not on aquatic sites, but on drained arable agricultural lands with
irrigation or water management controls to maintain water levels above
the soil surface during part of the growing season.  Regionally, rice
fields can be rotated into corn, cotton, or soybean fields, for example.
 EPA must clarify if aquatic crop uses such as rice and cranberries
would require a terrestrial field dissipation study (evaluating residues
in soil) during the dry-land phase, in addition to an aquatic field
dissipation study (evaluating residues in water and soil) during the
flooded phase, both under actual use conditions.  They pointed out that
the statement in the Preamble indicates that “the frequency of
requesting this study will be quite low” due to the limited
applicability of the change.  But they believe that the statement is
misleading, however, if both Terrestrial Field Dissipation (TFD) and
Aquatic Field Dissipation (AFD) studies are required for the aquatic
crops, on top of TFD requirements for terrestrial crops.  These
“aquatic” agricultural lands need to be clearly distinguished from
aquatic sites that cannot be used for upland agricultural purposes
(ponds, lakes, marshes, streams), where in most years water is present
throughout the year. 

RESPONSE   The Agency responds that, in fact, it made the suggested
distinction between “aquatic” agricultural lands and aquatic sites
that cannot be used for upland agricultural purposes (ponds, lakes,
marshes, streams), where in most years water is present throughout the
year.  This data requirement may be triggered for uses involving
applications to aquatic sites that are intermittently dry.  This was
supported by the Science Advisory Panel.  For example, in some types of
rice production, the fields are flooded for only a short period of time.
 Although rice is categorized as an aquatic use, a terrestrial field
dissipation study may be more appropriate than an aquatic dissipation
study for developing data to understand pesticide fate and transport
under actual use conditions.  The Agency believes that the conceptual
model approach described in the updated NAFTA-harmonized terrestrial
field dissipation guidance provides sufficient information upon which to
develop a protocol that may be submitted to the Agency for review prior
to study initiation.

COMMENT   One Agency proposal that received four comments (#113, 122,
124,134) was the merging of the terrestrial field study requirement with
the current long-term field dissipation study.  Instead of a separate
long-term study, the field dissipation study would be extended in
duration for persistent pesticides to characterize their decline curves.
 Commenters recommended that the Agency provide additional guidance on
what would trigger the need to progress into a long-term study and what
the endpoints would be.  Additional concerns regarding the merging of
the two studies related to the possibility that the analytical samples
collected in the field would not necessarily be analyzed at the current
18-month limit of the long-term study.  They expressed concern that the
data needed to determine if a study should continue would not be
available.  These commenters recommended the Agency refer to the
harmonized NAFTA Terrestrial Field Dissipation guideline and the TFD
Workgroup as the source for revising these changes.

RESPONSE   The Agency and PMRA of Canada developed a joint NAFTA
terrestrial field dissipation guidance document that went through
several rounds of public participation and comment over the past decade.
 The terrestrial field dissipation document is available on the websites
of EPA and PMRA.  In this guidance document, a conceptual model approach
to environmental fate testing is stressed.  With the deletion of the
long-term field dissipation data requirement, the Agency believes that
the trigger language for progressing into a longer term study is
correctly placed within the harmonized NAFTA Terrestrial Field
Dissipation guidance.  Guidance on the duration of the terrestrial field
dissipation is not a data requirement subject, and is included in the
NAFTA document.  The Agency does not believe that a separate test note
for this factor is needed.  Registrants may contact the Agency to
discuss issues regarding the terrestrial field dissipation study.

COMMENT   Two comments (#124, 134)  noted that there was no mention of a
storage stability study, as there is in subpart O (Residue Chemistry),
as this study is needed to address the stability of the field samples
collected in the terrestrial field dissipation study.  

RESPONSE   The Agency notes that the storage stability issues are
addressed in the NAFTA -harmonized guidance for conducting terrestrial
field dissipation studies.

3.  Aquatic Field Dissipation Data Requirement

We received eight comments from four commenters (#120, 122, 124, 134)
that expressed concern about the expansion of the conditional data
requirement to include all terrestrial uses and the relationship between
this field study and the expansion of the terrestrial field dissipation
study for some aquatic crops. These comments relate to both the preamble
and the regulatory data requirement table.

COMMENT   Several comments asked for clarification regarding the
conditions for requiring the aquatic field dissipation study.  The
conditions for requiring this study for terrestrial uses were very
general and nonspecific, and data gathered from such a study are not
germane to refining the issues identified by EPA as tripping the
conditions for these terrestrial uses (i.e., high persistence and high
mobility).  The current EPA environmental risk assessment process does
not utilize information from these studies in the quantitative portion
of the risk assessment, in effect asking for a high cost study with
limited benefit in making a risk management or regulatory decision.
Comments included statements that the aquatic field dissipation study
should only be triggered for terrestrial applications when soil mobility
studies indicate the pesticide is likely to move from the site of
application to nearby aquatic systems.  Furthermore, requiring this
study for terrestrial uses is unwarranted since these uses already
require the terrestrial dissipation study. 

RESPONSE   The aquatic field dissipation study is used to determine the
non-target fate of a terrestrially applied pesticide that has a high
potential to enter aquatic environments and to substantiate laboratory
findings, especially with respect to dissipation, accumulation, and
mobility.  The results of field studies are used to validate and/or
refine the established hypothesis that the pesticide dissipates in
accordance with the predictions made based on the laboratory studies and
environmental fate modeling.  

Data from these studies can reduce potential overestimation of exposure
and risk and can confirm assumptions of low levels of toxic degradates. 
Results can also be used to propose scenario-specific effective risk
mitigation.  The final rule makes Aquatic Field Dissipation
conditionally required (CR) for terrestrial use pesticides.  The test
note, which was harmonized under NAFTA with PMRA, details several
processes that must be considered when triggering an aquatic (sediment)
dissipation study for a terrestrial use.  The data requirement is based
on the potential of a pesticide applied to land to enter aquatic
systems, and if the pesticide and/or its degradates have the potential
for persistence, mobility, nontarget aquatic toxicity, or
bioaccumulation. 

While the laboratory studies are designed to address one dissipation
process at a time, aquatic field dissipation studies address pesticide
loss as a combined result of chemical and biological processes (e.g.,
hydrolysis, photolysis, microbial transformation) and physical migration
(e.g., volatilization, sediment-water partitioning, plant uptake, etc.)
under representative actual use conditions.  Pesticide dissipation may
proceed at different rates under field conditions and may result in
formation of degradates at levels different from those observed in
laboratory studies.  Data from these studies are used in the assessment
of each pesticide and can reduce potential overestimation of exposure
and risk and confirm assumptions of low levels of toxic degradates. 
Results can be used to propose use-site specific risk mitigation and,
therefore, are used by the risk managers in their decision-making
process.

In general, a valid aquatic field study allows the risk assessor to
quantitatively:

compare predicted routes of dissipation identified in the laboratory
with those measured in the aquatic environment;

characterize the rates of dissipation of the parent compound and
formation and decline of the major and/or toxicologically significant
transformation products under aquatic field conditions;

characterize the rates and relative importance of the different
transport processes, including accumulation, sediment binding,
water-sediment partitioning, and volatilization;

establish the distribution of the parent compound and the major
transformation products in the water and sediment layers;

characterize the persistence of the parent compound and major
transformation products in water and sediment, including the potential
for bioaccumulation;

characterize the effect(s) of different typical pesticide formulation
categories, where applicable.

On a pesticide specific basis, field studies are needed to demonstrate
fate in the environment and to substantiate laboratory findings,
especially with respect to dissipation, accumulation, and mobility
potential.  Well-designed aquatic field dissipation studies help to
answer the risk assessor’s question: “Where did the pesticide go
after reaching the aquatic environment?”

On a broader basis, the results of the aquatic field dissipation study
can be used to help evaluate the reasonableness of the aquatic exposure
model predictions based on laboratory derived input parameters. 
Differences between field study findings and these predictions may
suggest the need for a closer look at the information used to generate
the hypothesis and possibly the need for additional laboratory and/or
field studies, such as the surface water monitoring study.

In addition to its value in characterizing the dissipation of a
pesticide in the aquatic environment and evaluating environmental fate
modeling, dissipation study results have potential uses as inputs to
fate models under certain conditions, and as a source for potential
refinement of risk assessments and risk characterizations for endangered
species.

COMMENT   Several commenters expressed similar concerns as those above,
but they also asked that the guideline for this study undergo
significant revisions.  They asserted that the current guideline is
inadequate in its description of the goals and procedures needed to
conduct an aquatic field dissipation study.  One commenter stressed that
the exposure to an aquatic system, if it is not the intended target site
(e.g., runoff from a treated field), will be quite different than if it
is the intended site of application (e.g., aquatic herbicide, rice
paddy, etc.); thus registrants will need guidance on appropriate
application rates.  The requirement would also add the need for an
official analytical method for residues in water with a defined LOQ
(level of quantification), since water methods developed for
ecotoxicological analyses typically have fairly high LOQ.    Another
commenter added that recent aquatic fate field studies in the literature
use appropriate protocols, and the Agency should consider revising this
guideline in the near future with the help of experts in this area.

RESPONSE   The Agency agrees that field procedures will need to address
and reflect the pesticide conceptual model.  The Agency also recognizes
that the aquatic field dissipation guidance written in 1982 should be
updated and will explore options for doing so.  Registrants are
encouraged to incorporate improved methodologies found in the
literature, as appropriate, when conducting aquatic field dissipation
studies.   The Agency recommends that study protocols be submitted and
discussed prior to study initiation when the aquatic field dissipation
data requirement is triggered for a terrestrial use pesticide. 

COMMENT   One commenter (#124) recommended that to be consistent with
the terrestrial field dissipation data requirement the Agency should
state that aquatic food crops, like rice and cranberry uses, which are
managed to have a dry-land period for production, now must be conducted
under the TFD guideline.

RESPONSE   The Agency agrees with this recommendation and added the
following statement to test note 8:  “Field testing under the
terrestrial field dissipation guideline may be more appropriate for some
aquatic food crops, such as rice and cranberry uses that are managed to
have a dry-land period for production.”

4.  Forestry Dissipation Studies

COMMENT   The Agency received four comments (#82, 120, 122, 124)
regarding the change of the requirement from “required” to
“conditionally required” for forestry applications of pesticides. 
These commenters raised the concern that it was not clear what
conditions of pesticide use in forestry agriculture would trigger this
data requirement, especially since this study has generally been
required in the past for this use pattern.

RESPONSE   The Agency has found that the forestry dissipation studies
are very difficult to conduct and very difficult to interpret. 
Therefore, the trend over the past few years has been to rely on the
terrestrial field dissipation studies for forestry uses.  If based on
the use pattern and conceptual model developed using laboratory data, a
terrestrial field dissipation study will not be able to assess all of
the major routes of dissipation, a forestry dissipation study will be
triggered to fully assess fate and transport under actual use
conditions.  It is important to note that test note 9 requires prior
approval of a protocol for this study.

COMMENT   The Canadian government agency, PMRA (#82), also raised some
issues about the forestry dissipation data requirement.  PMRA does not
have a separate forestry dissipation study, but requires terrestrial
field dissipation studies for forestry pesticides.  They asked for
clarification as to why EPA does not require the terrestrial field
dissipation study for forestry uses.  PMRA also conditionally requires
aquatic field studies for forestry pesticides based on the potential for
aquatic exposure and the potential for persistence, mobility, non-target
aquatic toxicity and bioaccumulation of the pesticide residues.

RESPONSE   EPA generally finds that pesticides used in forestry
situations also have terrestrial food or feed uses as well.  The trend
over the past few years has been to rely on the terrestrial field
dissipation studies, as the forestry dissipation studies are very
difficult to conduct and very difficult to interpret.  We note that,
currently, PMRA does not have a separate Forestry Dissipation study.  If
based on the use pattern and conceptual model developed using laboratory
data, a terrestrial field dissipation study will not be able to assess
all of the major routes of dissipation of a forestry use pesticide, a
forestry dissipation study will be triggered.  In the case where a
pesticide is only registered for forestry uses, the forestry dissipation
study will be triggered and the protocol, which according to test note 9
in the final rule requires prior Agency approval, will need to include a
terrestrial component.  We note that the guidance for the forestry study
in the U.S. includes a terrestrial and an aquatic component.

5.  Combination and Tank-Mix Dissipation

The Agency received three comments from two commenters (#120, 124) about
the data requirements for conducting field dissipation studies with
combination and tank-mix pesticides.

COMMENT   One comment questioned the change in the data requirement from
NR to CR for terrestrial and aquatic uses as the basis for this change
is not identified.  All three comments identified proposed test note 9
as vague and with no useful information.  They suggested that this test
note be revised to clarify when this data requirement is needed, and the
relevance of this data.  

Two comments opined that, in general, all outdoor uses of a pesticide
should be supported by at least one field dissipation study for
whichever use pattern is most appropriate; and one study may be
sufficient to extrapolate for other use patterns.  With such data
available, there should rarely be a requirement for a specific study on
a combination product or tank mix, since the presence of one active
ingredient in soil does not significantly alter the rate of degradation
or route of dissipation of another substance.  EPA should only require
these data if there is scientific evidence for specific substances that
refute this premise.

RESPONSE   Taking their recommendation, the Agency has maintained the
CR classification for terrestrial and aquatic use patterns in the final
rule.  In addition, test note 10 for this requirement was rewritten to
clarify when the study may be required:  “This study may be triggered
if there is specific evidence that the presence of one pesticide can
affect the dissipation characteristics of another pesticide when applied
simultaneously or serially.”  This field study could be required where
there is evidence that the presence of one active ingredient affects the
dissipation of another.  It is important to note that this data
requirement is very rarely triggered. 

6.  Anaerobic Soil and Anaerobic Aquatic Metabolism

COMMENT   The Agency received twelve comments from seven commenters (#
54, 113, 120, 122, 124, 133, 134) regarding data requirements for the
anaerobic soil metabolism study and the anaerobic aquatic metabolism
study.  The comments focused on the fact that the anaerobic soil
metabolism requirement, which was written in 1982, was not in the 1991
version of 40 CFR 158.290, and, in their view,  including it in this
rule constitutes a new data requirement.

RESPONSE   The Agency maintains that this data requirement was never
formally removed from the Code of Federal Regulation; for example,
through announcement in the Federal Register, and therefore, cannot be
considered a new requirement.  It was a simple printing error which led
to its disappearance from 40 CFR 158 in 1991 and subsequent publications
of the CFR.  EPA has continued to require the anaerobic soil metabolisms
study as needed, notwithstanding its inadvertent omission from the CFR. 
The Agency restored the data requirement to the data table with no
changes in the scope and nature of the requirement as originally
proposed.  This data requirement is required only for terrestrial uses. 
The Agency does not expect other use patterns to trigger a need for this
study.

COMMENT   Several commenters also expressed concern that the Subdivision
N (162-2) guidelines of 1982 indicate that the anaerobic aquatic study
can be submitted in place of the anaerobic soil study, “data from an
anaerobic soil metabolism study need not be submitted if data from the
anaerobic aquatic metabolism study described in 162-3 of this
subdivision has been submitted.”  The commenters were also concerned
with the expansion of the anaerobic aquatic metabolism requirement to
include all terrestrial uses, such that they would be required to
conduct two studies, one with soil and water to satisfy 162-2 and one
with sediment and water to satisfy 162-3.  This added requirement, in
their estimate, would have a significant impact, doubling the time of
the anaerobic system requirement.  They requested that the policy of
substituting the aquatic study for the terrestrial study be continued.  

RESPONSE   The Agency did historically accept the anaerobic aquatic
study in place of the anaerobic soil study.  However, with the
harmonization of the OPP environmental fate guidelines with those of
OECD and with PMRA under NAFTA agreements, and with the publication of
this rule, this practice is no longer valid.  These studies, as
conducted according to the harmonized OECD test guidelines [OECD TG 307
(anaerobic soil metabolism) and TG 308 (anaerobic aquatic metabolism)]
use different test media and are conducted under different redox
conditions.  The results from the two studies will not necessarily be
compatible and will provide information on the fate of the chemical and
its degradates under different conditions.  Therefore, and in accordance
with NAFTA harmonization efforts, both studies are being required.  

COMMENT   A final comment discussed the proposal by the Agency to
change the requirement from not required (NR) to required (R) for the
anaerobic aquatic metabolism study for all terrestrial use patterns. 
They believe that this data requirement should be conditionally required
(CR) and required only when soil leaching and adsorption/desorption data
indicated the pesticide is likely to move from the site of application
to nearby aquatic systems. They asked for a further explanation of this
change.

RESPONSE   In addition to dissolved runoff, contamination of water
bodies can occur by way of spray drift and/or erosion of
pesticide-contaminated soil particles.  Pesticides may also reach
surface waters through ground water recharge, which is often under
anaerobic conditions until it reaches the surface water.  Finally, one
must factor in the proximity of water bodies to the treatment site in
order to understand the potential for contamination.  The anaerobic
aquatic metabolism study is a tier I study that is necessary to fully
understand the fate of pesticide residues in aquatic systems.  In
addition to being useful for developing ecological risk assessments,
this study is also valuable in refining drinking water exposure
estimates.

The Agency requires both anaerobic studies for terrestrial uses where
the pesticide is likely to move from the site of application to nearby
aquatic systems.  Since the degradation or dissipation rates and
pathways of pesticides in aquatic systems can be different from those of
terrestrial systems, soil metabolism studies alone may not be adequate
to cover these use patterns.

7.  Aerobic Soil and Aerobic Aquatic Metabolism

COMMENT   The Agency received five comments from four commenters (#52,
120, 122, 133) regarding the data requirements for the aerobic soil
metabolism study and the aerobic aquatic metabolism study.  The comments
addressed the inclusion of aquatic use sites such as rice paddies and
cranberry bogs that are intermittently dry for the soil metabolism
study, and the inclusion of all terrestrial and forestry uses for the
aquatic metabolism study.  They asked for further explanation of these
changes in the data requirements.  They believe that the aquatic data
requirement should only be required on a conditional basis when the soil
leaching and adsorption/desorption data indicated the pesticide is
likely to move from the site of application to nearby aquatic systems.

RESPONSE   Cranberry bogs and rice paddies are intermittently wet and
dry.  Therefore, these uses are not clearly terrestrial or aquatic, but
can be considered both, depending on timing and agronomic practices. 
While the Agency has categorized these two uses as aquatic, we recognize
the need for data under both terrestrial and aquatic conditions.  

In addition to dissolved runoff, contamination of water bodies can occur
by way of spray drift and/or erosion of pesticide-contaminated soil
particles.  Also, one must factor in the proximity of water bodies to
the treatment site in order to understand the potential for
contamination.  Since the degradation or dissipation rates and pathways
of pesticides in aquatic systems can be different from those of
terrestrial systems, soil metabolism studies alone may not be adequate
to cover these use patterns. The aerobic aquatic metabolism study is a
tier I study that is necessary to fully understand the fate of pesticide
residues in aquatic systems.  In addition to being useful for developing
ecological risk assessments, this study is also valuable in refining
drinking water exposure estimates.

8.  Photodegradation, Laboratory Volatility and Field Volatility

Data from the photodegradation in air studies provide information about
the potential of the pesticide to degrade in air when it interacts with
sunlight.  Because of the potential for exposure to highly volatile
pesticides in greenhouses, residential and certain outdoor uses, EPA is
expanding the data requirement to include all terrestrial, greenhouse,
forestry and residential outdoor uses. 

COMMENT   The Agency received three comments from two commenters (#120,
124) on the expansion of the use categories in the photodegradation in
air data requirement.   They asked for additional guidance on the
conditions that would trigger this data requirement, as vapor pressure,
or Henry’s Law Constant of the chemical.

RESPONSE   The measured vapor pressure of a chemical compound is a guide
to its volatility and to the probability of its movement into
atmosphere.  A volatility classification based solely on vapor pressure
is best suited to dry, non-adsorbing surfaces.  In general, pesticides
with vapor pressures < 1 x 10-6 mm Hg are considered relatively
non-volatile under field conditions, whereas pesticides with vapor
pressures > 3.9 x 10-5 mm Hg are considered to be of intermediate to
high volatility under field conditions and may become airborne and enter
the environment (Kennedy, J.M. and R.E. Talbert, 1977. Comparative
persistence of dinitroaniline type herbicides on the soil surface. Weed
Sci. 25(5): 373-381).  Thus, a vapor pressure of > 3.9 x 10-5 mm Hg
raises concern regarding potential volatilization.  

Henry’s Law addresses the partitioning of a compound between water and
air, a process that can increase or decrease the overall volatilization
of the compound from water or a moist surface.  Pesticides with a
Henry’s Law Constant > 1x 105 are generally considered non-volatile. 
(U.S. EPA. 1975. Volatilization Studies. Guidelines for registering
pesticides in the United States. 40 FR (123) 26889-26891).

COMMENT   The Agency received two comments (#124, 134) on test note 2
for the photodegradation in water data requirement.   One comment asked
for more specific guidance regarding the absorbance of the hydrolysis
mixture, and the other comment asked for clarification about the
structural identities of the hydrolysis products.  They questioned how
the UV spectra are to be determined.    If the hydrolysis mixture can be
used to measure the UV spectra, the proposed change would be more
useful.  If standards are required to generate the UV spectra, then the
usefulness of this change is limited to older products with available
standards or to products with hydrolytic stability.

RESPONSE   The Agency notes that the guidance in test note 2 is not a
requirement, but indicates what information may be provided to support a
waiver of the photodegradation in water data requirement.  A measurement
of the absorbance of the hydrolysis reaction mixture at various time
points during the study is one alternative.   With regard to the second
comment, the Agency finds that either approach proposed by the commenter
(either measure the UV-VIS spectra of the hydrolysis reaction mixture or
measure the spectra of the pure analytical standards) would be
acceptable.

COMMENT   The Agency received one comment (#133) about the
photodegradation on soil data requirement that questioned the change in
classification for conditionally required (CR) to required (R).

RESPONSE   The Agency codified a long-standing practice of requiring
this study for terrestrial and forestry uses.  The footnote has been
retained explaining that the study is not required when the chemical is
to be applied only by soil injection or is incorporated in the soil.  

9.  Hydrolysis

COMMENT   The Agency received two comments (#125, 133) on the
hydrolysis data requirement.  Two comments questioned the addition of
indoor uses to the use patterns that require this study.

RESPONSE   The preamble lists several sites that are considered indoor,
but where environmental exposure may be likely.  These sites include
agricultural premises, in or around farm buildings, barnyards, beehives,
and fish or seafood processing premises.  The proposed changes reflect
concern about the potential movement of pesticides and their degradates
into the environment.

10.  Use Patterns

The Agency received one comment (#120) on the categories of use patterns
in the environmental fate data requirements table.

COMMENT   Neither the indoor medical nor the aquatic nonfood industrial
use patterns are identified.  The commenter stated they could not
confirm whether either use is excluded from all requirements in this
section or whether the intent was to include them under one of the
listed use patterns.

RESPONSE   The data requirements for indoor medical are captured under
the indoor use pattern.  The data requirements for aquatic nonfood
industrial are captured under the aquatic use pattern.

11.  Soil Mobility

COMMENT   The Agency received three comments (#120, 122, 124) regarding
the data requirement for soil mobility or leaching and
adsorption/desorption studies.  Although the Agency is not proposing any
changes to this data requirement, we received several comments asking
for clarification of which test type the Agency prefers to fulfill this
data requirement.

RESPONSE   The Agency added a new test note for the leaching and
absorption/desorption data requirement.  The following test note, number
6, is now included in the data table:  “Adsorption and desorption
using a batch equilibrium method is preferred, however in some cases,
for example where the pesticide degrades rapidly, soil column leaching
with unaged or aged columns may be more appropriate to fully
characterize the potential mobility of the parent compound and major
transformation products.”

12.  Accumulation Studies

COMMENT   The Agency received eight comments from four commenters (#120,
122, 124, 134) regarding the fish and nontarget organism accumulation
studies.  Three of the commenters suggested that this data requirement
be placed in Subpart E, Terrestrial and Aquatic Nontarget Organism Data
Requirements and not subpart N.

RESPONSE   The Agency agrees with the comments, and, in the final rule,
moved the two studies under this subheading, Accumulation in Fish
(835.1730) and Accumulation in Aquatic Nontarget Organisms (835.1950) to
Subpart G, under the data requirement, Aquatic organisms --
bioavailability, biomagnification and toxicity.  Therefore, all the
ecological and fate requirements related to bioaccumulation are only
located in new Subpart G.  The associated guideline numbers are
850.1710, 850.1730, 850.1850 and 850.1950.  

COMMENT   Two comments stated that proposed test note 10 was well
written, and should also apply to the aquatic nontarget organism
accumulation study requirement in lieu of proposed test note 11.  They
also suggested that this test note is also appropriate for the three
accumulation studies in Subpart E (850.1710, 850.1730 and 850.1850).

RESPONSE   The Agency agrees with the commenters that the language of
proposed test note 10 (Accumulation in Fish) is also appropriate for the
accumulation in aquatic nontarget organisms data requirement.  Test note
10, “Not required when the octanol/water partition coefficients of the
pesticide and its major degradates are less than 1,000; or there are no
potential exposures to fish and other nontarget aquatic organisms; or
the hydrolytic half-life is less than 5 days at pH 5, 7, and 9.” was
moved to the table for terrestrial and aquatic organisms data
requirements and renumbered as test note19 in Subpart G.  This finalized
test note replaces test note 21 in proposed Subpart E.

COMMENT   One commenter stated that the guideline cited for aquatic
nontarget organisms (850.1950) is a guideline for the conduct of an
aquatic field study.  This guideline only mentions briefly the subject
of measuring residues in aquatic organisms, and provides no specific
guidance whatsoever on what constitutes an acceptable study for
bioconcentration in aquatic organisms.

RESPONSE   The Agency recognizes that the guidance provided on EPA’s
website for Accumulation in Aquatic Nontarget Organisms is not
appropriate for this data requirement.  Corrections to the website are
scheduled to be made in 2007.

COMMENT   One commenter stated that the test material for Aquatic
Nontarget Organism Accumulation should be PAIRA which would be more
useful in most cases.

RESPONSE   The Agency listed the test substance as TEP for this data
requirement because that is the test material consistent with the
recommended study design and  Subdivision N of the Pesticide Assessment
Guidelines for aquatic nontarget organism accumulation studies. 

COMMENT   One commenter stated that the Agency is inconsistent between
the subparts in the use pattern applicability and table notes for these
data requirements and suggests the Agency reconsider which are
appropriate for inclusion in Subpart E.

RESPONSE   The Agency acknowledges that this is an inconsistency and
harmonized the use patterns listed for the subparts.

13.  Ground Water Monitoring

The Agency received eight comments from seven commenters (#52, 120, 122,
124, 125, 133, 134) on the new data requirement for ground water
monitoring.  This study is conditionally required for all terrestrial
uses and all forestry uses. 

COMMENT   Because of the newness of this data requirement we received
several comments questioning the conditions that would trigger this
requirement.  Other comments asked for clarification about the
relationship among modeling, retrospective monitoring  and prospective
monitoring.  In addition to the use patterns above, one commenter
recommended that the ground water monitoring data requirement should be
conditionally required (CR) for residential outdoor uses.  

RESPONSE   The Agency agrees that there may be limited cases where a
ground water monitoring study would be needed to inform a risk
management decision for residential outdoor use pesticides.  We changed
the requirement to CR for this use category. 

COMMENT   Another three commenters (#120, 122, 124) asked for better
guidance in the test note for this requirement.  One of the commenters
additionally expressed the opinion that the conditions in the proposed
test note for this study should focus on the results of the field
dissipation studies rather than laboratory studies.  Another asked the
Agency to identify how the decision to require this study will be
decided within the current organizational structure of OPP.

RESPONSE   The Agency affirms that the conditions described in the test
note include both laboratory and field data.  The Agency additionally
points out that the test note (number11 in the final rule) describes
many factors that must be considered when deciding if this requirement
is triggered.  It is quite complex and virtually impossible to fully
explain all possible scenarios that could trigger a groundwater
monitoring requirement.  In summary, it uses a weight of evidence
approach.  As with all data requirements, the ultimate decision for
determining which studies are required lies with the risk manager.

COMMENT   One commenter opined that the current guidelines for
prospective and retrospective monitoring are not well defined, and
consultation with the EPA is always a prerequisite.  The proposed
guideline should include guidance on how to interpret study results.  If
a potential groundwater impact is in question, a retrospective
monitoring program (tap or drinking water wells) in targeted high-use
areas is more useful in determining human exposure.

RESPONSE   The Agency is working towards finalizing the draft guidance
that has been available for several years.  Because of the large
investment of resources required to conduct and evaluate these studies,
the Agency recommends protocol approval prior to study initiation.

COMMENT   One commenter (#124) suggested that modeling should replace
the Prospective Ground Water (PGW) study as a more appropriate
intermediate Tier in determining the upper bound estimates of potential
groundwater contamination.  They based this suggestion on a statement in
the Preamble that PGW studies “are also often the best tool with which
to estimate pesticide concentrations in drinking water drawn from
shallow private wells.”  This does not reflect reality, as people do
not generally drink shallow water from directly under treated fields. 
They furthermore question the statement in the Preamble that PGW studies
will continue to be used to “improve” models.  They believe that
enough PGW data has already been generated to improve existing models,
and develop effective new screening models (e.g., SCIGROW).  If a
potential groundwater impact is still in question, a retrospective
monitoring program (preferably tap water or drinking water wells) in
targeted high use areas is more useful in determining human exposure.

RESPONSE   The Agency reiterates that modeling, prospective groundwater
monitoring, and retrospective groundwater monitoring are all useful
tools.  Which one is more appropriate for a given case depends on the
question one is trying to answer and the level of uncertainty that is
acceptable for a given risk management decision.  Modeling is used to
provide a lower tier estimate of drinking water concentrations.  PGW
studies are required when a more refined estimate is needed for
regulatory purposes.

14.  Degradates 

COMMENT   The Agency received six comments from three commenters (#52,
122,124) regarding the need and potential triggers to test degradate
substances in the laboratory studies.  They all asked for clarification
of the potential requirement.

RESPONSE   The Agency generally does not require degradate substances to
undergo the set of fate data requirements as it requires of the active
ingredients.  The set of fate studies as currently designed and
conducted with the TGAI provide adequate information on the formation,
decline and mobility of the major degradates. 

Discussion of Comments on Residue Chemistry Data Requirements (Subpart
O)

	EPA proposed changes to the residue chemistry data requirements to
better estimate dietary exposure to pesticide residues in or on food or
feed.  EPA proposed to codify data requirements that have evolved since
the 1984 regulations were issued and clarify and simplify existing data
requirements.

General comments on the proposed data requirements

COMMENT:  Commenter 82 indicated that the residue data requirements in
the proposed rule exhibit a high degree of harmonization with the
Canadian requirements.  Commenters 120, 124, 133, and 134 all reflected
on including the residential outdoor use pattern in the proposed rule. 
They felt that EPA is proposing expanded requirements for home garden
uses and perceived that residue data will be required regardless of
whether the home garden use pattern differs from the agricultural use
pattern on which the tolerances are based.  In addition, they pointed
out that Test Note 3 should state “and” rather than “or.” 
Lastly, they said that home gardens did not fall under the scope of the
FFDCA.

RESPONSE:  There was no intent to expand the data requirement for
residential uses.  Even for uses on edible plants in home gardens,
residue data are rarely requested.  The existing practice is to require
the data only if the corresponding agricultural use on that crop is not
approved or the residential use is likely to have higher residues based
on increased application rates or shorter preharvest intervals.  The
“and” in the existing Test Note was inadvertently changed to
“or”. The Agency is now revising the footnote to clarify the limited
circumstances under which residue data would be required for residential
uses.  The Agency concurs that FFDCA does not apply to these uses and
tolerances are not established for residues on the treated plants;
however, EPA does assess whether any adverse effects (e.g., dietary
risks) could occur under the auspices of FIFRA.

The revised wording for Test Note 3 in the residue chemistry table is
the following: 

	“3.  Required  for residential outdoor uses on food crops if the
corresponding 	agricultural use is not approved or the residential use
is expected to produce higher 	residues based on the label
directions.”

COMMENT:  Commenters 120, 124 and 134 asked for a definition of
“indoor food uses” to clarify §158.1210(2)(b).

RESPONSE:  There is no section in the proposed rule with that exact
designation.  The Agency assumes that the commenter is referring to
§158.1210(b)(1) and (b)(2).  Paragraph (b)(1) states that food use
patterns include Indoor food use.  The Agency considers indoor food uses
primarily to be pesticide treatments in food areas of food handling
establishments (FHEs).  FHEs can be broken down into the three
categories: food servicing, food manufacturing, and food processing. 
Examples of application areas include crack, crevice and space
treatments where pests hide or through which they may enter the
building.  Additional details on the types of treatments, examples of
establishments under the three categories, and examples of food and
nonfood areas in such establishments can be found in OPPTS Guideline
860.1460 on Food Handling.  With the information in that guideline, the
Agency does not consider it necessary to provide additional details in
the definitions under §158.1200. 

	The FHE uses described above are considered to fall under the auspices
of FFDCA and require residue data and tolerances (or exemptions from
tolerances) for residues in food.  On the other hand, indoor residential
uses are nonfood uses that are not subject to FFDCA and the requirement
for tolerances.  However, as noted in §158.1210(b)(2), most products
used in or near residential kitchens require residue data for risk
assessment purposes.  These risk assessments are conducted under FIFRA
to determine if there are any unreasonable adverse effects. 

Tolerances and tolerance exemptions

 COMMENT:	Commenter 124 suggested the Agency reference (or reiterate) a
more useful and complete definition of “tolerance” because the
proposed definition implies that all of the data requirements apply to
applications for a tolerance exemption, which cannot be the case.

RESPONSE:  The term “tolerance” is not explicitly defined in FFDCA
or in EPA regulations.  The Agency considers a tolerance to be a
regulation established under 21 U.S.C. 346a prescribing the maximum
amount of a pesticide that may lawfully remain in or on food.  As noted
in the Applicability section (§158.5) of the proposed rule, the data
requirements apply to any applicant who petitions the Agency to
establish, modify, or revoke a tolerance or exemptions from a tolerance
in accordance with FFDCA section 408.   Consistent with § 158.5, the
definition of tolerance in the residue chemistry subpart 158.1200
includes tolerances and tolerance exemptions.  This broad definition
allows the Agency to refer to “tolerance” throughout the document
without having to repeat the phrase “tolerances and exemptions from
tolerances”.  Having said that, the Agency agrees with the commenter
that the proposed rule implies that all of the residue chemistry data
requirements and conditions apply to tolerance exemptions and that is
not the case.  In many instances such data are not needed for exemptions
due to the low toxicity of the pesticide or the ability to make a safety
finding using theoretical dietary exposure estimates.  Therefore, the
Agency is adding Test Note 25 for most of the residue chemistry data
requirements:

 “25.  Not required for an exemption from a tolerance provided that
dietary exposure estimates are not needed due to low toxicity or that
theoretical estimates of exposure are adequate to assess dietary risk."

The guideline numbers to which this Test Note 25 will be added are (in
order as presented in the table) 860.1650, 860.1300 (both entries),
860.1850, 860.1340, 860.1360, 860.1380, 860.1500, 860.1520, 860.1480,
860.1400 (all 3 entries), 860.1460, and 860.1900.

In conjunction with new Test Note 25, Test Note 8 for residue analytical
methods is being revised by striking out the phrase “and may be
required for a tolerance exemption.”

In addition, Test Note 26 is being added to the anticipated residues
study since the Agency would not consider granting an exemption from a
tolerance in a situation wherein such data were needed to make a safety
finding.

“26.  Not required for an exemption from a tolerance.”	

Storage stability

COMMENT:  Commenters 113 and 124 indicated that the requirement of an
explicit storage stability study is too rigid and removes the
flexibility to include the required storage stability data within the
magnitude of residue (MOR) study.  The commenters believed the
registrant should continue to have the option of including this data as
a stand-alone report or in the MOR report.

RESPONSE:  The Agency would not object to the storage stability data
being in the MOR report in those cases where the data were actually
generated concurrently as part of the MOR study.  Most storage stability
data submitted to EPA are generated by an independent study and reported
as such in a separate volume.  For this reason and due to the importance
of the storage stability data, the latter are now being listed as a
separate, explicit requirement in Part 158.  This does not preclude the
data being submitted in the MOR report under the scenario described
above.

 	

Multiresidue methods

There were no comments on the proposed codification of the multiresidue
methods study (guideline 860.1360) as a separate requirement;
multiresidue methodology data are currently part of the residue
analytical method requirement.

Nature of the residue in livestock

COMMENT:  Commenter 120 questioned the Agency’s reason for requiring
the study even when residues are not found in livestock feed items,
which is to have information on file "in cases where pesticide misuse
results in residues on feed items not expected to have residues from
approved uses."  The commenter believes that this is an inappropriate
basis for requiring data. 

RESPONSE:  The primary reason for requiring the livestock metabolism
study in cases where measurable residues are not found on feed items
from legal uses is to assess the potential bioconcentration of the
pesticide and metabolites of concern in animal products, not to address
potential misuse.  Although residues in the feed items may not be
quantifiable, the Agency wants assurance that residues do not
concentrate to measurable residue levels when livestock ingest the
treated feeds.  The fact that information would be provided on the
transfer of quantifiable feed residues to livestock from illegal
applications to crops is an additional benefit, but in itself would not
result in the Agency requiring the study. 

Residue analytical methods

COMMENT:  Commenter 124 said that the Agency has often sought
radiovalidation of the residue analytical method, because it is a
straightforward and scientifically valid demonstration that the method
is appropriate for quantifying the residue. However, if the metabolism
study shows acceptable material balance (>90%) and the extraction
procedure is identical to that for the residue method, radiovalidation
is not necessary. The commenter felt it would be appropriate to address
radiovalidation under both the Nature of the Residue and the Analytical
Method entries, since there are alternate solutions to this requirement.

RESPONSE:  EPA notes that the term “radiovalidation” does not appear
in the preamble or proposed regulation.  This topic is more
appropriately addressed under guidelines for analytical methods than in
Part 158.  Radiovalidation refers to a procedure used to confirm that
the method adequately extracts aged or weathered pesticide residues of
concern.  This procedure typically involves extracting a radiolabeled
sample from the metabolism (nature of the residue) study using the
proposed analytical method, quantifying the residue of concern in the
extract, and comparing the level of extracted residue to that found in
the metabolism study.  While the Agency views this as an element of the
analytical method requirement, it believes the issue may be addressed in
either the metabolism study report or the method validation report. 
Radiovalidation would not be necessary in the scenario where the
extraction procedures in the method and metabolism study are identical
or very similar and the metabolism study was deemed acceptable with
regard to the levels of residues extracted and characterized/identified.

COMMENT:  There were a variety of comments regarding independent
laboratory validation (ILV).  Commenter 134 pointed out that the policy
to require ILV of residue analytical methods has been in place since
1988 and was in general agreement with codification of this requirement.
 Commenter 119 suggested that “all registrants provide a third-party,
validated test method for soil, sediment, air and surface and
groundwater contamination.  The method (s) should have a detection
sensitivity low enough to assess the impact of the pesticide and its
toxicologically relevant metabolites on human health and the
environment.  The methods should be evaluated by EPA for validity and
made publicly available.”  In contrast, Commenters 125 and 133 felt
the proposed addition ILV adds more cost and no value in light of the
methods already being validated under good laboratory practices (GLPs).

RESPONSE:  The Agency does not agree that there is no value to the
independent laboratory validation (ILV) of tolerance enforcement
methods.  Prior to initiation of this testing in the 1980s, methods
frequently could not be validated in the EPA laboratory even though
applicants were reporting adequate recoveries.  Methods were often not
written in sufficient detail to permit chemists not familiar with the
procedures to achieve satisfactory results.  After ILVs were required in
1989, methods were successfully validated more frequently and in shorter
time frames by the Agency’s laboratory.  The ILV requirement helps to
ensure that methods are clearly written and include detailed
descriptions of all necessary steps.  With the present resource
situation at the EPA lab, a limited number of methods can be validated
by Agency chemists.  Therefore, there is even greater reliance on the
ILV as part of the review process to determine whether an adequate
tolerance enforcement method is available.

Magnitude of the residue in processed food and feed.

COMMENT:  Commenters 125 and 133 believed that changing the test
substances from end-use product (EP) to typical end-use product (TEP)
will cause an increase in the residue data as each formulation type
would need to be tested.

RESPONSE:  The Agency does not concur that the proposed change will
cause an increase in data requirements.  In fact, the opposite is true. 
Although it has not been implemented in this fashion, the existing EP
requirement from the 1984 rule would mean that residue data are needed
for each and every end-use product.  The practice has been to group
EP’s into formulation classes and request data on only one product
from each class.  Thus, EPA has been following a TEP concept that
requires considerably less data than an EP approach.  The proposed rule
revision would merely codify that current practice.  Further guidance on
how EPA views formulations for residue chemistry purposes can be found
in OPPTS Guideline 860.1500 on crop field trials.

Magnitude of the residue in meat, milk, poultry, and eggs

COMMENT:  Commenter 124 suggested that conducting separate feeding
studies for individual metabolites is an unnecessary and inappropriate
burden.  If different metabolites of concern occur in plants (livestock
feed) than result directly from livestock metabolism, the subsequent
fate of those compounds should be investigated in the livestock
metabolism study, not in the feeding study.  Combined results of the
metabolism studies in both livestock and plants should determine the mix
of compounds used in the livestock feeding studies.

RESPONSE:  The Agency agrees with the last point made by the commenter,
namely that the total residue is the appropriate data for magnitude of
the residue studies, whether by summing individual metabolites in the
same samples or by a common analyte formed by hydrolysis or other
degradative means  In addition to the metabolism studies, the Agency
considers results of other studies such as crop field trials and
toxicology as well as the capabilities of analytical methods when
determining the test substance for the meat, milk, poultry and egg
studies.  When separate livestock metabolism or feeding study data are
not submitted for a unique plant metabolite, the Agency carefully
examines all available data for the parent pesticide and its other
metabolites.  Only when the chemical structure of the unique plant
metabolite raises concerns over potential bioconcentration and/or
increased toxicity versus the parent would the Agency consider requiring
additional animal studies dosing with the plant metabolite.  Therefore,
as noted in the preamble to the proposed rule, “It is rare that this
study is requested.”  However, EPA prefers to maintain the proposed
test substance and footnote to make applicants aware of the possibility
of such data.

COMMENT:  A verbal comment on Test Note 17 at the May 3-4, 2005,
workshop on the proposed part 158 rule prompted Agency review of the
test note.  The comment is summarized as follows:  Test Note 17
indicates that the study may be waived in cases where residue levels are
low or livestock metabolism studies indicate negligible transfer to
tissues, milk and eggs.  In reality, the presence of low residues in
feed items by itself has not been sufficient grounds to waive the
feeding study.  The Agency’s practice is to estimate residues in
livestock commodities based on the maximum dietary burden (which does
take into account residues in feeds) and the results of the livestock
metabolism studies. 

RESPONSE:  The Agency concurs that the standard practice is to estimate
residues in tissues, milk, and eggs based on the maximum dietary burden
and the transfer observed in the metabolism studies.  A revised test
note clarifies this point.  In addition, an element dealing with the
presence of intentionally added residues in livestock drinking water is
being added to the test note since the same concept would be followed. 
Revised Test Note 17 now reads as follows:  “17.  Data are required if
pesticide residues are present in or on livestock feed items or
intentionally added to drinking water.  These studies, however, may not
be required in cases where the livestock metabolism studies indicate
negligible transfer of the pesticide’s residues of concern to tissues,
milk, and eggs at the maximum expected exposure level for the
animals.”  

Magnitude of the residue in potable water, fish and irrigated crops

COMMENT:  Commenter 52 compared this data requirement to the European
Union data requirement.  A requirement for pesticide residue in fish has
been proposed for the EU but has not been accepted yet.  A requirement
for pesticide residues in irrigated crops when products such as aquatic
herbicides are applied directly to water has not been proposed and none
is foreseen for the European Union.  

RESPONSE:  The differences between data requirements for the EU and the
U.S. in this area may offer opportunities for harmonization once the EU
finalizes its data requirements.

	

COMMENT:  Commenters 125 and 133 concluded that changing the test
substances from end-use product (EP) to typical end-use product (TEP)
will cause an increase in the residue data as each formulation type
would need to be tested.

RESPONSE:  The Agency does not concur that the proposed change will
cause an increase in data requirements.  In fact, the opposite is true. 
Although it has not been implemented in this fashion, the existing EP
requirement from the 1984 rule would mean that residue data are needed
for each and every end-use product.  The practice has been to group
EP’s into formulation classes and request data on only one product
from each class.  Thus, EPA has been following a TEP concept that
requires considerably less data than an EP approach.  The proposed rule
revision would codify that practice.  Further guidance on how EPA views
formulations for residue chemistry purposes can be found in OPPTS
Guideline 860.1500 on crop field trials.

Anticipated residues

COMMENT:  Commenter 52 pointed out that at the moment there is no
comparable data requirement in the European Union but needed EU
consideration in the future.

RESPONSE:   The differences between data requirements for the EU and the
U.S. in this area may offer opportunities for harmonization once the EU
finalizes its data requirements.

COMMENT:  Commenter 124 suggested the Agency clarify the relationship
between the requirements for anticipated residues to the provisions of
FFDCA section 408(b)(2)(E) on “Data and information regarding
anticipated and actual residue levels.”

RESPONSE:  To the extent that anticipated residue data are submitted to
EPA pursuant to the requirements in part 158, FFDCA section 408(b)(2)E)
clarifies that EPA may rely on anticipated residues in making tolerance
determinations.  Section 408(b)(2)(E) also places certain requirements
on EPA when it does rely on anticipated residue data. These requirements
would apply to anticipated residue data submitted under part 158, if
such data are used for tolerance determinations.  

COMMENT:  Commenters 120, 124 and 134 indicated that studies such as
market basket surveys (MBSs) should not be required, but instead should
be up to the discretion of the registrant or a conditional requirement. 
Residue data on acutely toxic pesticides in single servings should also
remain on a voluntary basis, as negotiated with the Agency.  Residue
distributions do not differ significantly between composite samples and
single servings of a given commodity, even in side-by-side comparisons. 
Before requiring MBS or single serving data, all refinements to the
acute dietary risk assessment should be considered including use of
monitoring data from the USDA Pesticide Data Program (PDP) and FDA.  It
is recommended that the Agency should: (1) support the direct use of PDP
monitoring data in acute dietary risk assessments for single chemicals,
(2) support direct use of PDP monitoring data in cumulative acute
dietary risk assessments, and (3) designate MaxLIP as the preferred
procedure if decompositing of PDP monitoring data is required for acute
dietary risk assessments.

RESPONSE:  The Agency agrees that all possible refinements to available
data should be considered before requiring MBS or single serving data. 
By following this practice, the Agency has required these special
studies in only a very few instances and anticipates very rarely to do
so in the future.  However, in order to retain the option of doing so,
the MBS and single serving studies will continue to be mentioned in the
test notes for anticipated residues.  With respect to the three
recommendations on monitoring data and decompositing procedures, this is
an evolving area in which the Agency is having discussions with other
regulatory authorities.  When definitive decisions have been made, they
will be communicated to registrants and other interested parties.

Confined and field rotational crops 

COMMENT:  Commenter 52 pointed out that these two data requirements go
beyond current European Union data requirements but these data are
accepted today in assessing residues in succeeding crops in Europe. 
Future EU data requirements will take over parts of the U.S. data
requirements.

RESPONSE:  The differences between data requirements for the EU and the
U.S. in this area may offer opportunities for harmonization once the EU
finalizes its data requirements.

COMMENT:	Commenters 113 and 124 suggested the Agency describe in detail
the triggers for progressing to the tier 2 and tier 3 studies and
explain how much data is needed to establish tolerances for inadvertent
residues in rotational crops.  The test notes for these studies have not
been modified from their use in the Environmental Fate table in the
current 158.290.

RESPONSE:  Upon further consideration, text was added to Test Note 7 to
include examples of permanent and semi-permanent food crops for which
the confined rotational crop study would not be required.  Test Note 23
was also expanded to provide more details on the trigger for requiring
the field rotational crop study.  That trigger is based primarily on the
level of residue of concern in crops in the confined studies.  EPA
believes that the triggers for the various rotational crop studies are
adequately described in the 860 Series guidelines, but does agree that
more details should have been presented in the proposed rule.  Upon
further consideration, Test Notes 7 and 23 are being revised as follows.

	“7.  Required when it is reasonably foreseeable that a food or feed
crop could be subsequently planted on the site of pesticide application
after harvest or failure of the treated crop .  Typically not required
for pesticide uses in permanent food crops (e.g., various tree crops,
vines) or semi-permanent crops (e.g., asparagus, pineapples).  

	“23.  Typically required if pesticide residues of concern greater
than 0.01 ppm are found in crops at the appropriate plant back intervals
(taking into account plant back restrictions on product labels) in the
confined rotational crop study.  If residues of concern in the confined
study are greater than 0.01 ppm but less than the limit of quantitation
of the analytical method to be used on field trial samples, the Agency
will consider not requiring, on a case-by-case basis, the limited field
trials.  If there are particular toxicological concerns with the parent
pesticide or any metabolites, limited field studies may be needed if
such residues were identified at levels below 0.01 ppm in the confined
study.”

	The Agency assumes the comment on triggers for the tier 3 studies is
referring to the crop field trials normally required when residues are
observed in the field rotational crop study, necessitating the
establishment of tolerances for residues in the rotated crops.  As noted
in the field rotational guideline (860.1900), the finding of
quantifiable residues in that study triggers the requirement for
tolerances.  The guideline further states that the number of crop field
trials needed in such circumstances are the same number as needed to
establish tolerances on directly treated crops.  However, on a
case-by-case basis the Agency has accepted fewer field trials for the
rotated crops, particularly when the uptake of residues is observed
primarily in livestock feed items such as forage, hay, and straw.  In
such situations, registrants are advised to contact the Agency to
discuss the necessary number of crop field trials.

		The preceding discussion on the number of crop field trials (i.e., how
much data) to establish tolerances is not appropriate for inclusion in
Part 158 because it applies to guideline issues not covered by part 158.
 However, the Agency does agree that Part 158 should address when crop
field trials are required for rotational crops.  Therefore, the
following Test Note 24 for crop field trials is being added to the
residue chemistry data requirement table.

	“24. Crop field trials are required to establish tolerances on
rotational crops when quantifiable residues of concern are observed in
the field rotational crops study.”  

X.	Discussion of Comments on Peer Review

	EPA proposed data requirements recommended by the 1993 National
Research Council report entitled “Pesticides in the Diets of Infants
and Children.”  The FIFRA SAP reviewed the proposed amendments to 40
CFR part 158 in 1994.  The FIFRA SAP also reviewed the data requirements
related to the application of the mandated FFDCA safety factor in 1998
and 1999.  No new scientific issues that warrant FIFRA SAP review have
arisen since those meetings.

National Research Council

COMMENT:  In referring to the 1993 NRC report entitled “Pesticides in
the Diets of Infants and Children,” Commenter 48 wondered if the
recommended modified reproduction/developmental toxicity study in the
rat is wise if the two-generation study (OPPTS guideline 870.3800) has
already been conducted.  The commenter felt that the modified
reproduction/developmental toxicity study might be a useful preliminary
study to the two-generation study, but his preference for preliminary
studies is to rear the litters at least to weaning.

RESPONSE:   EPA is considering how the number of longer term studies
might be reduced by examining the possibility of combining toxicological
endpoints from more than one study based on the recommendations from
ILSI/HESI.  For now, the Agency requires separate developmental and
two-generation reproduction studies for food use pesticides.

FIFRA Science Advisory Panel 

	There were no comments regarding the FIFRA SAP’s 1994 review of the
proposed amendments to the data requirements for pesticide registrations
in 40 CFR part 158.

Discussion of Comments on International Harmonization of Data
Requirements

	OECD member countries have had discussions about harmonizing data
requirements within the OECD community.   The U.S. and Canada have
worked together to harmonize data requirements across all disciplines;
U.S. data requirements are harmonized with Canada’s data requirements
to a high degree.

COMMENT:  Commenter 51, in comparing the U.S. data requirements with
those of the European Union, indicated that some parts are not
completely compatible with the EU data requirements, currently under
revision.  Additional harmonization with the EU within the framework of
OECD seems appropriate.

RESPONSE:  EPA will continue to work with the EU through the OECD to
harmonize data requirements, promote work-sharing opportunities, and
explore direct bilateral opportunities as well. 

COMMENT:	The following comments address test guideline issues, not the
data requirements in the proposed rule.  Commenter 51 said the European
Union relies on OECD test guidelines where available, while the U.S.
relies on OPPTS guidelines.

RESPONSE:  OPPTS’s test guidelines have been harmonized with OECD test
guidelines.  OPPTS test guidelines also provide registrants with
additional guidance from EPA to fulfill unique U.S. regulatory
requirements.

COMMENT:	Commenter 131’s interpretation of the Mutual Acceptance of
Data (MAD) for OECD countries obligates the latter to accept data
generated in accordance with an OECD test guideline and that refusal to
accept non-animal data would constitute a breach of the MAD. 

RESPONSE:  EPA disagrees with a strict interpretation of the member
country’s obligation to accept all OECD protocols.   OECD protocols
that have been harmonized with OPP guidelines would be acceptable.  An
OECD protocol that has not been harmonized with OPP guidelines may not
supply data of suitable quality and completeness for EPA to fulfill the
requirements of FIFRA to protect humans and the environment and
therefore would not be acceptable.  The commenter is directed to section
158.70(d)(2) of the regulatory text in the final rule for Agency policy
regarding OECD protocols.  For a discussion of animal testing, please
see Unit XIII.  Discussion of Comments on Animal Welfare Concerns below.

Discussion of Comments on Animal Welfare Concerns

	The Agency is committed to the development and use of alternative
approaches to animal testing.  The Agency participates in the Federal
Interagency Committee for the Validation of Alternative Methods
(ICCVAM). 

COMMENT:	The Agency received 52 comments from private citizens and one
from an international coalition of animal protection advocacy
organizations.  While most commenters supported EPA’s proposal to
eliminate the one-year dog study from the toxicology data requirements,
they urged increased minimization of animal testing, adoption of
alternative non-animal testing, and revision of testing strategies to
incorporate innovations such as the one developed by ILSI/HESI.  Other
commenters were concerned that the current testing was not protective
enough of human health or wondered if the NAS recommendations regarding
data requirements were tainted by possible ties to the pesticide
industry.

RESPONSE:	The Agency is committed to avoiding unnecessary animal testing
while taking into consideration principles of sound science and the
requirements of FIFRA to protect humans and the environment.  For
example, chemicals with a demonstrated pH indicating a strongly acidic
or alkaline substance need not be tested in animals for eye or skin
corrosivity potential.  Also, EPA will consider data from a validated in
vitro corrosivity assay as a screen to judge whether a chemical may be
corrosive to the eye or skin.  Making this determination may reduce or
avoid actual testing on animals.  EPA is considering how the number of
longer term studies might be reduced by examining the possibility to
combine toxicological endpoints from more than one study.  The Agency
already has bridging and batching policies in place to allow the use of
acute toxicity, sensitization, or irritation test data on products to be
used to support other products.  At EPA’s initiative, these policies
have been incorporated into the new Globally Harmonized System for
Classification and Labeling. 

	EPA is working closely with 15 other U.S. agencies to advance the
validation and adoption of alternative test methods through the Federal
Interagency Coordinating Committee on Validation of Alternative Methods
(ICCVAM) (    HYPERLINK "(http://iccvam.niehs.nih.gov)," 
http://iccvam.niehs.nih.gov),  established by the National Institute of
Environmental Health Sciences.  ICCVAM works towards: 

	1.  Encouraging the reduction of the number of animals used in
testing, where possible. 

2.  Seeking opportunities to replace test methods requiring animals with
alternative test methods when validated acceptable alternative methods
are available. 

	3.  Optimizing animal use by test method refinement. 

ICCVAM, together with the National Toxicology Program Interagency Center
for the Evaluation of Alternative Toxicological Methods (NICEATM),
convenes independent peer review panels, as appropriate, to evaluate the
validation status of proposed test methods and coordinates expert panel
meetings or workshops for validation or test method-related activities. 
ICCVAM has developed guidelines for the nomination and submission of
new, revised, and alternative test methods (  HYPERLINK
"http://iccvam.niehs.nih.gov/odcs/guidelines/subguide.pdf" 
http://iccvam.niehs.nih.gov/odcs/guidelines/subguide.pdf ).

	The Agency has also co-sponsored a number of major workshops to advance
alternative test method activities.  EPA, ICCVAM, and NICEATM
collaborated in the development of performance standard concepts for
validated alternative tests; the standards are detailed in the May 2004
NIH Publication No. 04-4510
(www.iccvam.niehs.nih.gov/methods/ps/ps044510.pdf).  Recently, at the
request of EPA, ICCVAM/NICEATM coordinated the review of four in vitro
test methods for identifying ocular corrosives and severe irritants. 
EPA is incorporating new alternative tests and testing strategies into
its programs to reduce animal use (e.g. in assessing acute oral toxicity
[870.1000 revised and 870.1100 revised], dermal sensitization [870.2600
revised], and dermal irritation /corrosion).  

	The Agency also recognizes the need for timely periodic review,
revision and/or supplementation, as applicable, of its test guidelines. 
As new tests and test batteries are validated, the Agency can present
them to the FIFRA SAP to review their applicability in meeting
regulatory needs.  EPA can seek comment from the SAP on test guideline
or other test method-related issues, depending on the circumstances.  As
other appropriate alternative or in vitro methods become available, they
will be considered for addition to the Agency’s test guidelines. 

	Finally, the Agency is committed to a more hypothesis-based testing
paradigm by advancing in silico, in vitro, and efficient focused in vivo
testing so that chemicals are tested in animals for those endpoints most
relevant to each chemical’s exposure or intended use.  The Agency
acknowledges that substantial research will be needed to achieve this
long term goal, but the Agency is also working on the important
short-term goal to make the existing animal testing paradigm more
efficient, reliable, and responsive to our risk assessment and
management needs.  The Agency has undertaken several activities to move
towards a more efficient animal paradigm, including analyzing and
updating the current data requirements.  As evidenced by this final
rule, the Agency has completed its analysis of dog toxicity studies and
determined that the one year dog study can be omitted as a core data
requirement for pesticides. 

XIV.   Water Quality Issues 

	The Agency received comments from four California water treatment
authorities and two California cities’ environmental agencies.  The
comments centered on their strong recommendations that FIFRA data
requirements should be equivalent to the data required to develop water
quality criteria (WQC) under the Clean Water Act (CWA) and should
consider water quality issues related to urban pesticide use. 
California water-treatment authorities questioned the adequacy of the
Agency’s assessment of risks with regard to water quality
considerations including: use of aquatic toxicity data, surface water
quality studies, and urban uses of pesticides, particularly when these
uses result in pesticide residues in receiving waters from storm sewers
or sewage treatment plants.  The goal of the 158 data requirements is to
require the registrants to submit scientifically sound data, conducted
according to recommended guidelines, to enable the scientists in the
Pesticide Program to conduct ecological risk assessments on a national
scale.  EPA believes the 158 data requirements are sufficient to conduct
high quality risk assessments. 

	Clean water is a critical EPA goal.  EPA’s 2006 - 2011 Strategic Plan
contains Office of Pesticide Programs (OPP) targets for water quality. 
It states that public health and the environment can be protected by
assessing, managing and reducing the risks from pesticide use in
cooperation with other water quality management agencies.  In order to
meet the strategic targets and other performance measures and
indicators, State and Tribal pesticide lead agencies are expected to use
water quality grant funds to develop and carry out management programs
to protect ground and surface water resources from pesticide risks.  The
State and Tribal agencies are expected to use the grant money to
evaluate “pesticides of interest”; take actions to reduce or prevent
contamination from this group of pesticides; and demonstrate the
progress of the management strategy in reducing or maintaining
concentrations below reference points.  “Pesticides of interest” are
those pesticides that have the potential to occur in surface or ground
water at concentrations approaching or exceeding a human health or
ecological reference point.  OPP, the Office of Water (OW) and EPA
Regions work together to identify and manage the risks of pesticide use
to water resources and to ensure that the State and Tribal water lead
agencies meet their work plan water quality commitments.

 

1.  FIFRA Data Should Satisfy Water Quality Criteria

COMMENT   Five commenters (#114, #116, #117,  #132, #127) emphasized
that data sufficient to develop WQC are needed. Under the Federal Clean
Water Act, the status of surface water aquatic habitats is determined,
in part, by evaluating whether water quality criteria have been
exceeded.  The range of toxicity tests proposed to be required for
pesticide registration does not include the minimum aquatic toxicity
data necessary to derive acute and chronic water quality criteria
following U.S. EPA guidelines.

RESPONSE   The Agency is confident that the pesticide registration
process, including its data requirement regulations, adequately consider
the endpoints that are protected under the CWA.  When acceptable data
are available, OPP uses these data in its risk assessment process.  

	The purpose of a water quality criterion under the CWA is to determine
the level at which a water body may be at risk for environmental damage.
 The purpose of the data requirements for pesticide registration is to
allow the Agency to determine ecological risk of using a pesticide. 
Thus, these programs have similar goals.  While EPA has developed
guidelines for developing WQ criteria, the Agency has also recognized
that WQC can be developed with a more limited data set.  For the Great
Lakes Program, the Agency developed a Tier II methodology (Final Water
Quality Guidance for the Great Lakes System. Federal Register, March 23,
1995. 40CFR) to be used in the absence of the full data set outlined in
the WQC guidelines.  The Agency recognized that for the WQC developed
under the Tier II methodology, greater uncertainty factors would be
needed.  The Agency deliberately uses conservative assumptions in its
pesticide risk assessment process to add in additional protections.

	Together, EPA’s OW and OPP developed aquatic life benchmarks for 71
pesticides or pesticide degradation products for States to use to
establish targets for safe levels of pesticides for aquatic plants and
animals.  The benchmarks are derived from data submitted to EPA for
pesticide registration.  Thus, pesticide registration data are valuable
in assessing water quality risks.

 COMMENT   Six commenters (# 114, #115, #116, #117, #127, #132)
recommended collecting toxicity test results for all standard water
quality test species used by water quality agencies.  The highest
priority, in their view, is to obtain both acute and chronic toxicity
data for standard freshwater toxicity testing species because these
tests are used to evaluate toxicity in wastewater effluent and ambient
waters. The typical species used are Pimephales promelas (fathead
minnow), Ceriodaphnia dubia (water flea) and Selenastrum capricornutum,
(green algae).  Likewise, freshwater acute and chronic sediment toxicity
data are a priority.  The typical test species is Hyalella azteca
(scud). Toxicity test results for sub-lethal end points other than
growth and reproduction are also necessary.  For example, effects on
behavior, swimming performance (which affects a fish’s ability to
maintain proper position in the water column, avoid predators, and
capture food), and reproduction can be critical to the survival of a
species.	

RESPONSE   The Agency’s OPP requires data from acute and chronic
studies on a number of aquatic organisms spanning several taxa of
vertebrates, invertebrates, and plants. The test species were chosen as
surrogates for the wide range of aquatic organisms which might be
exposed to pesticides during use. The number of tests and test species
reflects the desire to balance the need for adequate data for ecological
assessment, the use of live animals, and the need to consider the burden
imposed upon the regulated community.  The Agency accepts several
species of test organisms as defined by ASTM, as well as EPA
821-R-02-012. Ceriodaphnia dubia is an acceptable species and may or may
not be more sensitive than other invertebrates relative to a particular
pesticide.

	OPP does summarize sublethal endpoints in the risk assessment process
when this information is available. Acute and chronic study guidelines
specify that the study authors report sub-lethal effects if there is an
occurrence (swimming performance, lethargy, etc).  The extent to which
behavioral or swimming performance data are used in a quantitative
fashion is limited by uncertainty in relating these responses to
quantitative responses in demographic rates (e.g., mortality,
reproductive fitness) that underlie population responses. 

2.  Expand the Sediment Testing Requirement to More Use Sites

COMMENT   Five commenters (#114, #115, #116, #117, #127) stated that
most pesticides should be tested with the acute and chronic sediment
tests with freshwater and estuarine organisms.  One of the commenters
also requested that these studies be required for outdoor residential
uses as well as for indoor uses as the products may be washed from
indoor and outdoor surfaces into wastewater and sewer systems.

RESPONSE   The Agency listed the criteria for requirement of the acute
or chronic sediment toxicity studies in the test notes.  If a pesticide
meets those criteria, and problem formulation indicates the potential
for exposure and risk to sediment-dwelling organisms, then the data
requirement will be imposed.  The Agency agrees that pesticides used on
residential outdoor sites should be required to be supported by sediment
testing, based on the results of the problem formulation phase of the
preliminary risk assessment.  Therefore, we changed the condition of
requirement for requirement from NR in the proposed rule to CR in the
final rule for residential outdoor use patterns.  However, greenhouse
and indoor use patterns remain NR as the exposure to aquatic communities
from the applications of conventional pesticides to these sites is
relatively low from these uses.    

3.  Recommendations to Add More Use Patterns to Those Requiring Fate and
Aquatic Toxicity Testing

COMMENT The Agency received several related comments that discussed the
issues of addressing the non-agricultural uses of pesticides in urban
areas, including residential, indoor and aquatic residential use
patterns.  They wanted the use sites included in these use patterns to
be expanded to capture uses associated with drainage from the site of
application to storm drains and sewers, and to require the full
complement of aquatic toxicity and environmental fate data for all these
uses. (Commenters #114, #116 and #117).

COMMENT According to commenter #116 several categories of urban
pesticide use were inappropriately exempted from environmental testing
requirements.  These categories are: residential outdoor, aquatic
residential, non-residential outdoor urban and indoor.  The Agency
should require the toxicity and fate data for these sites, and use the
data to validate a model to predict environmental concentrations of
pesticides in urban areas. 

COMMENT   One commenter (#114) recommended that uses such as swimming
pools, spas, fountains and similar facilities, which are commonly
emptied into storm drains, be reclassified differently to recognize that
pesticides applied in water in urban areas will go either directly to
surface waters through discharge into storm drains or to municipal
wastewater treatment plants.  This commenter plus commenter # 117
recommended that the Agency capture these kinds of uses in a new use
pattern such as “terrestrial urban uses”.  This new category would
also include uses such as applications on commercial, institutional or
industrial outdoor locations around buildings, on landscaping, lawns,
golf courses, or other urban impervious or pervious surfaces.   They
believe that there is no scientific justification to require fewer
aquatic toxicity and environmental fate data for residential outdoor use
pesticides than terrestrial (crop) use pesticides, and there may often
be good reasons to require more data.

RESPONSE   EPA acknowledges that these issues relating to urban
applications of conventional pesticides will need to be evaluated, but
these issues will be addressed in a future update of the 158 rule.   At
this time, there are insufficient exposure and risk methodologies
available to adequately assess urban uses.

	If a conventional pesticide is applied to any of the use sites such as
fountains, swimming pools, lawns, around buildings, it is included in
use patterns listed in the final rule.  The type of data required varies
depending on the use pattern and chemical-specific characteristics of
the pesticide.  If additional data are needed to address uncertainty in
the risk assessment, EPA will employ assumptions to account for the
uncertainty or require the applicant to provide the data.

	EPA agrees that pesticide discharge into municipal sewage systems is an
important issue.  This is especially true for antimicrobial pesticides
which are typically rinsed down the drain.  EPA is currently developing
proposed data requirements for antimicrobial pesticides and intends to
consider this issue in that proposal.

4.  Urban Pesticide Runoff Modeling

COMMENT   There were four comments (#114, #115 #117, #127) that runoff
to surface water from urban pesticide use needs to be modeled using
high-quality modeling.  They indicated that data such as
pesticide-specific wash-off data for urban surfaces and other chemical
properties related to surface water transport from impervious surfaces
needs to be included among the environmental fate data requirements to
provide inputs for this type of modeling.  Additionally, to properly
assess risks from pesticides discharged to municipal wastewater
treatment plants (POTW), environmental fate data should be required.   

RESPONSE   The Agency does acknowledge the potential for environmental
risk from some nonagricultural uses of pesticides.  OPP has developed
methods and carried out assessments for indoor uses which ultimately
discharge through a POTW to surface water, but has made less progress in
estimating discharges resulting from urban outdoor uses.  OW conducts
modeling for water quality impacted by pesticides, but their models are
deficient as OPP conducts national level assessments and needs more
flexible models to simulate large numbers of sites nationally.  The
models used by OW simulate localized impacts.  If the selected models
indicate that additional fate information is needed for the input data,
the Agency can require the data on a case-by-case basis until future
updates of this rule are promulgated.  OPP will continue to rely
predominately on available monitoring data for characterizing aquatic
exposure from urban runoff.  Risk assessments indicate that these data
provide estimates of a lower bound of potential exposure.

	EPA agrees that pesticide discharge into municipal sewage systems is an
important issue.  This is especially true for antimicrobial pesticides
which are typically rinsed down the drain.  EPA is currently developing
proposed data requirements for antimicrobial pesticides and intends to
consider this issue in that proposal. 

	The Agency is currently evaluating various exposure models that might
be appropriate for evaluating urban pesticide uses and possible runoff
scenarios as down storm drains, for example.  As part of this
initiative, OPP sponsored a workshop in June 2007 to bring together
exposure modelers, fate scientists and risk assessors from state and
Federal government agencies, private companies, and other interested
parties for presentations and discussions of the challenges of
developing appropriate exposure models to simulate urban runoff and
entry in urban watersheds.  Some of the topics discussed were currently
available agricultural models and adaptability to urban scenarios; the
variability of urban scenarios that include not only sites exposed by
runoff across hard surfaces such as pavement, but also sites exposed
through runoff from large systems such as turfgrass; and the use of
Geographic Information Systems (GIS) to refine exposure estimates.  The
workshop afforded OPP the opportunity to gather information on modeling
techniques and available data that will improve the Program’s overall
exposure assessment methods.

5.  General Comments on Data Requirements

COMMENT  Three commenters (#114 #117, #132) stated that EPA should
require pesticide registrants to submit analytical methods with
detection limits at least 1/20 of the lowest environmentally relevant
concentration in several media, and the methods they use should be
validated.  

RESPONSE   The Agency included the requirement for independent
laboratory validation of analytical methods for aquatic and terrestrial
field studies in the draft proposal and the final rule.  The validation
must have detection limits that are sufficiently resolved to address
biologically significant environmental media levels for the pesticide. 
Setting the detection limits as recommended in the comment may not be
feasible for some chemicals.

COMMENT   Four commenters (#114, #117, #132) stated that the Agency
needs to require surface water monitoring in the same manner it is now
requiring ground water monitoring.

RESPONSE   The Agency’s ground water monitoring data requirement is
conditional (CR) pending a weight of evidence assessment.  Surface water
monitoring can be required on a case-by-case basis under FIFRA. 
Prospective ground water monitoring has been required for some
pesticides during their reregistration process.  Likewise, surface water
monitoring has also been required for registration actions for several
pesticides.  Additionally, the Agency uses several other sources for
surface water data such as the NAWQA (National Water Quality Assessment
Program of USGS) database and water resource data from individual
States, in addition to relevant data from OW.

COMMENT   Two commenters (#114, #116) stated that the rule should
require registrants to search the professional published literature and
to provide copies of all relevant publications to the Agency. 

RESPONSE   This is not a 158 data requirement issue.  Generally,
submission of published literature can be an option available for
selection by registrants to attempt to satisfy a data requirement.  It
is not uncommon for registrants to submit published studies as
supplemental data to support their registration packages.  In addition,
EPA supplements the required data sets with information obtained through
a systematic search of the open literature and through Agency databases
for aquatic toxicology and fate data.

6.  Degradate Testing

COMMENT   One commenter (#116) stated that the data requirements should
include degradates as they can present significant environmental risks. 
The proposed rule should be modified to require such data, which include
product chemistry data relevant to environmental fate and transport
(e.g., Section 158.310 tests for pH, UV/visible light absorption,
density, dissociation constant in water, octanol-water partition
coefficient, water solubility, and vapor pressure), aquatic toxicity
data (Section 158.400), and environmental fate data (Section 158.1100).

RESPONSE   The Agency evaluates degradates in relation to their
potential toxicity and does require appropriate testing if the degradate
appears toxic or likely to be present in the environment at levels of
concern.

	

7.  Testing with TEPs

COMMENT   Commenter # 116 stated that EPA should require full testing of
all active ingredient mixtures and parallel testing of active
ingredients and formulated products to ensure that additives will not
cause additional adverse effects.

RESPONSE   The data requirements table for nontarget aquatic organism
testing in Subpart G of the final rule lists the conditions under which
TEPs are required (test note 9).  The conditions include direct
introduction into the aquatic environment; toxicity levels of the active
ingredient relative to expected or estimated environmental
concentrations; or other ingredients that may enhance toxicity.  If the
pesticide meets any of those conditions, then TEP testing must be done.

XV.	  SEQ CHAPTER \h \r 1 Endangered Species

Incidental to its proposed data requirements for conventional
pesticides, EPA discussed the possibility of future data and information
needs to develop and/or refine risk assessments for endangered species. 
EPA did not propose any data requirements specific to endangered
species, but described its current level of information and data usage. 
EPA requested comment on the value and utility of location and usage
information, and on additional types of research that might yield
greater refinement in risk assessments for endangered species.

	EPA appreciates the response it received from commenters on these
topics, primarily from industry task forces and associations.  As
endangered species data requirements were not proposed, EPA has not
responded to the comments as part of this final rule, but will consider
them in the context of its ongoing risk assessments.   If EPA finds that
it needs to amend part 158 to normalize endangered species data
requirements, it will consider these comments in the development of a
future proposed rule.

XVI.	Economic Analysis 

	EPA prepared an economic analysis of the potential costs of the
proposed rule and placed it in Docket ID OPP-2004-0387.  Using the
currently codified requirements as the baseline for the analysis, the
total annual impact to the pesticide industry was estimated to be about
$51 million. 

COMMENT:	Commenter 112 claimed the proposed rule said it was codifying
existing practice in contrast to the three options presented in the
economic analysis.

RESPONSE:  Since the commenter did not pinpoint the statement in the
preamble from which the mistaken conclusion was drawn, it was not
possible to re-examine the wording for future clarification.  On p.
12282 of the proposed rule, the discussion spoke of three categories of
requirements:  new requirements never imposed on a registrant; newly
codified requirements that have been applied on a case-by-case basis,
but do not appear in the current CFR; and revisions to existing
requirements.  In addition, the detailed discussion categorized the
changes into two broad categories: substantive changes and technical
changes with no substantive effect.  These categories were further
broken down; there were seven subcategories of substantive changes and
four subcategories of technical changes. 

 

COMMENT:	Commenters 46 and 120 questioned how it was possible to
determine the cost of a study for which no guideline “has yet been
promulgated” and whether this shortcoming would have led to an
underestimation of the economic impact.

RESPONSE:  The Agency recognizes the commenters' concern about the test
guidelines.  The Economic Analysis used test costs for which guidelines
were publicly available, either in draft or in final form.  Many of the
guidelines have been finalized and are publicly available; a few of the
guidelines, although in draft form, are also publicly available.  Both
the finalized and draft guidelines have been used for registration
actions and therefore the laboratories were able to provide cost
estimates for them.  The draft guidelines are in various stages of
readiness for finalization.  The Agency has been preparing them for
finalization and will notify stakeholders when the final guideline will
be publicly available. In the meantime, applicants are directed to
websites where available draft guidelines are posted; the URLs are
listed under the individual disciplines.

COMMENT:	Commenter 112 believed the proposed apportionment per
registrant per year did not show that each registrant will not be
sharing the costs equally; some registrations will require a minimal
data set and others will require a more extensive data set.  Therefore,
the average $420,000 per registrant estimate will be substantially more.

RESPONSE:  Since it is not possible to know exactly how many
registrations will require a minimal data set and how many a more
extensive data set, the standard procedure is to use a simple average,
which resulted in the $420,000.  It was not intended to represent the
exact cost each registrant may incur to register a pesticide product. 
The Agency agrees that a typical registration of an active ingredient
for a food use would cost considerably more than one for a nonfood use.

COMMENT:	Commenter 112 claimed the cost estimates used by EPA to
determine the increased expenditures may not reflect the actual costs to
registrants.  This commenter felt the immunotoxicity test, for example,
was understated for purposes of the economic analysis.

RESPONSE:  The estimated costs for the proposed rule, as documented in
the economic analysis, are the result of a limited survey of commercial
laboratories.  EPA contacted a number of laboratories to obtain cost
information for each test; for a number of studies there was a wide
range of cost estimates.  Test costs can very considerably based on the
protocol chosen by the laboratory.  EPA’s estimates are based on the
average of high and low test costs submitted by the different
laboratories.  When the test was performed by only one laboratory, then
only one cost was available and no averaging of costs was possible.
In-house laboratories that many companies use were not surveyed; their
costs might be expected to be lower than those cited by independent
commercial laboratories.

Two laboratories responded to our requests for cost information for the
immunotoxicity test and the results were averaged.  Again, the average
cost is not an indicator of what specific costs will be for this test.

COMMENT:	Commenters 46 and 120 were concerned that the economic analysis
did not take into account any indirect costs, such as oversight of the
studies, review of protocols, drafting reports, test material
preparation and certification, and responding to “shortcomings” in
the proposed rule.  Commenter 112 felt the costs used by the Agency did
not include analytical support or study monitoring and overhead expenses
directly related to study conduct.

RESPONSE:  The “Estimation of the Burden of the Data Collection”
section of the Economic Analysis states that the additional report and
recordkeeping burden associated with the proposed rule is about 35,123
hours and the burden cost estimate is $3,041,816 per year.  This amount
is included in the total impact of $51 million.  The cost is shared by
all respondents and is an upper bound estimate.  The Agency has already
captured the burden for most of the data requirements it currently
imposes through ICRs for the Data Call-Ins.  The Agency’s estimated
test costs include analytical support, study monitoring, and overhead
expenses.

COMMENT:	Commenter 112 contended that the economic burden imposed on
registrants did not take into account continuing registrations such as
reregistration and registration review, thus not reflecting the “true
costs.”

RESPONSE:  The economic analysis was not intended to include every
possible type of special registration requirement that might occur or
has already occurred.  Reregistration is almost completed and factoring
in this procedure would provide a false impression of the costs of
future registrations.  Moreover, since it is not possible to precisely
predict in advance which pesticide products would be selected for the
registration review fifteen-year review cycle, an estimate for the
latter might not have significant meaning.  In addition, the burden
estimate for registration review was conducted separately and is
available at Docket Identification (ID) number EPA-HQ-OPP-2004-0404.

COMMENT:  Commenter 46 noted that he believed additional time was
necessary to assess the economic assumptions on which the proposed rule
was predicated and requested a 90-day extension of the comment period. 
Commenter 46 indicated that major areas of concern for a number of small
and medium-sized registrants are the cost of testing and related
administrative and overhead costs.  

RESPONSE:   The comment period was extended for an additional 90 days. 
EPA is mindful of the burden on the applicant to conduct studies which
may not yield additional useful information.  The “Estimation of the
Burden of the Data Collection” section of the Economic Analysis states
that the additional report and recordkeeping burden associated with the
proposed rule is about 35,123 hours and the burden cost estimate is
$3,041,816 per year.  This amount is included in the total impact of $51
million in the proposed rule.  The cost is shared by all respondents and
is an upper bound estimate.  The Agency has already captured the burden
for most of the data requirements it currently imposes through ICRs for
the Data Call-Ins.  The Agency’s estimated test costs include
analytical and overhead costs.

COMMENT:	Commenter 125 was concerned about a possible significant impact
on his small business.  The commenter was also concerned that large
producers focus their data development efforts on large volume
agricultural uses, leaving gaps in data needed to support smaller uses
such as minor uses or residential uses that do not have large markets. 
In the absence of data development by large producers, the commenter
suggests that small businesses may be called upon to develop
significantly more data.    

RESPONSE:   EPA acknowledges that there may be some impacts on small
businesses, and that in the situation described by the commenter, small
businesses that choose to register products intended solely for minor
uses or residential uses may incur data development costs to support
those uses.  Due to the elimination of several toxicology data
requirements and clarification of test notes throughout part 158 in the
final rule, the expected incremental costs of the final rule are 33%
less than what was estimated for the proposed rule.  The small business
impacts for the final rule were not re-estimated since they were not
significant under the proposed rule and will be less significant under
the final rule.

	However, EPA notes that the revisions to part 158 impose few totally
new data requirements and those are generally in a discipline (e.g.
toxicology) where the data support a broad spectrum of uses.  Data in
such a discipline routinely developed by large producers to support
major food uses also support minor food uses and residential uses. 
These data are available to any producer to support smaller-scale uses
under the data compensation provisions of FIFRA, including the
formulators’ exemption of section 3(c)(2)(D).  Few data requirements
are so specific to a use pattern that they post a significant cost or
burden on a single company.

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