[Federal Register Volume 71, Number 148 (Wednesday, August 2, 2006)]
[Rules and Regulations]
[Pages 43906-43924]
From the Federal Register Online via the Government Publishing Office [www.gpo.gov]
[FR Doc No: 06-6605]



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Part IV





Environmental Protection Agency





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40 CFR Part 180



Alachlor, Chlorothalonil, Methomyl, Metribuzin, Thiodicarb; Order 
Denying Petition To Revoke Tolerances; Final Rule

  Federal Register / Vol. 71, No. 148 / Wednesday, August 2, 2006 / 
Rules and Regulations  

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ENVIRONMENTAL PROTECTION AGENCY

40 CFR Part 180

[EPA-HQ-OPP-2005-0050; FRL-8079-8]


Alachlor, Chlorothalonil, Methomyl, Metribuzin, Thiodicarb; Order 
Denying Petition To Revoke Tolerances

AGENCY: Environmental Protection Agency (EPA).

ACTION: Order.

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SUMMARY: In this Order, EPA denies, in part, a petition requesting the 
modification or revocation of the pesticide tolerances for alachlor, 
chlorothalonil, methomyl, metribuzin, and thiodicarb established under 
section 408 of the Federal Food, Drug, and Cosmetic Act (``FFDCA''). 
The petition was filed on December 17, 2004, by the States of New York, 
California, and Connecticut, and the Commonwealth of Massachusetts 
(``the States''). In their petition, the States contend that the risks 
posed by these pesticide tolerances must be assessed utilizing the 
additional tenfold (10X) safety factor for the protection of infants 
and children and that once this additional factor is included the 
challenged tolerances no longer meet the safety standard under FFDCA 
section 408. EPA is denying the petition to modify or revoke as to the 
tolerances for the pesticides alachlor, chlorothalonil, and metribuzin. 
EPA is deferring action on the petition as regards the tolerances for 
methomyl and thiodicarb given the ongoing Agency proceedings to address 
the safety of these pesticides.

DATES: This Order is effective August 2, 2006. Objections and requests 
for hearings must be received on or before October 2, 2006, 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-2005-0050. All documents in the 
docket are listed in the index for the docket. Although listed in the 
index, some information is not publicly available, i.e., CBI or other 
information whose disclosure is restricted by statute. Certain other 
material, such as copyrighted material, is not placed on the Internet 
and will be publicly available only in hard copy form. Publicly 
available docket materials are available in the electronic docket at 
http://www.regulations.gov, or, if only available in hard copy, at the 
OPP Public Docket, in Rm. S-4400, One Potomac Yard (South Building), 
2777 S. Crystal Drive, Arlington, VA. This docket facility is open from 
8:30 a.m. to 4 p.m., Monday through Friday, excluding legal holidays. 
The docket telephone number is (703) 305-5805.

FOR FURTHER INFORMATION CONTACT: Terria Northern, Special Review and 
Reregistration Division, (7508P), Office of Pesticide Programs, 
Environmental Protection Agency, 1200 Pennsylvania Ave., NW., 
Washington, DC 20460-0001; telephone number: 703-305-7093; fax number: 
703-308-7070; e-mail address: [email protected].

SUPPLEMENTARY INFORMATION:

I. General Information

A. Does this Action Apply to Me?

    You may be potentially affected by this action if you are an 
agricultural producer, food manufacturer, or pesticide manufacturer. 
Potentially affected entities may include, but are not limited to:
     Crop production (NAICS code 111)
     Animal production (NAICS code 112)
     Food manufacturing (NAICS code 311)
     Pesticide manufacturing (NAICS code 32532)
    This listing is not intended to be exhaustive, but rather provides 
a guide for readers regarding entities likely to be affected by this 
action. Other types of entities not listed in this unit could also be 
affected. The North American Industrial Classification System (NAICS) 
codes have been provided to assist you and others in determining 
whether this action might apply to certain entities. To determine 
whether you or your business may be affected by this action, you should 
carefully examine the applicability provisions in [insert appropriate 
cite to either another unit in the preamble or a section in a rule]. If 
you have any questions regarding the applicability of this action to a 
particular entity, consult the person listed under.

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 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 the FFDCA, as amended by the FQPA, any 
person may file an objection to any aspect of this regulation and may 
also request a hearing on those objections. The EPA procedural 
regulations which govern the submission of objections and requests for 
hearings appear in 40 CFR part 178. You must file your objection 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-2006-0050 in the 
subject line on the first page of your submission. All requests must be 
in writing, and must be mailed or delivered to the Hearing Clerk on or 
before October 2, 2006.
    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 your copies, identified by docket ID 
number EPA-HQ-OPP-2006-0050, 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 
Building), 2777 S. Crystal Drive, Arlington, VA. Deliveries are only 
accepted during the Docket'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 telephone number is (703) 305-5805.

II. Introduction

A. What Action Is the Agency Taking?

    In this Order, EPA denies, in part, a petition requesting the 
modification or revocation of the pesticide tolerances for alachlor, 
chlorothalonil, methomyl, metribuzin, and thiodicarb established under 
section 408 of the FFDCA. The petition was filed on December 17,

[[Page 43907]]

2004, by the States of New York, California, and Connecticut, and the 
Commonwealth of Massachusetts (``the States'') (Ref. 1). In their 
petition, the States contend that EPA is lacking data for each of the 
five pesticides on developmental neurotoxicity, endocrine effects, and/
or cumulative effects of exposure to pesticides with a common mechanism 
of toxicity. The States argue that this lack of these data mandates 
that EPA retain the additional tenfold (10X) safety factor for the 
protection of infants and children. The States further allege that once 
the 10X safety factor is retained, the challenged tolerances no longer 
meet the safety standard under FFDCA section 408 and must be modified 
or revoked.
    In today's Order, EPA is denying the petition to modify or revoke 
as to the tolerances for the pesticides alachlor, chlorothalonil, and 
metribuzin. As to alachlor and metribuzin, EPA is denying the petition 
because the tolerances for these pesticides would continue to meet the 
safety standard even if the additional 10X safety factor sought by the 
States is applied. For chlorothalonil, EPA has determined, after 
reviewing the legal and factual contentions of the States, that there 
is reliable data showing that the additional 10X safety factor is not 
needed to protect the safety of infants and children. EPA is deferring 
action on the petition as regards the tolerances for methomyl and 
thiodicarb given the ongoing Agency proceedings to address the safety 
of these pesticides.

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

    Under section 408(d)(4) of the FFDCA, EPA is authorized to respond 
to a section 408(d) petition to revoke tolerances either by issuing a 
final rule revoking the tolerances, issuing a proposed rule, or issuing 
an order denying the petition.

III. Statutory and Regulatory Background

A. Statutory Background

    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. 
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, additional 
protections for infants and children, and the estrogenic substances 
screening program.
    EPA also regulates pesticides under the Federal Insecticide, 
Fungicide, and Rodenticide Act (``FIFRA''), (7 U.S.C. 136 et seq). 
While the FFDCA authorizes the establishment of legal limits for 
pesticide residues in food, FIFRA requires the approval of pesticides 
prior to their sale and distribution, (7 U.S.C. 136a(a)), and 
establishes a registration regime for regulating the use of pesticides. 
FIFRA regulates pesticide use in conjunction with its registration 
scheme by requiring EPA review and approval of pesticide labels and 
specifying that use of a pesticide inconsistent with its label is a 
violation of Federal law. (7 U.S.C. 136j(a)(2)(G)). In the FQPA, 
Congress integrated action under the two statutes by requiring that the 
safety standard under the FFDCA be used as a criterion in FIFRA 
registration actions as to pesticide uses which result in dietary risk 
from residues in or on food, (7 U.S.C. 136(bb)), and directing that EPA 
coordinate, to the extent practicable, revocations of tolerances with 
pesticide cancellations under FIFRA. (21 U.S.C. 346a(l)(1)).
    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)). Section 
408(b)(2)(D) directs EPA, in making a safety determination, to:
     consider, among other relevant factors- . . . .
     (v) available information concerning the cumulative effects of 
such residues and other substances that have a common mechanism of 
toxicity; . . .
     (vi) available information concerning the aggregate exposure 
levels of consumers (and major identifiable subgroups of consumers) 
to the pesticide chemical residue and to other related substances, 
including dietary exposure under the tolerance and all other 
tolerances in effect for the pesticide chemical residue, and 
exposure from other non-occupational sources.
     (viii) such information as the Administrator may require on 
whether the pesticide chemical may have an effect in humans that is 
similar to an effect produced by a naturally occurring estrogen or 
other endocrine effects. . . .
(21 U.S.C. 346a(b)(2)(D)(v), (vi) and (viii)).
    Section 408(b)(2)(C) requires EPA to give special consideration to 
risks posed to infants and children. Specifically, this provision 
states that EPA:
     shall assess the risk of the pesticide chemical based on-- . . 
.
     (II) available information concerning the special 
susceptibility of infants and children to the pesticide chemical 
residues, including neurological differences between infants and 
children and adults, and effects of in utero exposure to pesticide 
chemicals; and
     (III) available information concerning the cumulative effects 
on infants and children of such residues and other substances that 
have a common mechanism of toxicity. . . .
(21 U.S.C. 346a(b)(2)(C)(i)(II) and (III)).
This provision further 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 Order as 
the ``children's safety factor.'']
    3. Procedures for establishing, amending, or revoking tolerances. 
Tolerances are established, amended, or revoked by rulemaking under the 
unique procedural framework set forth in the FFDCA. Generally, the 
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 
either establishing, amending, or revoking the tolerance or denying the 
petition, any affected party has 60 days to file objections with EPA 
and seek an evidentiary hearing on those objections. (21 U.S.C. 
346a(g)(2)). EPA's final order on the objections is subject to judicial 
review. (21 U.S.C. 346a(h)(1)).
    4. Estrogenic Substances Screening Program. Section 408(p) of the 
FFDCA

[[Page 43908]]

creates the estrogenic substances screening program. This provision 
gives EPA 2 years from enactment of the FQPA to ``develop a screening 
program . . . to determine whether certain substances may have an 
effect in humans that is similar to an effect produced by a naturally 
occurring estrogen, or such other endocrine effect as the Administrator 
may designate.'' This screening program must use ``appropriate 
validated test systems and scientifically relevant information.'' (21 
U.S.C. 346a(p)(1)). Once the program is developed, EPA is required to 
take public comment and seek independent scientific review of it. 
Following the period for public comment and scientific review, and not 
later than 3 years following enactment of the FQPA, EPA is directed to 
``implement the program.'' (21 U.S.C. 346a(p)(2)).
    The scope of the estrogenic screening program was expanded by an 
amendment to the Safe Drinking Water Act (SDWA) passed 
contemporaneously with FQPA. That amendment gave EPA the authority to 
provide for the testing, under the FQPA estrogenic screening program, 
``of any other substance that may be found in sources of drinking water 
if the Administrator determines that a substantial population may be 
exposed to such substance.'' (42 U.S.C. 300j-17).

B. Setting and Reassessing Pesticide Tolerances Under the FFDCA

    1. In general. The process EPA follows in setting and reassessing 
tolerances under the FFDCA includes two steps. First, EPA determines an 
appropriate residue level value for the tolerance taking into account 
data on levels that can be expected in food. Second, EPA evaluates the 
safety of the tolerance relying on toxicity and exposure data and 
guided by the statutory definition of ``safety'' and requirements 
concerning risk assessment. Only on completion of the second step can a 
tolerance be established or reassessed. This bifurcation between 
selection of a tolerance level and evaluation of the safety of a 
tolerance has ramifications on how EPA responds when a tolerance is 
found to no longer meet section 408's safety standard. Generally, if an 
existing tolerance is shown to raise safety concerns, EPA would not 
address these concerns by modifying the tolerance through decreasing 
the tolerance level unless there were pesticide residue data showing 
how such a lower level could be achieved. Rather, where safety concerns 
are demonstrated and there is no available data demonstrating that a 
different application pattern would produce lower residue levels in 
food, the only appropriate action would be to revoke the tolerance. 
Below, EPA explains in detail, the reasons for this approach.
    2. Choosing a tolerance value. In the first step of the tolerance 
setting or reassessment process (choosing a tolerance value), EPA 
evaluates data from experimental crop field trials in which the 
pesticide has been used in a manner, consistent with the draft FIFRA 
label, that is likely to produce the highest residue in the crop in 
question (e.g., maximum application rate, maximum number of 
applications, minimum pre-harvest interval between last pesticide 
application and harvest). (Refs. 2 and 3). These crop field trials are 
generally conducted in several fields at several geographical 
locations. (Ref. Id. at 5, 7 and Tables 1 and 5). Several samples are 
then gathered from each field and analyzed. (Id. at 53). Generally, the 
results from such field trials show that the residue levels for a given 
pesticide use will vary from as low as non-detectable to measurable 
values in the parts per million (ppm) range with the majority of the 
values falling at the lower part of the range. EPA then chooses a value 
to be used in the tolerance by identifying the highest residue value 
found and rounding that value up or adding a small increment to it. 
(See 70 FR 46706, 46731, August 10, 2005). (As discussed below, the 
safety of the tolerance value chosen is separately evaluated.).
    There are three main reasons for closely linking tolerance values 
to the maximum value that could be present from maximum label usage of 
the pesticide. First, EPA believes it is important to coordinate its 
actions under the two statutory frameworks governing pesticides. (See 
The Pesticide Coordination Policy; Response to Petitions, (61 FR 2378, 
2379; January 25, 1996)). It would be illogical for EPA to set a 
pesticide tolerance under the FFDCA without considering what action is 
being taken under FIFRA with regard to registration of that pesticide 
use. (Cf. 40 CFR 152.112(g) (requiring all necessary tolerances to be 
in place before a FIFRA registration may be granted)). In coordinating 
its actions, one basic tenet that EPA follows is that a grower who 
applies a pesticide consistent with the FIFRA label directions should 
not run the risk that his or her crops will be adulterated under the 
FFDCA because the residues from that legal application exceed the 
tolerance associated with that use. Crop field trials require 
application of the pesticide in the manner most likely to produce 
maximum residues to further this goal. Second, choosing tolerance 
values based on FIFRA label rates helps to ensure that tolerance levels 
are established no higher than necessary. If tolerance values were 
selected solely in consideration of health risks, in some 
circumstances, tolerance values might be set so as to allow much 
greater application rates than necessary for effective use of the 
pesticide. This could encourage misuse of the pesticide. Finally, 
closely linking tolerance values to FIFRA labels helps EPA to police 
compliance with label directions by growers because detection of an 
overtolerance residue is indicative of use of a pesticide at levels, or 
in a manner, not permitted on the label.
    3. The safety determination - risk assessment. Once a tolerance 
value is chosen, EPA then evaluates the safety of the pesticide 
tolerance using the process of risk assessment. To assess risk of a 
pesticide, EPA combines information on pesticide toxicity with 
information regarding the route, magnitude, and duration of exposure to 
the pesticide.
    In evaluating toxicity or hazard, EPA examines both short-term 
(e.g., ``acute'') and longer-term (e.g., ``chronic'') adverse effects 
from pesticide exposure. (Ref. 2 at 8-10). EPA also considers whether 
the ``effect'' has a threshold - a level below which exposure has no 
appreciable chance of causing the adverse 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 8-9). Not all carcinogens, however, 
pose a risk at any exposure level (i.e., ``a non-threshold effect or 
risk''). Advances in the understanding of carcinogenesis have 
increasingly led EPA to conclude that some pesticides that cause 
carcinogenic effects only cause such effects above a certain threshold 
of exposure. EPA has traditionally considered adverse effects on the 
endocrine system to be a threshold effect; that determination is being 
reexamined in conjunction with the endocrine disruptor screening 
program.
    Once the hazard for a durational scenario is identified, EPA must 
determine the toxicological level of concern and then compare estimated 
human exposure to this level of concern. This comparison is done 
through either calculating a safe dose in humans (incorporating all 
appropriate safety factors) and expressing exposure as a percentage of 
this safe dose (the reference dose (``RfD'') approach) or dividing 
estimated human exposure into

[[Page 43909]]

an appropriate dose from the relevant studies at which no adverse 
effects from the pesticide are seen (the margin of exposure (``MOE'') 
approach). How EPA determines the level of concern and assesses risk 
under these two approaches is explained in more detail below. EPA's 
general approach to estimating exposure is also briefly discussed.
    a. Levels of concern and risk assessment--(i) threshold effects. In 
assessing the risk from a pesticide's threshold effects, EPA evaluates 
an array of toxicological 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 affect levels (``NOAEL''). Generally, EPA will use the 
lowest NOAEL from the available studies as a starting point in 
estimating the level of concern for humans. In estimating and 
describing the level of concern, however, the chosen NOAEL is at times 
manipulated differently depending on whether the risk assessment 
addresses dietary or non-dietary exposures.
    For dietary risks, EPA uses the chosen NOAEL to calculate a safe 
dose or RfD. The RfD is calculated by dividing the chosen NOAEL by all 
applicable safety or uncertainty factors. Typically, a combination of 
safety or uncertainty factors providing a hundredfold (100X) margin of 
safety is used: 10X to account for uncertainties inherent in the 
extrapolation from laboratory animal data to humans and 10X for 
variations in sensitivity among members of the human population as well 
as other unknowns. Further, 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.
    To quantitatively describe risk using the RfD approach, estimated 
exposure is expressed as a percentage of the RfD. Dietary exposures 
lower than 100 percent of the RfD are generally not of concern. Further 
complicating matters, EPA's Office of Pesticide Programs, in 
implementing FFDCA section 408, 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 assessment. (Ref. 4 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. For simplicity, this document refers to all safe dose 
calculations as RfDs. Today, RfDs are generally calculated for both 
acute and chronic dietary risks although traditionally a RfD was only 
calculated for chronic dietary risks.
    For non-dietary, and often for combined dietary and non-dietary, 
risk assessments of threshold effects, the toxicological level of 
concern is not expressed as a safe dose or RfD but rather as the margin 
of exposure (MOE) that is necessary to be sure that exposure to a 
pesticide is safe. A safe MOE is generally considered to be a margin at 
least as high as the product of all applicable safety factors for a 
pesticide. For example, if a pesticide needs a 10X factor to account 
for interspecies differences, 10X factor for intraspecies differences, 
and 10X factor for FQPA, the safe or target MOE would be a MOE of at 
least 1,000. To calculate the MOE for a pesticide, human exposure to 
the pesticide is divided into the lowest NOAEL from the available 
studies. In contrast to the RfD approach, the higher the MOE, the safer 
the pesticide. Accordingly, if the level of concern for a pesticide is 
1,000, MOE's exceeding 1,000 would generally not be of concern. Like 
RfDs, specific MOEs are calculated for exposures of different 
durations. For non-dietary exposures, EPA typically examines short-
term, intermediate-term, and long-term exposures. Additionally, non-
dietary exposure often involves exposures by various routes including 
dermal, inhalation, and oral.
    The RfD and MOE approaches are fundamentally equivalent. For a 
given risk and given exposure of a pesticide, if the pesticide were 
found to be safe under a RfD analysis it would also pass under the MOE 
approach, and vice-versa.
    (ii) Non-threshold effects. For risk assessments for non-threshold 
effects, EPA does not use the RfD or MOE approach. Rather, EPA 
calculates the slope of the dose-response curve for the non-threshold 
effects from relevant studies using a model that assumes that any 
amount of exposure will lead to some degree of risk. The slope of the 
dose-response curve can then be used to estimate the probability of 
occurrence of additional adverse effects as a result of exposure to the 
pesticide. For non-threshold cancer risks, EPA generally is concerned 
if the probability of increased cancer cases exceed the range of 1 in 1 
million. Because the States' petition concerns the children's safety 
factor and the children's safety factor is only applicable to threshold 
risks, no further discussion of non-threshold risk assessment is 
included here.
    b. Estimating human exposure. Equally important to the risk 
assessment process as determining the toxicological level of concern 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)). The focus of the States' petition, 
however, appears to be on pesticide 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 
U.S. Department of Agriculture. (Ref. 2 at 12). Information on residue 
values comes from a range of sources including crop field trials, data 
on pesticide reduction due to processing 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, conducts its exposure assessment using the worst case 
assumptions that 100 percent of the crop in question is treated with 
the pesticide and 100 percent of the food from that crop contains 
pesticide residues at the tolerance level. (Id. at 11). When such an 
assessment shows no risks of concern, EPA's resources are conserved 
because a more complex risk assessment is avoided and regulated parties 
are spared the cost of any additional studies that may be needed. If, 
however, a first tier 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.''
    Use of percent crop treated data and anticipated residue 
information is appropriate because EPA's worst case assumptions of 100 
percent treatment and residues at tolerance value significantly 
overstate residue values. There are several reasons this is true.

[[Page 43910]]

 First, all growers of a particular crop would rarely choose to apply 
the same pesticide to that crop; generally, the proportion of the crop 
treated with a particular pesticide is significantly below 100 percent. 
Second, as discussed above, the tolerance value is set above the 
highest value observed in crop field trials using maximum use rates. 
There may be some commodities from a treated crop that approach the 
tolerance value where the maximum label rates are followed, but most 
generally fall significantly below. If less than the maximum legal rate 
is applied, residues will be even lower. Third, residue values in the 
field do not take into account the lowering of residue values that 
frequently occurs as a result of degradation over time and through food 
processing and cooking.
    EPA uses several techniques to refine residue value estimates. (Id. 
at 17-28). First, where appropriate, EPA will take into account all the 
residue values reported in the crop field trials, either through use of 
an average or individually. Second, EPA will consider data showing what 
portion of the crop is not treated with the pesticide. Third, data can 
be produced showing pesticide degradation and decline over time, and 
the effect of commercial and consumer food handling and processing 
practices. Finally, EPA can consult monitoring data gathered by the 
Food and Drug Administration, the U.S. Department of Agriculture, or 
pesticide registrants, on pesticide levels in food at points in the 
food distribution chain distant from the farm, including retail food 
establishments.
    Another critical component of the exposure assessment is how data 
on consumption patterns are combined with data on pesticide residue 
levels in food. Traditionally, EPA has calculated exposure by simply 
multiplying high-end consumption by average residue values for 
estimating chronic risks and high-end consumption by maximum residue 
values for estimating acute risks. Although using average residues is a 
realistic approach for chronic risk assessment due to the fact that 
variations in residue levels and consumption amounts average out over 
time, using maximum residue values for acute risk assessment tends to 
greatly overstate exposure in narrow increments of time where it 
matters how much of each treated food a given consumer eats and what 
the residue levels are in the particular foods consumed. To take into 
account the variations in short-term consumption patterns and food 
residue values for acute risk assessments, EPA has more recently begun 
using probabilistic modeling techniques for estimating exposure when 
more simplistic models appear to show risks of concerns.
    All of these refinements to the exposure assessment process, from 
use of food monitoring data through probabilistic modeling, can have 
dramatic effects on the level of exposure predicted, reducing worst 
case estimates by 1 or 2 orders of magnitude or more.

C. 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 traditional 10X safety factors to account for 
differences between animals and humans when relying on studies in 
animals (inter-species safety factor) and differences among humans 
(intra-species safety factor) as well as the additional 10X children's 
safety factor added by the FQPA.
    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. 4 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 
mentioned 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). EPA's implementation of the safety factor provision is 
explained in greater detail in Unit VII.D.1.c.

D. Endocrine Disruptor Screening Program

    To aid in the design of the endocrine screening program called for 
in the FQPA and SDWA amendments, EPA created the Endocrine Disruptor 
Screening and Testing Advisory Committee (EDSTAC), which was comprised 
of members representing the commercial chemical and pesticides 
industries, Federal and State agencies, worker protection and labor 
organizations, environmental and public health groups, and research 
scientists. (63 FR 71542, 71544, Dec. 28, 1998). The EDSTAC presented a 
comprehensive report in August 1998 addressing both the scope and 
elements of the endocrine screening program. (Ref. 5). The EDSTAC's 
recommendations were largely adopted by EPA.
    As recommended by EDSTAC, EPA expanded the scope of the program 
from focusing only on estrogenic effects to include androgenic and 
thyroid effects as well. (63 FR at 71545). Further, EPA, again on the 
EDSTAC's recommendation, chose to include both human and ecological 
effects in the program. (Id.). Finally, based on EDSTAC's 
recommendation, EPA established the universe of chemicals to be 
screened to include not just pesticides but some 87,000 chemical 
substances and common mixtures. (Id.). As to the program elements, EPA 
adopted EDSTAC's recommended two-tier approach with the first tier 
involving screening ``to identify substances that have the potential to 
interact with the endocrine system'' and the second tier involving 
testing ``to determine whether the substance causes adverse effects, 
identify the adverse effects caused by the substance, and establish a 
quantitative relationship between the dose and the adverse effect.'' 
(Id.). Tier 1 screening is limited to evaluating whether a substance is 
``capable of interacting with'' the endocrine system, and is ``not 
sufficient to determine whether a chemical substance may have an effect 
in humans that is similar to an effect produced by naturally occurring 
hormones.'' (Id. at 71550). Based on the results of Tier 1 screening, 
EPA will decide whether Tier 2 testing is needed. Importantly, ``[t]he 
outcome of Tier 2 is designed to be conclusive in relation to the 
outcome of Tier 1 and any other prior information. Thus, a negative 
outcome in Tier 2 will supersede a positive outcome in Tier 1.'' (Id. 
at 71554-71555).
    The EDSTAC provided detailed recommendations for Tier 1 screening 
and Tier 2 testing. The panel of the EDSTAC that devised these 
recommendations was comprised of distinguished scientists from 
academia, government, industry, and the environmental community. (Ref. 
5, Appendix B). As suggested by the EDSTAC, EPA has proposed a battery 
of short-term in vitro and in vivo assays for the Tier 1 screening 
exercise. (63 FR at 71550-71551). Validation of these assays, however, 
has proved difficult and, more than 7 years after proposing the assays, 
validation of all of the assays in the battery is not yet complete. As 
to Tier 2 testing, EPA, on the recommendation of the EDSTAC, has

[[Page 43911]]

proposed using five longer-term reproduction studies that, with one 
exception, ``are routinely performed for pesticides with widespread 
outdoor exposures that are expected to affect reproduction.'' (Id. at 
71555). EPA is examining, pursuant to the suggestion of the EDSTAC, 
modifications to these studies to enhance their ability to detect 
endocrine effects.

E. Lawsuit Seeking the Revocation of Tolerances

    In 2003, the States of New York, New Jersey, Connecticut, and 
Massachusetts, filed suit against EPA seeking the revocation of the 
same pesticide tolerances challenged in this petition. The lawsuit, 
containing allegations nearly identical to those in this petition, 
argued that EPA's tolerance reassessment decisions as to alachlor, 
chlorothalonil, methomyl, metribuzin, and thiodicarb were in violation 
of FFDCA section 408. In 2004, this lawsuit was dismissed because the 
plaintiffs had not first presented their challenge to these tolerances 
to EPA in the form of section 408(d)(4) petition to revoke. (New York 
v. EPA, 350 F. Supp. 429 (S.D.N.Y. 2004)). The current petition was 
subsequently filed with EPA.

IV. The Challenged Tolerances

A. Alachlor

    Alachlor is a selective herbicide used in agriculture for the 
control of broadleaf weeds and grasses. Alachlor is registered under 
FIFRA for use on corn, soybeans, sorghum, peanuts, and beans and 37 
FFDCA tolerances are currently associated with those uses. (40 CFR 
180.249).
    In December 1998, EPA released a RED for alachlor finding it 
eligible for reregistration. (Ref. 6). The RED also reassessed 
alachlor's tolerances concluding that 22 met the requirements of 
section 408 but that 16 would have to be revised or revoked. (Id. at 
184-187; Ref. 7). (The current number of tolerances for alachlor and 
the other five pesticides may not match the number of reassessed 
tolerances due to subsequent actions to establish or revoke tolerances 
as well as to a generic administrative action amending tolerance 
nomenclature. (68 FR 39428, July 1, 2003)). The RED found that alachlor 
posed chronic and cancer risks as a result of dietary exposure but not 
any acute risk. The RfD, or safe dose, for chronic exposure was based 
on a chronic dog study in which hemosiderosis and hemolytic anemia were 
observed. (Ref. 6 at 39). Cancer studies revealed that alachlor caused 
nasal, gastric, and thyroid tumors in the rat. A chronic dietary risk 
assessment found that exposure to alachlor from food and drinking water 
posed minimal risks. The subgroup facing the highest risk from food is 
non-nursing infants < 1 year at 0.5 percent of the RfD. (Id. at 85). 
For drinking water, the highest risk is posed to children 1-6 years at 
2 percent of the RfD. (Id. at 87). The highest aggregate risk was 4 
percent of the RfD for children 1-6 years. (Id. at 91). Cancer risks 
were found to be negligible. (Id. at 91-94). These risk assessments 
were based on moderately conservative exposure assumptions that relied 
on crop field trial data and information of the percentage of the crop 
treated with alachlor for some crops. (Id. at 83-84).
    EPA removed the 10X children's safety factor based on its 
determination that (1) The toxicology database was complete; (2) the 
toxicology data showed no evidence of neurotoxicity and thus there was 
no need for a developmental neurotoxicity study for alachlor; (3) the 
toxicology data showed no evidence of increased susceptibility in the 
young; and (4) the exposure estimate was unlikely to understate 
exposure to infants and children. (Id. at 50). In the RED, EPA noted 
that alachlor is structurally similar to other chloroacetanilide 
pesticides (acetochlor, butachlor, propachlor, and metolachlor) and may 
share a common mechanism of toxicity with some or all of these 
pesticides. (Id. at 112). EPA indicated that no determination on this 
issue had been made at that time. (Id.). Subsequently, EPA did conclude 
that alachlor, acetochlor and butachlor share a common mechanism of 
toxicity with respect to the causation of nasal turbinate tumors. (Ref. 
8). EPA has also now completed a cumulative cancer risk assessment for 
these pesticides that shows no risk of concern. (Ref. 9). Finally, the 
RED indicated that alachlor does have effects on the endocrine system 
in that it disrupts the hormone balance leading to the formation of 
thyroid tumors. (Ref. 6 at 31). Subsequently, EPA determined that these 
endocrine effects only occurred at high doses which were well above any 
exposure levels humans would face from pesticidal uses of alachlor. 
(Ref. 8).

B. Chlorothalonil

    Chlorothalonil is a broad spectrum, non-systemic protectant 
pesticide mainly used as a fungicide to control fungal foliar diseases 
of vegetable, field, and ornamental crops. In connection with these 
uses there are 66 FFDCA tolerances currently established for 
chlorothalonil. (40 CFR 180.275).
    In April 1999, EPA released a RED for chlorothalonil finding it 
eligible for reregistration so long as various uses were prohibited and 
numerous risk mitigation steps were taken. (Ref. 10 at v-vi). The RED 
also reassessed chlorothalonil's tolerances concluding that all met the 
requirements of section 408 except one that would have to be raised. 
Further, an additional tolerance was found to be necessary in 
connection with one use site. (Id. at 171-174; Ref. 7 at 58-59). The 
RED found that chlorothalonil posed acute, chronic and cancer risks as 
a result of dietary exposure. The RfD, or safe dose, for chronic 
exposure was based on a chronic rat study in which increased kidney 
weights and hyperplasia were observed. (Ref. 10 at 21). EPA evaluated 
acute risk based on the LOAEL from a subchronic rat study showing 
lesions and hyperplasia. (66 FR 56233, 56235, Nov. 7, 2001). Because no 
NOAEL was identified in this study EPA added an extra 3X safety factor. 
(Ref. 10 at 23). Cancer studies revealed that chlorothalonil caused 
renal adenomas and carcinomas in the rat and mouse. An aggregate 
chronic dietary risk assessment found that exposure to chlorothalonil 
from food and drinking water would utilize 68 percent of the RfD for 
children 1-6, the most highly-exposed subgroup. (Id. at 100). EPA 
concluded that there was a MOE of 310 for adults (the highest exposed 
subgroup) with regard to aggregate acute risk. (Id.). The target or 
safe MOE was 300. Cancer risks were found to be negligible. (Id. at 
161-162). The acute and cancer risk assessments were based on 
relatively refined exposure assumptions including percent crop treated 
data on most crops and anticipated residue data based on field trial 
data or food monitoring data. The chronic risk assessment was more 
conservative in that it only relied upon percent crop treated 
information. (Id. at 36-41).
    Other than retaining an additional 3X safety factor as to acute 
risks, EPA removed the 10X children's safety factor for chlorothalonil 
based on its determination that (1) the toxicology database was 
complete; (2) the toxicology data showed no evidence of increased 
susceptibility in the young; and (3) the exposure estimate was unlikely 
to understate exposure to infants and children. (Id. at 170; 66 FR at 
56242). In the RED, EPA noted that chlorothalonil is a member of the 
polychlorinated fungicide class of pesticides which includes 
hexachlorobenzene, pentachlorophenol, and pentachloronitrobenzene. 
(Ref. 10 at

[[Page 43912]]

100). EPA indicated that no determination on the issue of common 
mechanism of toxicity had been made at that time. (Id.).

C. Methomyl

    Methomyl is an insecticide registered on a wide variety of sites 
including field, vegetable, and orchard crops; turf (sod farms only); 
livestock quarters; commercial premises; and refuse containers. There 
are 78 FFDCA tolerances currently associated with these uses. (40 CFR 
180.253).
    In December 1998, EPA released a RED for methomyl finding it 
eligible for reregistration. (Ref. 11). The RED also reassessed 
methomyl's tolerances concluding that 65 met the requirements of 
section 408 but that 15 would have to be revised or revoked. (Id. at 
103-111; Ref. 7 at 175-176). The RED found that methomyl posed chronic 
and acute risks as a result of dietary exposure. The RfD, or safe dose, 
for chronic exposure was based on a chronic dog study in which 
histopathological effects in the kidney were observed. (Ref. 11 at 24). 
EPA evaluated acute risk based on a rabbit developmental study that 
showed deaths in the dams on days 1-3 after dosing. (Id. at 25). 
Aggregate risks from methomyl were assessed taking into account that 
another pesticide, thiodicarb, degrades into methomyl and thus serves 
as another source of exposure to the compound. A chronic dietary risk 
assessment found that exposure to methomyl from food utilized no 
greater than 7 percent of the RfD for any subgroup. (Id. at 35). EPA 
concluded that there was a MOE of 417 for children 1-6 years (the 
highest exposed subgroup) with regard to acute risk from residues in 
food. (Id. at 37). Exposure to methomyl in drinking water was not 
expected to make either of these risk estimates exceed the level of 
concern. (Id. at 38). These risk assessments were based on moderately 
conservative exposure assumptions that relied on crop field trial data 
and information of the percentage of the crop treated with methomyl. 
(Id. at 35-36).
    EPA reduced the 10X children's safety factor to 3X for methomyl. 
Although the data provided no indication of increased sensitivity of 
rats or rabbits to in utero or postnatal exposure to methomyl, there 
were data gaps for acute and subchronic neurotoxicity studies. (Id. at 
24). In the RED, EPA indicated that no determination as to whether 
methomyl shared a common mechanism of toxicity with other substances 
had been made at that time. (Id. at 55-56). Subsequently, EPA did 
conclude that methomyl shares a common mechanism of toxicity with other 
N-methyl carbamate pesticides. (Ref. 8). EPA is re-examining the safety 
finding it made for methomyl in light of this conclusion. EPA has 
completed a preliminary cumulative risk assessment for the N-methyl 
carbamates. EPA expects to finish this cumulative risk assessment and 
make a safety determination as to all of the N-methyl carbamates in the 
near future.

D. Metribuzin

    Metribuzin is a herbicide used on a wide range of sites, including 
vegetable and field crops, turf grasses (recreational areas), and non-
crop areas, to selectively control certain broadleaf weeds and grassy 
weed species. In connection with these uses there are 61 FFDCA 
tolerances currently established for metribuzin (40 CFR 180.332).
    In February 1999, EPA released a RED for metribuzin finding it 
eligible for reregistration based on various risk mitigation steps 
proposed by the registrant. (Ref. 12 at iv). The RED also reassessed 
metribuzin's tolerances concluding that 22 met the requirements of 
section 408 but that 38 would have to be revised or revoked. (Id. at 
101-107; Ref. 7 at 187-188). The RED found that metribuzin posed acute 
and chronic risks as a result of dietary exposure. The RfD, or safe 
dose, for chronic exposure was based on a chronic rat study which 
showed increased thyroid weight, decreased lung weight, and increases 
of certain enzyme levels in blood. (Ref. 12 at 16). EPA evaluated acute 
risk based on the NOAEL from a developmental rabbit study showing 
decreased fetal body weight, increased number of runts, and increased 
incidence of extra and partial ribs. (Id. at 17). An aggregate chronic 
dietary risk assessment found that exposure to metribuzin from food and 
drinking water would utilize 79 percent of the RfD for children 1-6, 
the most highly-exposed subgroup. (Id. at 54). EPA concluded that there 
was a MOE of 1,200 for females 13-50 years (the highest exposed 
subgroup) with regard to aggregate acute risk. (Id. at 52). These risk 
assessments were based on the extremely conservative exposure 
assumptions that all commodities covered by the tolerances were treated 
with metribuzin and the residue levels were at the tolerance level. 
(Id. at 39-40).
    EPA removed the 10X children's safety factor for metribuzin based 
on its determination that the toxicology database was complete and it 
showed no evidence of increased susceptibility in the young. (Id. at 
51). In the RED, EPA indicated that no determination as to whether 
metribuzin shared a common mechanism of toxicity with other substances 
had been made at that time. (Id. at 55-56).

E. Thiodicarb

    Thiodicarb is an insecticide used primarily on cotton, sweet corn, 
and soybeans. It is also registered for use on leafy vegetables, cole 
crops, ornamentals, and other minor use sites. In connection with these 
uses there are nine FFDCA tolerances currently established for 
thiodicarb. (40 CFR 180.407).
    In December 1998, EPA released a RED for thiodicarb finding it 
eligible for reregistration. (Ref. 13). The RED also reassessed 
thiodicarb's tolerances concluding that 6 met the requirements of 
section 408 but that 34 would have to be revised or revoked. (Id. at at 
89-91). The RED found that thiodicarb posed chronic, acute, and cancer 
risks as a result of dietary exposure. The RfD, or safe dose, for 
chronic exposure was based on a chronic rat study in which increased 
incidence of extramedullary hemopoiesis and decreased RBC 
cholinesterase were observed. (Ref. 13 at 20). EPA evaluated acute risk 
based on a rabbit developmental study that showed decreased body weight 
and increased developmental variations in the fetuses and a rat 
developmental study that found decreased body-weight gain in the dams. 
(Id. at 16, 21). Cancer studies showed that thiodicarb caused liver 
tumors in mice and testicular tumors in rats. Aggregate risks from 
thiodicarb were assessed taking into account that thiodicarb degrades 
into methomyl, another pesticide, and thus both pesticides serve as a 
source of exposure to the compound. A chronic dietary risk assessment 
found that exposure to thiodicarb from food utilized 104 percent of the 
RfD for the most highly-exposed subgroup, children 1-6 years. Although 
the exposure for this subgroup slightly exceeded the RfD, EPA concluded 
that this exposure estimate was significantly overstated because it 
assumed all treated crops had residues at the tolerance level. (Id. at 
29). Cancer risks were found to be negligible. (Id. at 30). EPA 
concluded that there was a MOE of 1,680 for infants (the most highly-
exposed subgroup) with regard to acute risk from residues in food. (Id. 
at 31). Exposure to thiodicarb in drinking water was not expected to 
make any of these risk estimates exceed the level of concern. (Id. at 
33). The chronic risk assessment was based on very conservative 
exposure assumptions that relied on information of the percentage of 
the crop treated with thiodicarb and assumed residues were present at 
the tolerance level. (Id. at 29). The cancer

[[Page 43913]]

risk assessment and acute risk assessments used the less conservative 
approach of relying on percent crop treated data and anticipated 
residue data. (Id. at 30). Risk assessments for combined exposure to 
methomyl as a result of the use of thiodicarb and methomyl were 
identical to the risk assessments in the methomyl RED.
    EPA reduced the 10X children's safety factor to 3X for thiodicarb. 
Although the data provided no indication of increased sensitivity of 
rats or rabbits to in utero or postnatal exposure to thiodicarb, there 
were data gaps for acute and subchronic neurotoxicity studies as to 
methomyl, a thiodicarb degradate. (Id. at 19). In the RED, EPA 
indicated that no determination as to whether thiodicarb shared a 
common mechanism of toxicity with other substances had been made at 
that time. (Id. at 55-56). Subsequently, EPA did conclude that 
thiodicarb shares a common mechanism of toxicity with other N-methyl 
carbamate pesticides. (Ref. 8). EPA is re-examining the safety finding 
it made for thiodicarb in light of this conclusion. EPA has completed a 
preliminary cumulative risk assessment for the N-methyl carbamates. EPA 
expects to finish this cumulative risk assessment and make a safety 
determination as to all of the N-methyl carbamates in the near future.

V. The Petition to Modify or Revoke

    The States' petition requests that EPA modify or revoke all of the 
tolerances for alachlor, chlorothalonil, methomyl, metribuzin, and 
thiodicarb. (Ref. 1 at 1). These tolerances must be modified or 
revoked, the States assert, because they do not meet the safety 
standard in section 408 of the FFDCA. (Ref. 1 at 2). The States argue 
that the tolerances are unsafe because EPA's latest safety conclusion 
for these tolerances did not include the full 10X children's safety 
factor and, if that full 10X safety factor is included, EPA cannot make 
the required reasonable certainty of no harm determination.
    The States claim that ``as a matter of law'' the full 10X 
children's safety factor must be retained for each of these pesticides 
because of missing data concerning developmental neurotoxicity, 
endocrine effects, and/or cumulative effects of pesticides having a 
common mechanism of toxicity. It is ``legally impermissible,'' the 
States assert, if any of these data are absent for EPA to conclude that 
there are ``reliable data'' to choose an additional safety factor other 
than 10X. (Ref. 1 at 2, 5, 9, 11). As statutory support for this 
allegation, the States cite several provisions in section 408. First, 
as to developmental neurotoxicity, the States point to section 
408(b)(2)(C)'s requirement that EPA assess the risk to children based 
on ``available information concerning the special susceptibility of 
infants and children to the pesticide chemical residues, including 
neurological differences between infants and children and adults . . . 
.'' The States note that EPA has announced that it plans to require 
developmental neurotoxicity (``DNT'') studies on all pesticides that 
are neurotoxic. (Ref. 1 at 10 citing 64 FR 42945, August 6, 1999). 
Second, as to endocrine effects, the States cite both the provision in 
section 408(b)(2)(D)(vii) requiring consideration of ``such information 
as the Administrator may require on whether the pesticide chemical may 
have an effect in humans that is similar to an effect produced by a 
naturally occurring estrogen or other endocrine effects'' and the 
requirement in section 408(p) for EPA to develop and implement an 
endocrine screening program. Finally, with regard to cumulative 
effects, the States reference the provision in section 408(b)(2)(D)(v) 
requiring consideration of ``available data on the cumulative effects 
of such residues and other substances that have a common mechanism of 
toxicity,'' and the requirement in section 408(b)(2)(C) mandating that 
EPA assess the risk to children based on similar considerations.
    As to the individual pesticides, the States' allegations differ to 
some extent regarding developmental neurotoxicity data and cumulative 
effects data. The States claim that alachlor, methomyl, and thiodicarb 
are ``neurotoxin[s]'' and therefore, under EPA's own criterion, require 
a DNT study. (Ref. 1 at 14, 17, 19). No such claim is made as to 
chlorothalonil or metribuzin. As to cumulative effects, the States 
assert that for alachlor, methomyl, and thiodicarb, EPA has concluded 
that they share a common mechanism of toxicity with other substances, 
yet EPA has not assessed the risk posed by these pesticides' tolerances 
taking into account the cumulative effects from their respective common 
mechanism groups. (Ref. 1 at 13, 16-17, 19). For chlorothalonil, the 
States note that EPA has indicated that it may share a common mechanism 
with other pesticides in the same chemical class and argue that EPA has 
not determined whether in fact there is such a common mechanism. (Ref. 
1 at 15). For metribuzin, the States allege that EPA has not evaluated 
whether it shares a common mechanism with other substances. (Ref. 1 at 
18). As to endocrine effects, the States' claim is the same as to all 
five pesticides - endocrine effects data have not been submitted under 
the endocrine screening program for any of the pesticides.
    Finally, the States present the following risk assessment figures 
for the five pesticides which the States claim would, if the full 10X 
safety factor was incorporated, exceed section 408's safety standard:
     Alachlor - exposure from residues in food equals 33 
percent of the RfD for non-nursing infants, 17 percent for children 1-
6, and 12 percent for children 7-12, (Ref. 1 at 14).
     Chlorothalonil - exposure from residues in food equals 60 
percent of the RfD for non-nursing infants and children 1-6, and 32 
percent of the RfD for the U.S. population, (Ref. 1 at 15-16).
     Methomyl - exposure from residues in food equals 67 
percent of the RfD for non-nursing infants, 62 percent for children 1-
6, and 34.6 percent for the U.S. population, (Ref. 1 at 17).
     Metribuzin - exposure from food equals 62 percent of the 
RfD for non-nursing infants, 75 percent for children 1-6 and 36 percent 
for the U.S. population, (Ref. 1 at 18-19).
     Thiodicarb - exposure from food equals 43 percent of the 
RfD for non-nursing infants, 104 percent of the RfD for children 1-6, 
and 68 percent for the U.S. population, (Ref. 1 at 20).

VI. Public Comment

A. In General

    On March 9, 2005, EPA published a notice in the Federal Register 
announcing receipt of the States' petition to modify or revoke 
tolerances and requesting comments on the petition. (70 FR 11646, March 
9, 2005). The notice included a short summary of the petition and 
referenced readers to EPA's electronic docket for a full copy of the 
petition. A period of 60 days was initially allowed for comment. EPA 
received two requests to extend the comment period. Because EPA could 
not publish notice of an extension prior to expiration of the 60 days, 
EPA reopened the comment period for 30 days on May 16, 2005. The 
comment period closed on June 15, 2005. (See 70 FR 25826, May 16, 
2005). EPA received 13 comments on the petition. These comments are 
summarized below. EPA has not repeated comments in instances where they 
were made by more than one commenter.

B. Individual Comments

    1. CropLife America. CropLife America (``CLA'') is a trade 
association

[[Page 43914]]

representing members of the pesticide industry. CLA provided extensive 
comments on the petition. (Ref. 14). CLA notes that, although the 
petition only concerned five pesticides, if the arguments in the 
petition are accepted it would have a ``far broader impact'' because 
the result would be that EPA would ``almost always [have] to apply the 
tenfold safety factor'' in pesticide tolerance decisions. (Id. at 3). 
CLA contends that routinely applying the 10X safety factor across the 
board would cause ``serious market disruption'' and not allow EPA to 
distinguish between ``conventional'' and reduced-risk pesticides.
    According to CLA, the petitioners' assertion that the FQPA mandates 
an ``automatic'' retention of the 10X children's safety factor whenever 
there is a ``data gap'' is not supported by the statute or legislative 
history. (Id. at 5, 11). CLA points out that the statute does not use 
the term ``data gap'' but instead requires an additional safety factor 
to ``take into account the completeness of the data . . . .'' (Id. at 
13). Moreover, CLA argues the statute gives EPA ``broad discretion'' to 
choose a different factor. Additionally, CLA claims that the statute 
bars application of the 10X factor to a pesticide due to the absence of 
data unless the registrant has first been given an opportunity to 
conduct and submit the study. (Id. at 17). Nonetheless, CLA admits that 
the additional 10X factor ``should be imposed . . . if the already 
available data give substantive reason for concern . . . .'' (Id. at 
19).
    As to data on endocrine effects, CLA notes that section 
408(b)(2)(C) - the provision addressing the protection of infants and 
children - does not even address this issue. (Id. at 11). Further, even 
the general provisions of section 408 only require EPA to consider 
``such information as the Administrator may require'' on endocrine 
effects. CLA concludes that ``[s]ince no data requirements pertaining 
to endocrine effects have been imposed, a data base cannot be said to 
be `incomplete' because such endocrine data have not been generated.'' 
(Id. at 12). On cumulative effects, CLA asserts that the statute 
provides no data requirements; rather, EPA is directed to review 
``available data'' on the issue. Thus, CLA argues that the database 
cannot be incomplete as to cumulative effects. (Id.)
    The legislative history, CLA claims, supports its reading of the 
statute as granting EPA broad discretion in determining whether to 
apply the children's safety factor. CLA references portions of the 
National Research Council's report titled ``Pesticides in the Diets of 
Infants and Children'' and the legislative debate and reports which 
refer to the need for EPA ``consider'' an additional factor, and EPA's 
``discretion'' and ``flexibility'' in choosing the appropriate factor 
to protect children. (Id. at 5-8).
    CLA notes several examples of situations relevant to the current 
petition which demonstrate the wisdom of giving EPA discretion in 
applying the children's safety factor. CLA asserts that where there is 
no evidence that a pesticide causes neurotoxicity or developmental 
effects, the absence of a DNT study is unlikely to raise any concern 
regarding such effects. Additionally, where a cumulative assessment has 
not been performed, CLA argues there could be a number of circumstances 
where an additional 10X factor would be unnecessary because various 
exposure considerations would make any meaningful cumulation of effects 
unlikely. (Id. at 13-14).
    Finally, CLA asserts that the databases for the five pesticides 
challenged in the petition are ``data-rich'' and support EPA's decision 
on the children's safety factor for these pesticides. Specifically as 
to alachlor, CLA challenges the States' claim that alachlor is a 
neurotoxin arguing this assertion is ``utterly baseless.'' (Id. at 22).
    2. Pesticide Policy Coalition. The Pesticide Policy Coalition 
(``PPC'') is a group sponsored by organizations representing pesticide 
manufacturers, pesticide applicators, commodity groups, and food 
processors. (Ref. 15). The PPC's comments contain many of the same 
arguments presented by the CLA. Additional information is included, 
however, regarding the endocrine screening program and DNT studies.
    The PPC asserts that the States are wrong in their claim that 
tolerance reassessments ``must include an assessment of [a pesticide's] 
endocrine effects in accordance with the prescribed endocrine effects 
(EE) screening program called for by FFDCA 408(p).'' (Id. at 8). This 
claim is inconsistent with sections 408(p) and 408(q), according to the 
PPC, because section 408(p) specifies ``an August 1999 date for 
starting the EE testing and [subsection 408(r) requires] . . . that a 
third of all tolerance reassessments be completed on the exact same 
date - three years after the date of enactment of the FQPA.'' (Id. at 
8-9) (emphasis in original). The PPC notes that the tolerance 
reassessments which appear to have been the genesis of the States' 
petition ``were issued prior to that EE implementation date.'' (Id. at 
9). Additionally, the PPC asserts that, even in the absence of 
endocrine screening tests, EPA has information bearing on endocrine 
effects from its existing toxicity database. (Id. at 8).
    On DNT studies, the PPC argues that the States incorrectly assert 
that a DNT study is needed for all neurotoxic pesticides. EPA, 
according to the PPC, has now determined that in some circumstances 
other tests more appropriately address issues regarding developmental 
neuorotoxicity. (Id. at 10-11). Further, the PPC claims that DNT 
studies ``almost never affect the regulatory `bottom line,''' and this 
information should be taken into account in determining the need for 
the children's safety factor. (Id. at 11).
    3. Monsanto Company. Monsanto Company is the basic manufacturer and 
primary registrant for alachlor and its comments focused on that 
pesticide. (Ref. 16). Monsanto argues that EPA was justified in 
removing the children's safety factor for alachlor at the time of the 
alachlor RED given that the database was complete and there was no 
evidence of increased susceptibility in the young. (Id. at 3). Monsanto 
contends there is no data gap for a DNT study because EPA has not 
requested such a study for alachlor. No basis for requesting such a 
study is present, according to Monsanto, because it ``is unaware of any 
data indicating the alachlor is neurotoxic, even at lethal dose 
levels.'' (Id. at 4). Monsanto also disputes the States' assertion that 
alachlor is an endocrine disruptor. Although noting that alachlor has 
been found to cause thyroid tumors, Monsanto notes that ``significant 
increases in thyroid tumors occurred only at an excessive dose level 
that exceeded the Maximum Tolerance Dose, and occurred via a well-known 
mode of action that is generally not considered to be of concern at 
anticipated human exposure levels.'' (Id.). Monsanto submitted a report 
that discussed in more detail alachlor's potential for endocrine 
disruption. (Ref. 17). As to cumulative effects, Monsanto states that 
now that a decision on common mechanism concerning the 
chloroacetanilides has been made, it has conducted a cumulative 
assessment and the results show there is no cause for concern. (Ref. 18 
at 4). Finally, Monsanto argues that the States misstated the risks 
presented by alachlor. The figures cited by the States, Monsanto notes, 
were from a worst-case assessment by EPA. A more refined assessment by 
EPA produced significantly lower risk numbers, according to Monsanto. 
In fact, Monsanto contends given these refined risk numbers the 
alachlor tolerances would still meet the safety standard

[[Page 43915]]

even if the children's safety factor is retained. (Id. at 5).
    4. GB Biosciences Corporation. GB Biosciences is the basic 
manufacturer and primary registrant of chlorothalonil. It filed initial 
comments during the public comment period and submitted more detailed 
comments at a later date. (Ref. 18 and 19). GB Biosciences contends 
that a complete database on chlorothalonil was available to EPA at the 
time of the chlorothalonil RED and a 2001 chlorothalonil tolerance 
action. GB Biosciences states that this database indicates that further 
study of chlorothalonil through a DNT study is ``not justified.'' (Ref. 
18 at 3). According to GB Biosciences, ``chlorothalonil has been shown 
in the numerous studies submitted by several registrants, including a 
subchronic neurotoxicity study, not to have any neurotoxic potential, 
even at doses that are clearly lethal in either short or long-term 
administration.'' (Ref. 19 at 5).
    Further, GB Biosciences asserts that ``[t]he extensive database of 
mammalian and ecological toxicity studies that exists for 
chlorothalonil provides no evidence of potential to cause endocrine 
disruption.'' (Ref. 18 at 4). GB Biosciences notes that the type of 
studies needed for higher level (Tier II) endocrine screening are 
available for chlorothalonil. These studies include ``teratology 
studies performed in both rats and rabbits, and two well-conducted 2-
generation reproduction studies with endocrine endpoints evaluated.'' 
(Ref. 19 at 6). According to GB Biosciences, ``[if] this chemical were 
an endocrine disruptor, it would have been obvious from the results of 
these studies, as well as evident in the numerous subchronic and 
chronic/carcinogenicity studies performed.'' (Id.). In these studies, 
``any changes or perturbations in the hormone balance or maintenance of 
homeostasis would have been recognized, with endpoints such as tumors 
of the mammary gland, testicular or ovarian tumors or hyperplasia, 
decreased fertility or other reproductive indices in 2-generation 
reproduction studies at doses that are not toxic to the dams.'' (Id.). 
GB Biosciences asserts that the rat forestomach and kidney tumors seen 
in the chlorothalonil animal data ``are not indicative of any toxicity 
related to endocrine disruption.'' (Id.).
    Finally, GB Biosciences argues that an examination of 
chlorothalonil and other similar pesticides in its class 
(polychlorinated pesticides) reveals that chlorothalonil does not share 
a common mechanism with these pesticides. GB Biosciences claims that of 
the polychlorinated pesticides only chlorothalonil and HCB result in 
kidney tumors. A close examination of these kidney tumors, according to 
GB Biosciences, shows that chlorothalonil and HCB work through 
different mechanisms. GB Biosciences argues that any potential common 
mechanism between chlorothalonil and HCB is irrelevant in any event 
since HCB has not been used as a pesticide for many years and only 
exists as a minor contaminant now in certain products. (Ref. 18 at 5).
    5. Bayer CropScience. Bayer CropScience is the registrant for 
metribuzin and thiodicarb and its comments address both of these 
pesticides. (Ref. 20).
    a. Metribuzin. Bayer contends that EPA's decision in the metribuzin 
RED that metribuzin did not cause cumulative effects with other 
substances was supported by reliable data because metribuzin is the 
only asymmetrical triazinone pesticide registered in the United States. 
(Id. at 5). Further, Bayer argues that ``the metribuzin database 
provides very robust data on potential endocrine effects from numerous 
studies'' addressing many parameters relevant to endocrine effects. 
(Id.). Finally, Bayer notes that EPA's risk assessment for metribuzin 
in the metribuzin RED was a worst-case assessment and asserts that a 
more refined assessment ``would result in an exposure well below EPA's 
level of concern even if an additional tenfold factor were applied.'' 
(Id.).
    b. Thiodicarb. Bayer notes that a 3X FQPA safety factor was 
retained for thiodicarb in the thiodicarb RED due to outstanding 
studies on acute and sub-chronic neurotoxicity. (Id. at 6). These 
studies were submitted to EPA in 2000, according to Bayer, and ``show 
no unexpected or unreasonable neurotoxic effects.'' Thus, it is Bayer's 
view ``that the EPA extra 3X FQPA safety factor can now be removed from 
the risk assessment.'' (Id. at 7). Further, Bayer contends that based 
on the thiodicarb database ``there is no evidence that thiodicarb 
causes endocrine disruption.'' (Id. at 8). Bayer asserts that EPA is 
currently conducting a cumulative risk assessment for thiodicarb and 
other N-methyl carbamate pesticides but that this assessment ``has no 
bearing on the current petition.'' (Id. at 9). Finally, Bayer claims 
that, if a more refined risk assessment was performed for thiodicarb, 
it would demonstrate risks to be so low (in the range of 0.1 percent of 
the RfD) that applying an additional 10X factor would not matter in the 
safety determination. Bayer also claims that the States misunderstand 
the function of how risk assessment and the FQPA safety factor are used 
in evaluating the residue levels chosen as tolerance values. For 
example, Bayer states that the States are incorrect when they assert 
that the unacceptably high risks of these pesticides would require ``a 
reduction in the residue tolerance'' and that the tolerances ``must be 
recalculated applying the full tenfold safety factor.'' (Id. at 10). 
Risk determinations or safety factors are not used directly in 
selecting the values used in tolerances.
    6. DuPont Crop Protection. Dupont Crop Protection is the basic 
manufacturer and primary registrant of methomyl. (Ref. 21). DuPont 
asserts that it has addressed the data gap for methomyl on 
neurotoxicity by submitting acute and subchronic neurotoxicity studies. 
(Id. at 2). Additionally, DuPont claims that the extensive database for 
methomyl contains ``no scientific evidence to suggest that methomyl 
induces a direct and adverse effect on endocrine function.'' (Id. at 
3). In particular, DuPont argues that a review of the relevant studies 
shows that ``[i]n none of these studies was there a treatment-related 
effect on either organ weights or histopathology in tissues that would 
be indicative of endocrine system dysfunction.'' (Id.).
    7. NRDC. NRDC submitted comments on behalf of various environmental 
organizations and individuals. (Ref. 22). Relative to the States' 
petition, NRDC asserted that the DNT study is more sensitive than other 
required studies and thus ``DNT testing is essential for assessing 
pesticide effects, not only as a measure of toxicity to the developing 
brain and nervous system, but also as a measure of developmental and 
reproductive effects generally.'' (Id. at 2). NRDC submitted various 
other comments concerning the children's safety factor that involved 
issues not raised in the States' petition (e.g., exposure of farm 
children to pesticides).
    8. Other comments. The other comments received either repeated the 
arguments made by one of the commenters above, touted the benefits of 
one or more of the pesticides, or stated agreement with the petition 
without providing any supporting basis.

VII. Ruling on Petition

A. Introduction

    This Order denies the States' petition to modify or revoke the 
tolerances as to the pesticides alachlor, chlorothalonil, and 
metribuzin. For the alachlor and metribuzin tolerances this denial is 
based on EPA's finding that, even if the additional 10X children's 
safety factor

[[Page 43916]]

was retained as to these tolerances, they would still meet the section 
408(b) safety standard. The request for revocation or modification of 
the chlorothalonil tolerances is denied because EPA determined that, as 
to that pesticide, the grounds asserted for retaining the children's 
safety factor (lack of data on developmental neurotoxicity, endocrine 
effects, and cumulative effects) are without basis. This Order does not 
address methomyl and thiodicarb because EPA is currently re-evaluating 
the risk of these pesticides as part of the overall reassessment of the 
tolerances for carbamates.
    This Unit of the Order is organized as follows: Unit VII.B. 
discusses EPA's reasons for not ruling on the petition's requests as to 
methomyl and thiodicarb; Unit VII.C. explains EPA's basis for denying 
the petition as to alachlor and metribuzin; and Unit VII.D. addresses 
EPA's conclusions regarding the alleged absence of data on 
developmental neurotoxicity, endocrine effects, and cumulative effects 
for chlorothalonil.
    Before proceeding to the merits of the petition, several 
preliminary matters need to be addressed. First, the States initially 
raised their concerns regarding these pesticides in a 2003 lawsuit 
challenging the reassessment decisions for the pesticides. That lawsuit 
was dismissed because the States had not first presented their 
contentions to EPA in the form of a petition to revoke tolerances. (New 
York v. EPA, 350 F. Supp. 429 (S.D.N.Y. 2004)). The States have now 
presented such a petition to EPA but they continue to protest that 
EPA's regulation governing petitions to revoke is ``designed to be used 
by manufacturers seeking changes to tolerances on technical grounds'' 
and that they, as non-manufacturers ``cannot realistically make the 
factual assertions'' required under EPA's regulation. (Ref. 1 at 3, 5). 
EPA would clarify that the regulation in question, 40 CFR 180.32, does 
mandate that certain technical factors mostly relevant to pesticide 
manufacturers are ``reasonable grounds'' to seek modification or 
revocation of tolerances but the regulation does not, in any way, imply 
that these technical factors are the only reasonable grounds for 
seeking modification or revocation of a tolerance. Certainly, a 
petition, such as this one, asserting that a tolerance does not meet 
the safety standard would be an appropriate petition under section 
408(d) and 40 CFR 180.32.
    Second, the States' lawsuit was styled solely as a challenge to the 
tolerance reassessment decisions. The petition focuses heavily on the 
reassessment decision in arguing for modification or revocation but 
also cites matters arising after the reassessment decisions. EPA 
believes that this is appropriate. A section 408(d) petition to revoke 
or modify is the proper way to challenge a tolerance reassessment 
decision, and if such a petition follows immediately on the heels of a 
tolerance reassessment decision, the reassessment decision will likely 
be the sole focus in EPA's review of the petition. When several years 
have passed between the release of the tolerance reassessment decision 
and the filing of a petition to revoke or modify, however, the 
reassessment decision may be superseded in whole or in part by new 
information. In such circumstances, EPA believes it is appropriate to 
evaluate the petition in light of EPA's current knowledge regarding the 
risks of a pesticide.
    Finally, it should be noted that EPA is treating this petition as a 
petition to revoke tolerances not to modify tolerances. The States 
argue that the children's safety factor should be retained for the 
objected-to tolerances and that, if the factor is retained, the safety 
finding cannot be made. Such a claim, if it could be substantiated, 
would be grounds for revocation of the tolerances. At times, the 
petition mentions reducing tolerance levels or recalculating tolerance 
levels to take into account the children's safety factor. As explained 
in Unit III.B.2., however, EPA determines appropriate tolerance levels 
(as opposed to the safety of tolerances) based on data bearing on the 
maximum pesticide residues that will appear on crops following use 
according to the FIFRA label. The petition presents no such data 
supporting a different tolerance level and therefore is treated solely 
as a petition to revoke.

B. Methomyl and Thiodicarb

    Methomyl and thiodicarb are both N-methyl carbamates. This group of 
pesticides has been found to share a common mechanism of toxicity and 
EPA is now working on completing an assessment of the cumulative 
effects from the N-methyl carbamates, including methomyl and 
thiodicarb. A preliminary cumulative risk assessment has been prepared 
and released for public comment. The final cumulative risk assessment 
is expected in the near future.
    EPA did complete reregistration and tolerance reassessment for 
methomyl and thiodicarb in 1998, shortly after the passage of FQPA. 
Subsequent to release of the REDs for these pesticides, EPA made the 
common mechanism determination for the N-methyl carbamates. Because 
methomyl and thiodicarb are N-methyl carbamates and are thus part of 
the cumulative risk assessment, EPA is revisiting the safety of the 
tolerances for these pesticides as part of the overall tolerance 
reassessment decision on N-methyl carbamates. Once EPA completes the N-
methyl carbamate cumulative risk assessment, it will make a 
determination on whether all N-methyl carbamate pesticide tolerances 
meet the FFDCA section 408 standard. This determination will 
necessarily include the methomyl and thiodicarb tolerances. It would be 
disruptive of the overall N-methyl carbamate reassessment effort to 
separately respond to the States' petition regarding two of the N-
methyl carbamates. Such a disruption would make it more difficult for 
EPA to comply with its statutory deadline for completing the tolerance 
reassessment process. Accordingly, EPA will not address the States' 
petition to revoke the methomyl and thiodicarb tolerances until the 
cumulative risk assessment for the N-methyl carbamates is completed and 
overall tolerance reassessment determinations are made.

C. Alachlor and Metribuzin

    The States' petition is based on the premise that, EPA should 
retain the additional 10X safety factor for the five pesticides in 
question, the additional factor renders the tolerances for these 
pesticides unsafe. For two of the pesticides - alachlor and metribuzin 
- however, the States' logic collapses at its inception because 
retention of the 10X factor would not affect EPA's safety finding with 
regard to these pesticides and the States' petition as to those two 
pesticides is denied for that reason.
    As to alachlor, the States maintain that EPA has assessed the risk 
in the alachlor RED as equaling 33 percent of the RfD for non-nursing 
infants, 17 percent for children 1-6, and 12 percent for children 7-12. 
The States correctly note that if an additional 10X safety factor was 
used in such assessments, the assessments would then indicate that 
exposure exceeded the RfD. Retaining an additional 10X factor would 
reduce the RfD by a factor of 10 and, correspondingly, estimated 
exposure as a percentage of the RfD would increase tenfold.
    The States failed to take into account, however, that the RED also 
contained a revised risk assessment for alachlor that showed the 
highest aggregate risk estimate to be that exposure of children aged 1-
6 is 4 percent of the RfD. (Ref. 6 at 91). Even incorporating an 
additional 10X safety factor into such a risk estimate would increase 
the risk estimate to no greater than 40 percent of the RfD, or still 
well within the safe level. Since completion of the RED, EPA

[[Page 43917]]

has conducted an assessment of the cumulative affects of alachlor and 
the other pesticides with which it shares a common mechanism of action. 
That assessment showed the cumulative risk to have a MOE of 7,700 for 
the most-exposed subgroup. (Ref. 9). Even applying an additional 10X 
factor in evaluating this risk would not raise concerns because the 
level of concern would be for a MOE falling below 1,000.
    As to metribuzin, the States cite EPA's conclusion in the 
metribuzin RED that it poses a risk equaling 62 percent of the RfD for 
non-nursing infants, 75 percent for children 1-6 and 36 percent for the 
U.S. population. Again, the States correctly note that if an additional 
10X safety factor was used in such assessments, the assessments would 
show that exposure exceeded the RfD. This risk assessment, however, was 
based on the worst case exposure assumptions that all crops on which 
metribuzin is registered are treated and that all commodities from 
those crops have metribuzin residues at the tolerance level. EPA is 
aware that such assumptions grossly overstate risk but EPA does not 
spend resources to conduct more realistic assessments if a risk 
assessment using these conservative assumptions shows no concerns. 
Because the States are now claiming that the additional 10X safety 
factor should be retained, EPA has conducted a revised risk assessment 
for metribuzin assuming that an additional 10X safety factor is needed.
    This revised risk assessment uses relatively minor refinements to 
the worst case exposure assumptions used in the RED. (Ref. 23). For the 
acute risk assessment, EPA used tolerance level residues for most 
commodities, monitoring data for some commodities, and an anticipated 
residue value for milk. In addition to these refinements, the chronic 
risk assessment relied upon percent crop treated data for most 
commodities. Overall, the refinements were fairly conservative, and 
thus the assessment still overstates exposure. For example, monitoring 
data were used to estimate residue values in potatoes and potato 
products. U.S. Department of Agriculture monitoring data revealed 1,472 
samplings of potatoes for metribuzin. Of those 1,472 samples, only one 
showed a detectable residue of metribuzin. Nonetheless, in its risk 
assessment, EPA assumed that all potatoes contained metribuzin at the 
level found in that one sample (0.05 parts per million). EPA also used 
monitoring data for beef and poultry products. Monitoring of these 
commodities revealed no detection of metribuzin in 3,299 samples. Yet, 
EPA assumed that all of these commodities had metribuzin present at the 
level of detection of the analytical method. The revised risk 
assessment - which contained an additional 10X safety factor - found 
the highest acute and chronic risks for any population subgroup to be 
75 percent and 69 percent, respectively, of the RfD. Thus, even if an 
additional 10X safety factor is required for metribuzin, metribuzin 
still meets the safety standard in section 408.
    Because the States are incorrect in their assertion that retaining 
the additional 10X factor for alachlor and metribuzin would demonstrate 
that their tolerances are unsafe, the States' petition is denied as to 
alachlor and metribuzin. It appears at this time that retention of the 
additional 10X factor may make a significant difference in the 
characterization of the safety of the chlorothalonil tolerances. For 
that reason, EPA addresses below the grounds asserted in the petition 
for retaining the additional 10X factor for the chlorothalonil 
tolerances.

D. Chlorothalonil

    The States' petition seeks the revocation of tolerances for the 
named pesticides for EPA's alleged unlawful removal of the children's 
safety factor for these pesticides despite an alleged absence of DNT 
studies and data bearing on endocrine effects and cumulative effects 
from substances sharing a common mechanism of toxicity. Below each of 
these claims are examined in detail with regard to chlorothalonil. 
First, however, EPA explains its interpretation of the discretion 
granted it under the children's safety factor provision and the manner 
in which it has implemented the children's safety factor provision 
focusing on its current policy guidance document on the children's 
safety factor.
    1. The children's safety factor--a. The statutory provision. The 
statutory requirements pertaining to the additional children's safety 
factor are contained in two sentences in section 408(b)(2)(C). The 
first sentence commands that as to ``threshold effects, for the 
purposes of [making the reasonable certainty of no harm finding], an 
additional tenfold margin of safety for the pesticide chemical residue 
and other sources of exposure shall be applied for infants and 
children.'' (21 U.S.C. 346a(b)(2)(C)). This sentence also explains that 
the purpose for this additional safety factor is ``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.'' (Id.). 
Switching course, the second sentence then countermands the mandatory 
language in the first sentence (``shall be applied'') and makes clear 
that, EPA has the authority to deviate from the requirement to apply an 
additional 10X safety factor. The second sentence reads 
``[n]othwithstanding such requirement for an additional margin of 
safety, the Administrator may use a different margin of safety for the 
pesticide chemical residue only if, on the basis of reliable data, such 
a margin will be safe for children.'' Importantly, other than requiring 
that EPA act only on the basis of reliable data, Congress did not 
impose an elevated standard upon EPA as a requirement for choosing a 
factor different than an additional factor of 10X. The substantive 
standard that Congress did include was that any factor different than 
the 10X factor be ``safe'' for infants and children. (Id.). This 
standard is equivalent to the overall substantive standard for 
approving tolerances. (21 U.S.C. 346a(b)(2)(A)). Essentially, the two 
sentences addressing the additional safety factor direct EPA, in 
determining whether a tolerance poses a reasonable certainty of no harm 
to children, to apply an additional 10X factor unless EPA concludes, 
based on reliable data, that a different factor provides a reasonable 
certainty of no harm to children. Viewed in this light, the children's 
safety factor provision gives EPA broad discretion in choosing the 
level of any additional safety factor, subject to the constraint that 
EPA must rely only on reliable data and the guidance that EPA should 
focus on the completeness of the database and potential pre- and post-
natal toxicity.
    b. Legislative history. The legislative history of this provision 
also recognizes that EPA should be accorded discretion concerning the 
size of any additional factor to protect children based on the 
circumstances surrounding each pesticide. In the House Commerce 
Committee Report, the committee urged EPA to construe the children's 
safety provision ``in futherance of the following recommendations of 
the National Research Council's Study, `Pesticides in the Diets of 
Infants and Children.''' The committee then quoted two paragraphs from 
the Study including the conclusion that: ``Because there exist specific 
periods of vulnerability during postnatal development, the committee 
recommends that an uncertainty factor up to the tenfold factor 
traditionally used by EPA and [the Food and Drug Administration] for 
fetal developmental toxicity should also be considered when

[[Page 43918]]

there is evidence of postnatal developmental toxicity and when data 
from toxicity testing relative to children are incomplete.'' (H.Rep. 
104-669, Part 2 at 43 (1996)) (emphasis added). This emphasis on the 
exercise of judgment by EPA was highlighted in a pre-enactment EPA 
letters to key legislators regarding how EPA interpreted the children's 
safety provision. In that letter EPA stated that it ``believe[d] that 
[the children's safety factor] provision is consistent with the 
recommendations in [the NRC Study] and would allow the Agency to ensure 
that pesticide tolerances are safe for children in those situations 
where an additional margin of safety is necessary to account for 
inadequate or otherwise incomplete data.'' (142 Cong. Rec. S8737 (July 
24, 1996) (letter to Rep. Bliley included in the record by Sen. Lugar) 
(emphasis added)). EPA explicitly concluded that the children's safety 
factor provision ``provides the Agency with discretion, based on sound 
science, to set the margin of safety at an appropriate level to protect 
infants and children.'' (Id. at S8737-S8738).
    c. EPA policy and implementation of safety factor provision. On 
January 31, 2002, EPA released its current science policy guidance on 
the children's safety factor. (Ref. 4) [This policy is hereinafter 
referred to as the ``Children's Safety Factor Policy'']. That policy 
had undergone an intensive and extended process of public comment as 
well as internal and external science peer review. An EPA-wide task 
force was established to consider the children's safety factor in March 
1998. Taking into account reports issued by the task force on both 
toxicity and exposure issues, EPA's Office of Pesticide Programs 
(``OPP'') released a draft children's safety policy document in May 
1999. That document was subject to an extended public comment period as 
well as review by the FIFRA Scientific Advisory Panel. (Id. at 5). 
Although EPA's overall weight-of-the-evidence approach for evaluating 
safety factor determinations has remained fairly consistent over the 
years, EPA's implementation of the approach, and the weight given 
certain considerations, has evolved as the Agency has gained experience 
in applying the safety factor provision in various circumstances. The 
January 31, 2002 policy reflects a continued evolution in EPA's 
implementation of the safety factor provision.
    The Children's Safety Factor Policy emphasizes throughout that EPA 
interprets the children's safety factor provision as establishing a 
presumption in favor of application of 10X safety factor for the 
protection of infants and children in addition to the traditional 
inter- and intra-species safety factors. (Id. at 4, 11, 50, A-5). 
Further, EPA notes that the children's safety factor provision permits 
a different safety factor to be substituted for this default 10X factor 
only if reliable data are available to show that the different factor 
will protect the safety of infants and children. (Id.). Given the 
wealth of data available on pesticides, however, EPA indicates a 
preference for making an individualized determination of a protective 
safety factor if possible. (Id. at 12). EPA states that use of the 
default factor could under- or over-protect infants and children due to 
the wide variety of issues addressed by the children's safety factor. 
(Id.). EPA notes that ``[i]ndividual assessments may result in the use 
of additional factors greater or less than, or equal to 10X, or no 
additional factor at all.'' (Id.).
    In making such individual assessments regarding the magnitude of 
the safety factor, EPA stresses the importance of focusing on the 
statutory language that ties the children's safety factor to concerns 
regarding potential pre- and post-natal toxicity and the completeness 
of the toxicity and exposure databases. (Id. at 12-13). As to the 
completeness of the toxicity database, EPA recommends use of a weight-
of-the-evidence approach which considers not only the presence or 
absence of data generally required under EPA regulations and guidelines 
but also the availability of ``any other data needed to evaluate 
potential risks to children.'' (Id. at 23). Under this weight-of-the-
evidence approach, the fact that data are missing is not outcome 
determinative with regard to retention of the children's safety factor. 
Rather, when data are absent, EPA indicates that the principal inquiry 
of the weight-of-the-evidence evaluation would center on whether the 
missing data would significantly affect calculation of a safe exposure 
level (commonly referred to as the Reference Dose (``RfD'')). (Id. at 
24-25; accord 67 FR 60950, 60955, September 27, 2002) (finding no 
additional safety factor necessary for triticonazole despite lack of 
DNT study because the ``DNT [study] is unlikely to affect the manner in 
which triticonazole is regulated.'')). When the missing data are data 
above and beyond general regulatory requirements, EPA indicates that 
the weight of evidence would generally only support the need for an 
additional safety factor where the data ``is being required for 
`cause,' that is, if a significant concern is raised based upon a 
review of existing information, not simply because a data requirement 
has been levied to expand OPP's general knowledge.'' (Ref. 4 at 26). 
The extent to which the policy stresses the need for EPA's evaluation 
of the completeness of the database to focus directly on whether 
missing data might possibly lower an existing RfD was a change in 
emphasis from past actions.
    In evaluating the completeness of the exposure database, EPA 
explains that a weight-of-the-evidence approach should be used to 
determine the confidence level EPA has as to whether the exposure 
assessment ``is either highly accurate or based upon sufficiently 
conservative input that it does not underestimate those exposures that 
are critical for assessing the risks to infants and children.'' (Id. at 
36). EPA describes why its methods for calculating exposure through 
various routes and aggregating exposure over those routes generally 
produce conservative exposure estimates - i.e., health-protective 
estimates due to overestimation of exposure. (Id. at 43-47). 
Nonetheless, EPA emphasizes the importance of verifying that the 
tendency for its methods to overestimate exposure in fact were 
adequately protective in each individual assessment. (Id. at 48-49).
    As to potential pre- and post-natal toxicity, the Children's Safety 
Factor Policy lists a variety of factors that should be considered in 
evaluating the degree of concern regarding any identified pre- or post-
natal toxicity. (Id. at 31). As with the completeness of the toxicity 
database, EPA emphasizes that the analysis should focus on whether any 
identified pre- or post-natal toxicity raises uncertainty as to whether 
the chosen RfD is protective of infants and children. (Id. at 35). Once 
again, the presence of pre- or post-natal toxicity, by itself, is not 
regarded as determinative as to size of the children's safety factor. 
Rather, EPA stresses the importance of evaluating all of the data under 
a weight of evidence approach focusing on the safety of infants and 
children. (Id.). This attention on the overall database also indicated 
a shift in emphasis for EPA's implementation of the children's safety 
factor provision as previous decisions had often treated a finding of 
increased sensitivity in the young as almost necessitating some 
additional safety factor.
    EPA's experience in making decisions under the 2002 policy is that 
while for many pesticides the safety factor determination has not 
changed, for others the safety factors may go up or down. To 
generalize, in situations where the database is incomplete, EPA's 
heightened emphasis on whether the

[[Page 43919]]

missing data may affect the assessment of risk has tended to make it 
more likely that EPA will retain the full 10X children's safety factor. 
(See, e.g., 70 FR 7876, 7882, February 16, 2005) (avermectin - 10X 
factor retained due to lack of DNT study and acute and subchronic 
neuorotoxicity studies and residual toxicological concerns as to safety 
of young; 70 FR 7886, 7891, February 16, 2005) (clothianidim - 10X 
factor retained due to lack of developmental immunotoxicity study; 69 
FR 58058, 58062-58063, September 29, 2004) (fenamidone - 10X factor 
retained due to lack of DNT study); but see 69 FR 52182, 52187, August 
25, 2004) (folpet - 10X removed despite lack of DNT study because the 
DNT study is unlikely to change RfD). On the other hand, EPA's weight-
of-the-evidence evaluation of any identified increased sensitivity in 
the young has tended to have the opposite effect. Rather than retaining 
the 10X factor simply because increased sensitivity is found, EPA has 
evaluated whether, in the context of the entire database, there exists 
a clearly-defined no effect threshold for the more sensitive effects in 
the young (i.e. is the effect ``well-characterized'') and whether EPA's 
RfD selection has provided an adequate margin of safety to protect 
against the effects seen in the young. In circumstances where the 
increased sensitivity is well-characterized and the RfD otherwise 
provides at least a 100X margin of safety for these effects, EPA has 
concluded it is safe to remove the additional children's safety factor. 
(See, e.g., 69 FR 63083, 63092-63093, October 29, 2004) (pyraclostrobin 
- 10X factor removed because additional sensitivity well-characterized 
and an adequate margin of safety); 69 FR 58290, 58295, September 30, 
2004) (cyazofamid - 10X factor removed because additional sensitivity 
well-characterized and an adequate margin of safety); but see 69 FR 
62602, 62610, October 27, 2004) (deltamethrin - 10X factor lowered but 
not removed taking into consideration level at which additional 
sensitivity was observed)). As these decisions evidence, the 
determination on the children's safety factor is heavily dependent on 
the results from the toxicity studies specific to the pesticide in 
question. (See, e.g., 70 FR 14535, 14541-14542, March 23, 2005) 
(dinotefuran - 10X factor retained as to some risk assessments due to 
the lack of a developmental immunotoxicity study; no additional factor 
on any risk assessment found necessary to address lack of a DNT study).
    2. The Developmental Neurotoxicity Study and chlorothalonil. The 
States claim that several of the pesticides named in the petition are 
``neurotoxins'' and that, therefore, a DNT study is required and EPA 
must retain the children's safety factor until the DNT study is 
submitted. As to the alleged legal requirement to retain the children's 
safety factor due to the absence of a DNT study, the States argue ``the 
statute requires that a tolerance safety determination include 
consideration of . . . the special neurological susceptibility of 
infants and children as reflected in developmental neurotoxicity 
studies.'' (Ref. 1 at 9).
    Precisely what the States are arguing here is somewhat unclear. To 
the extent they are claiming that the statute requires that pesticides 
be evaluated in a DNT study, their argument is without a basis. 
Although the statute does require EPA to consider the ``special 
susceptibility of infants and children to pesticide chemical residues, 
including neurological differences between infants and children and 
adults . . .,'' (21 U.S.C. 346a(b)(2)(C)(i)(II)), it does not specify 
any particular study that must be reviewed, leaving the matter to EPA's 
discretion. In fact, all of the five core toxicological studies 
required for agricultural pesticides (developmental toxicity study in 
two species, 2-generation reproduction study in rats, and chronic 
toxicity study in two species) include an evaluation of potential 
neurological effects. (Ref. 24 at 2).
    It appears more likely that the States are arguing that EPA has 
concluded that a DNT study is required for neurotoxins. (Ref. 1 at 10). 
The States, however, do not claim that chlorothalonil is a neurotoxin. 
EPA agrees that the evidence does not show chlorothalonil to be 
neurotoxic and has accordingly not required a DNT for this pesticide. 
(Ref. 24 at 2-3). Therefore, this portion of the States' petition does 
not support its claim that the additional 10X factor should be retained 
as to chlorothalonil.
    Moreover, even had the States claimed that a DNT is required as to 
chlorothalonil, that allegation alone would not have been enough to 
demonstrate that the 10X factor should be retained. In the Children's 
Safety Factor Policy, EPA makes clear that, like any other missing 
study, the absence of the DNT study does not trigger a mandatory 
requirement to retain the default 10X value. Rather, whether the 
additional safety factor is retained depends on an individualized 
assessment centering on the question of whether ``a DNT study is likely 
to identify a new hazard or effects at lower dose levels of the 
pesticide that could significantly change the outcome of its risk 
assessment . . . .'' (Ref. 4 at 27). For this reason, EPA denied 
objections to various tolerance rulemakings filed by the Natural 
Resources Defense Council (NRDC) regarding DNT studies and the 
children's safety factor. There, DNT studies had been required but not 
yet submitted. EPA rejected NRDC's argument that the potential for a 
DNT study to identify harmful effects at lower levels than seen in 
other studies alone requires that the children's safety factor be 
maintained. EPA wrote:

    The statute specifically grants EPA discretion to apply a 
different additional safety factor where EPA can conclude based on 
reliable data that the different factor is safe for infants and 
children. NRDC has made no argument that would justify an across-
the-board conclusion that in the absence of a DNT study an 
individual examination of the existing data pertaining to a 
pesticide cannot provide a reliable basis for concluding that a 
different safety factor would be safe for infants and children. 
NRDC's claim that a DNT study may lower EPA's RfD (which EPA does 
not disagree with) is not by itself sufficient to bar EPA from 
making a case-by-case inquiry into the safety of a different 
additional safety factor for the protection of infants and children 
in the absence of such a study.

(70 FR 46706, 46724 (August 10, 2005)). Because NRDC made no pesticide-
specific allegations regarding the challenged pesticides, EPA dismissed 
NRDC's objections to a lowering of the children's safety factor.
    3. Endocrine effects. The States note that the statute requires EPA 
to consider, in making safety determinations as to tolerances, whether 
a pesticide has an effect that mimics estrogen or has other endocrine 
effects, (see 21 U.S.C. 346a(b)(2)(D)(viii)), and to establish an 
endocrine screening program, (see 21 U.S.C. 346a(p)). The States claim 
that, as a matter of law, because assessments under the endocrine 
screening program have not been completed, EPA must retain the 
children's safety factor as to the pesticides in the petition (and 
presumably for all other pesticides as well). The States are incorrect. 
The statute imposes no mandatory bar on, or other limitation of EPA's 
discretion regarding, adjustment or removal of the children's safety 
factor pending completion of the endocrine screening program. Further, 
EPA has acted reasonably in not rigidly tying its safety factor 
decisions to completion of the endocrine screening program given the 
available data it has on the potential for pesticides in general, and 
chlorothalonil in particular, to cause adverse endocrine effects.

[[Page 43920]]

    a. The States' position is contradicted by the statute and 
legislative history. As discussed above, the children's safety factor 
does not apply in some type of automatic manner whenever any data gap 
is identified. Rather, the statute, in clear and unmistakable language, 
grants EPA discretion to make a fact-based determination of whether a 
safety factor different than the 10X default value is safe for 
children:

    Notwithstanding such requirement for an additional margin of 
safety, the Administrator may use a different margin of safety for 
pesticide chemical residue only if, on the basis of reliable data, 
such margin will be safe for infants and children.

21 U.S.C. 346a(b)(2)(C). There is nothing in FFDCA section 408(p) 
concerning the endocrine screening program that contradicts the 
discretion given EPA in the children's safety factor provision. In 
fact, subsection (p)(6) expressly addresses ``Agency Action'' required 
on the basis of the endocrine screening program and that provision 
mentions only agency action upon the finding of an endocrine effect, 
not actions, such as retaining the children's safety factor, that might 
be mandated by the mere establishment of the program. 21 U.S.C. 
346a(p)(6). If Congress had intended that the mere establishment of the 
endocrine screening program should have the dramatic and far-reaching 
effect of requiring EPA to apply automatically an additional 10X safety 
factor for each and every pesticide for the several years needed to 
complete the screening program, it is surprising that this intent finds 
neither mention in the statutory language nor any comment in the 
legislative history.
    This lack of a connection between the endocrine screening provision 
and the children's safety factor provision is understandable given the 
legislative origins of the endocrine screening program. The endocrine 
screening provision was not a well-integrated component in the bills 
comprising the long history of the legislative debate over revision of 
section 408. Rather, the endocrine screening provision arose in a 
context outside of FFDCA section 408, and even outside the context of 
pesticide regulation. The endocrine screening provision first appeared 
as an amendment to an unenacted bill updating the Safe Drinking Water 
Act (``SDWA'') in 1994. (S. 2019, 103rd Cong., 2d Sess, 
20(l) (June 15, 1994)). It was again appended to amendments to the SDWA 
in 1995 although no final action was taken on the bill that year. (S. 
1316, 104th Cong., 1st Sess., 28(g) (December 4, 
1995)). It was only at the last minute that the endocrine screening 
program language proposed for the SDWA was inserted in the FQPA, 
(compare H.R. 1627, 104th Cong., 2nd Sess., 142 
Cong. Rec. H8127 (July 23, 1996) with H.R. 1627, 104th 
Cong., 1st Sess. (May 12, 1995)), and much more modest 
language on endocrine screening included in amendments to the SDWA 
passed contemporaneously with the FQPA. (See S. 1316, 104th 
Cong., 2nd Sess. 404 (July 18, 1996) (full estrogenic 
screening program present in SDWA bill only 2 weeks before passage of 
FQPA); H.R. 3604, 104th Cong., 2nd Sess. (June 
18, 1996) (same)).
    In sum, under section 408(b)(2)(C) EPA clearly has the discretion 
to determine, in any given case, whether it has reliable data to choose 
a factor different than the 10X default value. Not only is there no 
statutory language supporting the States' argument in favor of 
automatic retention of the 10X until completion of the endocrine 
screening program but the legislative history is in no way supportive 
of construing the enactment of the program as intended to have such a 
dramatic impact. Further, since the enactment of the FQPA, EPA's 
contemporaneous and consistent approach to the endocrine screening 
program has been to treat that information-gathering exercise as not 
imposing some type of statutorily-prescribed, automatic injunction 
barring removal of the children's safety factor until completion of 
information-gathering under the program.
    b. Endocrine screening program builds upon the existing pesticide 
database bearing on endocrine effects. The endocrine screening program 
was not created in a vacuum. Rather, the endocrine screening program, 
developed in consultation with knowledgeable scientists from academia, 
government, industry, and environmental groups and a wide range of 
interested stakeholders, builds upon work performed by EPA's Office of 
Pesticide Programs in examining the potential adverse endocrine effects 
of pesticides. Most of the critical tests that are projected to be used 
in the endocrine disruptor screening program are built on tests that 
have been developed and used for years in evaluating the safety of 
pesticides. Thus, while the endocrine screening program will further 
extend the Agency's understanding of the potential for pesticides and 
other substances to cause adverse endocrine effects, EPA already has 
substantial information on the degree to which pesticides cause such 
effects. These available data allow EPA to make weight-of-the-evidence 
assessments of a pesticide's ability to cause adverse effects due to 
endocrine disruption.
    As described in detail in Unit III.D., EPA's endocrine disruptor 
screening program closely follows recommendations made to EPA by the 
Endocrine Disruptor Screening and Testing Advisory Committee (EDSTAC), 
a task force comprised of members representing the commercial chemical 
and pesticides industries, Federal and State agencies, worker 
protection and labor organizations, environmental and public health 
groups, and research scientists. 63 FR 71542, 71544 (December 28, 
1998). The EDSTAC presented a comprehensive report in August 1998 
addressing both the scope and elements of the endocrine screening 
program. The EDSTAC's recommendations were largely adopted by EPA.
    As recommended by EDSTAC, EPA adopted a two-tier testing regime 
with the first tier involving screening ``to identify substances that 
have the potential to interact with the endocrine system'' and the 
second tier involving testing ``to determine whether the substance 
causes adverse effects, identify the adverse effects caused by the 
substance, and establish a quantitative relationship between the dose 
and the adverse effect.'' (Id. at 71545). ``The outcome of Tier 2 is 
designed to be conclusive in relation to the outcome of Tier 1.'' (Id. 
at 71554-71555). EPA also accepted the EDSTAC's detailed 
recommendations concerning the assays for Tier 1 screening and Tier 2 
testing including a battery of short-term in vitro and in vivo assays 
for the Tier 1 screening exercise and five longer-term reproduction 
studies for Tier 2 testing that, with one exception, ``are routinely 
performed for pesticides with widespread outdoor exposures that are 
expected to affect reproduction.'' (Id. at 71555). EPA is examining, 
pursuant to the suggestion of the EDSTAC, modifications to these 
studies to enhance their ability to detect endocrine effects.
    The primary proposed Tier 2 study relevant to endocrine effects on 
humans is the 2-generation reproductive toxicity study in rats. This is 
one of the core studies required for all food-use pesticides since 
1984. (40 CFR 158.340(a)). In this reproduction study, ``potential 
hormonal effects can be detected through behavioral changes, ability to 
become pregnant, duration of gestation, signs of difficult or prolonged 
parturition, apparent sex ratio (as ascertained by anogenital 
distances) of the offspring, feminization or masculinization of 
offspring, number of pups, stillbirths, gross pathology and 
histopathology of the vagina, uterus, ovaries, testis, epididymis, 
seminal

[[Page 43921]]

vesicles, prostate, and any other identified target organs.'' 63 FR at 
71555. In fact, EPA, in 1998, in discussing this study's use in Tier 2, 
identified 39 endpoints examined in this study relevant to estrogenic, 
androgenic, or thyroid effects. At that time, EPA noted that it was 
evaluating whether to add another 10 endocrine-related endpoints to the 
study protocol to enhance the utility of the study to detect endocrine 
effects. Id. at 71555-71556. Despite the ongoing evaluation of 
additional endpoints, EPA has concluded that ``the existing 2-
generation mammalian assay is valid for the identification and 
characterization of reproductive and developmental effects, including 
those due to endocrine disruption, based on the long history of its 
use, the endorsement of the 1998 test guideline by the FIFRA Scientific 
Advisory Panel, and acceptance by member countries of the Organizations 
for Economic Cooperation and Development (OECD).'' (Ref. 25).
    Although the 2-generation rat reproduction study currently is 
considered the definitive mammalian study to evaluate the adverse 
outcomes of endocrine disruptors for the endocrine screening program, 
it is not the only study routinely required or submitted for pesticides 
that provides information on potential endocrine effects. Information 
regarding endocrine effects is available from the other standard 
required toxicity studies including the subchronic bioassays (rat and 
dog), chronic bioassays (rat and dog), the cancer bioassays (rat and 
mouse), and prenatal development toxicity studies (usually the rat and 
rabbit). The subchronic, chronic, and cancer bioassays evaluate, among 
other things, the clinical signs and symptoms of the test animals 
exposed to a pesticide. In addition, at the conclusion of the test, 
animals are sacrificed and their organs are removed, weighed and 
subjected microscopically to examination for evidence of any pathology. 
The organs that play a critical role in the endocrine system (e.g., 
testes, epididymides, uterus, ovaries, mammary glands, and thyroid with 
parathyroid) are included in this evaluation. If an endocrine tissue 
(e.g., thyroid, testes, mammary gland) is identified as a target organ 
(particularly for carcinogenesis) in the standard toxicity studies, 
often the pesticide registrant will submit special studies that measure 
circulating levels of certain hormones (e.g., thyroid, luteinizing 
hormone, estrogen, or testosterone) to identify the mode of action. The 
required standard prenatal developmental toxicity studies would also 
detect the consequences of endocrine influences on fertility and 
pregnancy (e.g., litter size and loss) and development (e.g., fetal 
viability, altered sex ratios, and morphology). For example, 
developmental anomalies indicative of endocrine disruption would be 
assessed and include hypospadias, anogenital distance, and undescended 
testis. If a DNT study is required for a pesticide, that study will 
provide further information concerning potential endocrine effects. The 
DNT study involves exposure of the test animals from gestation through 
lactation and observation of effects on neurological function including 
motor activity, auditory startle, learning and memory and 
neuropathology at various ages through postnatal day 60. Additionally, 
DNT studies include evaluations of such potential endocrine-mediated 
effects such as effects on postnatal growth, reproduction and on 
developmental landmarks of puberty.
    For food-use pesticides, therefore, EPA generally has an 
substantial database bearing on potential adverse endocrine effects. 
Not only does EPA require a 2-generation reproduction study in rats for 
such pesticides, but also requires data in multiple species on 
subchronic and chronic toxicity and developmental toxicity which bear 
on, among other things, potential endocrine effects, including effects 
beyond those examined in the 2-generation reproduction study. Thus, EPA 
believes that in many instances the totality of the information gleaned 
from current data required for pesticides used on food will make it is 
possible to develop a meaningful weight-of-the-evidence determination 
on the potential of the pesticide to adversely effect the endocrine 
system.
    c. Data bearing on chlorothalonil. EPA has multiple data sets on 
chlorothalonil submitted both prior to and subsequent to the 1998 
reregistration eligibility decision for chlorothalonil. This database 
includes subchronic and chronic toxicity testing in multiple species, 
developmental toxicity testing in multiple species, and 2-generation 
rat reproduction tests, including a 2-generation rat reproduction test 
under the most recent testing guidelines. None of these tests show any 
evidence of endocrine effects. Rather, the main toxic effects 
associated with exposure to chlorothalonil appear to be gastric lesions 
and kidney toxicity. As explained in more detail in the following unit, 
these two adverse effects occur through a non-hormonally-mediated 
mechanism. The gastric lesions are due to chlorothalonil's irritant 
effect on the stomach causing forestomach lesions. The kidney toxicity 
is produced as a result of enzymatic reactions in the kidney that cause 
perturbation of mitochondrial respiration, osmotic changes, and 
vacuolar degeneration.
    Accordingly, EPA concludes that it has adequate reliable data on 
the potential of chlorothalonil to disrupt the endocrine system to 
support its decision that it will be safe for children to remove the 
additional 10X safety factor.
    4. Cumulative effects. The States assert that ``as a matter of 
law'', EPA must retain the children's safety factor for each of the 
pesticides due to an alleged lack of data on cumulative effects from 
substances sharing a common mechanism of toxicity. With regard to 
chlorothalonil in particular, the States note that EPA acknowledged in 
the RED that chlorothalonil is a member of the polychlorinated 
fungicide class of pesticides but had not issued a determination on 
common mechanism by the time the States filed their petition. (Ref. 1 
at 15). The States argue that EPA ``did not have reliable data on which 
to base a deviation from the tenfold factor'' because it lacked, among 
other things, data on the cumulative risk of chlorothalonil and other 
pesticides with a common mechanism of toxicity. (Id. at 16).
    The States are incorrect. First, as discussed above, FFDCA does not 
require the children's safety factor to be applied automatically 
whenever any data gap is identified. EPA has discretion to establish an 
appropriate safety factor based on the particular facts related to a 
chemical. Second, as discussed below, available reliable data indicate 
that there is no common mechanism of toxicity for chlorothalonil with 
other members of the polychlorinated fungicide class of pesticides so a 
cumulative risk assessment is not appropriate and removal of the 
children's safety factor is authorized.
    a. Agency approach to conducting cumulative risk assessments. 
Section 408(b)(2)(C)(i)(III) of the FFDCA directs EPA to assess risk of 
pesticide chemical residues to infants and children based on 
``available evidence concerning the cumulative effects on infants and 
children of such residues and other substances that have a common 
mechanism of toxicity.'' 21 U.S.C. 346a(b)(2)(C)(i)(III). The Agency's 
process for determining whether a substance has a cumulative effect 
includes two primary steps: determining whether a substance has a 
common mechanism of toxicity with another

[[Page 43922]]

chemical and if so, then conducting a cumulative effects risk 
assessment.
    The EPA defines a common mechanism of toxicity as ``two or more 
pesticide chemicals or other substances that cause a common toxic 
effect to human health by the same, or essentially the same, sequence 
of major biochemical events. Hence, the underlying basis of the 
toxicity is the same, or essentially the same, for each chemical.'' 
(Ref. 26 at 4). To determine whether substances have a common mechanism 
of toxicity, EPA first identifies a preliminary grouping of substances 
that might cause a common toxic effect based on factors such as 
structural similarity, mechanism of pesticidal action, general 
mechanism of mammalian toxicity, and particular toxic effect. After 
conducting a detailed evaluation of available toxicological data for 
each substance and determining the mechanism by which each substance 
causes a common toxic effect, the Agency selects a common mechanism 
group based on similarities in the nature and sequence of the major 
biochemical events that cause toxicity. (See generally Ref. 24).
    Once EPA concludes that a group of pesticides have a common 
mechanism of toxicity, EPA conducts a cumulative effects risk 
assessment. Depending upon the number of substances in the group, the 
extent of the pesticide use, the level of risk posed by the individual 
members in the group, and the levels of residues, EPA will determine 
whether a screening-level or more refined comprehensive cumulative 
effects risk assessment is appropriate. (See generally Ref. 27). EPA 
evaluates a range of data to conduct the cumulative effects risk 
assessment, including consideration of the relevant timeframe for the 
common mechanism effect, the pathways of exposure, the amount of 
exposure, and the population of concern, including any important 
subpopulations (e.g., children). In its final characterization of the 
cumulative effects risk, EPA determines the need for any uncertainty 
and safety factors based on any uncertainties identified during the 
risk assessment process or any need to protect against risks to exposed 
populations and important subgroups who may be at disproportionate risk 
(e.g., children).
    b. Common mechanism of toxicity evaluation of chlorothalonil and 
other polychlorinated fungicides. In the chlorothalonil RED, 
chlorothalonil was mentioned as a member of the polychlorinated 
fungicide class of pesticides. (Ref. 10 at 100). Other members of this 
class include hexachlorobenzene (HCB), pentachlorophenol (PCP), and 
pentachloronitrobenzene (PCNB). This class was loosely assembled based 
only on structural similarities between chlorothalonil and other 
chemicals and mention of the class was not intended to demonstrate that 
these pesticides shared a common mechanism of action. Subsequent to the 
promulgation of the chlorothalonil RED, EPA has gained experience in 
making common mechanism of toxicity determinations and has released a 
policy guidance regarding how common mechanism questions should be 
approached. (Ref. 26). After reviewing the available data on 
chlorothalonil and the other polychlorinated fungicides, EPA can now 
conclude that chlorothalonil does not share a common mechanism of 
toxicity with these pesticides.
    The available data demonstrate that chlorothalonil produces cancer 
effects (i.e., renal (kidney) tubular adenomas and carcinomas and 
papillomas of the forestomach in rats) as well as noncancerous effects 
(i.e., gastric lesions and kidney toxicity). (Ref. 24 at 5-8). 
Chlorothalonil induces renal tumors and kidney toxicity by 
bioactivating cysteine conjugates which leads to the production of 
chlorothalonil's thiol metabolites. These metabolites disrupt 
mitochondrial respiration in the kidney resulting in irritation, 
cytotoxicity, cell necrosis, increased cell proliferation, and 
restorative hyperplasia. The noncancerous kidney toxicity occurs during 
this process prior to the end result, which is adenomas in the tubular 
cells of the kidneys. (See Ref. 28). Similarly, chlorothalonil causes 
forestomach tumors and gastric lesions through a non-genotoxic 
mechanism involving irritation, cytotoxicity, cell necrosis, increased 
cell proliferation, and restorative hyperplasia.
    None of the other chemicals in the polychlorinated fungicide class 
cause forestomach tumors and only one, HCB, causes renal tumors. HCB's 
toxicological profile, however, is far different than chlorothalonil's. 
HCB's primary target organ is the liver. HCB causes liver damage and 
tumors through disruption of the enzymes producing heme (an essential 
component of hemoglobin) leading to the build up of a heme-precusor, 
porphyrins, which can be toxic in excessive amounts. This condition is 
commonly referred to as porphyria, and hepatic (liver) porphryia is 
characterized by, in addition to liver damage, neurological effects. 
Although the liver is the organ most sensitive to HCB exposure; some 
studies have shown that HCB can cause renal toxicity and tumors. HCB, 
however, does not produce these renal effects by the same biochemical 
mechanism of action as chlorothalonil. HCB studies show that renal 
tumors may result from an accumulation of protein droplets in the 
kidney caused by an accumulation of a kidney cell substance called 
alpha-2U-globulin or an accumulation of porphyrins in the urine. There 
is no evidence that chlorothalonil leads to the accumulation of either 
of these substances. Further, metabolism studies with HCB show no 
evidence that HCB results in the production of cysteine conjugates and 
their byproducts, which lead to the renal toxicity seen with 
chlorothalonil.
    Based on the foregoing, the available data show that chlorothalonil 
does not have a common mechanism of toxicity with any of the chemicals 
in the polychlorinated fungicide class. FFDCA does not require EPA to 
conduct a cumulative effects risk assessment for chemicals that do not 
have a common mechanism of toxicity. Therefore, EPA concludes that it 
has adequate reliable data on the potential cumulative effects of 
chlorothalonil to support its decision that it will be safe for 
children to remove the additional 10X safety factor.
    5. Conclusion. Contrary to the States' contentions, EPA does not 
lack reliable data on chlorothalonil pertaining to neurotoxicity, 
endocrine effects, or cumulative effects from substances with a common 
mechanism of toxicity. Therefore, the States' objection to the removal 
of the children's safety factor has not been substantiated. Because the 
States' argument that the chlorothalonil tolerances are unsafe rested 
wholly on their assertion that retention of the children's safety 
factor was required, their petition to revoke the chlorothalonil 
tolerances is denied.

VIII. Response to Comments on the Petition to Revoke

    Many points raised in comments from the pesticide industry groups 
and individual pesticide manufacturers have been specifically relied 
upon by EPA in its decision. To the extent these commenters addressed 
issues not addressed in this Order or presented arguments that were not 
necessary to reach in responding to the petition, EPA expresses no 
opinion on such comments. One such issue, however, deserves brief 
mention. GB Biosciences contested the States' claim regarding the 
potential cumulative effects of chlorothalonil and HCB by pointing out 
that HCB is only a minor contaminant of certain pesticides and, thus, 
it is relatively meaningless whether chlorothalonil and HCB share a 
common mechanism because cumulative exposure to chlorothalonil

[[Page 43923]]

and HCB would not be substantially greater than chlorothalonil alone. 
(Ref. 18 at 5). This assertion appears to have some force but EPA did 
not analyze it closely due to its conclusion that chlorothalonil and 
HCB operate by different mechanisms.
    Some of the comments made by CLA have previously been submitted in 
the public participation procedures EPA used in developing the various 
FQPA science policies, including the children's safety policy. EPA 
reaffirms its earlier responses to such comments. (See Ref. 29). 
Further, EPA notes its disagreement with CLA's claim that a pesticide 
database cannot be incomplete with regard to endocrine effects because 
EPA has not imposed data requirements pursuant to the endocrine 
screening program. This claim is no more correct than the States' 
opposite assertion - that all pesticide databases are incomplete and 
require retention of the 10X factor because EPA has not imposed data 
requirements under the endocrine screening program. EPA's standard data 
requirements on pesticides address many endocrine-related issues and to 
the extent any of those data are missing, the relative incompleteness 
of the database relative to endocrine effects would have to be taken 
into account in making a decision on the children's safety factor.
    NRDC's comment on the sensitivity of the DNT study was previously 
addressed by EPA in its Order denying NRDC's objections to various 
tolerances. See 70 FR 46706, 46722-46724 (August 10, 2005). NRDC's 
other comments concerned matters (e.g., exposure of farm children to 
pesticides) that were not raised in the States' petition and thus are 
not relevant to EPA's response to that petition.
    Comments citing the alleged benefits of some of the pesticides 
named in the petition are not relevant to the petition because benefit 
considerations are strictly circumscribed under section 408 and have no 
applicability to the threshold risk issues involved in the petition. 
See 21 U.S.C. 346a(b)(2)(B).

IX. Regulatory Assessment Requirements

    As indicated previously, this action announces the Agency's order 
denying, in part, a petition filed under section 408(d) of FFDCA. As 
such, this action is an adjudication and not a rule. The regulatory 
assessment requirements imposed on rulemaking do not, therefore, apply 
to this action.

X. Submission to Congress and the Comptroller General

    The Congressional Review Act, (5 U.S.C. 801 et seq.), as added by 
the Small Business Regulatory Enforcement Fairness Act of 1996, does 
not apply because this action is not a rule for purposes of 5 U.S.C. 
804(3).

XI. References

     1. Petition of New York, California, Connecticut and Massachusetts 
for Modification of Tolerances for Pesticide Chemical Residues 
Established in Reregistration Eligibility Determinations for the 
Following Chemicals: Alachlor; Chlorothalonil; Methomyl; Metribuzin; 
Thiodicarb (December 17, 2004) (petition addressed to Michael O. 
Leavitt, Administrator, United States Environmental Protection Agency).
     2. U.S. EPA, A User's Guide to Available EPA Information on 
Assessing Exposure to Pesticides in Food 11 (March 2000) [hereinafter 
cited as ``User's Guide''].
     3. U.S. EPA, Residue Chemistry Test Guidelines: OPPTS 860.1500 
Crop Field Trials 1 (August 1996).
     4. Office of Pesticide Programs, US EPA, Determination of the 
Appropriate FQPA Safety Factor(s) in Tolerance Assessment 13-16 
(January 31, 2002) (available at http://www.epa.gov/oppfead1/trac/science/determ.pdf).
     5. US EPA, Endocrine Disruptor Screening and Testing Advisory 
Committee Final Report (August 1998) (available at http://www.epa.gov/scipoly/oscpendo/edspoverview/finalrpt.htm).
     6. Office of Prevention, Pesticides, and Toxic Substances, US EPA, 
Reregistration Eligibility Decision: Alachlor (December 1998).
     7. US EPA, Permanent Tolerances by Pesticide: Aug. 1996 TIS 13-14 
(August 2002) (available at http://www.epa.gov/oppsrrd1/tolerance/pdf_files/TolUniv8-05-2002.PDF).
     8. Office of Prevention, Pesticides, and Toxic Substances, US EPA, 
Memorandum from Marcia E. Mulkey to Lois Rossi, A Common Mechanism of 
Toxicity Determination for Chloroacetanilide Pesticides (July 10, 
2001).
     9. Office of Prevention, Pesticides, and Toxic Substances, 
Memorandum from Alberto Proetzel to Felicia Fort, ACETOCHLOR/ALACHLOR: 
Cumulative Risk Assessment for the Chloroacetanilides (March 8, 2006).
     10. Office of Prevention, Pesticides, and Toxic Substances, US 
EPA, Reregistration Eligibility Decision: Chlorothalonil (April 1999).
     11. Office of Prevention, Pesticides, and Toxic Substances, US 
EPA, Reregistration Eligibility Decision: Methomyl (December 1998).
     12. Office of Prevention, Pesticides, and Toxic Substances, US 
EPA, Reregistration Eligibility Decision: Metribuzin (February 1998).
     13.Office of Prevention, Pesticides, and Toxic Substances, US EPA, 
Reregistration Eligibility Decision: Thiodicarb (December 1998).
     14. Croplife America, Comments of CropLife America on the Petition 
of New York, California, Connecticut, and Massachusetts for 
Modification of Tolerances for Certain Pesticides (June 2005).
     15. Pesticide Policy Coalition, Comments on Petition of Attorney 
Generals of New York, California, Connecticut and Massachusetts to 
Revoke or Modify Tolerances (June 15, 2005).
     16. Monsanto Company, Docket ID Number OPP-2005-0050 (April 28, 
2005).
     17. Monsanto Company, Alachlor: Evaluation of the Potential for 
Endocrine Disruption (December 20, 2002).
     18. GB Biosciences Corp., Docket ID Number OPP-2005-0050 (June 14, 
2005).
     19. GB Biosciences Corp., Chlorothalonil White Paper on 
Neurotoxicity and Endocrine Disruption (December 20, 2005).
     20. Bayer Crop Science, Comments by Bayer CropScience Specific to 
the Named Chemicals Metribuzin (EPA 738-R-97-066) and Thiodicarb (EPA 
738-R-98-022) (June 15, 2005).
     21. DuPont Crop Protection, Re: Petition of New York, California, 
Connecticut, and Massachusetts for Modification of Tolerances for 
Certain Pesticides (June 9, 2005).
     22. NRDC, Re: Petition of New York, California, Connecticut, and 
Massachusetts to Modify Tolerances for Alachlor, Chlorothalonil, 
Methomyl, Metribuzin, and Thiodicarb (May 9, 2005).
    23. Office of Prevention, Pesticides, and Toxic Substances, US EPA, 
Memorandum from Douglas Dotson to Paula Deschamp, Metribuzin Acute and 
Chronic Dietary Exposure Assessments (April 17, 2006).
     24. Office of Prevention, Pesticides, and Toxic Substances, US 
EPA, Memorandum from P.V. Shah to Pete Caulkins, HED Response to 
Questions Raised by SRRD Regarding Chlorothalonil (June 22, 2006).
     25. Office of Prevention, Pesticides, and Toxic Substances, US 
EPA, Letter from Clifford Gabriel to Erik Olson, Attachment B (March 8, 
2005).

[[Page 43924]]

     26. U.S. EPA, Guidance for Identifying Pesticide Chemicals and 
Other Substances that Have a Common Mechanism of Toxicity (Jan. 29, 
1999).
     27. Office of Pesticide Programs, U.S. EPA, Guidance on Cumulative 
Risk Assessment of Pesticide Chemicals That Have a Common Mechanism of 
Toxicity (Jan. 14, 2002).
     28. McMahon, Timothy, U.S. EPA, The Carcinogenicity of 
Chlorothalonil: Data in Support of a Non-linear Mechanism of 
Carcinogenicity (Presented to the July 29-30, 1998 FIFRA Scientific 
Advisory Panel).
    29. Office of Pesticide Programs, US EPA, Office of Pesticide 
Programs' Policy on the Determination of the Appropriate FQPA Safety 
Factor(s) For Use in the Tolerance Setting Process: Response to 
Comments (February 28, 2002) (available at http://www.epa.gov/oppfead1/trac/science/fqpa_resp.pdf).

List of Subjects

    Environmental protection, pesticides, and pest.

    Dated: July 24, 2006.
James Jones,
Director, Office of Pesticide Programs.
[FR Doc. 06-6605 Filed 8-1-06; 8:45 am]
BILLING CODE 6560-50-S