Pesticides; Data Requirements for Conventional Chemicals, 60934-60988 [E7-20826]

Agencies

• ENVIRONMENTAL PROTECTION AGENCY

[Federal Register Volume 72, Number 207 (Friday, October 26, 2007)]
[Rules and Regulations]
[Pages 60934-60988]
From the Federal Register Online via the Government Printing Office [www.gpo.gov]
[FR Doc No: E7-20826]



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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

Federal Register / Vol. 72, No. 207 / Friday, October 26, 2007 / 
Rules and Regulations

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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 
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

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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

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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 https://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 https://www8.nationalacademies.org/cp/
projectview.aspx?key=74), Organization for Economic Co-Operation and 
Development (OECD) Integrated Approaches to Testing and Assessment 
(https://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 (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 committe