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[Federal Register: August 6, 2010 (Volume 75, Number 151)]
[Rules and Regulations]               
[Page 47465-47475]
From the Federal Register Online via GPO Access [wais.access.gpo.gov]
[DOCID:fr06au10-10]                         

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ENVIRONMENTAL PROTECTION AGENCY

40 CFR Part 180

[EPA-HQ-OPP-2005-0190; FRL-8836-8]

 
Pymetrozine; Regulation Denying NRDC's Objections on Remand

AGENCY: Environmental Protection Agency (EPA).

ACTION: Final Regulation.

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SUMMARY: In this regulation, EPA again denies objections by the Natural 
Resources Defense Council (NRDC) to an action establishing tolerance 
regulations for the pesticide pymetrozine under section 408 of the 
Federal Food, Drug, and Cosmetic Act (FFDCA). EPA's previous denial of 
NRDC's objections, published in the Federal Register on August 10, 
2005, was remanded to EPA by the U.S. Court of Appeals, Ninth Circuit, 
for further explanation of EPA's decision on the application of the 
FFDCA's requirement concerning an additional tenfold safety factor for 
the protection of infants and children to these pesticide tolerances. 
In the challenged action, EPA had applied a reduced additional safety 
factor to several risk assessments for pymetrozine. EPA has reviewed 
its decision on the children's safety factor in light of the current 
data on pymetrozine and now determined that the full additional 
children's safety factor should be applied in assessing the risk of the 
pymetrozine tolerances. However, EPA still denies NRDC's objections 
because the increase in the children's safety factor does not change 
EPA's conclusion that the tolerances are safe. EPA's explanation for 
its decisions on the children's safety factor and the safety of 
pymetrozine tolerances are included in this regulation.

DATES: This regulation is effective August 6, 2010. Objections and 
requests for hearings must be received on or before October 5, 2010, 
and must be filed in accordance with the instructions provided in 40 
CFR part 178 (see also Unit I.C. of the SUPPLEMENTARY INFORMATION).

ADDRESSES: EPA has established a docket for this action under docket 
identification (ID) number EPA-HQ-OPP-2004-0190. To access the 
electronic docket, go to http://www.regulations.gov, and search for the 
docket number. Follow the instructions on the regulations.gov website 
to view the docket index or access available documents. All documents 
in the docket are listed in the docket index available in 
regulations.gov. Although listed in the index, some information is not 
publicly available, e.g., Confidential Business Information (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 in the electronic 
docket at http://www.regulations.gov, or, if only available in hard 
copy, at the OPP Regulatory Public Docket in Rm. S-4400, One Potomac 
Yard (South Bldg.), 2777 S. Crystal Dr., Arlington, VA. The Docket 
Facility is open from 8:30 a.m. to 4 p.m., Monday through Friday, 
excluding legal holidays. The Docket Facility telephone number is (703) 
305-5805.

FOR FURTHER INFORMATION CONTACT: Meredith Laws, Registration Division 
(7510P), Office of Pesticide Programs, Environmental Protection Agency, 
1200 Pennsylvania Ave., NW., Washington, DC 20460-0001; telephone 
number: (703) 304-7038; e-mail address: laws.meredith@epa.gov.

SUPPLEMENTARY INFORMATION:

I. General Information

A. Does this Action Apply to Me?

    In this document EPA denies objections by the NRDC to EPA's 
establishment of certain pesticide tolerances. This action may also be 
of interest to agricultural producers, food manufacturers, or pesticide 
manufacturers. Potentially affected entities may include, but are not 
limited to those engaged in the following activities:
     Crop production (NAICS) code 111), e.g., agricultural 
workers; greenhouse, nursery, and floriculture workers; farmers.
     Animal production (NAICS code 112), e.g., cattle ranchers 
and farmers, dairy cattle farmers, livestock farmers.
     Food manufacturing (NAICS code 311), e.g., agricultural 
workers; farmers; greenhouse, nursery, and floriculture workers; 
ranchers; pesticide applicators.
     Pesticide manufacturing (NAICS code 32532), e.g., 
agricultural workers; commercial applicators; farmers; greenhouse, 
nursery, and floriculture workers; residential users.
    This listing is not intended to be exhaustive, but rather to 
provide 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) codes have been provided to assist you and others in 
determining whether this action might apply to certain entities. If you 
have any questions regarding the applicability of this action to a 
particular entity, consult the person listed under FOR FURTHER 
INFORMATION CONTACT.

B. How Can I Access Electronic Copies of this Document?

    In addition to accessing an electronic copy of this Federal 
Register document through the electronic docket at http://www.regulations.gov, you may access this Federal Register document 
electronically through the EPA Internet under the ``Federal Register'' 
listings at http://www.epa.gov/fedrgstr. You may also access a 
frequently updated electronic version of EPA's tolerance regulations at 
40 CFR part 180 through the Government Printing Office's pilot e-CFR 
site at http://www.gpoaccess.gov/ecfr.

C. Can I File an Objection or Hearing Request?

    Under section 408(g) of FFDCA, 21 U.S.C. 346a, any person may file 
an objection to any aspect of this regulation and may also request a 
hearing on those objections. You must file your objection

[[Page 47466]]

or request a hearing on this regulation in accordance with the 
instructions provided in 40 CFR part 178. To ensure proper receipt by 
EPA, you must identify docket ID number EPA-HQ-OPP-2005-0190 in the 
subject line on the first page of your submission. All requests must be 
in writing, and must be received by the Hearing Clerk as required by 40 
CFR part 178 on or before October 5, 2010.
    In addition to filing an objection or hearing request with the 
Hearing Clerk as described in 40 CFR part 178, please submit a copy of 
the filing that does not contain any CBI for inclusion in the public 
docket that is described in ADDRESSES. Information not marked 
confidential pursuant to 40 CFR part 2 may be disclosed publicly by EPA 
without prior notice. Submit this copy, identified by docket ID number 
EPA-HQ-OPP-2005-0190, by one of the following methods:
     Federal eRulemaking Portal: http://www.regulations.gov. 
Follow the on-line instructions for submitting comments.
     Mail: Office of Pesticide Programs (OPP) Regulatory Public 
Docket (7502P), Environmental Protection Agency, 1200 Pennsylvania 
Ave., NW., Washington, DC 20460-0001.
     Delivery: OPP Regulatory Public Docket (7502P), 
Environmental Protection Agency, Rm. S-4400, One Potomac Yard (South 
Bldg.), 2777 S. Crystal Dr., Arlington, VA. Deliveries are only 
accepted during the Docket Facility's normal hours of operation (8:30 
a.m. to 4 p.m., Monday through Friday, excluding legal holidays). 
Special arrangements should be made for deliveries of boxed 
information. The Docket Facility telephone number is (703) 305-5805.

II. Introduction

A. What Action Is the Agency Taking?

    This action is being taken in response to a remand to EPA of a 
final order denying objections filed by the NRDC to regulations 
establishing pesticide tolerances for pymetrozine under section 408 of 
the FFDCA, 21 U.S.C. 346a. (70 FR 46706, August 10, 2005); (Ref. 1). 
The order was remanded to EPA by the U.S. Court of Appeals, Ninth 
Circuit, for an explanation of the basis for EPA's decision on the 
FFDCA's provision requiring a presumptive additional tenfold (10X) 
safety factor for the protection of infants and children. (NCAP v. EPA, 
544 F.3d 1043, 1052 (9th Cir. 2008)). Specifically, the court held that 
EPA did not provide ``enough information'' on why in evaluating the 
risk of pymetrozine it chose to deviate from this presumptive safety 
factor. (Id.). In response to the remand, EPA is again denying the 
objections. In light of new data received on pymetrozine, EPA has now 
determined that the presumptive safety factor for infants and children 
should be retained; however, the objections are denied because 
retention of this additional safety factor does not show the 
pymetrozine tolerances to be unsafe.
    Because EPA has taken new information into account in issuing this 
decision upon remand, EPA is issuing the remand decision as a 
regulation under FFDCA section 408(d)(4)(i). Any person may file 
objections to a FFDCA section 408(d)(4)(i) regulation with EPA and 
request a hearing on those objections. (Id.). If this decision was 
issued as a revised final order on NRDC's objections under FFDCA 
section 408(g)(2)(C), (21 U.S.C. 346a(g)(2)(C)), then any party who 
wished to contest EPA's determination would have no opportunity to 
submit factual contentions to the record concerning the new information 
prior to seeking judicial review.

B. What Is the Agency's Authority for Taking This Action?

    EPA's authority for issuing pesticide tolerances is contained in 
FFDCA section 408(d) and the statutory provisions governing the 
administrative review process for tolerances is in FFDCA section 
408(g)(2). (21 U.S.C. 346a(d) and (g)(2)).

III. Statutory and Regulatory Background

    In this Unit, EPA provides background on the relevant statutes and 
regulations governing NRDC's objections as well as on pertinent Agency 
policies and practices. Unit III.A. summarizes the requirements and 
procedures in section 408 of the FFDCA and applicable regulations 
pertaining to pesticide tolerances. Unit III.B. provides an overview of 
EPA's risk assessment process. It contains an explanation of how EPA 
identifies the hazards posed by pesticides, how EPA determines the 
level of exposure to pesticides that pose a concern (``level of 
concern''), how EPA measures human exposure to pesticides, and how 
hazard, level of concern conclusions, and human exposure estimates are 
combined to evaluate risk. Further, this unit presents background 
information on the EPA's policy with regard to the statutory safety 
factor for the protection of infants and children.

A. FFDCA

    1. In general. EPA establishes maximum residue limits, or 
``tolerances,'' for pesticide residues in food under section 408 of the 
FFDCA. (21 U.S.C. 346a). Without such a tolerance or an exemption from 
the requirement of a tolerance, a food containing a pesticide residue 
is ``adulterated'' under section 402 of the FFDCA and may not be 
legally moved in interstate commerce. (21 U.S.C. 331, 342). Monitoring 
and enforcement of pesticide tolerances are carried out by the U.S. 
Food and Drug Administration and the U.S. Department of Agriculture 
(USDA). Section 408 was substantially rewritten by the Food Quality 
Protection Act of 1996 (FQPA), which added the provisions discussed 
below establishing a detailed safety standard for pesticides and 
additional protections for infants and children. (Public Law 104-170, 
110 Stat. 1489 (1996)).
    2. Safety standard for pesticide tolerances. A pesticide tolerance 
may only be promulgated by EPA if the tolerance is ``safe.'' (21 U.S.C. 
346a(b)(2)(A)(i)). ``Safe'' is defined by the statute to mean that 
``there is a reasonable certainty that no harm will result from 
aggregate exposure to the pesticide chemical residue, including all 
anticipated dietary exposures and all other exposures for which there 
is reliable information.'' (21 U.S.C. 346a(b)(2)(A)(ii)). The statute 
explains that aggregate exposure to a pesticide includes ``dietary 
exposure under the tolerance and all other tolerances in effect for the 
pesticide chemical residue, and exposure from other non-occupational 
sources.'' (21 U.S.C. 346a(b)(2)(D)(vi)).
    In making the safety determination for a tolerance, risks to 
infants and children are given special consideration. Specifically, 
section 408(b)(2)(C) creates a presumptive additional safety factor for 
the protection of infants and children. It directs that ``[i]n the case 
of threshold effects, ... an additional tenfold margin of safety for 
the pesticide chemical residue and other sources of exposure shall be 
applied for infants and children to take into account potential pre- 
and post-natal toxicity and completeness of the data with respect to 
exposure and toxicity to infants and children.'' (21 U.S.C. 
346a(b)(2)(C)). EPA is permitted to ``use a different margin of safety 
for the pesticide chemical residue only if, on the basis of reliable 
data, such margin will be safe for infants and children.'' (Id.). The 
additional safety margin for infants and children is referred to 
throughout this document as the ``children's safety factor.''
    3. Procedures for establishing, amending, or revoking tolerances. 
Tolerances are established, amended, or revoked by rulemaking under the

[[Page 47467]]

unique procedural framework set forth in the FFDCA. Generally, a 
tolerance rulemaking is initiated by the party seeking to establish, 
amend, or revoke a tolerance by means of filing a petition with EPA. 
(See 21 U.S.C. 346a(d)(1)). EPA publishes in the Federal Register a 
notice of the petition filing and requests public comment. (21 U.S.C. 
346a(d)(3)). After reviewing the petition, and any comments received on 
it, EPA may issue a final rule establishing, amending, or revoking the 
tolerance, issue a proposed rule to do the same, or deny the petition. 
(21 U.S.C. 346a(d)(4)).
    Once EPA takes final action on the petition by establishing, 
amending, or revoking the tolerance or denying the petition, any person 
may file objections with EPA and seek an evidentiary hearing on those 
objections. (21 U.S.C. 346a(g)(2)). Objections and hearing requests 
must be filed within 60 days after date of publication in the Federal 
Register. (Id.). EPA's final order on the objections is subject to 
judicial review. (21 U.S.C. 346a(h)(1)).

B. EPA Risk Assessment for Tolerances - Policy and Practice

    1. The safety determination-risk assessment. To assess risk of a 
pesticide tolerance, EPA combines information on pesticide toxicity 
with information regarding the route, magnitude, and duration of 
exposure to the pesticide. The risk assessment process involves four 
distinct steps:
     Identification of the toxicological hazards posed by a 
pesticide;
     Determination of the ``level of concern'' with respect to 
human exposure to the pesticide;
     Estimation of human exposure to the pesticide; and
     Characterization of the risk posed to humans by the 
pesticide based on comparison of human exposure to the level of 
concern.
    a. Hazard identification. In evaluating toxicity or hazard, EPA 
reviews toxicity studies, primarily in laboratory animals, to identify 
any adverse effects on the test subjects. Animal studies typically 
involve investigating a broad range of endpoints including gross and 
microscopic effects on organs and tissues, functional effects on body 
organs and systems, effects on blood parameters (such as red blood cell 
count, hemoglobin concentration, hematocrit, and a measure of clotting 
potential), effects on the concentrations of normal blood chemicals 
(including glucose, total cholesterol, urea nitrogen, creatinine, total 
protein, total bilirubin, albumin, hormones, and enzymes such as 
alkaline phosphatase, alanine aminotransfersase and cholinesterases), 
and behavioral or other gross effects identified through clinical 
observation and measurement. EPA examines whether adverse effects are 
caused by either short-term (e.g., acute) or longer-term (e.g., 
chronic) pesticide exposure and the effects of pre-natal and post-natal 
exposure in animals.
    EPA also considers whether the adverse effect has a threshold -- a 
level below which exposure has no appreciable chance of causing the 
effect. For non-threshold effects, EPA assumes that any exposure to the 
substance increases the risk that the adverse effect may occur. At 
present, EPA only considers one adverse effect, the chronic effect of 
cancer, to potentially be a non-threshold effect. (Ref. 2 at 4-9). Not 
all carcinogens, however, pose a risk at any exposure level (i.e., ``a 
non-threshold effect or risk''). Advances in the understanding of the 
mode of action of carcinogenesis have increasingly led EPA to conclude 
that some pesticides that cause carcinogenic effects in animal studies 
only cause such effects above a certain threshold of exposure.
    b. Level of concern/dose-response analysis. Once a pesticide's 
potential hazards are identified, EPA determines a toxicological level 
of concern for evaluating the risk posed by human exposure to the 
pesticide. In this step of the risk assessment process, EPA essentially 
evaluates the levels of exposure to the pesticide at which effects 
might occur. An important aspect of this determination is assessing the 
relationship between exposure (dose) and response. The assessment of 
this relationship is often referred to as the dose-response analysis. 
EPA follows differing approaches to identifying a level of concern for 
threshold and non-threshold hazards.
    i. Threshold effects. In examining the dose-response relationship 
for a pesticide's threshold effects, EPA evaluates an array of toxicity 
studies on the pesticide. In each of these studies, EPA attempts to 
identify the lowest observed adverse effect level (LOAEL) and the next 
lower dose at which there are no observed adverse effect levels 
(NOAEL). Generally, EPA will use the lowest NOAEL from the available 
studies as a starting point (called the Point of Departure) in 
estimating the level of concern for humans. (Ref. 2 at 9 (The Point of 
Departure ``is simply the toxic dose that serves as the `starting 
point' in extrapolating a risk to the human population.'')). At times, 
however, EPA will use a LOAEL from a study as the Point of Departure 
when no NOAEL is identified in that study and the LOAEL is close to, or 
lower than, other relevant NOAELs. The Point of Departure is in turn 
used in choosing a level of concern. EPA will make separate 
determinations as to the Points of Departure, and correspondingly 
levels of concern, for both short and long exposure periods as well as 
for the different routes of exposure (oral, dermal, and inhalation).
    In estimating and describing the level of concern, the Point of 
Departure is at times used differently depending on whether the risk 
assessment addresses dietary or non-dietary exposures. (Pymetrozine is 
not expected to result in any meaningful non-dietary exposure and thus 
risk assessment of non-dietary exposure is not further discussed in 
this document.) For dietary risks, EPA uses the Point of Departure to 
calculate an safe or acceptable level of exposure designated as the 
reference dose (RfD). The RfD is calculated by dividing the Point of 
Departure by applicable safety or uncertainty factors. Typically, EPA 
uses a baseline safety/uncertainty factor of 100X. That value includes 
a factor of ten (10X) where EPA is using data from laboratory animals 
to reflect potentially greater sensitivity in humans than animals and a 
factor of 10X to account for potential variations in sensitivity among 
members of the human population as well as other unknowns. Additional 
safety factors may be added to address data deficiencies or concerns 
raised by the existing data. Under the FQPA, an additional safety 
factor of 10X is presumptively applied to protect infants and children, 
unless reliable data support selection of a different factor. This FQPA 
additional safety factor largely replaces pre-FQPA EPA practice 
regarding additional safety factors. (Ref. 3 at 4-11).
    In implementing FFDCA section 408, EPA's Office of Pesticide 
Programs, also calculates a variant of the RfD referred to as a 
Population Adjusted Dose (PAD). A PAD is the RfD divided by any portion 
of the FQPA safety factor that does not correspond to one of the 
traditional additional safety factors used in general Agency risk 
assessments. (Ref. 3 at 13-16). The reason for calculating PADs is so 
that other parts of the Agency, which are not governed by FFDCA section 
408, can, when evaluating the same or similar substances, easily 
identify which aspects of a pesticide risk assessment are a function of 
the particular statutory commands in FFDCA section 408. Today, RfDs and 
PADs are generally calculated for both acute and chronic dietary risks 
although traditionally a RfD or PAD was only calculated for chronic 
dietary risks. Throughout this document general references to EPA's

[[Page 47468]]

calculated safe dose are denoted as a RfD/PAD.
    ii. Non-threshold effects. For risk assessments for non-threshold 
effects, EPA does not use the RfD/PAD approach to choose a level of 
concern if quantification of the risk is deemed appropriate. Rather, 
EPA calculates the slope of the dose-response curve for the non-
threshold effects from relevant studies using a linear, low-dose 
extrapolation model that assumes that any amount of exposure will lead 
to some degree of risk. This dose-response analysis will be used in the 
risk characterization stage to estimate the risk to humans of the non-
threshold effect. Linear, low-dose extrapolation is typically used as 
the default approach for estimating the risk to carcinogens, unless 
there are mode of action data indicating a threshold response (or 
nonlinearity).
    c. Estimating human exposure. Risk is a function of both hazard and 
exposure. Thus, equally important to the risk assessment process as 
determining the hazards posed by a pesticide and the toxicological 
level of concern for those hazards is estimating human exposure. Under 
FFDCA section 408, EPA is concerned not only with exposure to pesticide 
residues in food but also exposure resulting from pesticide 
contamination of drinking water supplies and from use of pesticides in 
the home or other non-occupational settings. (See 21 U.S.C. 
346a(b)(2)(D)(vi)).
    i. Exposure from food. There are two critical variables in 
estimating exposure in food: (1) The types and amount of food that is 
consumed; and (2) the residue level in that food. Consumption is 
estimated by EPA based on scientific surveys of individuals' food 
consumption in the United States conducted by the USDA. (Ref. 2 at 12). 
Information on residue values comes from a range of sources including 
crop field trials, data on pesticide reduction (or concentration) due 
to processing, cooking, and other practices, information on the extent 
of usage of the pesticide, and monitoring of the food supply. (Id. at 
17).
    In assessing exposure from pesticide residues in food, EPA, for 
efficiency's sake, follows a tiered approach in which it, in the first 
instance (i.e., Tier 1), assesses exposure using the worst case 
assumptions that 100 percent of the crops for which tolerances exist or 
are proposed are treated with the pesticide and 100 percent of the food 
from those crops contain pesticide residues at the tolerance level. 
(Id. at 11). When such an assessment shows no risks of concern, a more 
complex risk assessment is unnecessary. By avoiding a more complex risk 
assessment, EPA's resources are conserved and regulated parties are 
spared the cost of any additional studies that may be needed. If, 
however, a Tier 1 assessment suggests there could be a risk of concern, 
EPA then attempts to refine its exposure assumptions to yield a more 
realistic picture of residue values through use of data on the percent 
of the crop actually treated with the pesticide and data on the level 
of residues that may be present on the treated crop. These latter data 
are used to estimate what has been traditionally referred to by EPA as 
``anticipated residues.'' EPA refinement of an exposure assessment 
``can have dramatic effects on the level of exposure predicted, 
reducing worst case estimates by 1 or 2 orders of magnitude or more.'' 
(73 FR 42683, 42687, July 23, 2008). More information on how EPA 
refines estimates of exposure from pesticides in food can be found in 
the following EPA publication, ``A User's Guide to Available EPA 
Information on Assessing Exposure to Pesticides in Food.'' (Ref. 2; see 
also 73 FR at 42687).
    ii. Exposure from water. EPA may use either or both field 
monitoring data and mathematical water exposure models to generate 
pesticide exposure estimates in drinking water. Monitoring and modeling 
are both important tools for estimating pesticide concentrations in 
water and can provide different types of information. Monitoring data 
can provide estimates of pesticide concentrations in water that are 
representative of specific agricultural or residential pesticide 
practices and under environmental conditions associated with a sampling 
design. Although monitoring data can provide a direct measure of the 
concentration of a pesticide in water, it does not always provide a 
reliable estimate of exposure because sampling may not occur in areas 
with the highest pesticide use, and/or the sampling may not occur when 
the pesticides are being used.
    In estimating pesticide exposure levels in drinking water, EPA most 
frequently uses mathematical water exposure models. EPA's models are 
based on extensive monitoring data and detailed information on soil 
properties, crop characteristics, and weather patterns. (69 FR 30042, 
30054-30065 (May 26, 2004)). These models calculate estimated 
environmental concentrations of pesticides using laboratory data that 
describe how fast the pesticide breaks down to other chemicals and how 
it moves in the environment. These concentrations can be estimated 
continuously over long periods of time, and for places that are of most 
interest for any particular pesticide. Modeling is a useful tool for 
characterizing vulnerable sites, and can be used to estimate peak 
concentrations from infrequent, large storms.
    Typically EPA uses a two-tiered approach to modeling pesticide 
concentrations in surface and ground water. The first tier model uses 
high-end and worst-case assumptions as a screen to identify pesticides 
that will not result in residues in water that pose a concern. If the 
first tier model suggests that pesticide levels in water may be 
unacceptably high, a more refined model is used as a second tier 
assessment. Second tier models substitute more detailed information for 
the high-end or worst-case assumptions used in first tier models. For 
example, a second tier model may incorporate information on the maximum 
percentage of acreage surrounding a drinking water reservoir that may 
be devoted to agriculture instead of assuming that 100 percent of the 
watershed is, in fact, farmland.
    iii. Residential exposures. Generally, in assessing residential 
exposure to pesticides EPA relies on its Residential Standard Operating 
Procedures (SOPs). (Ref. 4). The SOPs establish models for estimating 
application and post-application exposures in a residential setting 
where pesticide-specific monitoring data are not available. SOPs have 
been developed for many common exposure scenarios including pesticide 
treatment of lawns, garden plants, trees, swimming pools, pets, and 
indoor surfaces including crack and crevice treatments. The SOPs are 
based on existing monitoring and survey data including information on 
activity patterns, particularly for children. Where available, EPA 
relies on pesticide-specific data in estimating residential exposures.
    d. Risk characterization. The final step in the risk assessment is 
risk characterization. In this step, EPA combines information from the 
first three steps (hazard identification, level of concern/dose-
response analysis, and human exposure assessment) to quantitatively 
estimate the risks posed by a pesticide. Separate characterizations of 
risk are conducted for different durations of exposure. Additionally, 
separate and, where appropriate, aggregate characterizations of risk 
are conducted for the different routes of exposure (dietary and non-
dietary).
    For threshold dietary risks, EPA typically estimates risk by 
expressing human exposure as a percentage of the RfD/PAD. Exposures 
lower than 100 percent of the RfD/PAD are generally

[[Page 47469]]

not of concern. Under current procedures, EPA aggregates pesticide 
exposure from food and drinking water prior to comparing exposure to 
the RfD/PAD.
    2. EPA policy on the children's safety factor. As the above brief 
summary of EPA's risk assessment practice indicates, the use of safety 
factors plays a critical role in the process. This is true for the use 
of traditional 10X safety factors to account for potential differences 
between animals and humans when relying on studies in animals (inter-
species safety factor) and potential differences among humans (intra-
species safety factor) as well as the use of FQPA's additional 10X 
children's safety factor.
    In applying the children's safety factor provision, EPA has 
interpreted it as imposing a presumption in favor of applying an 
additional 10X safety factor. (Ref. 3 at 4, 11). Thus, EPA generally 
refers to the additional 10X factor as a presumptive or default 10X 
factor. EPA has also made clear, however, that this presumption or 
default in favor of the additional 10X is only a presumption. The 
presumption can be overcome if reliable data demonstrate that a 
different factor is safe for children. (Id.). In determining whether a 
different factor is safe for children, EPA focuses on the three factors 
listed in section 408(b)(2)(C) -- the completeness of the toxicity 
database, the completeness of the exposure database, and potential pre- 
and post-natal toxicity. In examining these factors, EPA strives to 
make sure that its choice of a safety factor, based on a weight-of-the-
evidence evaluation, does not understate the risk to children. (Id. at 
24-25, 35).

IV. Challenged Tolerance Regulation for Pymetrozine

    1.  In general. NRDC challenged a December 27, 2001, action 
establishing tolerances for pymetrozine on cotton seed; cotton gin 
byproducts; fruiting, cucurbit, leafy, and Brassica vegetables; turnip 
greens; hops; and pecans. (66 FR 66786, December 27, 2001). Given 
pymetrozine's exposure pattern and toxicological characteristics, EPA 
determined that pymetrozine potentially presented acute, short-term, 
chronic, and cancer risks and EPA quantitatively assessed these risks 
in making its safety determination. (Id. at 66791-66792). All of these 
risks were found to be below the Agency's level of concern. (Id.).
    2. Children's safety factor determination. For pymetrozine, EPA 
concluded there was uncertainty regarding its effects on the young 
because a DNT was outstanding and a NOAEL had not been identified in an 
acute neurotoxicity study. (66 FR at 66791; 64 FR 52438, 52444, 
September 29, 1999). EPA determined, however, that these uncertainties 
were partially offset by a number of factors. First, EPA noted that 
there was no increased sensitivity in young animals observed in the 
pre- and post-natal studies conducted with pymetrozine, and that these 
studies showed no evidence of abnormalities in the fetal nervous 
system. (Ref. 5 at 5). Second, the evidence on pymetrozine's 
neurotoxicity was mixed. Although the acute neurotoxicity study had 
identified behavioral effects at 125 milligrams per kilogram of body 
weight per day (mg/kg bw/day), the subchronic neurotoxicity only showed 
``indefinite evidence'' of neurotoxicity at significantly higher doses 
(201 mg/kg/day for males, 228 mg/kg/day for females). (Id. at 2). 
Third, exposure data were deemed adequate not to underestimate 
exposure. (Id. at 5). Weighing all of this evidence, EPA determined 
that the safety of infants and children would be protected by an 
additional 3X safety factor applied to all risk assessments; (66 FR at 
55791) and a second additional 3X safety factor for assessing acute 
risks to the general population, including infants and children. The 
second additional safety factor was only applied to the acute 
assessment because it was only in an acute neurotoxicity study that a 
NOAEL had not been identified. (64 FR at 52444). Given the two 3X 
safety factors for acute risk, EPA essentially retained the full 10X 
FQPA safety factor for the acute risk assessment. The second additional 
3X safety factor was not retained as to the acute assessment for women 
of child-bearing age because this assessment was based on an acute 
study in which a NOAEL was obtained. (Id.).

V. Subsequent Tolerance Action for Pymetrozine

    Since December 2001, EPA has established an additional tolerance 
for pymetrozine on asparagus. (70 FR 43292, July 27, 2005). Because 
section 408 requires EPA, in setting a pesticide tolerance, to consider 
aggregate exposure to the pesticide, ``including dietary exposure under 
. . . all other tolerances for the pesticide chemical residue,'' in 
this subsequent action EPA took into account exposure to pymetrozine 
under challenged tolerances established on December 27, 2001 (cotton 
seed; cotton gin byproducts; fruiting, cucurbit, leafy, and Brassica 
vegetables; turnip greens; hops; and pecans). In its action on the 
asparagus tolerance in 2005, EPA concluded that the additional exposure 
from the new tolerance, when aggregated with exposure under existing 
tolerances, was safe. (70 FR at 43297).
    With regard to the children's safety factor in this subsequent 
action, EPA relied on a revised analysis taking into account its 
Children's Safety Factor Policy, which had not been released at the 
time of the December 27, 2001 tolerance action. This revised analysis 
focused on how the expected dose level in the requested DNT study 
compared to the existing Points of Departure for acute and chronic 
risks. The dose levels in the DNT study are generally guided by the 
results of the two-generation study in rats because it is a study 
involving the young and is conducted in the same species as the DNT 
study. Noting that the Points of Departure for acute risk were 
generally in the same order of magnitude of the NOAEL in the 
reproduction study, EPA concluded that full additional 10X safety 
factor should be retained for acute risk assessments because the DNT 
study could potentially lower the existing Point of Departure 
significantly and thus EPA lacked reliable data to choose a factor 
other than the default value. EPA reasoned that if the DNT study showed 
adverse effects at the lowest dose tested (presumably a dose in the 
range of the current Point of Departure), then a revised Point of 
Departure would be tenfold lower than the existing Point of Departure 
once EPA compensated for a lack of NOAEL in the DNT study. The opposite 
conclusion was reached for chronic risks because the Point of Departure 
for chronic risk assessment was already 30X lower than the expected low 
dose in the DNT study. Due to this significant difference in the 
chronic Point of Departure and the expected low dose in the DNT study, 
the results of the DNT study were unlikely to affect the chronic Point 
of Departure and thus an additional safety factor was not needed to 
protect infants and children in the absence of the DNT study. (Ref. 6).

VI. Summary of NRDC Objections, Administrative Review of the 
Objections, and Judicial Review of EPA's Order Denying the Objections

A. NRDC's Objections

    On four occasions in the first half of 2002, the NRDC and various 
other parties filed objections with EPA to final rules under section 
408 of the FFDCA, (21 U.S.C. 346a), establishing pesticide tolerances 
for various pesticides. The objections applied to 14 pesticides and 112 
separate pesticide tolerances. The challenged tolerances included the 
tolerances for pymetrozine addressed in

[[Page 47470]]

today's regulation. The objections to the pymetrozine tolerances were 
filed on February 25, 2002, and grouped with objections to tolerances 
for halosulfuron-methyl.
    Although NRDC's petitions raised dozens of issues, most of the 
issues related to two main claims: (1) That EPA had not properly 
applied the additional 10X safety factor for the protection of infants 
and children in section 408(b)(2)(C); and (2) that EPA had not 
accurately assessed the aggregate exposure of farm children to 
pesticide residues. Many of the issues were not fact-specific to the 
challenged tolerances but rather represented a generic challenge to 
EPA's implementation of the FQPA.
    Two specific issues raised by NRDC are worthy of greater 
description because they later figured in the judicial review of EPA's 
disposition of the objections. First, as to several of the pesticides, 
NRDC argued that EPA had unlawfully removed the 10X children's safety 
factor because EPA had required that a DNT study be submitted for the 
pesticides but such study had not yet been completed. Specifically as 
to pymetrozine, NRDC asserted that:
     Even though . . . DNT results are required and overdue, EPA has 
established new tolerances for pymetrozine. In doing so, EPA failed to 
apply the required 10X safety factor for children that is intended to 
compensate for just such data gaps.
(Ref. 1 at 4). Second, NRDC argued that EPA could not lawfully remove 
the children's safety factor as to all of the challenged pesticides 
because EPA relied on drinking water exposure models to estimate 
pesticide exposure levels in water instead of ``collect[ing] pesticide-
specific data on water-based exposure.'' (Ref. 7 at 5; Ref. 8 at 6). 
According to NRDC, drinking water models, as a definitional matter, 
could not supply the ``reliable data'' needed to choose a children's 
safety factor differing from the presumptive value. (Ref. 7 at 4-6; 
Ref. 8 at 6).

B. EPA's Denial of the Objections

    EPA denied NRDC's objections in two separate orders. The first was 
issued on May 26, 2004, and addressed only the tolerances for 
imidacloprid. (69 FR 30042, May 26, 2004). The second was released on 
August 10, 2005 and addressed the tolerances for the remaining 14 
pesticides. (70 FR 46706, August 10, 2005). The second order relied 
heavily on the imidacloprid order because in the process of resolving 
the claims pertaining to imidacloprid, EPA resolved many of NRDC's 
generic attacks on EPA's interpretation of the FQPA. (70 FR at 46711, 
46716, 46725, 46726, 46730).
    As to the DNT study and the children's safety factor, EPA rejected 
``NRDC's contention that an EPA finding that a DNT study is needed in 
evaluating the risks posed by the pesticide is outcome-determinative as 
regards to retaining the children's safety factor until such time as 
the DNT study is submitted and reviewed.'' (70 FR at 46724). EPA 
carefully reviewed all of the evidence cited by NRDC regarding the DNT 
study and concluded that NRDC had not shown that the DNT was so 
critical to the protection of children that in the absence of that 
study EPA was conclusively precluded from exercising its statutory 
authority to make a case-by-case determination regarding the 
appropriate children's safety factor. EPA specifically did not address 
the specific factual considerations relating to its individual 
children's safety factor decisions as to pymetrozine (and the other 
pesticides), noting that ``NRDC has offered no pesticide-specific 
arguments as to the pesticides in this proceeding as to why the absence 
of a DNT study requires the retention of the default 10X additional 
factor.'' (Id.)
    With regard to whether reliance on drinking water models precluded 
lowering of the children's safety factor, EPA exhaustively reviewed the 
underlying factual basis for its models, the scientific peer review 
they had received, and how the models had worked in practice. EPA 
concluded that ``they are based on reliable data and have produced 
estimates that EPA can reliably conclude will not underestimate 
exposure to pesticides in drinking water.'' (70 FR at 46726). 
Accordingly, NRDC's claim that only actual pesticide-specific water 
monitoring data could provide ``reliable data'' on the levels of 
pesticides in drinking water was rejected.

C. Judicial Review

    1. NRDC's petition for review. In August, 2005, NRDC and the 
Northwest Coalition for Alternatives to Pesticides (NCAP) filed 
petitions for review of EPA's August 10, 2005 order. NRDC had not 
challenged the May 26, 2004 imidacloprid order. The petitions were 
filed in the Second and Ninth Circuits and the matter was assigned to 
the Ninth Circuit. The consolidated petitions sought review as to EPA's 
denial of NRDC's objections as they pertained to the tolerances of the 
following seven pesticides: acetamiprid, fenhexamid, halosulfuron-
methyl, isoxadifen-ethyl, mepiquat, pymetrozine, and zeta-cypermethrin.
    NRDC/NCAP's brief argued that EPA had unlawfully removed or lowered 
the children's safety factor as to these seven pesticides and that 
EPA's establishment of tolerances for the seven pesticides was 
arbitrary and capricious. (Ref. 9). As to the contentions regarding the 
children's safety factor, NRDC/NCAP made several independent claims as 
to why EPA's action was unlawful. These claims were:
     a. As to acetamiprid, halosulfuron-methyl, mepiquat, pymetrozine, 
and zeta-cypermethrin, EPA had no discretion to alter the children's 
safety factor because it had determined that a DNT study was 
specifically needed to address concerns regarding these pesticides (DNT 
studies were not required on fenhexamid and isoxadifen-ethyl);
     b. EPA's decision on the children's safety factor could not be 
upheld because EPA provided ``no pesticide-specific response to NRDC's 
objections with respect to the missing DNT studies, and does not offer 
any explanation or justification for the agency's departure from the 
tenfold children's safety factor for these five pesticides;''
     c. EPA lacked the reliable data on pesticide exposure levels in 
drinking water for each of the pesticides and such data are necessary 
to justify altering the children's safety factor; and
     d. EPA must retain the children's safety factor for each of the 
pesticides because data showed that they resulted in pre- or post-natal 
toxicity.
NRDC/NCAP argued that EPA's decision was arbitrary and capricious 
because EPA determined that additional data were needed on the 
pesticides but had not waited for submission of that data before 
establishing the pesticide tolerances and because EPA had not offered a 
sufficient explanation of its decisions on the children's safety 
factor.
    2. The Ninth Circuit's decision. On September 19, 2008, the Ninth 
Circuit unanimously determined that:
     a. It was not arbitrary and capricious for EPA to have established 
the tolerances for acetamiprid, mepiquat, and pymetrozine without 
waiting for DNT studies for these pesticides;
     b. EPA had offered a reasoned explanation for why, as a general 
matter, the children's safety factor could be reduced in the absence of 
a DNT study; and
     c. It was reasonable for EPA to rely

[[Page 47471]]

in drinking water models in estimating pesticide levels in water in 
making children's safety factor determinations.
(NCAP v. EPA, 544 F.3d 1043, 1044-1051 (9th Cir. 2008)). Additionally, 
by a 2-to-1 vote, the court remanded to EPA its decision on the 
children's safety factor for acetamiprid, mepiquat, and pymetrozine. 
The majority found that EPA's order on NRDC's objections had not 
adequately explained the pesticide-specific reasons for removing or 
reducing the children's safety factor as to these pesticides in the 
absence of a required DNT study. (Id. at 1052). Without elaborating, 
the court dismissed all other issues raised by NRDC/NCAP. (Id. at 
1053).
    Although NRDC/NCAP's petition for review concerned seven 
pesticides, the court only remanded to EPA the tolerance decisions on 
acetamiprid, mepiquat, and pymetrozine. The petition for review was 
denied as to the other four pesticides because the remand only 
pertained to pesticides for which there was a question concerning EPA's 
pesticide-specific choice of a children's safety factor in the absence 
of a required DNT study. As to fenhexamid and isoxadifen-ethyl, a DNT 
study had not been required by EPA. For halosulfuron-methyl and zeta-
cypermethrin tolerances, a DNT study had been required and had not been 
submitted at the time of the tolerance action; however, by the time of 
the oral argument, the circumstances had changed. As to zeta-
cypermethrin, the DNT study had been submitted and reviewed by EPA and 
EPA had established further tolerances in reliance on the DNT study. As 
to halosulfuron-methyl, EPA had withdrawn the requirement for a DNT 
study. EPA notified the court that there was no longer a live 
controversy as to the tolerances for halosulfuron-methyl and zeta-
cypermethrin and NRDC/NCAP and the court agreed the petition was moot 
as to these pesticides. (544 F.3d at 1048 n.4; Refs. 10 and 11).

VII. Revised Regulation on Remand

    On remand, EPA has determined that NRDC's objections should again 
be denied because the remanded objections do not show that the 
pymetrozine tolerances are not safe. EPA has now received and reviewed 
a DNT study on pymetrozine. The results of the DNT study, when 
considered in combination with the rest of the pymetrozine database, 
convince EPA that the 10X children's safety factor should be retained 
for pymetrozine. EPA evaluated the risk of pymetrozine, taking into 
account the additional 10X children's safety factor and has concluded 
that pymetrozine tolerances are safe. A summary of EPA's reasons for 
retaining the 10X children's safety factor and of EPA's risk assessment 
is provided below.

A. DNT Study for Pymetrozine

    A DNT study with pymetrozine was performed in Wistar-derived rats. 
(Ref. 12). Dose levels in the study were 0 (control), 100, 500, or 
2,500 parts per million (ppm). To translate these doses to humans they 
are expressed in terms of the daily dose in milligrams of pymetrozine 
per kilogram of body weight of the experimental animals. Additionally, 
because of significant body weight changes between fetuses during the 
period of gestation and post-natal animals during lactation, that 
weight change is incorporated into the expression of dose by using 
separate dose calculations for gestation and lactation. Expressed in 
these terms, the doses in the pymetrozine DNT study were 0/0 
(gestation/lactation), 8.1/16.8, 38.7/82.6, and 173.1 milligrams/
kilogram of body weight/day (mg/kg/day). No dose is provided for the 
high dose group of lactation animals because higher than expected 
mortality was observed during littering, resulting in an insufficient 
number of litters. Therefore, the study was terminated for the high 
dose group prior to lactation.
    Effects in pups, as well as maternal animals, were evaluated 
through both in-life and post-mortem observations. To investigate 
potential neurotoxic effects, the in-life observations included 
monitoring of motor activity, testing of acoustic startle response, 
learning and memory evaluation, and use of a functional observation 
battery (FOB). The FOB is a noninvasive procedure designed to detect 
gross functional deficits resulting from exposure to chemicals and to 
better quantify neurotoxic effects detected in other studies. The FOB 
consists of six types of observations: home cage, handling, open field, 
sensory, neuromuscular, and physiological responses. Post-mortem 
evaluation included examination of the major portions of the central 
and peripheral nervous system for any sign of neuropathology.
    The primary effect seen in the maternal animals was loss of the 
litter. At the 38.7 mg/kg/day dose, total litter loss was experienced 
between birth and post-natal-day 5 by 5 out of 29 treated maternal 
animals (17.2%) compared to 2 out of 30 controls (6.7%). On gestation 
day 24, one maternal animal with staining around the nose was 
sacrificed due to difficult parturition, and another animal was pale. 
Food consumption was decreased ([darr]21%; statistical significance of 
p16.8 mg/
kg/day dose, no treatment-related effects were seen on litter loss, 
survival, clinical signs, body weight, body weight gain, food 
consumption, or reproductive performances. EPA determined that the 
maternal LOAEL is 38.7 mg/kg/day and the maternal NOAEL is 8.1 mg/kg/
day.
    Pymetrozine caused a dose-dependent increase in the number of pups 
dying during post-natal-days 1-5; 57 pups at 8.1/16.8 mg/kg/day, 95 
pups at 38.7/82.6 mg/kg/day, and 151 pups at 173.1 mg/kg/day, compared 
to 48 pups in the controls. This was due to the increase in the number 
of whole litter losses at 8.1/16.8 mg/kg/day (3 litters), 38.7/82.6 mg/
kg/day (5 litters), and 173.1 mg/kg/day (4 litters) compared to 
controls (2 litters). When whole litter losses are excluded, no 
treatment-related findings were observed on litter size or viability.
    Treatment had no adverse effects on pup body weight, body weight 
gain, food consumption, developmental landmarks, clinical signs, FOB, 
motor activity, auditory startle reflex, learning and memory, or brain 
weights. However, measurement of brain morphometry showed the following 
differences (p82.6 mg/kg/day males on post-natal-day 12 
([uarr]15%) and in the 8.1/16.8 mg/kg/day males on post-natal-day 63 
([uarr]4-13%); (ii) increased thickness of the inner granular and 
molecular layers of the pre-pyramidal fissure in the cerebellum in the 
38.7/82.6 mg/kg/day males on post-natal-day 63 ([uarr]4-19%); and (iii) 
increased thickness of the dorsal cortex in the 8.1/16.8 mg/kg/day 
females on post-natal-day 12 ([uarr]4-10%).
    EPA determined that the offspring LOAEL is 8.1 mg/kg/day, the 
lowest dose tested, based on morphometric changes in the brains of 
female pups on post-natal-day 12 and male pups on post-natal-day 63. 
The offspring NOAEL was not established.

B. Children's Safety Factor Decision for Pymetrozine

    In evaluating the children's safety factor for pymetrozine, EPA 
considered the completeness of the toxicity and exposure databases as 
well as the potential for pymetrozine to cause pre- or post-natal 
toxicity, particularly where such toxicity indicates increased 
sensitivity in juvenile animals compared to adult animals. (Ref. 13)
    1. Toxicity database. With the receipt of the DNT study, the 
toxicity database

[[Page 47472]]

for pymetrozine is complete in terms of the requirements in place at 
the time of the challenged pymetrozine tolerance action in 2001. 
However, since that time, EPA has amended data requirements pertaining 
to registration of pesticides under the Federal Insecticide, Fungicide, 
and Rodenticide Act, (7 U.S.C. 136 et seq.), and establishment of 
tolerances under the FFDCA. (72 FR 60934, October 26, 2007). Several 
new requirements apply to agricultural pesticides such as pymetrozine 
but the only new data requirement for pymetrozine that has not yet been 
fulfilled is the requirement for an immunotoxicity study.
    In the absence of this study, EPA examined the pymetrozine database 
to evaluate pymetrozine's immunotoxic potential. EPA concluded that the 
liver is the primary target organ of pymetrozine and that apparent 
immunotoxic effects are the result of exceedingly high doses.
    Potential immune organ effects include atrophy of the thymus in the 
subchronic rat and dog studies at 360 and 54 mg/kg/day, respectively; 
decreased thymus weight in the chronic mouse study at 675 mg/kg/day; 
increased leucocytes in the subchronic rat study at 360 mg/kg/day; and 
hyperplasia of the splenic lymphocyte follicles in the reproduction 
study at 136.9 mg/kg/day. Clear NOAELs were identified for these 
potential immunotoxic effects at higher doses than the endpoint that 
was selected for risk assessment, i.e., the 8.1 mg/kg/day LOAEL from 
the DNT study based on brain morphometric changes in the offspring. 
Lymphocytic infiltration in the prostrate and thyroid was observed at 
14 mg/kg/day in the subchronic dog study but these organs are not a 
primary part of the immune system and the lymphocytic infiltration is 
considered an immune system reaction to other toxic effects on these 
organs and not an immunotoxic effect.
    The Agency does not believe that conducting a functional 
immunotoxicity study will result in a lower Point of Departure than the 
endpoint currently selected for overall risk assessment (i.e. the 
extrapolated NOAEL from the DNT study--see discussion below in Unit 
VII.C.1.a.) based on:
     a. The only potential immunotoxic responses occurred at doses 
greater than the endpoint selected for risk assessment,
     b. Clear NOAELs were identified for the potential immunotoxic 
effects, again at doses greater the endpoint selected for risk 
assessment; and
     c. The lymphohistocytic effects were determined not to be 
immunotoxic effects but a reaction to other toxic effects.
    The other concern with the toxicity database is that a NOAEL was 
not identified for juvenile animals in the DNT study. The LOAEL in that 
study was based on differences from controls in the measurement of 
brain morphometrics. The concern with this effect, however, is lessened 
somewhat here in that no effects were seen in other barometers of 
effects on developmental neurology such as developmental landmarks, 
clinical signs, FOB, motor activity, auditory startle reflex, learning 
and memory, or brain weights.
    2. Potential pre- and post-natal toxicity. No indications of 
qualitative or quantitative sensitivity in the young were seen in the 
developmental studies in rats and rabbits or in the two generation 
reproduction study in rats. NOAELs were identified for all effects in 
the young seen in these studies. On the other hand, EPA has assumed 
that quantitative sensitivity was detected in the DNT study in rats 
given that toxicity was observed in the juveniles (brain morphometric 
changes) in the absence of maternal toxicity. This is a conservative 
assumption on EPA's part in that the maternal animals' brains were not 
examined for morphometric changes.
    3. Exposure database. EPA's exposure estimate is based mainly on a 
2005 exposure assessment performed for the last pymetrozine tolerance 
action. (70 FR 43292, July 27, 2005). For the acute exposure 
assessment, EPA used the very conservative approach of assuming 
pymetrozine was used on all foods with a tolerance and residues were at 
the tolerance level. The chronic exposure assessment is more refined in 
that for most crops EPA relied on average values from pesticide residue 
field trials for all commodities and data on the percentage of crops 
that are treated with pymetrozine for most of the more heavily-consumed 
commodities. Because several years have passed since the 2005 
pymetrozine tolerance action, EPA updated the percent crop treated data 
in assessing exposure. Although pymetrozine is licensed for use on 
ornamentals, EPA expects exposure to the public, including children, 
from this use to be negligible because pymetrozine may only be applied 
by commercial applicators (hence, no applicator exposure for the 
public) and post-application contact with ornamentals is infrequent and 
brief compared with, for example, turf.
    4. Conclusion. The primary factor of concern from the above is the 
weakness in the toxicity database due to the failure to identify a 
NOAEL in the DNT study. This deficiency is heightened by the fact that, 
although pre- and post-natal animals were generally not more sensitive 
than adults, the DNT study showed quantitative sensitivity in rat pups 
due to the identification of adverse brain morphometric changes in rat 
pups at a dose that did not cause maternal toxicity. Although the brain 
morphometric effects seen at the LOAEL in the DNT study were not 
confirmed by other barometers of developmental neurotoxicity, the 
absence of a NOAEL for these effects creates sufficient uncertainty 
that reliable data are not available to revise the default 10X 
children's safety factor. Therefore, EPA is retaining the full 10X 
children's safety factor in assessing risk based on the DNT study. As 
discussed in Unit VII.C.1. below, the DNT study provides the Point of 
Departure for both acute and chronic risk assessments. Retention of the 
full children's safety factor reduces any concerns from lack of an 
immunotoxicity study as the NOAELs from the potential immunotoxic organ 
effects are all greater than 1000X higher than the level of concern 
(aPAD and cPAD) when the 10X children's safety factor is taken into 
account. Despite the lack of a NOAEL in the DNT study and the increased 
sensitivity in juveniles shown in that study, EPA does not believe that 
the weight of the evidence supports an additional safety factor higher 
than 10X given that the brain morphometric effects seen at the LOAEL in 
the DNT study were not confirmed by any other measures of neurological 
effect.

C. Risk Assessment and Safety Determination for Pymetrozine

    Given the new data on developmental neurotoxicity and EPA's revised 
children's safety factor determination, EPA has recalculated the risks 
of pymetrozine taking this information into account. EPA last assessed 
the risks of pymetrozine in connection with a tolerance rulemaking for 
pymetrozine on asparagus in 2005. (70 FR 43292, July 27, 2005). The new 
information affects the hazard identification and dose-response aspects 
of the risk assessment for acute and chronic non-cancer risk. EPA has 
also updated the exposure assessment performed for the 2005 assessment 
because exposure information is needed in completing a revised acute 
and chronic risk assessment.
    1. Hazard identification/dose response--a. Point of Departure. As 
previously explained, EPA chooses a Point of Departure from toxicology 
studies for use in calculating a safe level of exposure to humans. This 
safe level

[[Page 47473]]

of exposure is called a Reference Dose (RfD) or Population-Adjusted 
Dose (PAD). In the 2002 tolerance rulemaking, EPA used the following 
Points of Departure: for acute risk to the general population 
(including infants and children) a LOAEL of 125 mg/kg/day from the 
acute neurotoxicity study in rats; for acute risk to pre-natal infants 
(focusing on exposure to females of child-bearing age) a NOAEL of 10 
mg/kg/day from the rabbit developmental study; and for chronic risk to 
the general population (including infants and children) a NOAEL of 
0.377 from the chronic toxicity study in rats. The same Points of 
Departure were used in risk assessment for the 2005 rulemaking.
    The Points of Departure have been changed based on a review of the 
DNT study. EPA determined that the LOAEL of 8.1 mg/kg/day from the DNT 
study (no NOAEL was established) would be used as the Point of 
Departure for both acute risk (all population groups including infants 
and children and women of child-bearing age) and chronic risk (again, 
all population groups). As described above, the effect seen at the 
LOAEL was changes in brain morphometrics in the offspring. The LOAEL 
from the DNT study was chosen for the Point of Departure for assessing 
acute risk because it is lower than either of the two doses previously 
used (the LOAEL from the acute neurotoxicity study and the NOAEL from 
the rabbit developmental study). Selection of this LOAEL for the Point 
of Departure for acute risk assessment is conservative because the 
brain morphometric changes were observed in the absence of impacts on 
other parameters, including developmental landmarks, clinical signs, 
FOB, motor activity, acoustic startle response, learning and memory, or 
brain weight. It is additionally conservative because EPA has assumed 
that these brain changes could occur from a single dose.
    The Agency is using the LOAEL from the DNT study as the Point of 
Departure for chronic risk because brain morphometric changes may be 
the result of single or multiple doses and this LOAEL produces the most 
protective cPAD. Previously, EPA used the NOAEL from the chronic rat 
study as the Point of Departure but the LOAEL from that study is based 
on hepatic hypertrophy and EPA no longer considers hepatic hypertrophy 
in the absence of liver pathology or changes in relevant clinical 
chemistry parameters to be an adverse effect. Hepatocellular 
hypertrophy is often an adaptive and reversible effect in response to 
the presence of a chemical (i.e. induction of microsomal enzymes in the 
liver). Although there are other NOAELs in the pymtrozine database at 
or slightly below the LOAEL from the DNT study, once an additional 
safety factor (see above) is retained to address the lack of a NOAEL in 
the DNT study, reliance on the LOAEL from this study produces the most 
protective cPAD.
    b. Dose response. To calculate both the aPAD and cPAD, EPA divided 
the LOAEL from the DNT study by 1,000, representing a 10X factor to 
account for inter-species variability, a 10X factor to account for 
intra-species variability, and an additional 10X safety factor for the 
protection of infants and children due to the lack of a NOAEL in the 
DNT study. As noted above, the retention of the full 10X children's 
safety factor is conservative given the fact that the brain 
morphometric changes were noted in the absence of any confirming 
clinical or neuropathological signs.
    2. Exposure. As explained in Unit VII.B. above, EPA relied on the 
exposure assessment for the 2005 pymetrozine tolerance rulemaking 
updated to incorporate more recent percent crop treated information. 
Residue levels in drinking water were estimated for that exposure 
assessment based upon EPA's screening level drinking water models. This 
assessment is very conservative with regard to acute exposure, and, 
while more refined for chronic exposure, still retains significant 
conservatisms. (Refs. 13 and 14).
    3. Safety Determination. Table 1 below shows how exposure to 
pymetrozine residues in food and drinking water compared to the aPAD 
and cPAD for the general population and major population subgroups 
based on age. The highest subgroups for acute and chronic exposure are 
shown in bold.

    Table 1--Summary of Combined Dietary (Food + Drinking Water) Exposure and Risk Estimates for Pymetrozine
----------------------------------------------------------------------------------------------------------------
                                                           Acute (95th Percentile)              Chronic
                                                      ----------------------------------------------------------
                 Population Subgroup                    Exposure (mg/                  Exposure(mg/kg/
                                                           kg/day)         % aPAD           day)         % cPAD
----------------------------------------------------------------------------------------------------------------
General U.S. Population                                      0.002831              35        0.000237        2.9
----------------------------------------------------------------------------------------------------------------
All Infants (1 year old)                                     0.003882              48        0.000707        8.7
----------------------------------------------------------------------------------------------------------------
Children 1-2 years old                                       0.004368              54        0.000350        4.3
----------------------------------------------------------------------------------------------------------------
Children 3-5 years old                                       0.004034              50        0.000329        4.1
----------------------------------------------------------------------------------------------------------------
Children 4-12 years old                                      0.003027              37        0.000224        2.8
----------------------------------------------------------------------------------------------------------------
Youth 13-19 years old                                        0.002312              28        0.000174        2.2
----------------------------------------------------------------------------------------------------------------
Adults 24-49 years old                                       0.002698              33        0.000222        2.7
----------------------------------------------------------------------------------------------------------------
Adults 50+ years old                                         0.002669              33        0.000235        2.9
----------------------------------------------------------------------------------------------------------------
Females 13-49 years old                                      0.002625              32        0.000217        2.7
----------------------------------------------------------------------------------------------------------------

    Given the data and analysis underlying the derivation of the 
pymetrozine aPAD and cPAD and the pymetrozine exposure assessment, EPA 
concludes that its finding that exposure for the highest exposed 
population subgroup is below the aPAD and cPAD shows that there is a 
reasonable certainty of no harm from aggregate exposure to pymetrozine 
for all population subgroups including infants and children. (Refs. 13 
and 14).

[[Page 47474]]

D. Conclusion

    Because EPA's revised risk assessment - which incorporates both the 
DNT study and the 10X children's safety factor - shows pymetrozine 
exposure to be safe, NRDC's objection to the establishment of the 
pymterozine tolerances is denied.

VIII. Regulatory Assessment Requirements

    This final rule reaffirms, over objections, tolerances established 
under section 408(d) of FFDCA in response to a petition submitted to 
the Agency. The Office of Management and Budget (OMB) has exempted 
these types of actions from review under Executive Order 12866, 
entitled Regulatory Planning and Review (58 FR 51735, October 4, 1993). 
Because this final rule has been exempted from review under Executive 
Order 12866, this final rule is not subject to Executive Order 13211, 
entitled Actions Concerning Regulations That Significantly Affect 
Energy Supply, Distribution, or Use (66 FR 28355, May 22, 2001) or 
Executive Order 13045, entitled Protection of Children from 
Environmental Health Risks and Safety Risks (62 FR 19885, April 23, 
1997). This final rule does not contain any information collections 
subject to OMB approval under the Paperwork Reduction Act (PRA), 44 
U.S.C. 3501 et seq., nor does it require any special considerations 
under Executive Order 12898, entitled Federal Actions to Address 
Environmental Justice in Minority Populations and Low-Income 
Populations (59 FR 7629, February 16, 1994).
    Since tolerances and exemptions that are established on the basis 
of a petition under section 408(d) of FFDCA, such as the tolerance in 
this final rule, do not require the issuance of a proposed rule, the 
requirements of the Regulatory Flexibility Act (RFA) (5 U.S.C. 601 et 
seq.) do not apply.
    This final rule directly regulates growers, food processors, food 
handlers, and food retailers, not States or tribes, nor does this 
action alter the relationships or distribution of power and 
responsibilities established by Congress in the preemption provisions 
of section 408(n)(4) of FFDCA. As such, the Agency has determined that 
this action will not have a substantial direct effect on States or 
tribal governments, on the relationship between the national government 
and the States or tribal governments, or on the distribution of power 
and responsibilities among the various levels of government or between 
the Federal Government and Indian tribes. Thus, the Agency has 
determined that Executive Order 13132, entitled Federalism (64 FR 
43255, August 10, 1999) and Executive Order 13175, entitled 
Consultation and Coordination with Indian Tribal Governments (65 FR 
67249, November 9, 2000) do not apply to this final rule. In addition, 
this final rule does not impose any enforceable duty or contain any 
unfunded mandate as described under Title II of the Unfunded Mandates 
Reform Act of 1995 (UMRA) (Public Law 104-4).
    This action does not involve any technical standards that would 
require Agency consideration of voluntary consensus standards pursuant 
to section 12(d) of the National Technology Transfer and Advancement 
Act of 1995 (NTTAA), Public Law 104-113, section 12(d) (15 U.S.C. 272 
note).

IX. Congressional Review Act

    The Congressional Review Act, 5 U.S.C. 801 et seq., generally 
provides that before a rule may take effect, the agency promulgating 
the rule must submit a rule report to each House of the Congress and to 
the Comptroller General of the United States. Here, the underlying rule 
establishing pymetrozine tolerances is currently in effect. (See 66 FR 
66786, December 27, 2001). The EPA order denying objections to that 
rule, however, has been remanded to EPA for a further explanation of 
the basis for EPA's decision on the objections. Importantly, the court 
remanded the matter to EPA without vacating the underlying rule. 
Today's action reaffirming the prior rule responds to the judicial 
remand and does not affect the status of the underlying rule. EPA will 
submit a report containing today's action reaffirming the pymetrozine 
tolerance regulation and other required information to the U.S. Senate, 
the U.S. House of Representatives, and the Comptroller General of the 
United States prior to publication of this final rule in the Federal 
Register. The reaffirmed pymetrozine tolerance regulation is not a 
``major rule'' as defined by 5 U.S.C. 804(2).

X. References

    1. Objections to the Establishment of Tolerances for Pesticide 
Chemical Residues: Halosulfuron-methyl and Pymetrozine Tolerances 
(filed February 25, 2002).
    2. USEPA, A User's Guide to Available EPA Information on Assessing 
Exposure to Pesticides in Food (June 21, 2000).
    3. Office of Pesticide Programs, USEPA, Office of Pesticide 
Programs' Policy on the Determination of the Appropriate FQPA Safety 
Factor(s) For Use in the Tolerance Setting Process (February 28, 2002).
    4. Office of Pesticide Programs, USEPA, Standard Operating 
Procedures (SOPs) for Residential Exposure Assessments (Draft December 
19, 1997).
    5. Office Of Prevention, Pesticides and Toxic Substances, USEPA, 
Memorandum from Brenda Tarplee to Michael Doherty, Pymetrozine - Report 
of the FQPA Safety Factor Committee (July 21, 1999).
    6. Office Of Prevention, Pesticides and Toxic Substances, USEPA, 
Memorandum from Brenda Tarplee to Michael Doherty, Pymetrozine - 3rd 
Report of the Hazard Identification Assessment Review Committee 
(February 9, 2003).
    7. NRDC, Objections to the Establishment of Tolerances for 
Pesticide Chemical Residues: Isoxadifen-ethyl, Acetamiprid, 
Propiconazole, Furilazole, Fenhexamid, and Fluazinam Tolerances (filed 
May 20, 2002).
    8. NRDC, Objections to the Establishment of Tolerances for 
Pesticide Chemical Residues: Imidacloprid, Mepiquat, Bifenazate, Zeta-
cypermethrin, and Diflubenzuron Tolerances (filed March 19, 2002).
    9. Petitioners' Brief, NCAP v. EPA, Case Nos. 75255, 76807 (9th 
Cir. March 6, 2006).
    10. Letter from Kent E. Hanson, U.S. Department of Justice to Cathy 
Catterson, Clerk of the Court, United States Court of Appeals, Ninth 
Circuit, Notice of Supplemental Authority in Northwest Coalition for 
Alternatives to Pesticides v. EPA, Nos. 04-75255 & 04-76807 (May 25, 
2007).
    11. Letter from Aaron Colangelo, U.S. Department of Justice to 
Cathy Catterson, Clerk of the Court, United States Court of Appeals, 
Ninth Circuit, Response to EPA's Notice of Supplemental Authority in 
Northwest Coalition for Alternatives to Pesticides v. EPA, Nos. 04-
75255 & 04-76807 (May 29, 2007).
    12. Office Of Prevention, Pesticides and Toxic Substances, USEPA, 
Memorandum from Robert J. Mitkus to Daniel Peacock, Pymetrozine - 
Review of Developmental Neurotoxicity Study in Rats (July 13, 2005).
    13. Office Of Prevention, Pesticides and Toxic Substances, USEPA, 
Memorandum from Christina Swartz to Daniel B. Peacock and Meredith F. 
Laws, Pymetrozine. Updated Aggregate Human Health Risk Assessment 
(April 2, 2010).
    14. Office Of Prevention, Pesticides and Toxic Substances, USEPA, 
Memorandum from Christina Swartz to Daniel B. Peacock and Meredith F.

[[Page 47475]]

Laws, Pymetrozine - Acute, Chronic and Cancer Combined Dietary (Food + 
Drinking Water) Exposure and Risk Assessments (April 2, 2010).

List of Subjects in 40 CFR Part 180

    Environmental protection, Administrative practice and procedure, 
Agricultural commodities, Pesticides and pests, Reporting and 
recordkeeping requirements.

    Dated: July 27, 2010.
Steven Bradbury,
Director, Office of Pesticide Programs.

[FR Doc. 2010-19423 Filed 8-5-10; 8:45 am]
BILLING CODE 6560-50-S
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