UNITED STATES ENVIRONMENTAL PROTECTION AGENCY
WASHINGTON, D.C. 20460
January 31, 1997
OFFICE OF
PREVENTION, PESTICIDES, AND
TOXIC SUBSTANCES
PESTICIDE REGISTRATION (PR) NOTICE NO. 97 -1
NOTICE TO MANUFACTURERS, FORMULATORS, PRODUCERS, AND REGISTRANTS
OF PESTICIDE PRODUCTS
ATTENTION: Persons Responsible for the Registration and Reregistration of Pesticides
SUBJECT: Agency Actions under the Requirements of the Food Quality Protection Act
I. INTRODUCTION
The Food Quality Protection Act of 1996 (FQPA) requires the Environmental Protection
Agency (EPA) to consider new factors when making pesticide regulatory decisions. Registrants,
applicants, or petitioners for pesticide product registrations or reregistrations, or for tolerances or
tolerance exemptions, whether pending or future, are advised to consider comprehensively the
provisions contained in the Food Quality Protection Act (FQPA), specifically the factors relevant
to aggregate exposure assessment, children's exposure, and other issues raised by the new
statutory standard. This PR Notice explains to registrants how EPA will, on an interim basis,
implement the new statutory provisions.
Although this PR Notice does not require registrants to submit any additional information,
the Agency recognizes that because the Agency is required to consider additional information in
order to make the necessary decisions, many registrants, applicants and petitioners may wish to
provide the supplemental information to the Agency even without a requirement to do so. The
Agency has already received a number of requests for information about the type of information
that the Agency will need to consider under the new statutory provisions, as well as instructions
for ensuring that the proper requests are updated with any supplemental information the
registrant, applicant or petitioner wishes the Agency to consider. For those registrants, applicants
or petitioners who wish to supplement their original submissions with additional information, the
Appendices to this Notice describe what information the Agency would consider helpful, when
and how material may be submitted to allow for the most efficient processing and review.1
1 The collection of information related to the registration, reregistration, and tolerance
programs has been approved by the Office of Management and Budget (OMB) pursuant to the
Paperwork Reduction Act under OMB Control Numbers 2070-0024; 2070-0032; 2070-0040;
2070-0060; 2070-0122; 2070-0107. These approvals cover the original submissions by the
Recycled/Recyclable .Printed with Vegetable Oil Based Inks on 100% Recycled Paper (40% Postconsumer)
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Pesticide Registration Notice 97-1
H. APPLICABILITY
This Notice applies to most applicants with registration applications, non-crop-destruct
experimental use permit applications, tolerance or tolerance exemption petitions, or reregistration
eligibility decisions pending within the Agency. It also applies to most future applicants seeking
new or amended pesticide registrations. This Notice includes all actions for synthetic chemicals,
antimicrobials, biochemical and microbial pesticides. Those who may be affected are pesticide
manufacturing companies, Interregional Research Project No. 4 (IR-4) petitioners, and other third
party registrants. This Notice, however, does not apply to applicants seeking fast track "me-too"
registrations or amendments not involving new uses.
Although the new standard in FQPA is clearly applicable to food use pesticides and
chemicals related to such pesticides, EPA intends to apply a similar standard to actions involving
non-food use pesticides that may pose significant non-dietary risks to infants and children.
HI. EFFECTIVE DATE
This PR Notice is effective immediately.
IV. BACKGROUND
On August 3, 1996, the Food Quality Protection Act was signed into law. Effective upon
signature, the new statute significantly amended the Federal Insecticide, Fungicide, and
Rodenticide Act (FIFRA) and the Federal Food, Drug and Cosmetic Act (FFDCA). It was
designed, among other things, to provide increased protection for infants and children from
pesticide risks.
FOPA Title IV of the statute amends the Federal Food, Drug and Cosmetic Act. The
most important aspect of this title is the establishment of a single, health-based standard for
setting pesticide residue tolerances. This eliminates the longstanding problems posed by different
standards for pesticides in raw and processed foods. The provision removes the requirement of
food additive tolerances for processed foods and instead regulates them all under the same
tolerance provision. A tolerance (or exemption from tolerance) for a pesticide residue on a raw
agricultural commodity (RAC) also applies to residues in a processed food derived from the RAC
that are not higher than the RAC tolerance. If the levels in the processed food are higher,' a
registrant, applicant or petitioner. In addition, EPA believes that the discussions within these
existing Information Collection Requests also serve to cover any registrant's voluntary submission
of information intended to supplement their original submissions.
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Pesticide Registration Notice 97-1
separate tolerance must be set for that processed food. Residue levels in both the RAC and the
processed food must be determined by EPA to be "safe."
The new safety standard, provided in section 408(b)(2)(A)(ii) of the statute, is a
"reasonable certainty of no harm" standard for aggregate exposure using dietary residues and all
other reliable exposure information. When setting new or reassessing existing tolerances or
tolerance exemptions under the new standard, EPA must now focus explicitly on exposures and
risks to children and infants. EPA must, 1) explicitly determine that the tolerance, or exemption
from tolerance, is safe for children; 2) consider the need for an additional safety factor of up to
ten-fold to account for uncertainty in the data base relative to children unless there is evidence
that a different factor should be used; and 3) consider children's special sensitivities and often
unique exposure patterns to pesticides.
In addition, when making a determination as to whether or not there is a reasonable
certainty that a pesticide chemical will cause "no harm," EPA must now consider other
non-occupational sources of pesticide exposure when performing risk assessments and setting
tolerances. This includes dietary exposure from drinking water, non-occupational exposure,
exposure from like pesticides that share a common mechanism of toxicity as well as other
exposure scenarios. When setting new or reassessing existing tolerances and tolerance
exemptions, EPA must also evaluate the potential for endocrine disruption. The new law directs
the Agency to use its authority to require specific tests and information on estrogenic effects for
all pesticide chemical residues.
Initial Communication to Registrants EPA began the task of implementing the
requirements of the FQPA by explaining its goals and immediate plans in a letter sent August 21,
1996, to all current pesticide manufacturers, grower and other pesticide user groups, industry,
environmental, consumer, and public interest groups. A second letter, containing more detailed
information, was sent on September 6, to all holders of pesticide registrations. In its September 6
letter, the Agency stressed that work was continuing on many registration and reregistration
activities and that interim decisions were being made. However, to ensure compliance with the
new law's provisions to protect against pesticide uses which may pose unacceptable risks to
children, additional time was needed to adequately review certain applications, especially food use
applications. A letter has been sent to the States outlining the additional materials and
information needed to make section 18 emergency exemption tolerance decisions.
Program Implementation - Status of Food Use Phase-in Process To deal with day-to-
day decisions and procedural changes that must occur, EPA has identified key implementation
processes on which to focus for all of the food and tolerance provisions of the Act. One area of
immediate concern is phasing-in and applying the new requirements to currently pending
registration, reregistration, and tolerance decisions. The Agency is inventorying all pending
actions, and sorting them according to the applicable requirements of FQPA. The Agency
estimates that there are more than a thousand actions pending at various stages of review. The
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inventory of all the registration priority actions, biopesticide actions, and scheduled reregistration
actions is almost complete. Criteria for ranking the inventory are being developed and, once
actions are ranked, a process for handling each category will be devised and put into place.
V. INTERIM APPROACH TO RTSK MANAGEMENT
The Food Quality Protection Act does not provide an explicit transition or phase-in period
for many of the new requirements in the law. Some of the new requirements call for scientific
analyses which have not been part of EPA's current risk assessment procedures. For example,
traditionally EPA has assessed pesticide exposures separately by source and has not combined
risks. Developing methodologies to address these issues requires a new way of approaching risk
assessment and risk management.
While FQPA did not specify time frames for phasing in most of these provisions (with the
exceptions of the 3-year time frame for developing a plan to assess endocrine effects, 1 year to
develop an antimicrobial program, and a few others), the law contains sufficient flexibility to allow
for a transition period while EPA develops new, long-term assessment practices. Congress, in
discussions regarding the law, has confirmed this flexibility. EPA's goal even during this interim
period is to fulfill the intent of the new law to increase the protectiveness of its regulatory process.
While it is necessary to develop new assessment procedures and policies to implement the new
requirements to the fullest, the Agency also needs to make timely decisions about the use of
pesticide products. Delaying decisions does not achieve greater health protection and, in some
instances, can cause harm. An interim decision logic allows decisions to be made now which are
protective, more economic of resources, and which can be revisited as knowledge increases. EPA
has designed an interim strategy to meet the new FQPA reasonable certainty of no harm standard
in the absence of full data and fully developed exposure and risk assessment methodologies.
Tnterim Decision Logic for Aggregate Exposure The Agency's interim decision logic is
a screening process for making regulatory decisions that are protective of public health and are
workable within the current risk assessment practices with available data and methodologies. It
also is designed to be flexible so that when actual data are submitted, earlier assumptions can be
easily replaced with new information. Outcomes, at least initially, will be conservative and any
approvals will most likely result in time limited or conditional decisions. As additional exposure
data and improved methods and models are developed, decisions based on the interim logic will
be revisited and modified as appropriate.
The new law says the Agency must now consider aggregate exposures from dietary and
non-occupational sources when assessing the risks of a chemical and setting tolerances. In
addition to dietary exposure, such sources as drinking water, residential and lawn care use need to
be considered. For most pesticides, EPA has insufficient information on specific exposures
through these routes. While new data are being generated and new exposure models developed,
EPA will estimate the exposure components and risk, and allocate portions of that total aggregate
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risk to drinking water, and residential and lawn use exposures (provided the pesticide is to be
used indoors or on lawns). The remainder of the aggregate risk will be allocated to dietary
exposure.
"The Risk Cup" EPA's interim decision logic is based on the concept that the total level
of acceptable risk to a pesticide is represented by the pesticide's Reference Dose (RfD). This is
the level of exposure to a specific pesticide that a person could receive every day over a seventy-
year period without significant risk of a long-term or chronic non-cancer health effect. The
analogy of a "risk cup" is being used to describe aggregate exposure estimates. The full cup
represents the total RfD and each use of the pesticide contributes a specific amount of exposure
that adds a finite amount of risk to the cup. As long as the cup is not full, meaning that the
combined total of all estimated sources of exposure to the pesticide has not reached 100% of the
RfD, EPA can consider registering additional uses and setting new tolerances. If it is shown that
the risk cup is full, no new uses could be approved until the risk level is lowered. This can be
done by the registrant providing new data which more accurately represent the risk or by
implementing risk mitigation measures. While this explanation is focused on chronic non-cancer
risk, the Agency will use a similar logic to assess acute risk and cancer risk.
The important issue for making interim decisions which take aggregate exposure into
account is how much of the "risk cup" should be set aside or reserved for sources of possible
exposure for which the Agency has limited or no actual data. Unless actual exposure data are
available for these non-dietary pathways, the size of the "reserve" portion will be based on various
characteristics of the pesticide, such as toxicity, mobility and persistence in soils, and use pattern.
It has been decided that, in general, between 5% and 20% of the risk cup will be set aside for non-
dietary exposures. The remainder of the risk cup will be left for dietary risk for which reliable
data are available.
Interim Decision Logic for Common Mechanism of Toxicity Similar to the decision
logic for aggregate exposure, the Agency has developed a conservative approach for assessing a
common mechanism of toxicity for pesticides, ensuring that it is protective of public health,
workable, and flexible for making timely regulatory decisions. If a pesticide shares a common
toxicological endpoint and structural similarity with other substances, EPA will assume that a
common mechanism of toxicity may exist. For such pesticides, any approvals will be time limited
or conditional. As the Agency's understanding of common mechanism of toxicity increases, it will
revisit such time limited or conditional decisions.
Making Interim Regulatory Decisions The decision logic for aggregate and cumulative
risk, as described above, applies when EPA lacks data to estimate specific exposures from the
various routes. If data were submitted which permitted a more precise estimate of exposure from
a particular source, that information would be used to assign the appropriate portion of the risk
cup for that source, rather than the more general default assumption. Further, if a registration or
reregistration action did not pass the decision logic screen, additional data could be used to
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reassess the risk or risk mitigation measures could be adopted which could lower the risk
sufficiently to grant the action.
Using this interim decision logic, EPA is making regulatory decisions on pending actions,
and registrants can now submit applications as instructed in the Appendices of this PR Notice.
Over time, the decision logic will be revised and updated as new exposure data are generated.
The interim decisions made will also be. revisited, as necessary, based on new information and/or
new methodologies.
VI. NEXT PR NOTICES
EPA places a very high priority on the development of new policies and procedures to
implement the new law quickly and efficiently and to achieve its pre-enactment pace of regulatory
activities. Even while activities resulting from this PR Notice are being put in place, work is
continuing on many registration and reregistration activities, and interim decisions are being made.
Biopesticide registration activities have continued although all pending tolerance actions have to
be reannounced to meet the new FQPA requirements. For chemical pesticides, the Agency
intends to issue a PR Notice requesting that registrants submit their next round of five priorities
within several months. These priorities will include those required under the new law for minor
use pesticides. The Agency also will be issuing a Notice similar to this one specifically directed to
the minor use registrant community.
As the Agency works on a number of fronts to implement the new law fully and resume
processing of all actions, it will provide registrants and applicants early and continuous
information relating to their applications and petitions. The Agency also plans to issue a final
document once it has gained significant experience in reviewing the applications and has put in
place appropriate administrative procedures. The final document will include revised policy
decisions and refinements of the items included in this PR Notice.
VH. FOR FURTHER INFORMATION
For further information, applicants may contact Stephen Johnson, Director, Registration
Division at 703-305-5447; Lois Rossi, Director, Special Review and Reregistration Division at
703-308-8000; Janet Andersen, Director, Biopesticides and Pollution Prevention Division at 703-
308-8712, or Frank Sanders, Director, Antimicrobials Division at 703-305-5440.
Daniel M. Barolo, Director
JAN 3 I 1997 Office of Pesticide Programs
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APPENDIX A
CONTENT OF SUPPLEMENTAL INFORMATION
As indicated at the beginning of the PR Notice, registrants, applicants and petitioners are
not currently required to submit any additional information. Nevertheless, since the new statute
requires the Agency to consider additional information in order to make the necessary decisions,
EPA recognizes that many registrants, applicants and petitioners may wish to provide the
supplemental information to the Agency even without a requirement to do so. For those
registrants, applicants or petitioners who wish to supplement their original submissions with
additional information, this Appendix describes what information the Agency would consider
helpful additions for its review.2
All tolerances or tolerance exemptions and associated registration actions under FIFRA
section 3 or reregistration actions under FIFRA section 4, whether pending or future, will need to
comply with the new safety standard of section 408(b)(2) of the Federal Food, Drug and
Cosmetic Act. In addition, because EPA intends to apply a similar standard to actions involving
non-food use pesticides that may pose significant non-dietary risks to infants and children, all
registration and reregistration actions also will need to comply with this standard with respect to
the Agency's consideration of infants and children exposure to the pesticide.
In preparing a package to be submitted, those seeking a registration, reregistration,
tolerance, or an exemption from the requirement of a tolerance for a food use pesticide, or a
registration or reregistration of a non-food use pesticide that may result in significant exposure to
children, may need to provide additional information and/or materials to address adequately the
factors and specific questions contained here. Those who wish to submit additional information
should keep in mind that the Agency will consider each factor listed below (and perhaps others as
Agency policies are developed) in addition to any data and information already required. In
addition, it is important to note that the information identified here may not be definitive in all
cases. Additional information or more detailed information may be needed in individual cases. If
a registrant, applicant, or petitioner can identify additional information that would assist the
Agency in addressing the FQPA provisions, EPA welcomes such information. Although the
submission of this information is not currently required by the regulations, if such information is
2 An agency may not conduct or sponsor, and a person is not required to respond to, a
collection of information unless it either displays a currently valid OMB control number or is
imposed on the person by statute (5 CFR 1320.6(a) & (e)). The collection of information relating
to the registration, reregistration, and tolerance programs have are approved under OMB Control
Numbers 2070-0024 (expires: 6/30/99); 2070-0032 (expires: 5/3/98); 2070-0040 (expires:
11/30/99); 2070-0060 (expires: 5/31/98); 2070-0122 (expires: 11/30/97); 2070-0107 (expires:
7/31/99). If you should have any comments on the collection activities, please send them to the
Director, OPPE Regulatory Information Division, U.S. Environmental Protection Agency
(Mailcode 2137), 401 M St., S.W., Washington, D.C. 20460. Include the OMB control number
in any correspondence. Note that this address is ONLY for comments on the collection activity.
Do not submit your information to this address.
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not submitted, the Agency must rely on previously submitted data, if applicable, or on broad or
default assumptions when considering the factors listed. As a result, favorable action on an
application, petition, or reregistration decision may be significantly delayed or precluded
altogether.
It would be helpful for any submitted documentation to contain a discussion of each of the
following factors as it relates to the pesticide and proposed tolerance or tolerance exemption. If
information on any factor is not known, that fact, along with an explanation, should be noted in
the rationale. It is important to note that EPA does not expect the registrant, applicant, or
petitioner at this time to perform any additional testing to derive the data necessary to develop its
rationales. However, if it has in its possession data from preliminary reports of ongoing studies,
articles from published literature, unpublished report information, previously unsubmitted studies,
or supplemental data that are otherwise pertinent to the Agency's concerns, the party is
encouraged to submit them. Likewise, if a registrant, applicant, or petitioner believes that a factor
is not applicable to its product, a discussion as to why this view is held should also be included.
The Agency will consider all relevant factors hi determining an application's completeness and in
setting priorities for review.
Based on the new safety standard, EPA will need the following additional information in
order to make appropriate regulatory decisions: (For details on each factor, please refer to the
explanations below in parts A and B.)
1. An informative summary of the petition or application, including a summary of the
supporting data, information, accompanying rationales, and a statement providing
permission to publish such summary, and
2. Information and discussion pertaining to a specific safety determination for infants and
children including their special susceptibilities and exposure patterns to the particular
pesticide.
A. Food Use Pesticides; Registration and Reregistration Actions. Experimental Use
Permits. Tolerance (or Exemption) Petitions and
Reassessments
In the format described in Appendix C of this PR Notice, address each of the following
with respect to the pesticide and its use(s):
Special Sensitivities
a) Chronic Endpoints
For a chemical pesticide: Discuss and/or provide evidence as to whether or not the
current Reference Dose (RfD) is sufficient to adequately protect infants and children.
Discuss and/or provide evidence as to whether or not infants and children are more
susceptible to the chemical. If you believe that an additional safety factor of 10X, to take
into account potential pre- and post-natal toxicity to infants and children is not necessary,
provide evidence to support the additional safety factor, if any, you believe to be more
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appropriate. Please bear in mind that the Agency may accept a different margin of safety
only if, based on reliable data, EPA concludes that the margin will be safe for infants and
children.
For a biochemical pesticide:3 Does the toxicity testing indicate that the establishment of
an RfD is warranted? If so, then discuss whether or not the RfD is sufficient to adequately
protect infants and children. Discuss and/or provide evidence as to whether or not infants
and children are more susceptible to the biochemical pesticide.
For a microbial pesticide:4 Discuss the potential for chronic dietary risks for infants and
children. Discuss and/or provide evidence as to whether or not infants and children are
more susceptible to the microbial pesticide than is the adult population.
b) Acute Endpoints
Discuss the potential for greater acute dietary risk for infants and children. If the chemical
or biochemical pesticide demonstrates acute effects, then discuss the endpoint used to
perform the assessment including relevance to infants and children and the details as to
how the exposure assessment was conducted and whether the estimated risk is within the
Agency's levels of concern.
c) Carcinogenic Endpoints
If the chemical or biochemical has been determined to be a carcinogen and has a cancer
potency factor (Q!*), discuss the aggregate excess lifetime cancer risk resulting from
exposure to the chemical from residues in food and drinking water (ground and surface
water) and from residential and other non-occupational source(s).
Aggregate Exposure
a) Water
For a chemical or biochemical pesticide: Discuss the potential for the transfer of residues
(of both the parent pesticide and any degradates) to drinking water. The discussion
should include, but not be limited to, information indicating whether the pesticide is
persistent and/or mobile, relevant product chemistry, and any available modeling data.
3 A biochemical is a naturally-occurring compound, or substantially similar to a naturally-
occurring compound, with a non-toxic mode of action to the target pest.
4 Certain subpopulations are more susceptible to certain disease-causing microorganisms;
however, these are not the types of microorganisms that are considered for registration or use as
microbial pesticides. The Agency has not registered, and does not expect to register a microbial
active ingredient that is known to be a common human pathogen. To address the potential risk
from microbial pesticides, the Agency requires a battery of acute toxicity/pathogenicity studies in
order to perform a risk assessment. If results of the acute exposure studies indicate a toxicity
concern, then subchronic or chronic studies are required.
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