[Federal Register: October 26, 2007 (Volume 72, Number 207)]
[Rules and Regulations]
[Page 60933-60988]
From the Federal Register Online via GPO Access [wais.access.gpo.gov]
[DOCID:fr26oc07-14]
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Part II
Environmental Protection Agency
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40 CFR Parts 9, 152, 156, 159 et al.
Pesticides; Data Requirements for Conventional Chemicals, Technical
Amendments, and Data Requirements for Biochemical and Microbial
Pesticides; Final Rules
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ENVIRONMENTAL PROTECTION AGENCY
40 CFR Parts 9 and 158
[EPA-HQ-OPP-2004-0387; FRL-8106-5]
RIN 2070-AC12
Pesticides; Data Requirements for Conventional Chemicals
AGENCY: Environmental Protection Agency (EPA).
ACTION: Final rule.
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SUMMARY: EPA is updating its data requirements in part 158 of Title 40
in the Code of Federal Regulations for the registration of conventional
pesticide products. As scientific understanding of potential hazards
posed by pesticides has evolved, some data requirements have been
imposed on a case-by-case basis but not codified since 1984. Besides
providing the regulated community with clearer and more transparent
information, the updated data requirements will enhance the development
of health and environmental data to conduct scientifically sound
chemical hazard/risk assessments to protect human health and the
environment. In a companion final rule also being promulgated today,
EPA is making technical changes arising from this final rule.
DATES: This final rule is effective on December 26, 2007.
ADDRESSES: EPA has established a docket for this action under Docket
identification number EPA-HQ-OPP-2004-0387. All documents in the docket
are listed on the regulations.gov web site. Although listed in the
index, some information is not publicly available, i.e., CBI or other
information whose disclosure is restricted by statute. Certain other
material, such as copyrighted material, is not placed on the Internet
and will be publicly available only in hard copy form. Publicly
available docket materials are available either electronically through
http://www.regulations.gov or in hard copy at the Office of Pesticide Programs
(OPP) Regulatory Public Docket (7502P), Room S-4400, One Potomac Yard
(South Building), 2777 S. Crystal Drive, Arlington, VA 22202. This
Docket is open from 8:30 a.m. to 4 p.m., Monday through Friday,
excluding legal holidays. The Docket telephone number is (703) 305-
5805.
FOR FURTHER INFORMATION CONTACT: For information on the data
requirements for ecological effects and environmental fate, contact:
Ann Stavola, Field and External Affairs Division (FEAD), Office of
Pesticide Programs (OPP) (7506P), Environmental Protection Agency, 1200
Pennsylvania Avenue NW, Washington, DC 20460; telephone number: (703)
305-5354; fax number: (703) 305-5884; e-mail address:
stavola.ann@epa.gov . For all other questions, contact: Vera Au, FEAD
(7506P), OPP, Environmental Protection Agency, 1200 Pennsylvania Ave.,
NW., Washington, DC 20460-0001; telephone number:(703) 308-9069; fax
number: (703) 305-5884; e-mail address: au.vera@epa.gov.
SUPPLEMENTARY INFORMATION:
I. General Information
A. Does this Action Apply to Me?
You may be potentially affected by this action if you are a
producer or registrant of a pesticide product, including agricultural,
residential, and industrial, but not including antimicrobial
pesticides, biochemical pesticides, or microbial pesticides.
This action may also affect any person or company who might
petition the Agency for new tolerances, hold a pesticide registration
with existing tolerances, or any person or company who is interested in
obtaining or retaining a tolerance in the absence of a registration,
that is, an import tolerance. This latter group may include pesticide
manufacturers or formulators, importers of food, grower groups, or any
person or company who seeks a tolerance. Potentially affected entities
may include, but are not limited to:
Chemical Producers (NAICS 32532), e.g., pesticide manufacturers or
formulators of pesticide products, importers or any person or company
who seeks to register a pesticide or to obtain a tolerance for a
pesticide.
This listing is not intended to be exhaustive, but rather provides
a guide for readers regarding entities likely to be affected by this
action. Other types of entities not listed in this unit could also be
affected. The North American Industrial Classification System (NAICS)
code has been provided to assist you and others in determining whether
this action might apply to certain entities. To determine whether you
or your business may be affected by this action, you should carefully
examine the applicability provisions in Unit II.C. If you have any
questions regarding the applicability of this action to a particular
entity, consult the persons listed under FOR FURTHER INFORMATION
CONTACT.
II. Background
A. What Action is the Agency Taking?
The Agency is updating and revising its data requirements for the
registration of conventional pesticide products. The data requirements
for the registration of antimicrobial products, product performance,
and biochemical and microbial pesticides are not being revised in this
action. EPA issued a proposed rule addressing data requirements for
biochemical and microbial pesticides on March 8, 2006 (71 FR 12072).
Antimicrobial data requirements have been moved to new part 161.
As scientific understanding of potential hazards posed by
pesticides has evolved, some data requirements have been imposed on a
case-by-case basis but not codified since 1984. By codifying the data
requirements that have been applied on a case-by-case basis, the Agency
believes the pesticide industry and other partners in the regulated
community will be better prepared for the pesticide registration
process.
B. What is the Agency's Authority for Taking this Action?
This rule is issued under the authority of FIFRA sections 3, 4, 5,
12, and 25; and FFDCA section 408.
C. Is this Final Rule Applicable to Antimicrobial Pesticides Products?
In current part 158, the data requirements cover both conventional
and antimicrobial pesticides. Biochemical and microbial pesticides are
set apart at Sec. 158.690 and Sec. 158.740. 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 received no key comments
concerning the proposed limited applicability of part 158, and
accordingly, EPA is adopting its proposed scope. Elsewhere in today's
Federal Register, EPA is promulgating a final rule establishing data
requirements for biochemical and microbial 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. Applicants would have to rely solely on consultations with
EPA to determine the data requirements for their antimicrobial products
without the benefit of regulatory data requirements. However, EPA has
decided to preserve the current data requirements to provide regulatory
coverage for antimicrobial
[[Page 60935]]
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 today will only
apply to conventional pesticides.
Part 161 is intended to be transitional and will be revoked upon
the effective date of a replacement regulation tailored to
antimicrobial pesticide data requirements. EPA recognizes that current
data requirements of this transitional part are not optimal for
registrants of antimicrobial pesticides. Because the 1984 data
requirements were developed primarily to address agricultural
chemicals, it has been difficult for antimicrobial registrants to
discern data requirements that apply to antimicrobial products. This
difficulty will not be corrected in simply transferring the current
requirements to a new location. As a result, applicants should continue
to routinely consult with the Agency to interpret the requirements of
new part 161 as they apply to antimicrobial products. EPA supports and
encourages the consultation process for all applicants, as the data
requirements are highly dependent on pesticide type and use pattern.
EPA is fully committed to the development of tailored data requirements
for antimicrobial pesticides and expects to issue a proposed rule by
the end of 2008.
III. Discussion of the March 11, 2005, Notice of Proposed Rulemaking
(NPRM)
EPA published an NPRM on March 11, 2005 (70 FR 12275), proposing to
update and revise its data requirements for the registration of
conventional pesticide products in 40 CFR part 158. The data
requirements identify the types of information that EPA needs to:
determine that a pesticide product can be registered; issue a tolerance
or tolerance exemption for pesticide residues in food; or allow the
experimental use of the pesticide. The proposed rule was intended to:
improve the scientific basis for pesticide decisions; update the
requirements last codified in 1984; and reorganize part 158 to improve
usability. These efforts will help protect human health and the
environment by providing an up-to-date scientific framework for
identifying and assessing the risks of conventional pesticides for use
in the United States. The closing date of the 90-day comment period for
the NPRM was June 9, 2005. The comment period was extended to September
7, 2005, to allow stakeholders additional time to assess the impact of
the proposed revisions on their particular situations and prepare their
comments (40 FR 33414). One hundred seven public comments were filed in
Docket ID OPP-2004-0387. For a detailed response to comments, refer to
Docket ID OPP-2004-0387. In addition, EPA convened a 2-day public
workshop in Arlington, Virginia, to explain the provisions of the NPRM
on May 3-4, 2005. There were 126 attendees at the public workshop.
IV. Discussion of Key Comments on the Order of Subparts
EPA's proposed rule structured the subparts of part 158 to match
the original sequence of guidelines. A number of commenters found this
structure confusing, and one commenter submitted an alternative
structure, which was considered along with other alternative
structures. EPA agrees with commenters that the current relatively
random structure is not ideal for the average registrant who is seeking
to determine the data requirements that apply to his product.
Accordingly, in the final rule, EPA is restructuring the subparts to be
more user-friendly.
EPA reasons that the users most in need of clarity are the
infrequent, follow-on applicants, whose actual data requirements are in
many cases limited to end-use product data of various types. In
general, larger pesticide companies that routinely submit complex new
chemical/new use applications and petitions for tolerance are
responsible for the bulk of toxicology, residue chemistry, ecological
effects and environmental fate data developed using the pure active
ingredient (PAI), technical grade of active ingredient (TGAI) or the
typical end-use product (TEP). In the case of exposure data, a variety
of industry task forces, again primarily comprising large companies,
are developing surrogate databases, so that newly generated data may
not be necessary for many exposure scenarios.
In all these cases, FIFRA sec. 3(c)(1)(F) and its regulations in
part 152 provide for the use of data developed by others, either under
the formulators' exemption of section 3(c)(2)(D), or with appropriate
permission or compensation offers. These provisions were put in place
specifically to obviate the need for duplicate data development while
protecting the rights of data submitters. Thus, smaller follow-on or
me-too registrants often are required to generate only product-specific
chemistry data, acute toxicity data, and efficacy data (generally
designated in part 158 tables with End Use Product (EP) as the test
substance). These applicants will benefit by the restructured part 158
so that they don't have to search for applicable data requirements by
sifting through voluminous data requirements that may be satisfied by
formulators' exemption, citation or offer-to-pay procedures.
EPA believes that major registrants will not be disrupted by a
restructuring of the subparts because they are familiar with the data
requirements, and, in any case, should be able to easily find the data
requirement applicable to their product or petition in the current
structure. Accordingly, EPA has restructured the subparts to place
those data requirements applicable to the bulk of applications (new
end-use products and me-too products) towards the beginning of part
158.
The resulting order does not correspond to the previous guidelines
issued in 1982 et seq. (upon which the order of the proposed rule was
based), or the sequence of the OPPTS Harmonized Guidelines. It is not
critical that they do, as the tables refer to the appropriate
individual Guideline for each data requirement.
The structure of part 158 in the final rule proceeds from product
chemistry to efficacy to hazard/toxicity requirements of all types
(human health, ecological toxicity) then exposure data requirements of
all types (pre- and post-application human exposures, exposure to
residues in food), and environmental fate, which overlap human exposure
through drinking water, and ecological exposure, and spray drift. EPA
has reserved subparts among these various segments for future additions
on the same topic. EPA has also consolidated subparts addressing the
same topics: plant protection data requirements (proposed as subpart J)
have been incorporated into new subpart G (ecological effects data
requirements) as have terrestrial and aquatic nontarget organisms data
requirements (proposed as subpart E).
Finally, EPA intends that freestanding data requirements subparts
such as biochemical pesticides, microbial pesticides, and antimicrobial
pesticides be located at the end of the series. Product performance
requirements, which span all categories of pesticides, would at present
remain a separate subpart near the beginning of the series. In the
proposed rule, EPA had reserved subpart P for Pesticide Management and
Disposal but has removed the topic from the final rule while reserving
subpart P. At present, EPA has no plans to develop data requirements
specific to disposal. If EPA does so in the future, it will
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determine where such requirements should be located.
EPA has placed data requirements for experimental use permits in
subpart C of part 158. EPA eliminated the current use of brackets in
each discipline to indicate which data requirements applied to an
experimental use permit (see Unit VII.).
The final structure of part 158 is as follows:
Subpart A General provisions
Subpart B How to use the data tables
Subpart C Experimental use permits
Subpart D Product chemistry
Subpart E Product performance
Subpart F Toxicology
Subpart G Ecological effects [comprising aquatic, terrestrial and
plant species]
Subparts H - I [Reserved]
Subpart J [Reserved] [Plant protection has been consolidated into
subpart G]
Subpart K Human exposure [comprising pre-application and post-
application exposure]
Subpart L Spray drift
Subpart M [Reserved]
Subpart N Environmental fate
Subpart O Residue chemistry
Subparts P - T [Reserved]
Subpart U Biochemical pesticides
Subpart V Microbial pesticides
Subpart W Antimicrobial pesticides
Subparts X - Z [Reserved]
V. Discussion of Key Comments on General Provisions of Part 158
(Subpart A)
A. 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 the Federal
Insecticide, Fungicide, and Rodenticide Act (FIFRA) and the Federal
Food, Drug and Cosmetic Act (FFDCA) that apply to part 158. Deletions
from subpart A include: timing of the imposition of data requirements;
flexibility of the data requirements; consultation with the Agency;
agricultural versus non-agricultural pesticides; and biochemical and
microbial pesticides.
EPA proposed deleting the section on minor uses but based on the
comments and subsequent review, the Agency has in the final rule
retained portions of the minor use section with an introductory
paragraph. The section on the formulators' exemption was updated and
relocated to 40 CFR part 152, subpart E.
B. Format for Data Submissions
EPA proposed minor revisions to Sec. 158.32, describing how data
are to be formatted for submission to EPA. Commenters supported
revising Pesticide Registration (PR) Notice 86-5 to clarify provisions
and avoid rejection of data for formatting reasons; one commenter also
suggested integrating formatting guidance from PR 86-5 with Sec.
158.32 in the final rule. The Agency has begun the process of updating
the guidance in PR Notice 86-5 to further clarify the submission
process. The improved guidance, together with consultation with the
Agency, should help reduce the formatting conflicts. EPA will provide
the public an opportunity to comment on the proposed revisions to PR
86-5. Since the details of the revisions are still underway, EPA has
not changed the final rule.
C. Confidential Business Information
EPA proposed a number of minor revisions to Sec. 158.33 concerning
requirements for identification of and Agency treatment of confidential
business information (CBI) under FIFRA sec. 10. These revisions were
intended to clarify the provisions governing the Agency's ability to
release information, and to bring the regulations in line with a court
decision (District Court for the District of Columbia in NCAP v.
Browner, 941 F.Supp. 197, 201 (D.D.C. 1996) supporting broader release
of information to the public.
EPA received four comments concerning these proposed revisions, all
from industry trade organizations. In general, the commenters disputed
the Agency's positions or interpretations of the status of certain
types of information as non-confidential (and therefore eligible for
disclosure). One commenter misunderstood the provisions of FIFRA sec.
10 and based his comments upon an erroneous conception. EPA disagrees
with all commenters and made no revisions in the final rule. EPA
intends to abide by the Court decision which supports the Agency's
interpretation of FIFRA sec. 10. EPA has responded to all comments in
its Response to Comments document in the docket for this rule.
There were no comments on the confidentiality claims for plant-
incorporated protectant information or on releasing information to
state and foreign governments with consent.
D. Flagging Requirements
EPA proposed to revise the flagging requirements by updating and
clarifying the criteria by:
Reducing the number of study criteria from 11 to 7 by
combining certain studies under one criterion;
Combining reproductive, prenatal developmental toxicity
and developmental neurotoxicity under one criterion to reflect the
focus on infants and children.
Commenters requested clarification on the criteria and suggested
the revisions would increase the burden to registrants. All of the
listed flagging criteria need not apply to a toxicology study. If any
of the criteria listed are applicable to the study, then the
corresponding criterion number is to be included in the flagging
statement submitted with the study. In the proposed rule, the Agency
acknowledged that the revisions could flag more studies but this was
expected because of the new types of toxicity studies to further
protect infants and children. EPA made no revisions to the flagging
requirements in the final rule. EPA has responded to comments in its
Response to Comments document in the docket for this rule.
E. Data Waivers
EPA proposed reformatting the waiver process while retaining the
provisions. Several commenters expressed their concerns about clarity,
timelines and organization of information for waiver requests and made
several suggestions. EPA refined data requirements and test notes to
help the registrant determine if a waiver request is in order.
Applicants are encouraged to discuss the waiver with the Agency before
developing and submitting supporting data, information, or other
materials. The Agency is committed to timely decisions and notification
of the applicant. Organizational changes that were proposed will be
retained for the final rule. EPA has responded to comments in its
Response to Comments document in the docket for this rule.
F. Formulators' Exemption
EPA proposed to remove or revise provisions in part 158 that
directly or indirectly arise from the statutory formulators' exemption
of FIFRA sec. 3(c)(2)(D). First, EPA proposed to remove language in
Sec. 158.50 pertaining to the statutory formulators' exemption.
Second, EPA proposed removing the asterisks denoting the application of
the formulators' exemption to product chemistry and toxicology data
requirements.
A number of commenters objected to the removal of formulators'
exemption language, and others were confused by the removal of the
asterisks. It is clear that commenters are 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
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formulators' exemption). In short, part 158 specifies the ``what'' and
part 152 specifies the ``how'' of data requirements.
The primary purpose of part 158 is to specify the data requirements
pertaining to a pesticide product. Part 158 was never intended to serve
the broader purpose of specifying the various means by which an
individual applicant can legally satisfy the data requirements: that is
the purpose of the data compensation provisions of part 152. Part 152
explains all of the means of satisfying a data requirement specified in
part 158, including 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. Rather, 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 manner in which the asterisks were
displayed was such that it was not clear precisely when the
formulators' exemption did and did not excuse an applicant from the
requirement to submit data. Further, it was unclear because it
potentially 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 the
product, merely that the data requirement has been satisfied by another
means. Usually the requirement has been satisfied by submission of data
by the producer of the registered TGAI or manufacturing use product
(MP) that the applicant purchases.
Additionally, 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 Sec. 152.85 nor
Sec. 158.50 is accurate or complete. For this reason, EPA believes it
is important to consolidate the formulators' exemption language in a
single location.
All commenters correctly pointed out that although EPA indicated in
the preamble that the formulators' exemption text of Sec. 158.50 was
to be relocated to part 152, no proposed regulatory language was
included. EPA agrees that it did not include in the proposal the actual
regulatory text that would be incorporated into part 152. In a
companion final rule making technical changes, and which is published
elsewhere in this issue of the Federal Register, EPA has included the
revised language, which would incorporate the provisions of Sec.
158.50 into Sec. 152.85 with needed conforming text changes. EPA has
also corrected Sec. 152.85 to reflect current FIFRA sec. 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.
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 Sec. 158.70(a), by including a new
paragraph (1) which explains that the provisions of part 158 should be
read in conjunction with those of part 152, subpart E.
G. Minor Uses
EPA proposed to delete material in Sec. 158.60 concerning minor
uses. Minor use policies in existence in 1984 and information in
anticipation of reregistration needs for data were included in original
part 158. The information is by no means complete concerning EPA
policies on minor uses, which have since expanded by statute.
Nonetheless, several commenters wanted EPA to retain the information in
paragraphs (a)(2) and (3). EPA has in the final rule retained
paragraphs (a)(2) and (3), but has removed the remaining material and
renumbered those paragraphs. 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)).
H. Weight-of-Evidence Approach
The weight-of-evidence approach is referenced in part 158 under
several disciplines. The approach requires a critical analysis of the
entire body of available data for consistency and biological
plausibility. Some considerations in this approach are listed below:
Sufficiency of data. Studies that completely characterize
both the effects and exposure of the agent have more credibility and
support than studies that contain data gaps.
Quality of the data. Potentially relevant studies are
judged for quality and studies of high quality are given more weight
than those of lower quality.
Evidence of causality. The degree of correlation between
the presence of an agent and some adverse effect is an important
consideration.
Corroborative information. Supplementary information
relevant to the conclusions reached in the assessment is incorporated,
e.g., studies demonstrating agreement between model predictions and
observed effects.
The weight-of-evidence considers the kinds of evidence available, how
they fit together in drawing conclusions, and significant issues/
strengths/limitations of the data and conclusions. Weight-of-evidence
is not to be interpreted as simply tallying the number of positive or
negative studies.
In the case of the developmental neurotoxicity (DNT) study, such a
weight of the evidence approach is used when evaluating:
1. Treatment-related neurological effects in adult animal studies,
such as:
Clinical signs of neurotoxicity
Neuropathology
Functional or behavioral effects
2. Treatment-related neurological effects in developing animals,
following pre- and/or postnatal exposure, such as:
Nervous system malformations or neuropathy
Brain weight changes in offspring
Functional or behavioral changes in the offspring
3. Causative association between exposures and adverse neurological
effects in human epidemiological studies
4. A mechanism that is associated with adverse effects on the
development of the nervous system, such as:
SAR relationship to known neurotoxicants
Altered neuroreceptor or neurotransmitter responses
A compound could be subject to a DNT requirement under a variety of
circumstances using these criteria in a weight of evidence approach
that considers dose response, logical pattern of effects, data quality,
biological plausibility, consistency of observations in the broader
toxicological database, likeness of the case to structural analogues,
and mode of action understanding. For example, the following scenarios
for 3 different chemicals (chemicals A, B, and C) describe findings
that could lead to the conclusion that a DNT study is needed. Chemical
A is found to result in
[[Page 60938]]
responses consistent with an effect on the central nervous system
(CNS): staggering (i.e., abnormal gait) at the mid and high doses and
convulsions at the high dose are seen in a study, and abnormal gait at
the mid and high doses and cortical lesions in the brain at the high
dose are seen in another study. Chemical B is a GABA (gamma-
aminobutyric acid) receptor antagonist (i.e., a CNS mode of action that
block inhibitory systems that are involved in nerve responses) and is
found to result in functional effects in the animal studies consistent
with this mode of action, such as hyperactivity, altered response to
sudden loud noises, and seizures (only at very high doses). In
developmental toxicity studies, Chemical C results in dose-related
microcephaly, a rare finding indicative of the brain neurons not
proliferating normally.
However, a single effect would not necessarily always trigger a
DNT. For example, a small decrease in brain weight at the highest dose
tested in one adult animal study but no indications of neurotoxicity,
including the lack of corresponding decreases in brain weight in other
adequate toxicity studies, would not necessarily trigger a DNT.
Similarly, a decreased response to stimuli at doses that result in
significant body weight loss and poor health of the animal may not
provide a weight-of-evidence basis for triggering the DNT.
VI. Discussion of Key Comments on the Data Tables (Subpart B)
A. Use Patterns
EPA proposed subdividing the current nine major use patterns to 15
major use patterns to fully address nonagricultural uses. Commenters
asked for definitions of the proposed major use patterns and the
phrases ``major use pattern,'' and ``pesticide use site groups.'' One
commenter suggested adding a new major use pattern in addition to the
ones proposed by EPA. Commenters also identified inconsistencies in
major use patterns between the preamble and the regulatory text. EPA
believed that the resulting use patterns from the subdivision of
existing major use patterns were fairly self-explanatory and believed
that adding the suggested terrestrial nonfood non-crop uses might
create too fine a distinction and add to the already existing
confusion. However, the Agency does appreciate the commenters'
assistance in locating inconsistencies between the regulatory text and
the preamble and believes the inconsistencies have been corrected.
One major use pattern in the proposed rule, Indoor medical, has
been eliminated from the final rule. It is a use pattern primarily
applied to antimicrobial products, not conventional pesticides, and
will be considered for subpart W when proposed for comment. There were
several variations of aquatic nonfood use patterns that commenters
found confusing. The definition of the aquatic nonfood residential
category was questioned by several commenters who assumed it referred
to indoor tropical fish aquaria or koi fish ponds in yards. A survey of
labels associated with this use category produced only a handful of
products. Therefore EPA has consolidated the various aquatic nonfood
use patterns into one aquatic nonfood use pattern, thus reducing the
number of aquatic nonfood patterns to one. The elimination of Indoor
medical and several aquatic nonfood use patterns reduced the final
number of major use patterns. Thus, the final number of major use
pattern for conventional pesticides will be 12, rather than the 15 in
the proposed rule. The final 12 use patterns are: terrestrial food
crop; terrestrial feed crop; terrestrial nonfood crop; aquatic food;
aquatic nonfood; greenhouse food crop; greenhouse nonfood crop;
forestry; residential outdoor; residential indoor; indoor food; and
indoor nonfood.
In addition, not all the general use patterns will 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 Sec. 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, a compendium of
pesticide use sites associated with major use patterns to assist
registrants in determining which data requirements might apply to their
products. EPA also proposed removing the updated Appendix A from 40 CFR
part 158 and placing it on the OPP website and titled as Pesticide Use
Site Index. This change in location would allow EPA to correct and
update the pesticide use sites with some regularity without a
complicated and lengthy rulemaking. Commenters either wanted to retain
Appendix A in 40 CFR part 158 or were in favor of posting it on the OPP
website. The latter were more concerned that the information be updated
and revised more frequently. Since Appendix A is meant to be an index
of pesticide use sites and major use patterns but not a requirement for
applicants, EPA believes that it is more properly posted on the OPP
website to assist applicants in locating the relevant pesticide use
site(s) and the corresponding data requirements. Users are encouraged
to submit comments and suggestions to the contacts listed on the Web
page. OPP will update the Pesticide Use Site Index on a timely basis to
keep the information current for users. Accordingly in the final rule,
EPA has removed Appendix A from 40 CFR part 158. The information in the
current Appendix A has been updated, titled Pesticide Use Site Index,
and is available at http://www.epa.gov/pesticides/regulating/registering/
data--sources.htm.
C. Test Substances
EPA is continuing its longstanding system of identifying test
substances in the tables as follows: Technical grade of the active
ingredient (TGAI); manufacturing-use product (MP); pure active
ingredient (PAI); pure active ingredient, radiolabeled (PAIRA); end-use
product (EP); and typical end-use product (TEP).
D. Required and Conditionally Required Data
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
[[Page 60939]]
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.
VII. Discussion of Key Comments on Identifying Data for Experimental
Use Permits (EUPs) (Subpart C)
EPA requested comment on a way to identify data requirements for
EUPs to replace the current bracketing system within each data table. A
commenter suggested that EPA should separate out the data requirements
applicable to experimental use permits, which have been expressed since
1984 by simply bracketing a registration data requirement in the
tables. Other commenters misunderstood the bracketing, assuming that
bracketed data requirements were somehow conditional in nature. EPA
agrees that the bracket system diminishes the visibility of the EUP
data requirements and leaves them scattered throughout the registration
data requirements, and has therefore separated out and consolidated
them. At the same time, EPA has updated the test notes to reflect those
in the subparts on registration data requirements.
Because an experimental use permit is intended to precede a full
registration, EPA has elected to place those data requirements early in
the part 158 organizational structure. An alternative location for EUP
data requirements would have been to locate them in part 172, thereby
consolidating all EUP requirements in one place. However, examination
of part 172 yielded no logical location for the data requirements
except at the very end. Accordingly EPA has placed EUP requirements in
subpart C of part 158, preferring to keep all data requirements
pertaining to conventional pesticides in one place for ease of use.
Where test notes for registration requirements have been revised based
on comments to the proposed rule, in separating out EUP requirements,
EPA has also revised those same test notes as they apply to EUPs.
VIII. Discussion of Key Comments on Product Chemistry Data Requirements
(Subpart D)
EPA proposed a few changes in product chemistry requirements and it
received a number of comments on elements of the data requirements that
EPA had not proposed changing. They include:
certified limits
preliminary analysis
submittal of samples
definition of TGAI vs. MP
statement of formula
grouping of products to reduce or consolidate product
chemistry requirements
data on pesticide degradates
These comments are outside the scope of the proposal and may be
considered for future revisions of part 158. Accordingly, EPA has not
revised the final rule.
IX. Discussion of Product Performance Data Requirements (Subpart E)
EPA has transferred the contents of the product performance section
(current Sec. 158.640) essentially unchanged into the revised part
158. The regulatory text of the product performance section is
reprinted in this final rule for clarity and completeness.
X. Discussion of Key Comments on Toxicology Data Requirements (Subpart
F)
A. Data Requirements
1. 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. While the Agency
understands that traditional subchronic and chronic rodent studies can
provide much useful information on certain immunological endpoints such
as hematology, lymphoid organ weights and histopathology, these studies
do not provide a full and integrated evaluation of immune function. As
a result of recommendations from the National Research Council (NRC)
review and the FIFRA Scientific Advisory Panel (SAP), the Agency
proposed requiring functional immunotoxicity testing along with the
data from endpoints in other studies to assess the potential risk of
pesticides on the immune system more fully.
Fifteen commenters submitted a variety of comments on this data
requirement. All comments are addressed in the detailed Response to
Comments document in the docket. Key comments are discussed in this
unit.
Two commenters requested clarification of when this testing would
be required and one commenter compared the U.S. requirement with that
of the European Union (EU). Three commenters strongly supported
including immunotoxicity testing in the toxicology data requirements
for all pesticides. Six commenters opposed the codification of this
data requirement on several bases and offered alternatives: divergence
in immunological structure and response between species that gives
animal studies limited predictive power for immunogenicity in humans;
using data from other toxicity studies as a trigger for immunotoxicity
studies; and changing from R to CR. EPA disagrees with these comments
because data and analysis have shown that functional immunotoxicity
testing, particularly when considered in conjunction with data already
required by EPA on immunotoxic endpoints, is likely to increase EPA's
ability to identify pesticides with immunotoxic effects. Additionally,
functional immunotoxicity testing allows for better characterization of
the possible effects of an immunotoxicant.
Three commenters had detailed technical questions about the test
guideline which were not appropriate for discussion in part 158 since
the latter concerns only data requirements. Their comments and
suggestions were forwarded to the appropriate scientists for review and
consideration in the context of guideline revision. While EPA agrees
that the testing protocol may need further refinement, discussions on
alternative testing paradigms will continue through the various
scientific venues (e.g., International Life Sciences Institute/Health
and Environmental Sciences Institute (ILSI/HESI) cooperative effort) as
well as through future consultation with stakeholders on the
development and validation of this test guideline.
EPA recognizes that there are a range of opinions on the necessity
of an across-the-board requirement for functional immunotoxicity
testing. However, EPA's judgment, as supported by the recommendations
of the NRC and FIFRA SAP, is that there is value-added from requiring
functional immunotoxicity testing for all pesticides. Therefore in the
final rule, EPA retains a requirement for immunotoxicity testing on all
food and nonfood pesticides on the TGAI. EPA has responded to comments
in its Response to Comments document in the docket for this rule.
2. Prenatal developmental toxicity. EPA proposed amending the name
of the requirement to correspond with the current terminology and to
require two species for all nonfood pesticides. Commenters suggested
making this requirement conditional based on results of other Tier 1
studies or on a
[[Page 60940]]
likely exposure pattern. EPA proposed requiring a second species
because it believes the data will provide some assurance that the
Agency will not be basing an assessment on a single species that might
be highly sensitive (or the opposite) when compared to another. The
final rule will maintain these changes to adequately characterize
potential hazards to pregnant women and their fetuses.
3. 21-day dermal and 90-day dermal toxicity. EPA proposed a 21- to
28-day dermal toxicity test for all food use pesticides since it is
generally needed for worker risk assessments. Analyses of exposure
information have shown that this duration of exposure is typical for
agricultural workers in various components of their job. EPA proposed
not requiring the 21- to 28-day dermal toxicity test for nonfood uses.
However, if the dermal route is the primary route of exposure for
nonfood uses, a 90-day study would be required because EPA believes the
21- to 28-day subchronic dermal toxicity test is insufficient to
identify potential hazards.
Several commenters questioned requiring a 90-day study for nonfood
uses when exposures rarely exceed 45 days. EPA considers the 21- to 28-
day dermal study insufficient for nonfood use assessment because higher
tiered oral studies (i.e., chronic or carcinogenicity studies) are not
usually 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 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.
4. Reproduction and fertility effects. EPA proposed to require a
reproduction study for nonfood uses but emphasized that the requirement
is based on potential exposure. Commenters requested further
clarification when the study would be required. Requiring the 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 primarily an
exposure-based data requirement and will not always be necessary.
Registrants should consult with the Agency if there is any question
whether the study must be conducted.
5. Developmental neurotoxicity (DNT). EPA proposed that
developmental neurotoxicity testing (DNT) be conditionally required for
food and nonfood use pesticides. Thirteen commenters were unclear about
the conditionality of this requirement and requested clarification
about Test Note 27. Test Note 27 identified the effects to be
considered in the weight-of-evidence approach.
One commenter questioned whether the results of standard tests in
developing animals were sufficient to trigger a DNT test and whether
the inhibition of cholinesterase activity (ChEI) would be the most
sensitive effect for organophosphorus and N-methyl carbamate
pesticides. The Agency has completed review of 20 DNT studies conducted
with organophosphorus pesticides. In 13 out of 20 studies, ChEI was
measured in the pups; cholinesterase was the most sensitive endpoint in
those 13. Only a limited number of DNT studies are available for
carbamates, and the endpoint for only one chemical was used to assess
acute dietary risk.
Two commenters suggested amending the 2-generation reproduction
study to include findings of thyroid effects, thus providing another
criterion for DNT testing. Although such a criterion was included in
the proposed weight-of-evidence approach, experience gained with the
study resulted in the removal of this criterion. Instead, when thyroid
effects of concern are observed, the Agency may require a more specific
special study. In the final rule, EPA continues to encourage
registrants to conduct DNT studies in combination with a 2-generation
reproduction study when addressing the DNT requirement.
Ten commenters asked for clarification of Test Note 27 to indicate
whether the listed effects were part of the approach and not individual
triggers. EPA has revised this Test Note to eliminate the impression
that the items in the list were individual triggers and referred
commenters to its published Risk Assessment Guidelines for a more
detailed explanation of the terms used in the test note. Due to an
addition of a test note, Test Note 27 in the proposed rule was re-
numbered to Test Note 28 in the final rule.
Therefore, the Agency is conditionally requiring the DNT study in
the rat for food and nonfood pesticides. All available toxicology data
for the pesticide will contribute to the weight-of-evidence
determination of the need for a DNT study. The criteria for the weight-
of-evidence determination are listed in Test Note 28 and include
neurological effects from adult animal studies as well as
neurobehavioral effects after pre- and post-natal exposure of the
pesticide to young animals.
6. Scheduled-controlled operant behavior, peripheral nerve
function, and neurophysiology - sensory evoked potentials. Commenters
wondered if these tests would be commonly required and requested
specific triggers for these studies. EPA discovered upon review that
these studies were seldom required during the reregistration process
and determined the studies could be removed from the table of commonly
required studies. If the need arises in the future, the Agency may
require any of these studies on a case-by-case basis. Validated OPPTS
guidelines are in place.
7. Non-rodent chronic studies (1-year dog study). In the proposed
rule, EPA considered eliminating the requirement because evidence from
the published literature was consistent with EPA's belief from its
reviews that the study may not be needed. EPA currently requires a 90-
day dog study and a 1-year dog study for all food and nonfood uses to
fulfill the non-rodent data requirements. EPA referenced published
literature that suggested that the 1-year dog study may not be
necessary. Based on a retrospective analysis of a large body of 1-year
dog studies in its toxicology database, EPA proposed to eliminate the
1-year dog study but retain the 90-day study. EPA solicited review and
comment by the FIFRA Scientific Advisory Panel (SAP) on the results of
the preliminary analysis for reference dose (RfD) derivation on May 5-
6, 2005 [Ref. 10].
The FIFRA SAP reviewed the Agency's retrospective analysis of the
toxicity studies and encouraged the Agency to continue its analysis
with a larger database. The FIFRA SAP made the following
recommendations:
i. Increase the robustness of data analysis by including dog study
datasets that were not used for the RfD determination.
ii. 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)
[[Page 60941]]
independent of the 1-year study and establish data review criteria.
iii. Consider data analysis for separate classes of pesticides.
iv. Include additional background information on RfD that provides
better perspectives for reviewing the Agency position paper.
v. Revise the title of the Agency position paper to reflect the
purpose of the data analysis.
The FIFRA SAP said in its report that ``if the results of the
analysis continue to indicate little added value from the 1-year dog
studies, the Agency could move toward eliminating them on a stronger
basis.''
In response, EPA conducted a more extensive analysis of dog
toxicity studies on 110 chemicals representing over 50 different
classes of pesticides [Ref. 12]. EPA concluded from this analysis that
extending a dog toxicity study beyond a 13-week duration does not
provide additional essential toxicity information; eliminating the 1-
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, 2-generation rat
reproductive study, and the 13-week dog toxicity study provides 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, EPA would require
the appropriate Tier II metabolism and pharmacokinetic studies to more
precisely evaluate bioavailability, half life, and steady state to
determine if a longer duration dog toxicity study is needed. The
circumstances that might lead to a request for the 1-year dog study are
identified in Test Note 36.
B. Alternative Testing Paradigms
In the proposed rule published March 2005, EPA discussed the work
underway on alternative testing paradigms by the International Life
Sciences Institute (ILSI)/Health and Environmental Sciences Institute
(HESI). EPA is in conceptual agreement with the ILSI/HESI philosophy of
moving toxicology testing away from a rigid guideline-based screening
approach and towards a more knowledge-based approach. The ILSI/HESI
approach was published in a series of papers in the January 2006 issue
of Critical Reviews in Toxicology.
Eleven commenters addressed the ILSI/HESI testing paradigm, all
supporting its development and early adoption. One commenter suggested
that EPA update the proposed rule with the ILSI/HESI study findings and
reissue a revised proposed rule for comment. In a similar vein, another
suggested incorporating a timetable into the final rule for modifying
subpart F (Toxicology). Another commenter believed a number of the
concepts developed in by ILSI/HESI were ripe for incorporation into
pesticide testing requirements at this time. This same commenter
suggested not finalizing the proposed rule until there was an
opportunity to consider and incorporate the important concepts
developed by Agricultural Chemical Safety Assessment (ACSA). EPA
believes that incorporating the concepts into the final rule is
premature since EPA has not had the opportunity to determine if the new
testing paradigm will meet its risk assessment needs. EPA believes that
delaying the remaining proposed changes which comprise the bulk of the
proposal would be a disservice to the regulated community. In a
differing view, a commenter was concerned about the lack of public
interest representatives in ILSI-EPA discussions and recommended that
EPA terminate its collaborative working relationship with ILSI and
industry trade groups. Since the Agency is interested in more efficient
risk assessment paradigms, it will continue to work with all
stakeholders in investigating efforts in that direction and welcomes
the participation of any public interest representatives in the
discussions.
EPA is committed to moving towards a more efficient and refined
testing/risk assessment paradigm. Given the Agency's experience with
regulating pesticides over the last 30 years, the Agency is interested
in improving certain aspects of the testing process. In particular, EPA
is more attuned to risk assessment needs (i.e., an integrated approach)
that avoids requesting data not used in risk assessment and that
reduces and refines the use of laboratory animals.
In the proposed rule, EPA discussed the relevance and importance of
the ILSI/HESI project, Agricultural Chemical Safety Assessment (ACSA):
a Tiered Approach. This project, with the participation of EPA
scientists, represents a pursuit of a more efficient and accurate
tiered testing of pesticide chemicals. A series of reports authored by
ILSI/HESI was published in a special edition of the Journal of Critical
Reviews in Toxicology in January 2006, Volume 36, Issue 1 [Refs. 1, 2,
3 and 5], summarizing their findings and initial recommendations.
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.
For example, in the case of the developmental neurotoxicity study,
for some chemicals, it might be concluded that adequate testing of the
developing nervous system would be best accomplished with a standard
developmental neurotoxicity study. Refinements to the guideline study
could include, for example, changes to the route and/or duration of
exposure (e.g., initiation of dosing to maternal animals prior to
gestation day 6, or direct gavage administration to pups during
lactation), the evaluation of appropriate biomarkers of exposure or
effect, the use of more targeted functional, behavioral, or cognitive
testing in offspring, or the histopathological and/or morphometric
evaluation of particular regions of the central or peripheral nervous
system that are known to be affected by either the chemical or chemical
class. For other chemicals, the information in the toxicological
database could lead to the conclusion that an alternative test should
be performed instead of a guideline developmental neurotoxicity study.
Alternative chemical-specific methods could be identified as a
preferred option.
EPA has multiple activities underway to address the remaining
science and policy issues associated with the ACSA proposal. One
essential step towards
[[Page 60942]]
adopting the ACSA 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 ACSA 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 ACSA 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 ACSA scheme works in
practice. There are plans to conduct several case studies using the
ACSA 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 ACSA 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 will 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 at http://www8.nationalacademies.org/cp/projectview.aspx?key=74
), Organization for Economic Co-Operation and
Development (OECD) Integrated Approaches to Testing and Assessment
(http://www.oecd.org/document/42/0,2340,en--2649--34377--36283562--1--
1--1--1,000.html), as well as predictive toxicity tools (QSAR, -omics,
etc.) being developed by EPA's Office of Research and Development (ORD)
Computational Toxicology Program (http://www.epa.gov/comptox). With regard to
the OECD effort, EPA is currently playing a leadership role in planning
a workshop scheduled for December 2007. The workshop will evaluate the
current state of science and regulatory programs to evaluate pesticide
inert ingredients and active ingredients using the data derived from in
silico (performed on computer or via computer simulation), in vitro,
and short-term in vivo models and bioassay systems.
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. Internal review
includes review by the FIFRA SAP and opportunities for public comment.
External peer review as well as 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. International regulations currently require studies that were
omitted in ACSA; this would pose significant problems for registrants
if a harmonized approach is not adopted world-wide.
Lastly, EPA is committed to review part 158 data requirements
frequently to incorporate new science that has been fully documented
and peer reviewed.
XI. Discussion of Key Comments on Ecological Effects Data Requirements
(Subpart G)
A. Generic Issues
EPA received comments in several areas that were common to all
science disciplines under this subpart.
1. Data harmonization and lack of availability of current
guidelines. The Agency received several comments stating that the data
requirements for nontarget terrestrial and aquatic organisms, plants
and environmental fate testing should not be promulgated if the test
guidlines upon which the data requirements rely are not finalized. The
Agency recognizes the importance of the connection between these 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. The terrestrial and aquatic animal guidelines are scheduled to be
finished 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.
2. Elimination of species names in the test notes. EPA eliminated
the inclusion of preferred species names from the data requirements in
subpart G. This does not represent an actual change in the
requirements. Rather, the Agency determined that the indication of
preferred species is a matter of guidance and should not be part of the
requirements document. Species names are covered in the Agency's test
guidelines, which are cited in the data requirements tables.
3. Independent laboratory validation. Concerns were raised by some
commenters that the requirement to now have independent laboratory
validation (ILV) of the chemistry methods used for residue measurements
in the ecological and environmental fate field studies would add cost
and time to these studies. They view these studies as already required
and conducted under Good Laboratory Practice Standards (GLP) in 40 CFR
part 160 for other data requirements. However, GLP Standards do not
require an ILV. The requirement for an ILV has been in effect since the
1990s and, as such, is a codification of current practice. The ILV, as
well as the original method validation, should be conducted under the
GLP.
[[Page 60943]]
B. Data Requirements
1. Terrestrial organisms. i. Acute oral toxicity test with a
passerine species. EPA proposed to require a second avian acute oral
study on a passerine species (i.e., red-winged blackbird) to support
all outdoor uses, including residential outdoor uses. The other avian
acute oral study must be conducted on either a waterfowl or an upland
gamebird, which has been standard policy. This revision of the avian
acute toxicity data requirement elicited a significant number of
comments. The comments not only concerned the addition of a passerine
species to the avian acute oral data requirement, but also the test
note which specifically named the red-winged blackbird (Agelaius
phoeniceus) as the preferred passerine species. Some commenters
suggested that the passerine requirement should be based on the results
of either the mallard or bobwhite acute oral test results. They based
their concerns on the fact that the red-winged blackbird is a wild
species, and is not reared in a laboratory, unlike some commonly tested
passerines as the canary and zebra finch. Because it is a wild species,
the laboratories must request permits from the U.S. Fish and Wildlife
Service (USFWS) to trap the birds. Also, there were concerns about the
possible exposure of laboratory personnel to the avian flu virus from
the trapped birds. Others suggested that EPA continue its policy of
extrapolating the data from the mallard and bobwhite acute studies to
passerine species in its risk assessments, and reserve the passerine
study for cases when extrapolation does not significantly reduce
uncertainty. Still others requested that the Agency consider other
passerine species and provide a list of recommended species to the
regulatory community, rather than prescribing solely the red-winged
blackbird.
Based on these comments, in the final rule the Agency is no longer
specifying 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 the upland gamebird or the waterfowl. 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 than previously required mallards and
bobwhites (Refs. 8 and 9).
EPA will consider studies using alternative species, as long as the
alternative species meet the Agency's needs. EPA also intends to revise
the avian acute oral toxicity guideline to include a passerine species,
with the red-winged blackbird listed as among the preferred species.
The Agency will revisit the issue of an acceptable species list with
this goal in mind. Testing protocols may list other acceptable species
upon reconsideration of this issue.
ii. Japanese quail. EPA did not propose to add the Japanese quail
as a test species for the acute toxicity test and as an alternate for
the avian reproduction test. Nonetheless, the Agency received two
comments requesting that EPA accept the use of the Japanese quail as a
test species, particularly as this species is accepted by OECD. The
Agency presented its rationale for not listing Japanese quail as a
preferred test species in its correspondence with OECD on March 24,
2003 (Ref. 14). Many years of domestication and artificial selection in
this species may have biased the response of this species to chemicals.
When comparing dietary study results of the same pesticide in both
species the Japanese quail responds differently to toxicants, showing
less sensitivity than the northern bobwhite quail. In addition, the EPA
has a long history of requiring testing with the bobwhite and has
accumulated a large database of acute toxicity results for this
species. Abitrarily using another test species now would increase
uncertainty and not add much value to the risk assessment process. Also
the Japanese quail has an extremely high reproduction rate that is not
representative of North American species, and therefore is not a
suitable test species for the avian reproduction study.
iii. Avian reproduction. EPA proposed to change the requirement
from conditionally required to required for terrestrial, aquatic,
forestry and residential outdoor use patterns. Two commenters stated
that the need for these data should be based on the pesticides'
properties. EPA does not agree with the comments and has not revised
the final rule. Adverse effects on avian reproduction can occur at
levels of exposure several magnitudes lower than those that can cause
acutely toxic effects. A pesticide's properties are not adequate
predictors of avian reproduction effects.
One commenter 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) and passerine birds are
altricial (birds that are born naked and blind and depend on their
parents for food). 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 are not likely to be developed in the near
future. Thus, the Agency is not expanding avian reproduction testing to
passerine species at this time.
iv. Wild mammal testing. EPA did not propose to change the
conditionality of the wild mammal toxicity test, but to maintain its
requirement on a case-by-case basis. The Agency received three comments
regarding this data requirement and its test note, which referred to
some of the lower tier data that could indicate a need for the study.
One comment stated that the test note was unclear, and 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. The second comment 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. A third comment proposed that the test note 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) [RQ = Risk Quotient = exposure/
toxicity] for a given use pattern based on laboratory toxicity
endpoints and a refined exposure assessment.
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. 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
nontarget species. Accordingly, the Agency has not revised the final
rule.
v. Acute toxicity studies with reptiles. Although EPA did not
propose acute toxicity studies with reptiles as test species, one
commenter stated that effects on reptiles still are inadequately
addressed in this new regulation. They do not believe that the avian
studies adequately assess risks to reptiles.
The Agency will consider any peer-reviewed reptile testing
protocols for
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possible future addition in required testing. Information demonstrating
a biologically significant difference in sensitivity or exposure
between birds and reptiles, which would suggest that the bird risk
assessment is not adequately protective, can still be considered in
individual risk assessments.
vi. Field testing. The only changes that EPA proposed for the
simulated or actual field testing for birds and mammals were to expand
the requirement to include more use patterns under the conditional
requirement, and to ask for independent laboratory validation of the
chemistry methods. EPA did not propose to change the conditionality of
the field test, but to maintain its requirement on a case-by-case
basis.
EPA received five comments regarding the data requirement for
simulated or actual field testing with terrestrial animals. One comment
stated that the information provided in the test note for this data
requirement was nebulous and asked for clarification. Three comments
stated that additional testing, particularly with wild species in the
natural environment, should only be conducted when refined risk
assessments indicate a potential concern. The fifth comment supported
the continued requirement of the study.
The Agency evaluates the need for field testing on a case-by-case
basis. 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. To this end, the Agency
has retained the existing field testing data requirements in part 158.
One of the commenters proposed a change to the test note for the
terrestrial field study (test note 6 in the final rule). Their
rationale was that a refined risk assessment should be the basis for
requiring this higher tier study. A refined assessment may indicate
that field data are needed to resolve uncertainties in the risk
assessment. If so, then the field test is required. The Agency agrees
with the comment and changed test note 6.
vii. TEP testing. EPA proposed to expand the testing of birds in
the acute oral and dietary studies to conditionally require testing
with the TEP based on the results of these tests with the TGAI,
environmental fate data and the use patterns.
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 and the conditions that would trigger TEP
testing with birds. Two commenters stated that TEP testing of birds
should only be triggered when the risk from the TGAI is high, and birds
are expected to encounter the intact end-use formulation in the field
or expected to use the formulation itself as a food source. In
contrast, a commenter recommended TEP testing for all products with
potential aquatic or terrestrial nontarget exposure.
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, adverse effects information
submitted under FIFRA sec. 6(a)(2), European regulatory testing, and
confidential statements of formula. The potential for nontarget
organism exposure to TEP would naturally be a consideration as well. In
light of the number of comments received on this issue, and past
experience that shows TEP testing has only been required for granular
formulations or other special situations, the conditional requirement
has been removed from the data requirements and does not appear in the
final rule. It will remain consistent with past policy and be required
on a case-by-case basis.
2. Aquatic organisms--i. Sediments. EPA proposed to add testing of
aquatic organisms exposed to treated sediment to better assess the
effects of sediment-bound pesticides on aquatic environments. The whole
sediment tests are acute toxicity studies of freshwater and marine
invertebrates and a chronic study with invertebrates. The Agency
received many comments about these newly codified data requirements.
Most of the comments concerned the conditions for requiring these
tests. The commenters cited not only the test notes, but also the
sections of the draft preamble where the sediment data requirements
were discussed in detail. Most asked for better guidance regarding the
criteria for the studies. Several commenters also proposed alternative
criteria for both studies. Some of the comments discussed risk
assessment issues, or issues with the guidelines for the studies. These
latter two areas are not the focus of this rule, and therefore, are not
addressed in this document. The Response to Comments document has
comprehensive details regarding these issues. 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. Toxicity will be taken into consideration
relative to potential exposure. EPA will not define specific use
patterns or applications that will not automatically require sediment
testing.
Two criteria, the soil-binding ability and persistence of the
pesticide, were the focus of many comments. The criteria, as listed in
the proposal, are the soil partition coefficient (Kd) value >= 50
Liters/kilogram (L/kg) and the half-life of the pesticide in sediment
<= 10 days for the acute test and > 10 days for the chronic test.
Commenters asked for justification for the selection of the value of 50
for the Kd value.
The Agency's justification 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 of a chemical to sediment
organic carbon (2%). In the 1980s the Agency had proposed a Kd >= 3 to
10 L/kg as a trigger for adsorption. At that time the Agency put in
place a Kd >= 50 L/kg. The Kd criterion represents the mean value
observed in the soil adsorption studies.
EPA received a comment that questioned the appropriateness of using
the Kd value as a trigger for sediment testing. 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. Their method indicated that pesticides with Kd values lower
than 50 L/kg, our proposed value, could also bind to sediment.
Agency scientists re-analyzed the value for the Kd criterion with
United States Geological Survey (USGS) data (Ref. 13) and found that Kd
values for pesticides commonly detected in sediments can range as low
as 1.6 and as high as 2,095. 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
[[Page 60945]]
may consider changing the Kd value in future updates to part 158
requirements.
The criteria for persistence is determined by using the aerobic
aquatic metabolism data and the aerobic soil metabolism data. The
anaerobic soil metabolism data are not used for this purpose.
Commenters questioned the half-life value of < = 10 days for the acute
test and assumed it was a typographical error and should be >= 10 days.
They also questioned if an acute study must be done prior to conducting
the chronic study.
It appears from the above comments that the commenters
misunderstand the purpose of the persistence trigger. Refer to Test
Notes 21 and 22. EPA affirms that the intent of the triggers for the
acute and chronic sediment tests are 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 EPA concerning
type of study and test organism selection. The Kd trigger is the same
for either the acute or chronic sediment test. It is the persistence
(i.e. half-life) that drives the decision regarding which 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 the 10 day (acute)
sediment study, unless there are clear reproductive issues a priori.
For half lives greater than 10 days, a 28 to 65 day (chronic) study
would be more appropriate. Consultation with the Agency is needed if
the registrant is uncertain as to which length of study is appropriate.
Two commenters 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. EPA agrees that the Kow, along with the Koc, are
valid environmental fate values to use as criteria for these studies.
The log Kow of 3 is equivalent to a Koc value of 1,000. Both values are
frequently more available than either the Kd or half-life values.
Consequently, the requirement for submission of sediment studies can be
determined by either of these two values. The test notes in the final
rule have been revised to include the Kow and Koc.
One commenter wanted EPA to specify in the test notes when
freshwater or marine organisms must be tested for sediment toxicity.
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 significant concentrations, either by runoff or erosion,
because of its expected use or mobility pattern. The test notes are
amended to clarify when marine organism testing is required.
ii. Fish acute toxicity testing. EPA proposed that indoor and
greenhouse uses would only require one fish acute toxicity test, unless
the chemical is stable in the environment, in which case, a second fish
test with a different species is required. The Agency received three
comments regarding the fish acute data requirement. The comments asked
for clarification regarding the number of freshwater fish studies that
are now required to support greenhouse and indoor uses.
With regard to greenhouse and indoor uses, the Agency requires the
testing of one fish species to adequately assess the hazards to fish.
If the LC50 is < 1 ppm, no other fish species testing is
required. However, if the LC50 is between 1 - 10 ppm, a
second species will be required to substantiate the potential for
hazard to aquatic organisms.
iii. Fish and invertebrate chronic toxicity testing. EPA proposed
several revisions to clarify the applicability of the requirements for
the chronic toxicity tests. The Agency received one comment requesting
more information on the fish early life stage test and the invertebrate
life cycle with saltwater organisms. Another comment suggested that the
Agency take into consideration the difficulties of using estimated
environmental concentration-based triggers for the chronic studies.
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. This condition applies to estuarine as well as freshwater
environments. 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 in assessing
acute and/or chronic risk, this factor must be defined and addressed.
The test notes for these studies list the details.
iv. Testing with estuarine organisms. EPA proposed to change the
conditionality of the acute testing from conditionally required to
required for several use patterns. The comments regarding this set of
data requirements primarily addressed test species and TEP testing with
estuarine organisms.
The commenters stated that proposed test notes 13 and 15 were
inconsistent with regard to the preferred estuarine fish species in the
test note. As discussed in the Generic Issues unit (Unit XI.A.), the
test notes in the final rule no longer indicate the names of preferred
test species as they are fully discussed in the appropriate guidelines.
The comment regarding TEP with estuarine organisms is similar to
that for TEP testing with freshwater organisms discussed in Unit
XI.B.2.vii., except that the commenter recommended estuarine organisms
should only be tested with the TEP if testing with the TGAI indicated
that estuarine organisms are more sensitive than freshwater organisms,
or if the freshwater organism tests demonstrate that the TEP is more
toxic than the TGAI. The Agency response to the comment on TEP testing
is addressed in Unit XI.B.2.vii.
v. Testing of degradates. EPA did not specifically propose any data
requirements requiring toxicity testing with degradates of pesticides.
However, one commenter stated that degradates should be included as
they can also present significant environmental risks. The Agency
requires appropriate testing of a pesticide's degradates on a case-by-
case basis. 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.
vi. Bioaccumulation testing. EPA proposed to eliminate the
requirement for these studies for aquatic nonfood residential or
residential outdoor uses since the exposure is expected to be minimal.
One comment asked for clarification as to when they would, most likely,
be required. The Agency anticipates that these studies may be required
on a case-by-case basis depending on the results of lower tier
ecological toxicity tests and potential environmental fate
characteristics. The potential for accumulation is triggered when a
chemical has a half-life >= 4 days and log Kow >= 3.
EPA proposed to change the conditions under which the accumulation
in fish and accumulation in aquatic organisms would be required. EPA
received eight comments regarding the fish and nontarget organism
accumulation studies. Three of the commenters suggested that this data
requirement be placed in proposed subpart E (now subpart G),
Terrestrial and Aquatic Nontarget Organism Data Requirements, and not
proposed subpart N. There were two comments stating that test note 10
was well written, and
[[Page 60946]]
should also apply to the aquatic nontarget organism accumulation study
requirement in lieu of test note 11 in the environmental fate data
table. They suggested that this test note is also appropriate for the
three accumulation studies in proposed subpart E, bioavailability,
biomagnification and toxicity of aquatic organisms.
The Agency agrees with the comments, and has moved the two studies
under proposed subpart N, Accumulation in Fish and Accumulation in
Aquatic Nontarget Organisms to subpart G, under the data requirements
for aquatic organisms - bioavailability, biomagnification and toxicity.
Therefore, all the ecological and fate requirements related to
bioaccumulation are located solely in subpart G. We also agree with the
comment that the language of Test Note 10 (Accumulation in Fish) in the
proposed environmental fate data table is appropriate for the
Accumulation in aquatic nontarget organisms data requirement in subpart
G. 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 subpart G and renumbered as test note
19. This test note replaces test note 21 in proposed subpart E (now
subpart G).
vii. Testing with TEPs. EPA proposed to require acute testing with
the TEP for freshwater and estuarine organisms based on 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 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.
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 TEP in addition to
the TGAI, if the triggers in the test note 9 are met.
3. Nontarget plant testing. EPA proposed to eliminate the
requirement for the seed germination study because the information from
this study can also be obtained from the seedling emergence study. The
germination study has not been required for several years, so its
removal from the final rule simply codifies the current standard
practice. Commenters agreed with this change.
EPA proposed to expand Tier I and Tier II seedling emergence,
vegetative vigor and aquatic plant growth studies to include
terrestrial food and feed crops, aquatic food crops, forestry and
residential outdoor uses. The conditional requirements for Tier III
phytotoxicity terrestrial and aquatic field studies were also expanded
with the addition of the same use patterns. The use patterns were
expanded beyond terrestrial and aquatic nonfood uses and forestry uses
in order to capture scenarios which may be impacted by drift and runoff
from pesticide applications in neighboring areas.
Two comments requested explanations for including outdoor
residential uses and indoor uses among those requiring plant testing.
Outdoor residential use patterns are now included among the sites
requiring plant testing because data indicate that herbicide uses on
sites such as turf can harm nontarget plants through runoff. Turf is
classified as an outdoor residential terrestrial use, and therefore
requires nontarget plant testing. The Agency acknowledges that
including indoor uses among those requiring aquatic plant growth
testing in Table 3 in the proposed rule was an error as EPA did not
intend to propose such a requirement. Plant testing is not required for
indoor uses. Additionally, testing for aquatic nonfood residential use,
also included by error in Table 3, has been eliminated in the final
rule.
i. Test substance. EPA proposed to change the test substance for
the terrestrial plant studies from TGAI to TEP. This change was made to
address Agency concerns that end-use products can contain ingredients
that enhance the bioavailability or toxicity of the active ingredient.
Seven commenters expressed concerns regarding the change in the test
material to the TEP for the terrestrial plant studies. They preferred
to continue to use the TGAI as the test substance. The most common
concern expressed by the commenters was the possibility that the final
composition of the end-use product under development may differ from
the product used in testing. EPA recognizes this may occur, but the TEP
is required as the test material because the formulations contain
adjuvants and other chemicals that aid the movement of the active
ingredient into the plant, making it more effective, and therefore,
possibly more toxic to nontarget plant species. The Agency has been
routinely requesting nontarget terrestrial plant tests with TEP for a
number of years, so this change is codifying current policy and
reflects the needs of the Agency in assessing impacts on nontarget
organisms.
ii. Species testing. Recommended plant test species are not
designated in part 158, but are included in the guidelines for
conducting the studies. Species issues should be addressed in the
context of guideline development and revision and not the data
requirements. Accordingly, EPA has not revised part 158 based on
comments about the plant test species.
iii. TIER III guidelines. The only changes that EPA proposed for
the Tier III terrestrial and aquatic field studies for nontarget plants
was to expand the requirements to include more use patterns under the
conditional requirement, and to propose independent laboratory
validation of the chemistry methods. EPA did not propose to change the
conditionality of the field test, but to maintain its requirement on a
case-by-case basis. The Agency received three comments regarding the
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. These comments relate more towards guidance about the field
studies and not to the data requirements themselves. As such, these
comments are being considered in context of revisions to guidelines and
not to this final rule.
iv. Test note revisions. The vegetative vigor studies are no longer
required for granular and bait formulations. This change acknowledges
that these formulations are not practical test materials, as the
vegetative vigor study requires the test substance to be applied
directly to the plant surface.
The Agency received one comment regarding an apparent error in the
placement of test note 3 for the Tier I and Tier II seedling emergence
studies. EPA acknowledges that test note 3 was inaccurately placed next
to the seedling emergence studies. This has been
[[Page 60947]]
corrected, and this test note now refers to the Tier I and Tier II
vegetative vigor studies.
v. Test notes 5 and 6--the conditions for moving from Tier I to
Tier II studies. EPA received one comment asking for clarification of
test notes 5 and 6 of the proposed rule. The Agency agrees that the
wording of both test notes is ambiguous, and rewrote both test notes.
Test notes 5 and 6 in Sec. 158.660 are now accurate. The draft test
notes implied that all the plants tested in the tier I studies were
also required to be tested in Tier II. We rewrote the two test notes to
clarify that only the plant species that exhibited the stated level of
the detrimental effect are required to be tested at Tier II.
Another commenter referred to the findings of the FIFRA SAP in 2001
when it convened to discuss the proposed NAFTA (North America Fair
Trade Act) Nontarget Plant Toxicity Tests. [Ref. 4] The FIFRA 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, EPA should use
the 25% for progression from Tier I to Tier II for terrestrial plant
studies. For terrestrial plants, the Agency agrees 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 threatened and endangered species, and additional testing at
Tier II may be needed to mitigate the presumption of risk to listed
species.
4. Insect pollinator testing. EPA eliminated the requirement for a
honey bee subacute feeding study as the information from this test can
be covered under the field study requirement. The proposed rule listed
four requirements for testing of aquatic insects and terrestrial
predators and parasites. Even though EPA did not propose to delete
these requirements, continuing to include potential data requirements
that have not been routinely imposed and for which no guidelines have
been developed, serves no useful purpose. Therefore EPA eliminated
these four data requirements in the final rule.
The Agency also proposed to include additional use patterns and
exposure scenarios under the data requirement for the honey bee acute
contact toxicity study. Previously, the requirement was limited to
outdoor use patterns when the crop may be in bloom and thereby
attractive to honey bees. The change addresses not only blooming but
also pollen-shedding and nectar-producing parts of nontarget plants
that may be attractive to honey bees and may be in or near the site of
a pesticide application. The criteria for requiring the honey bee
residue study was corrected from an LD50 value of < 1
microgram/bee for the acute contact study to < 11 micrograms/bee, as
originally published in 1982 (48 FR 53192).
There were several comments pertaining to the field study
requirement for pollinators concerning the criteria that the
requirement could be based on data from arthropods other than bees.
These commenters asked for clarification to confirm that the data
pertain solely to terrestrial and not aquatic arthropods. The test note
for the pollinator field study was modified to clarify this point.
Another comment concerned the designation of the acute contact toxicity
study as R for the aquatic uses, citing several application scenarios
or formulation types, such as direct application to water or granular
formulations, that would reduce exposure to honey bees. The Agency
agrees with the comment and changed the requirement for aquatic uses to
CR.
XII. Discussion of Key Comments on Human Exposure Data Requirements
(Subpart K)
A. Applicator Exposure
A commenter recommended that EPA rely on surrogate data from other
agencies such as the Occupational Safety and Health Administration's
(OSHA) permissible exposure limits that are regulatory limits on the
amount of concentration of hazardous substances in the air. Other
commenters indicated that exposure data were available from several
reliable sources besides the Pesticide Handlers Exposure Database and
the Outdoor Residential Exposure Task Force mentioned in the proposed
rule. These commenters identified other task forces that have generated
exposure data--Indoor Residential Exposure Task Force, the Agricultural
Handlers Exposure Task Force, and the Agricultural Reentry Task Force.
The Agency assumes that the commenter is referring to Permissible
Exposure Limits (PELs) when he speaks of ``OSHA workplace exposure
limits.'' The Agency does consider regulatory levels set by other
authorities during risk assessment, including OSHA PELs; however, EPA
and OSHA have different legislative mandates. OSHA does not have the
authority under FIFRA to regulate pesticide exposures and therefore
does not set PELs for chemicals used solely for pesticides.
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
for pesticides of low volatility 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. In contrast, OSHA evaluates exposures on a site-
specific basis by collecting samples on workers and does not rely on
surrogate databases.
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.
Some commenters questioned the currency of several guidelines in
the context of dermal exposure and inhalation exposure data
requirements. EPA will consider the comments as its scientists work to
revise/update the guidelines. The Agency has reviewed and accepted many
studies that are not conducted in accordance with current guidelines,
but which serve its needs and provide suitable information for risk
assessment purposes. In addition, some guidelines have not been
finalized but are available in draft form. Notwithstanding such
flexibility, EPA intends to finalize these test draft guidelines by the
end of 2008.
EPA made no revisions in the final rule. EPA received other
comments on this topic and has responded in its Response to Comments
document in the docket for this rule.
B. Post-Application Exposure
EPA proposed changing several existing post-application data
requirements from CR to R, expanding the use sites that those data
requirements cover to include residential uses sites, and codifying
certain data that had been previously sought on a case-by-case basis.
Currently, EPA frequently conducts post-application exposure
assessments, particularly with regard to residential
[[Page 60948]]
exposures, based upon conservative extrapolations from generic data.
The new data will ensure that EPA can more realistically assess post-
application exposure. The possibility of using generic task force data
or modeling for dermal and inhalation exposure was suggested by many
commenters because some of the studies might place additional testing
burdens on formulators as to products that did not raise safety
concerns under very conservative modeling. EPA believes that modeling
and generic task force data would be acceptable absent any specific
problems. Registrants who are not members of task forces need to submit
their own data or otherwise satisfy the data requirements. Comments
about surrogate exposure data and the Task Forces that generate them
arose in the following data requirements: Product use information;
description of human activity; nondietary ingestion exposure; and
dislodgeable foliar residue dissipation and turf transferable residues.
Commenters also identified test guidelines that still exist only in
draft form and are absent from the list of OPPTS harmonized guidelines.
EPA agrees that these test guidelines need to be finalized and intends
to finalize them by the end of 2008.
EPA made no revisions in the final rule. EPA received other
comments on this topic and has responded to comments in its Response to
Comments document in the docket for this rule.
XIII. Discussion on Spray Drift Data Requirements (Subpart L)
EPA has transferred the contents of the spray drift section
(current Sec. 158.440) essentially unchanged into subpart L of part
158. The regulatory text of the spray drift sections is reprinted in
this final rule for clarity and completeness.
XIV. Discussion of Key Comments on Environmental Fate Data Requirements
(Subpart N)
A. Generic Issues
1. Data harmonization and lack of availability of current
guidelines. The Agency received several comments stating that the data
requirements for nontarget terrestrial and aquatic organisms, plants
and environmental fate testing should not be promulgated if the test
guidelines upon which the data requirements rely are not finalized. The
Agency recognizes the importance of the connection between these data
requirements and the guidance documents that provide information on how
the data requirements may be satisfied. Guidelines are scheduled to be
finished 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
for each group of guidelines.
2. Independent laboratory validation (ILV). Concerns were raised by
some commenters that the requirement to now have ILV of the chemistry
methods used for residue measurements in the ecological and
environmental fate field studies would add cost and time to these
studies. They view these studies as already required and conducted
under GLP 40 CFR part 160 for other data requirements. The requirement
for an ILV has been in effect since the 1990s. The ILV, as well as the
original method validation, is subject to the GLP.
3. Data requirements--i. Hydrolysis. The Agency received three
comments on the hydrolysis data requirement. Two comments questioned
the addition of indoor uses to the use patterns that require this
study. EPA included 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 expansion of the use patterns
requiring this study reflects concern about the potential movement of
pesticides and their degradates into the environment.
ii. Photodegradation, laboratory volatility and field volatility.
EPA proposed to expand the data requirement for photodegradation in air
adding all terrestrial, greenhouse, forestry and residential outdoor
use patterns. The Agency's rationale relates to the potential for
exposure to highly volatile pesticides in greenhouses, residential and
certain outdoor use situations. The Agency received three comments on
the expansion of the use patterns for this data requirement, asking for
additional guidance on the conditions that would trigger this data
requirement. EPA uses the measured vapor pressure of a chemical
compound or the chemical's Henry's Law Constant, as guides to the
chemical's volatility and the probability of its movement into the
atmosphere. 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 [Ref. 7].
EPA received two comments on the test note for the photodegradation
in water data requirement which provided values for the electronic
absorption spectra for the pesticide at which the study is not
required. 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. EPA believes the test note is clear, but the commenters
detailed concerns that could be addressed on an individual basis.
EPA proposed to change the designation of the requirement for the
photodegradation on soil study from conditionally required (CR) to
required (R) for terrestrial food crop and forestry uses patterns. The
Agency received one comment about this photodegradation requirement
that questioned the proposed change in classification as stated in the
proposed rule. EPA is codifying a long-standing practice of requiring
this study for terrestrial and forestry use patterns. The test note
explaining that the study is not required when the chemical is to be
applied only by soil injection or is incorporated in the soil has been
retained.
iii. Aerobic soil and aerobic aquatic metabolism. EPA proposed to
expand the use patterns that require the aerobic soil metabolism study
by including aquatic uses if the pesticide is applied to aquatic sites
that are intermittently dry. The aerobic aquatic metabolism study
requirements were expanded to include all terrestrial and forestry use
patterns, and to clarify its requirement for aquatic residential use
patterns. The Agency received five comments regarding the data
requirements for the aerobic soil metabolism study and the aerobic
aquatic metabolism study. The comments questioned 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 patterns for the aquatic metabolism
study. They asked for further explanation of these changes. EPA
categorizes uses such as cranberry bogs and rice paddies as aquatic,
but such sites can be considered both aquatic and terrestrial depending
on timing and agronomic practices. As explained in the proposed rule,
both the aerobic aquatic and terrestrial studies are needed to better
characterize the fate of chemicals applied to aquatic sites that are
intermittently dry. Aquatic metabolism studies are needed for
pesticides applied terrestrially since these chemicals can be
transported, e.g., through run-off or spray drift, to water bodies.
Since the degradation or dissipation rates and pathways of pesticides
in aquatic systems can be different from those of terrestrial
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systems, both soil metabolism and aquatic metabolism studies are needed
to fully describe the fate of pesticides that may be found in both
terrestrial and aquatic environments. In addition to being useful for
developing ecological risk assessments, this study is also valuable in
refining drinking water exposure estimates.
iv. Anaerobic soil and anaerobic aquatic metabolism. EPA proposed
to correct a technical error in current part 158 by reinstating the
requirement for the anaerobic soil metabolism study. The requirement
appeared in 40 CFR 158.290 prior to 1991, but a simple printing error
led to its omission from the CFR in 1991 and subsequent CFRs. The
twelve comments that the Agency received about the anaerobic metabolism
studies generally asserted that the anaerobic soil metabolism
requirement in the proposed rule constituted a new data requirement.
This data requirement was never intentionally removed from the CFR by
notice and comment rulemaking, and therefore is not considered a new
requirement.
EPA has continued to require the anaerobic soil study as needed,
notwithstanding its inadvertent omission from the CFR, but has also
upon occasion accepted the anaerobic aquatic study in lieu of the
anaerobic soil study. However, with the harmonization of the OPP
environmental fate guidelines with those of the OECD and with PMRA
under NAFTA agreements, and with the technical correction and
clarification of the requirements in this rule, this practice of
substituting the anaerobic aquatic study is no longer appropriate. In
the harmonized guidelines, the two studies use different test media and
redox conditions, so the results of these two studies will not
necessarily be comparable. Continuing to use the anaerobic aquatic
study when the Agency requires the anaerobic soil study will not fully
address Agency risk assessment needs.
The commenters were also concerned about the expansion of the
anaerobic aquatic metabolism requirement to include all terrestrial use
patterns, such that the applicants would be required to conduct two
anaerobic studies. This added requirement, in their estimate, would
have a significant impact, doubling the time of the anaerobic system
requirement. With this rule EPA now 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 terrestrial use patterns.
v. Soil mobility. EPA did not propose any changes to the data
requirement for soil mobility studies. However, the Agency received
three comments asking for clarification about which test type we prefer
to fulfill this data requirement. Therefore, in the final rule, we
added a new test note for the leaching and absorption/desorption data
requirement that explains which test procedure is preferred.
vi. Terrestrial, aquatic and forestry field dissipation studies.
EPA proposed to expand the use patterns that require the terrestrial
field dissipation study to include aquatic food crops and aquatic
nonfood uses when the pesticide is applied to aquatic sites that are
intermittently dry (rice and cranberries were given as examples).
Likewise, EPA proposed to expand the requirement for an aquatic field
dissipation study from solely aquatic use patterns to conditionally
include terrestrial use patterns as well. The third change the Agency
proposed with the field dissipation studies was to merge the long-term
field dissipation study into the terrestrial 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. A number of commenters were very concerned about
the changes in the conditions and requirements for the dissipation
studies. One issue raised by several commenters pertained to the
likelihood that some chemicals and use patterns would now require two
separate field dissipation studies instead of just one, as was the
policy in the past. Several of the commenters asked for greater
justification and clarification of the test notes from the Agency to
explain the expansion of the data requirements. They also asked for
additional guidance on the triggers and endpoints of the long-term
study.
EPA acknowledges that some pesticides, based on their environmental
fate profile and uses, may require both the aquatic and the terrestrial
field dissipation studies, but we estimated that the frequency of this
occurring is low. The Agency expanded the terrestrial field dissipation
data requirement to gain a better understanding of the patterns of a
pesticide's fate and transport when applied to crops that grow in both
flooded and dry conditions in one growing season. This decision was
endorsed by the FIFRA SAP in 1994. The data provided by the aquatic
field study for terrestrial applications will provide data necessary to
understand the fate of a terrestrially applied pesticide that has a
high potential to enter aquatic environments. Data from these studies
can reduce potential overestimation of exposure and risk and can
confirm assumptions of low levels of toxic degradates. The test note
for the aquatic study is based on harmonized language with PMRA under
NAFTA, and provides the details that must be considered to determine if
an aquatic (sediment) dissipation study is necessary for a terrestrial
use.
One commenter 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 Terrestrial Field Dissipation (TFD) requirement. EPA agrees
with this comment and has amended the test note for this study. The TFD
guideline is available on the websites of EPA and PMRA.
EPA changed the requirement for the forestry dissipation study from
required to conditionally required for pesticides used in forests. The
Agency received five comments expressing the concern that with this
change it is no longer clear what conditions of pesticide use in
forestry would trigger this requirement. The Agency made the change
because these studies are very difficult to conduct and very difficult
to interpret. The trend over the past few years has been to rely on the
terrestrial field dissipation studies for forestry uses. If this
terrestrial dissipation study cannot assess all of the major routes of
dissipation, the forestry study will be required.
The Agency did not propose any changes in the requirement for a
field dissipation study for combination and tank mixes. Three comments
identified the test note for this study as vague and with no useful
information. They suggested that the test note be revised to clarify
when this data requirement is needed, and the relevance of this data.
EPA took their recommendation and rewrote this test note to clarify
that 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.
vii. Accumulation studies. EPA proposed to change the conditions
under which the accumulation in fish and accumulation in aquatic
organisms would be required. EPA received eight
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comments regarding the fish and nontarget organism accumulation
studies. Three of the commenters suggested that this data requirement
be placed in proposed subpart E (now subpart G), Terrestrial and
Aquatic Nontarget Organism Data Requirements, and not subpart N. There
were two comments stating that test note 10 was well written, and
should also apply to the aquatic nontarget organism accumulation study
requirement in lieu of test note 11, in the environmental fate data
table. They suggested that this test note is also appropriate for the
three accumulation studies in proposed subpart E, bioavailability,
biomagnification and toxicity of aquatic organisms.
The Agency agrees with the comments, and moved the two studies
under proposed subpart N, Accumulation in Fish and Accumulation in
Aquatic Nontarget Organisms to subpart G, under the data requirement
for aquatic organisms - bioavailability, biomagnification and toxicity.
Therefore, all the ecological and fate requirements related to
bioaccumulation are located solely in subpart G. We also agree with the
comment that the language of Note 10 (Accumulation in Fish) in the
proposed environmental fate data table is appropriate for the
Accumulation in aquatic nontarget organisms data requirement in subpart
G. 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 subpart G and renumbered as test note
19. This test note replaces draft test note 21 in proposed subpart E
(now G).
viii. Ground water monitoring. EPA proposed to conditionally
require a groundwater monitoring study for all terrestrial and forestry
uses. EPA received six comments on the proposed new data requirement
for ground water monitoring. This study is conditionally required for
all terrestrial uses patterns and all forestry uses patterns. Because
of the newness of this data requirement we received several comments
questioning the conditions that would trigger this requirement. Three
additional commenters asked for better guidance in the test note for
this requirement. One of the commenters additionally expressed the
opinion that the conditions in the test note for this study should
focus on the results of the field dissipation studies rather than
laboratory studies. The Agency affirms that the conditions described in
the test note include both laboratory and field data, but points out
that this test note also describes many factors that must be considered
to determine if this requirement is triggered. It is quite complex and
difficult to fully explain all possible scenarios that could trigger a
groundwater monitoring study. In summary, EPA uses a weight-of-evidence
approach that incorporates the results of the other environmental fate
studies plus use patterns along with factors specific to the pesticide
of concern.
In addition to these use patterns, one commenter recommended that
the ground water monitoring data requirement be conditionally required
(CR) for residential outdoor uses. We agree that there may be certain
cases where a ground water monitoring study would be needed to inform a
risk management decision for residential outdoor use pesticides. In the
final rule, EPA made this study CR, but we expect that the need for
this study is likely to be rare.
ix. Degradates. EPA received six comments regarding the need and
potential triggers to test degradate substances in the laboratory
studies. They all asked for clarification of the potential requirement.
The Agency 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. Testing with degradates as the primary test
substance is not required for the environmental fate data requirements.
XV. Discussion of Key Comments on Residue Chemistry Data Requirements
(Subpart O)
EPA proposed codifying the residue chemistry data requirements that
have arisen since the 1984 regulations were issued and clarifying and
simplifying the 1984 data requirements. EPA has responded to comments
in its Response to Comments document in the docket for this rule.
Some commenters viewed the proposed residential outdoor use pattern
as an expansion of requirements for home garden uses and believed such
uses do not fall under the scope of the FFDCA. EPA did not intend to
expand the data requirement for residential uses; the current practice
is to require data based on residential use only if the corresponding
agricultural use on that crop is not approved or if the residential use
is likely to have higher residues based on increased application rates
or shorter preharvest intervals. EPA agrees that FFDCA does not apply
to commodities that are not introduced into interstate commerce and
tolerances are not established for residues on home garden crops. EPA
does assess under FIFRA whether any adverse effects (e.g. dietary
risks) could occur.
Some commenters requested a definition of indoor food use. EPA
considers indoor food uses to be primarily pesticide treatment in food
areas of food handling establishments (FHEs). FHEs include food
servicing, food manufacturing, and food processing. Crack, crevice and
space treatments are examples of application areas where pests hide or
through which they enter a building. The FHE uses described above fall
under the auspices of FFDCA and generally require residue data and
tolerances (or exemptions from tolerances) for residues of conventional
pesticides in food.
1. Tolerances and tolerance exemptions. A commenter requested a
more complete definition of tolerance because the proposed definition
implies that all the data requirements apply to applications for a
tolerance exemption. EPA agrees with the commenter that the proposed
rule implies that all the residue chemistry data requirements and
conditions apply to tolerance exemptions, which is not the case. In
many instances such data are not needed for an exemption due to the low
toxicity of the pesticide or the ability to make a safety finding using
theoretical dietary exposure estimates. The Agency added Test Note 25
to most of the data requirements to clarify when a residue chemistry
data requirement may not be required for an exemption from a tolerance.
2. Storage stability. EPA proposed separately identifying the
requirement t