Carbaryl; Order Denying NRDC's Objections and Requests for Hearing, 55997-56013 [2010-22987]

Agencies

• ENVIRONMENTAL PROTECTION AGENCY

[Federal Register Volume 75, Number 178 (Wednesday, September 15, 2010)]
[Rules and Regulations]
[Pages 55997-56013]
From the Federal Register Online via the Government Printing Office [www.gpo.gov]
[FR Doc No: 2010-22987]


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ENVIRONMENTAL PROTECTION AGENCY

[EPA-HQ-OPP-2008-0347; FRL-8843-7]

40 CFR Part 180


Carbaryl; Order Denying NRDC's Objections and Requests for 
Hearing

AGENCY: Environmental Protection Agency (EPA).

ACTION: Order.

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SUMMARY: In this order, the Environmental Protection Agency (EPA) 
denies objections, and requests for hearing on those objections, to a 
prior order denying a petition requesting that EPA revoke all pesticide 
tolerances for carbaryl under section 408(d) of the Federal Food, Drug, 
and Cosmetic Act. The objections and hearing requests were filed on 
December 29, 2008, by the Natural Resources Defense Council (NRDC). The 
original petition was also filed by NRDC.

FOR FURTHER INFORMATION CONTACT: Jacqueline Guerry, Pesticide Re-
evaluation Division (7508P), Office of Pesticide Programs, 
Environmental Protection Agency, 1200 Pennsylvania Ave., NW., 
Washington, DC 20460-0001; telephone number: (215) 814-2184; e-mail 
address: guerry.jacqueline@epa.gov.

SUPPLEMENTARY INFORMATION:

I. General Information

A. Does this Action Apply to Me?

    In this document, EPA denies objections, and requests for hearing 
on those objections, submitted by NRDC in response to a prior order 
denying NRDC's petition requesting that EPA revoke all pesticide 
tolerances for carbaryl. In addition to NRDC, and others interested in 
food safety issues generally, this action may be of interest to 
agricultural producers, food manufacturers, or pesticide manufacturers. 
Potentially affected entities may include, but are not limited to those 
engaged in the following activities:
     Crop production (NAICS code 111), e.g., agricultural 
workers; greenhouse, nursery, and floriculture workers; farmers.
     Animal production (NAICS code 112), e.g., cattle ranchers 
and farmers, dairy cattle farmers, livestock farmers.
     Food manufacturing (NAICS code 311), e.g., agricultural 
workers; farmers; greenhouse, nursery, and floriculture workers; 
ranchers; pesticide applicators.
     Pesticide manufacturing (NAICS code 32532), e.g., 
agricultural workers; commercial applicators; farmers; greenhouse, 
nursery, and floriculture workers; residential users.
    This listing is not intended to be exhaustive, but rather to 
provide a guide for readers regarding entities likely to be affected by 
this action. Other types of entities not listed in this unit could also 
be affected. The North American Industrial Classification System 
(NAICS) codes have been provided to assist you and others in 
determining whether this action might apply to certain entities. If you 
have any questions regarding the applicability of this action to a 
particular entity, consult the person listed under FOR FURTHER 
INFORMATION CONTACT.

B. How Can I Get Copies of this Document and Other Related Information?

    EPA has established a docket for this action under docket 
identification (ID) number EPA-HQ-OPP-2008-0347. Publicly available 
docket materials are available either in the electronic docket at 
https://www.regulations.gov, or, if only available in hard copy, at the 
Office of Pesticide Programs (OPP) Regulatory Public Docket in Rm. S-
4400, One Potomac Yard (South Bldg.), 2777 S. Crystal Dr., Arlington, 
VA. The hours of operation of this Docket Facility are from 8:30 a.m. 
to 4 p.m., Monday through Friday, excluding legal holidays. The Docket 
Facility telephone number is (703) 305-5805.

II. Introduction

A. What Action Is the Agency Taking?

    In this order, EPA denies objections, and requests for a hearing on 
those objections, to an earlier EPA Order, (73 FR 64229 ), denying a 
petition to revoke all tolerances established for the pesticide, 
carbaryl, under the Federal Food, Drug, and Cosmetic Act (FFDCA), 21 
U.S.C. 346a, (Refs. 1 and 2). Both the objections and hearing requests, 
as well as the petition, were filed with EPA by NRDC.
    NRDC's original petition, dated January 10, 2005, submitted to the 
carbaryl public docket during the public comment period for the 2004 
Amended Interim Reregistration Eligibility Decision (IRED) for 
Carbaryl, and filed pursuant to FFDCA section 408(d)(1), asserted a 
number of grounds why carbaryl tolerances allegedly fail to meet the 
FFDCA's safety standard. The main arguments raised in the petition 
concerned EPA's drinking water assessment and EPA's decision on the 
statutory safety factor to protect infants and children that supported 
the 2004 IRED decision. NRDC also petitioned the Agency to cancel all 
carbaryl uses pursuant to the Federal Insecticide, Fungicide, and 
Rodenticide Act (FIFRA) 7 U.S.C. 136(bb) and 136a, and argued 
unreasonable risks on the environment. Subsequently, on November 26, 
2007, NRDC petitioned EPA to cancel all carbaryl pet collar uses under 
FIFRA. (Ref. 3). EPA consolidated this latter petition with the 2005 
FFDCA petition because NRDC argued in it that exposure to carbaryl pet 
collars make the risks presented by carbaryl unsafe within the meaning 
of FFDCA section 408.
    On October 29, 2008, EPA responded to both the 2005 petition to 
revoke all carbaryl tolerances and the 2007 petition to cancel all pet 
collar uses, denying them in their entirety. (73 FR 64229, October 29, 
2008) (Ref. 4).
    NRDC then filed objections to EPA's denial of NRDC's petition to 
revoke all carbaryl tolerances and requested a hearing on its 
objections. These objections and hearing requests were filed pursuant 
to the procedures in the FFDCA, section 408(g)(2). (21 U.S.C. 
346a(g)(2)). The objections narrowed NRDC's claims to two main topics - 
that EPA lacks reliable data to reduce the Food Quality Protection Act 
(FQPA) Children's Safety Factor and that EPA's exposure assessment for 
carbaryl is flawed and underestimates the exposure to children from pet 
collar uses. After carefully reviewing the objections and hearing 
requests, EPA has determined that NRDC's hearing requests do not 
satisfy the regulatory requirements for such requests and that its 
substantive objections are without merit. Therefore, EPA, in this final 
order, denies NRDC's

[[Page 55998]]

objections and its requests for a hearing on those objections.

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

    NRDC petitioned to revoke the carbaryl tolerances pursuant to the 
petition procedures in FFDCA section 408(d)(1). (21 U.S.C. 346a(d)(1)). 
Under section 408(d), EPA may respond to such a petition by either 
issuing a final or proposed rule modifying or revoking the tolerances 
or issuing an order denying the petition. (21 U.S.C. 346a(d)(4)). Here, 
EPA responded by issuing an order under section 408(d)(4)(iii) denying 
the petition. (73 FR 64229, October 29, 2008).
    Orders issued under section 408(d)(4)(iii) are subject to a 
statutorily-created administrative review process. (21 U.S.C. 
346a(g)(2)). Any person may file objections to a section 408(d)(4)(iii) 
order with EPA and request a hearing on those objections. (Id.). EPA is 
required by section 408(g)(2)(C) to issue a final order resolving the 
objections to the section 408(d)(4)(iii) order. (21 U.S.C. 
346a(g)(2)(C)).

III. Statutory and Regulatory Background

    In this Unit, EPA provides background on the relevant statutes and 
regulations governing NRDC's objections and requests for hearing as 
well as on pertinent Agency policies and practices. As noted, NRDC's 
objections and requests for hearing raise two main claims: (1) that EPA 
has unlawfully failed to retain the full tenfold FQPA safety factor for 
the protection of infants and children and failed to apply an 
additional threefold factor due to a deficiency in a critical study; 
and (2) that EPA underestimated the exposure to children from pet 
collar uses. The first claim is based on assertions that additional 
safety factors are needed because of effects observed in a 
developmental neurotoxicity (DNT) study with carbaryl. The pet collar 
claim is primarily based upon allegations that EPA does not have 
sufficient or reliable data with which to assess pet collar exposures 
and that the assumptions made by EPA underestimate exposure to 
children. Background information on each of these topics is included in 
this Unit.
    Unit III.A. summarizes the requirements and procedures in section 
408 of the FFDCA and applicable regulations pertaining to pesticide 
tolerances, including the procedures for petitioning for revocation of 
tolerances and challenging the denial of such petitions and the 
substantive standards for evaluating the safety of pesticide 
tolerances. This unit also discusses the closely-related statute under 
which EPA regulates the sale, distribution, and use of pesticides, 
FIFRA, (7 U.S.C. 136 et seq.).
    Unit III.B. provides an overview of EPA's risk assessment process. 
It contains an explanation of how EPA identifies the hazards posed by 
pesticides, how EPA determines the level of exposure to pesticides that 
pose a concern (level of concern), how EPA measures human exposure to 
pesticides, and how hazard, level of concern conclusions, and human 
exposure estimates are combined to evaluate risk. Further, this unit 
presents background information on Agency policies with particular 
relevance to this action.

A. FFDCA/FIFRA and Applicable Regulations

    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 (FDA) and the U.S. Department of 
Agriculture (USDA). Section 408 was substantially rewritten by the Food 
Quality Protection Act of 1996 (FQPA), which added the provisions 
discussed below establishing a detailed safety standard for pesticides, 
additional protections for infants and children, and the estrogenic 
substances screening program. (Public Law 104-170, 110 Stat. 1489 
(1996)).
    EPA also regulates pesticides under 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. ... EPA must also consider, in evaluating the 
safety of tolerances, ``safety factors which . . . are generally 
recognized as appropriate for the use of animal experimentation data.''
(21 U.S.C. 346a(b)(2)(D)(ix).
    Risks to infants and children are given special consideration. 
Specifically, section 408(b)(2)(C) 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

[[Page 55999]]

on infants and children of such residues and other substances that have 
a common mechanism of toxicity. ...
    This provision also creates a presumptive additional safety factor 
for the protection of infants and children. Specifically, it directs 
that ``[i]n the case of threshold effects, ... an additional tenfold 
margin of safety for the pesticide chemical residue and other sources 
of exposure shall be applied for infants and children to take into 
account potential pre- and post-natal toxicity and completeness of the 
data with respect to exposure and toxicity to infants and children.'' 
(21 U.S.C. 346a(b)(2)(C)). EPA is permitted to ``use a different margin 
of safety for the pesticide chemical residue only if, on the basis of 
reliable data, such margin will be safe for infants and children.'' 
(Id.). The additional safety margin for infants and children is 
referred to throughout this 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, a 
tolerance rulemaking is initiated by the party seeking to establish, 
amend, or revoke a tolerance by means of filing a petition with EPA. 
(See 21 U.S.C. 346a(d)(1)). EPA publishes in the Federal Register a 
notice of the petition filing and requests public comment. (21 U.S.C. 
346a(d)(3)). After reviewing the petition, and any comments received on 
it, EPA may issue a final rule establishing, amending, or revoking the 
tolerance, issue a proposed rule to do the same, or deny the petition. 
(21 U.S.C. 346a(d)(4)).
    Once EPA takes final action on the petition by either establishing, 
amending, or revoking the tolerance or denying the petition, any person 
may file objections with EPA and seek an evidentiary hearing on those 
objections. (21 U.S.C. 346a(g)(2)). Objections and hearing requests 
must be filed within 60 days. (Id.). The statute provides that EPA 
shall ``hold a public evidentiary hearing if and to the extent the 
Administrator determines that such a public hearing is necessary to 
receive factual evidence relevant to material issues of fact raised by 
the objections.'' (21 U.S.C. 346a(g)(2)(B). EPA regulations make clear 
that hearings will only be granted where it is shown that there is ``a 
genuine and substantial issue of fact,'' the requestor has identified 
evidence ``which, if established, resolve one or more of such issues in 
favor of the requestor,'' and the issue is ``determinative'' with 
regard to the relief requested. (40 CFR 178.32(b)). In addition, EPA 
regulations prescribe the form and manner of submissions for objections 
and for an evidentiary hearing. (40 CFR 178.25 and 178.27). EPA's final 
order on the objections is subject to judicial review. (21 U.S.C. 
346a(h)(1)).
    4. Tolerance reassessment and FIFRA reregistration. The FQPA 
required that EPA reassess the safety of all pesticide tolerances 
existing at the time of its enactment. (21 U.S.C. 346a(q)). EPA was 
given 10 years to reassess the approximately 10,000 tolerances in 
existence in 1996. In this reassessment, EPA was required to review 
existing pesticide tolerances under the new ``reasonable certainty that 
no harm will result'' standard set forth in section 408(b)(2)(A)(i). 
(21 U.S.C. 346a(b)(2)(A)(i)). This reassessment was substantially 
completed by the August 3, 2006 deadline. Tolerance reassessment was 
generally handled in conjunction with a similar program involving 
reregistration of pesticides under FIFRA. (7 U.S.C. 136a-1). 
Reassessment and reregistration decisions were generally combined in a 
document labeled a Reregistration Eligibility Decision (RED).

B. EPA Risk Assessment for Tolerances--Policy and Practice

    1. The safety determination - risk assessment. To assess risk of a 
pesticide tolerance, EPA combines information on pesticide toxicity 
with information regarding the route, magnitude, and duration of 
exposure to the pesticide. The risk assessment process involves four 
distinct steps:
     Identification of the toxicological hazards posed by a 
pesticide;
     Determination of the dose-response analysis in test 
animals and ``level of concern'' with respect to human exposure to the 
pesticide;
     Estimation of human exposure to the pesticide; and
     Characterization of risk posed to humans by the pesticide 
based on comparison of human exposure to the level of concern.
    a. Hazard identification. In evaluating toxicity or hazard, EPA 
reviews toxicity studies, primarily in laboratory animals, to identify 
any adverse effects on the test subjects. Animal studies typically 
involve investigating a broad range of effects including gross and 
microscopic effects on organs and tissues, functional effects on bodily 
organs and systems, effects on blood parameters (such as red blood cell 
count, hemoglobin concentration, hematocrit, and a measure of clotting 
potential), effects on the concentrations of normal blood chemicals 
(including glucose, total cholesterol, urea nitrogen, creatinine, total 
protein, total bilirubin, albumin, hormones, and enzymes such as 
alkaline phosphatase, alanine aminotransfersase and cholinesterase), 
and behavioral or other gross effects identified through clinical 
observation and measurement. EPA examines whether adverse effects are 
caused by different durations of exposure ranging from short-term 
(e.g., acute) to longer-term (e.g., chronic) pesticide exposure, and 
different routes of exposure (oral, dermal, inhalation). EPA also 
evaluates potential adverse effects in different age groups. EPA 
requires testing for different durations and routes of exposure and 
different age groups in multiple species of laboratory animals (e.g., 
rat, mouse, dog, rabbit).
    EPA also considers whether the adverse 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. 5 at 8-9). Because this matter involves a pesticide with 
threshold effects, assessment of non-threshold effects is not further 
discussed. Moreover, the toxic effects of carbaryl are short in 
duration (1 day or less) and, as such, long-term, chronic threshold 
effects are not discussed further here.
    b. Level of concern/dose-response analysis. Once a pesticide's 
potential hazards are identified, EPA determines a toxicological level 
of concern for evaluating the risk posed by human exposure to the 
pesticide. In this step of the risk assessment process, EPA essentially 
evaluates the levels of exposure to the pesticide at which effects 
might occur. An important aspect of this determination is assessing the 
relationship between exposure (dose) and response (often referred to as 
the dose-response analysis).
    In examining the dose-response relationship for a pesticide's 
threshold effects, EPA evaluates an array of toxicity studies on the 
pesticide. In each of these studies, EPA attempts to identify the 
lowest observed adverse effect level (LOAEL) and the next lower dose at 
which there are no observed adverse affect levels (NOAEL). Often, EPA 
will use the lowest NOAEL from the relevant available studies -- for 
the duration and route for which risk is being assessed, as a starting 
point (called the Point of Departure (POD)) in estimating the level of 
concern for

[[Page 56000]]

humans. (Ref. 5 at 9 (The POD is simply the ``dose that serves as the 
starting point in extrapolating a risk to the human population.'')). At 
times, however, EPA will use a LOAEL from a study on the most sensitive 
endpoint as the POD when no NOAEL is identified in that study. 
Alternatively, in the absence of a NOAEL for the most sensitive adverse 
effect, EPA will use the LOAEL as the risk assessment POD, and 
determine an extrapolated NOAEL by dividing the LOAEL by an uncertainty 
factor.
    EPA is increasingly using modeling to ascertain what is referred to 
as a Benchmark Dose (BMD) as a substitute for a NOAEL in selecting a 
POD. In its revised assessment of carbaryl, EPA used a BMD approach for 
deriving the POD from the available rat toxicity studies. (Ref. 8). A 
benchmark dose, or BMD, is a point estimate along a dose-response curve 
that corresponds to a specific response level. For example, a 
BMD10 represents a 10% change from the background level (the 
background level is typically derived from the control group). 
Generically, the direction of change from background can be an increase 
or a decrease depending on the biological parameter and the chemical of 
interest. In the case of carbaryl, a reduction in acetylcholinesterase 
(AChE) activity (referred to as ``inhibition'' of AChE) is the toxic 
effect of concern. In addition to a BMD, a ``confidence limit'' may 
also be calculated. Confidence limits express the uncertainty in a BMD 
that may be due to sampling and/or experimental error. The lower 
confidence limit on the dose used as the BMD is termed the BMDL, which 
the Agency uses as the POD. Use of the BMDL for deriving the POD 
rewards better experimental design and procedures that provide more 
precise estimates of the BMD, resulting in tighter confidence 
intervals. Use of the BMDL also helps ensure with high confidence 
(e.g., 95% confidence) that the selected percentage of AChE inhibition 
is not exceeded.
    Numerous scientific peer review panels over the last decade have 
supported the Agency's application of the BMD approach as a 
scientifically supportable method for deriving PODs in human health 
risk assessment, and as an improvement over the historically applied 
approach of using NOAELs or LOAELs. The NOAEL/LOAEL approach does not 
account for the variability and uncertainty in the experimental 
results, which are due to characteristics of the study design, such as 
dose selection, dose spacing, and sample size. With the BMD approach, 
all the dose response data are used to derive a POD. Moreover, the 
response level used for setting regulatory limits can vary based on the 
chemical and/or type of toxic effect (Refs. 6, 7 and 8).
    The POD is, in turn, used in choosing a level of concern. EPA will 
make separate determinations as to the Points of Departure, and 
correspondingly levels of concern, for both short and long exposure 
periods as well as for the different routes of exposure (oral, dermal, 
and inhalation). In estimating and describing the level of concern, the 
POD is at times used differently depending on whether the risk 
assessment addresses dietary or non-dietary exposures. For dietary 
risks, EPA uses the POD to calculate an acceptable level of exposure or 
safe dose. This safe dose has been traditionally referred to as the 
reference dose (RfD). The RfD is defined as the risk assessment POD 
divided by all uncertainty/safety factors (UF/SFs) except those 
specific to FQPA. The Population Adjusted Dose (PAD), on the other 
hand, is defined as the POD divided by all UF/SFs, including those 
specific to FQPA. In cases where there are no UF/SFs specific to FQPA, 
the RfD and PAD are numerically identical. Typically, EPA uses a 
baseline safety/uncertainty factor equal to 100. These factors include 
a factor of 10 (10X) where EPA is using data from laboratory animals 
(inter-species factor) to reflect potentially greater sensitivity in 
humans than laboratory animals and a factor of 10X to account for 
potential variations in sensitivity among members of the human 
population (intra-species factor) as well as other unknowns. Additional 
uncertainty factors may be added to address data deficiencies or 
concerns raised by the existing data. Under the FQPA, a safety factor 
of 10X is presumptively applied to protect infants and children, unless 
reliable data support selection of a different factor. This FQPA safety 
factor largely replaces pre-FQPA EPA practice regarding additional 
safety factors. (Ref. 9 at 4-11).
    c. Estimating human exposure. Risk is a function of both hazard and 
exposure. Thus, equally important to the risk assessment process as 
determining the hazards posed by a pesticide and the toxicological 
level of concern for those hazards is estimating human exposure. Under 
FFDCA section 408, EPA is concerned not only with exposure to pesticide 
residues in food but also exposure resulting from pesticide 
contamination of drinking water supplies and from use of pesticides in 
the home or other non-occupational settings. (See 21 U.S.C. 
346a(b)(2)(D)(vi)). EPA considers multiple routes of exposure (oral, 
dermal, and inhalation) and aggregates these exposures where 
scientifically appropriate. Because EPA exposure estimates are not 
involved in EPA's determination of this matter, no further description 
of EPA exposure assessment practices is included.
    d. Risk characterization. The final step in the risk assessment is 
risk characterization. In this step, EPA combines information from the 
first three steps (hazard identification, level of concern/dose-
response analysis, and human exposure assessment) to quantitatively 
estimate the risks posed by a pesticide. Separate characterizations of 
risk are conducted for different durations of exposure. Additionally, 
where appropriate, EPA aggregates exposures across different routes in 
characterizing risk.
    In estimating and describing the level of concern, the POD is at 
times used differently depending on whether the risk assessment 
addresses dietary or non-dietary exposures. For threshold risks, EPA 
estimates risk in one of two ways. Where EPA has calculated a RfD/PAD, 
risk is estimated by expressing human exposure as a percentage of the 
RfD/PAD. Exposures lower than 100 percent of the RfD/PAD are generally 
not of concern. Alternatively, EPA may express risk by comparing the 
Margin of Exposure (MOE) between estimated human exposure and the POD 
with the acceptable or target MOE. The acceptable or target MOE is the 
product of all applicable safety factors. To calculate the actual MOE 
for a pesticide, estimated human exposure to the pesticide is divided 
into the POD. In contrast to the RfD/PAD approach, the higher the MOE, 
the less risk posed by the pesticide. Accordingly, if the target MOE 
for a pesticide is 100, MOEs equal to or exceeding 100 would generally 
not be of concern.
    As a conceptual matter, the RfD/PAD and MOE approaches are 
fundamentally equivalent. For a given risk and given exposure of a 
pesticide, if exposure to a pesticide were found to be acceptable under 
an RfD/PAD analysis it would also pass under the MOE approach, and 
vice-versa. However, for any specific pesticide, risk assessments for 
different exposure durations or routes may yield different results. 
This is a function not of the choice of the RfD/PAD or MOE approach but 
of the fact that the levels of concern and the levels of exposure may 
differ depending on the duration and route of exposure.
    2. EPA policy on the children's safety factor. As the above brief 
summary of EPA's risk assessment practice indicates, the use of safety 
factors plays

[[Page 56001]]

a critical role in the process. This is true for traditional 10X safety 
factors to account for potential differences between animals and humans 
when relying on studies in animals (inter-species safety factor) and 
potential differences among humans (intra-species safety factor) as 
well as the FQPA 10X children's safety factor.
    In applying the children's safety factor provision, EPA has 
interpreted it as imposing a presumption in favor of applying a 10X 
safety factor to the 10X inter-species and 10X intra-species safety 
factors. (Ref. 9 at 4, 11). Thus, EPA generally refers to the 10X 
children's safety factor as a presumptive or default 10X factor. EPA 
has also made clear, however, that this presumption or default in favor 
of the 10X children' safety is only a presumption. The presumption can 
be overcome if reliable data demonstrate that a different factor is 
safe for children. (Id.). In determining whether a different factor is 
safe for children, EPA focuses on the three factors listed in section 
408(b)(2)(C) - the completeness of the toxicity database, the 
completeness of the exposure database, and potential pre- and post-
natal toxicity. In examining these factors, EPA strives to make sure 
that its choice of a safety factor, based on a weight-of-the-evidence 
evaluation, does not understate the risk to children. (Id. at 24-25, 
35).
    3. EPA policy on cholinesterase inhibition. Carbaryl is a member of 
the N-methyl carbamate class of pesticides. Each member of this class 
shares the ability to inhibit the enzyme, acetylcholinesterase, leading 
to neurotoxicity. N-methyl carbamate neurotoxicity is characterized by 
the rapid onset (often 15-30 minutes) and rapid recovery (within 
hours). Cholinesterase inhibition is a disruption of the normal process 
in the body by which the nervous system chemically communicates with 
muscles and glands. Communication between nerve cells and a target cell 
(i.e., another nerve cell, a muscle fiber, or a gland) is facilitated 
by the chemical, acetylcholine. When a nerve cell is stimulated it 
releases acetylcholine into the synapse (or space) between the nerve 
cell and the target cell. The released acetylcholine binds to receptors 
in the target cell, stimulating the target cell in turn. As EPA has 
explained, ``the end result of the stimulation of cholinergic 
pathway(s) includes, for example, the contraction of smooth (e.g., in 
the gastrointestinal tract) or skeletal muscle, changes in heart rate 
or glandular secretion (e.g., sweat glands) or communication between 
nerve cells in the brain or in the autonomic ganglia of the peripheral 
nervous system.'' (Ref. 10 at 10).
    Acetylcholinesterase (AChE) is an enzyme that breaks down 
acetylcholine and terminates its stimulating action in the synapse 
between nerve cells and target cells. When AChE is inhibited, 
acetylcholine builds up, prolonging the stimulation of the target cell. 
This excessive stimulation potentially results in a broad range of 
adverse effects on many bodily functions including muscle cramping or 
paralysis, excessive glandular secretions, or effects on learning, 
memory, or other behavioral parameters. Depending on the degree of 
inhibition these effects can be serious, even fatal.
    EPA's cholinesterase inhibition policy statement explains EPA's 
approach to evaluating the risks posed by cholinesterase-inhibiting 
pesticides such as carbaryl. (Ref. 10). The policy focuses on three 
types of effects associated with cholinesterase-inhibiting pesticides 
that may be assessed in animal and human toxicological studies: (1) 
physiological and behavioral/functional effects; (2) cholinesterase 
inhibition in the central and peripheral nervous system; and (3) 
cholinesterase inhibition in red blood cells and blood plasma. The 
policy discusses how such data should be integrated in deriving a POD 
for a cholinesterase-inhibiting pesticide.
    EPA uses a weight-of-the-evidence approach to determine the toxic 
effect that will serve as the appropriate POD for a risk assessment for 
AChE inhibiting pesticides, such as carbaryl (Id). The neurotoxicity 
that is associated with these pesticides can occur in both the central 
(brain) and the peripheral nervous system. In its weight-of-the-
evidence analysis, EPA reviews data, such as AChE inhibition data from 
the brain, peripheral tissues and blood (e.g., red blood cell (RBC) or 
plasma), in addition to data on clinical signs and other functional 
effects related to AChE inhibition. Based on these data, EPA selects 
the most appropriate effect on which to regulate; such effects can 
include clinical signs of AChE inhibition, central or peripheral 
nervous tissue measurements of AChE inhibition, or RBC AChE measures 
(Id). Although RBC AChE inhibition is not adverse in itself, it is a 
surrogate for inhibition in peripheral tissues when peripheral data are 
not available. As such, RBC AChE inhibition provides an indirect 
indication of adverse effects on the nervous system (Id.). Measures of 
AChE inhibition in the peripheral nervous system are very rare for N-
methyl carbamate pesticides and no such peripheral data exists for 
carbaryl. For these reasons, other state and national agencies such as 
California, Washington, Canada, the European Union, as well as the 
World Health Organization (WHO), all use blood measures in human health 
risk assessment and/or worker safety monitoring programs.
    4. EPA policy on assessing risk from cumulative effects from 
pesticides with a common mechanism of toxicity. Section 408(b)(2)(D) of 
the FFDCA directs EPA to consider available information on the 
cumulative effects on human health resulting from exposure to multiple 
pesticide chemicals that have a common mechanism of toxicity. EPA 
begins a cumulative risk assessment by identifying a group of 
pesticides, called a common mechanism group, that bring about the same 
toxic effect by a common mechanism of toxicity. Pesticides share a 
common mechanism of toxicity if they act the same way in the body; that 
is, if the same toxic effect occurs in the same organ or tissue by 
essentially the same sequence of major biochemical events.
    There are many steps involved in quantitatively assessing the 
potential human health risk associated with exposure to the N-methyl 
carbamate pesticides. The complex series of evaluations involve hazard 
and dose-response analyses; assessments of food, drinking water, 
residential/non-occupational exposures; combining exposures to produce 
a cumulative risk estimate; and risk characterization. Given the 
complexity of the analyses, EPA's policy is to only conduct a 
cumulative assessment if each of the individual chemicals in the 
assessment has been determined to be ``safe,'' based on aggregate 
exposures only to that individual chemical.

IV. Regulatory History of Carbaryl

A. In General

    Carbaryl is a carbamate insecticide and molluscide that was first 
registered in 1959 for use on cotton. Carbaryl has many trade names, 
but is most commonly known as Sevin[reg]. At the time carbaryl was 
assessed for purposes of reregistration, carbaryl was registered for 
use on over 400 agricultural and non-agricultural use sites, and there 
were more than 140 tolerances for carbaryl in the Code of Federal 
Regulations (40 CFR 180.169). The primary risk of concern from exposure 
to carbaryl is acute neurotoxic effects. Carbaryl is a member of the N-
methyl carbamate class of pesticides. This group shares a common 
mechanism of toxicity; namely, the ability to inhibit

[[Page 56002]]

the enzyme acetylcholinesterase (AChE) through carbamylation of the 
active site. Pesticides included is this group, other than carbaryl, 
are aldicarb, carbofuran, formetanate hydrochloride, methiocarb, 
methomyl, oxamyl, pirimicarb, propoxur, and thiodicarb.

B. FFDCA Tolerance Reassessment and FIFRA Pesticide Reregistration

    1. Interim reregistration eligibility decision. EPA completed an 
interim reregistration eligibility decision (IRED) for carbaryl on June 
30, 2003 (2003 IRED). The decision on reregistration was treated as 
interim because of carbaryl's membership in the N-methyl carbamate 
cumulative group. When EPA determines that a pesticide shares a common 
mechanism of toxicity with other substances, EPA cannot complete either 
the assessment or reassessment of a tolerance or a registration or 
reregistration determination until it has assessed available 
information regarding exposures to the other substances. For these 
pesticides, EPA's practice is to issue an IRED pending completion of 
the tolerance reassessment activities. An IRED memorializes EPA's 
determination on a narrowly defined issue: Whether a given active 
ingredient alone is eligible for reregistration under FIFRA and 
tolerance reassessment under the FFDCA, pending a cumulative assessment 
for pesticides sharing a common mechanism of toxicity.
    Although EPA found in the 2003 IRED that carbaryl dietary exposures 
from food and water were below the relevant safe doses (i.e., the acute 
PAD (aPAD) and chronic PAD (cPAD)), EPA concluded that numerous 
residential uses posed a risk of concern. Accordingly, the 2003 IRED 
specified various changes to the carbaryl registration to address these 
risks, including: Canceling liquid broadcast applications to home lawns 
pending EPA review of pharmacokinetic data to refine post-application 
risk estimates; repackaging home garden/ornamental dust products in 
ready-to-use shaker can containers, with no more than 0.05 lbs. active 
ingredient (ai) per container; canceling the following uses and 
application methods -- all pet uses (dusts and liquids) except collars, 
aerosol products for various uses, belly grinder applications of 
granular and bait products for lawns, hand applications of granular, 
and bait products for ornamentals and gardens.
    2. Amended interim reregistration eligibility decision. The Agency 
amended the 2003 IRED on October 22, 2004 (2004 Amended IRED), and 
published a formal Notice of Availability for the document, which 
provided for a 60-day public comment period. EPA received numerous 
comments on the carbaryl 2004 Amended IRED, including the NRDC petition 
requesting that EPA cancel all carbaryl registrations and revoke all 
tolerances. The mitigation detailed in the 2004 Amended IRED for 
residential uses included limiting applications of liquid formulations 
to residential turf areas to spot treatment only; requiring dust 
formulations to be packaged in a ready-to-use container containing no 
more than 0.05 lbs ai/container; and cancelation of all pet uses, 
except for carbaryl treated pet collars. On March 9, 2005, EPA issued a 
cancellation order for the liquid broadcast use of carbaryl on 
residential turf to address post-application risk to toddlers. (Ref. 
11). In March 2005, EPA also issued generic and product-specific data 
call-ins (DCIs) for carbaryl. The carbaryl generic DCI required several 
studies of the active ingredient carbaryl, including additional 
toxicology, worker exposure monitoring, and environmental fate data. 
The product-specific DCI required acute toxicity and product chemistry 
data for all pesticide products containing carbaryl; these data are 
being used for product labeling. EPA has received numerous studies in 
response to these DCIs, and, where appropriate, these studies were 
considered in the tolerance reassessment.
    In response to the DCIs, many carbaryl registrants chose to 
voluntarily cancel their carbaryl products, rather than revise their 
labels or conduct studies to support these products. EPA published a 
notice of receipt of these requests in the Federal Register on October 
28, 2005 (70 FR 62112), followed by a cancellation order issued on July 
3, 2006. One technical registrant, Burlington Scientific, chose to 
cancel their technical product, leaving Bayer CropScience (Bayer) as 
the sole technical registrant for carbaryl. Approximately two-thirds of 
all of the carbaryl products registered at the time of the 2003 IRED 
have been canceled through this process.
    Bayer subsequently requested that all of their carbaryl 
registrations be amended to delete the following uses: carbaryl use in 
or on pea and bean, succulent shelled (subgroup 6B); millet; wheat; 
pre-plant root dip for sweet potato; pre-plant root dip/drench for 
nursery stocks, vegetable transplants, bedding plants, and foliage 
plants; use of granular formulations on leafy vegetables (except 
Brassica); ultra low volume (ULV) application for adult mosquito 
control; and dust applications in agriculture. EPA notified all 
affected registrants that these uses and application methods must be 
deleted from their carbaryl product labels. EPA identified 34 product 
labels from 14 registrants (other than Bayer) bearing these end uses. 
All of these registrants requested that their affected carbaryl product 
registrations be amended to delete these uses. EPA published Notices of 
receipt of these requests from Bayer and all 14 registrants in the 
Federal Register on August 20, 2008 and October 15, 2008. On March 18, 
2009, the Agency published an order granting the requests to delete 
uses (74 FR 11553). Most recently, in a letter dated September 30, 
2009, Wellmark International submitted a request to voluntarily cancel 
its pet collar registrations pursuant to section 6(f) of FIFRA (74 FR 
54045, October 21, 2009). These are the only carbaryl pet collar 
registrations and the last remaining pet product registrations for 
carbaryl. EPA issued its final order cancelling carbaryl registrations 
for pet collar uses on December 16, 2009. (74 FR 66642, December 16, 
2009).
    3. Reregistration eligibility decision. As noted, the 
reregistration eligibility decision had to remain interim in nature 
until the N-methyl carbamate cumulative risk assessment was completed. 
That assessment was issued on September 26, 2007, and EPA concluded 
that the cumulative risks associated with the N-methyl carbamate 
pesticides meet the safety standard set forth in section 408(b)(2) of 
the FFDCA, provided that the mitigation specified in the N-methyl 
carbamate cumulative risk assessment is implemented, such as 
cancellation of all uses of carbofuran, termination of methomyl use on 
grapes, etc. EPA has therefore terminated the tolerance reassessment 
process under 408(q) of the FFDCA. (See Ref. 12 for additional 
information).
    In conjunction with the N-methyl carbamate cumulative risk 
assessment, EPA completed a RED for carbaryl on September 24, 2007 (the 
RED was issued on October 17, 2007 with a formal Notice of Availability 
in the Federal Register (72 FR 58844)). (Ref. 12). In addition to 
relying on the N-methyl carbamate cumulative risk assessment to 
determine that the cumulative effects from exposure to all N-methyl 
carbamate residues, including carbaryl, was safe, the carbaryl RED 
relied upon the revised assessments and the mitigation that had already 
been implemented (e.g., cancellation of pet uses except for collars). 
Additionally, the RED included additional mitigation with respect to 
granular turf products for residential use; namely, that product labels 
direct users to water the product in immediately after application. EPA

[[Page 56003]]

subsequently completed an addendum to the carbaryl RED, dated August 
25, 2008, which incorporated the results of a revised occupational risk 
assessment and modified mitigation measures for the protection of 
workers. The Agency issued a Notice of Availability for the RED 
addendum in the October 29, 2008 Federal Register (73 FR 64317).
    4. Risk assessment issues with the IRED and RED relevant to NRDC 
petition--a. selection of POD. When deriving Points of Departure and 
assigning uncertainty/safety factors in risk assessment, EPA looks at 
all the appropriate data available at a given time. In cases when new 
data become available improving the quality of the overall 
toxicological database, it is typical practice to re-consider previous 
decisions of the most appropriate Point(s) of Departure and uncertainty 
factors. Specific to carbaryl, Points of Departures and uncertainty/
safety factors have changed over time as new data have become available 
to fill data gaps, provide additional information on existing data, and 
describe the effects in juvenile animals.
    For the 2003 IRED and 2004 Amended IRED, the POD for acute exposure 
was from a developmental neurotoxicity (DNT) study. The POD used for 
risk assessment was 1 milligrams/kilogram/day (mg/kg/day) based upon 
the results of the DNT study. In the DNT study the LOAEL was 10 mg/kg/
day based upon functional observational changes (pinpoint pupils, 
tremors, and gait abnormalities). Also occurring in this study were 
morphometric changes in the brain with a LOAEL of 10 mg/kg/day: 
bilateral decrease in the size of the forebrain in adult males; a 
bilateral decrease in the length of the cerebella in female pups; and a 
bilateral increase in the length of the cerebella in female adults. A 
NOAEL for these effects was not identified in the study because a 
morphometric analysis was conducted in only the control and high-dose 
groups (10 mg/kg/day), but not in low-dose (0.1 mg/kg/day) or mid-dose 
(1.0 mg/kg/day) groups. Initially, upon review of the data, EPA had 
requested that morphometric analysis of the low-dose and mid-dose 
groups be conducted, but this was not possible because the brain 
tissues had dried during the preservation process. Nonetheless, EPA 
determined that the developmental NOAEL was likely 1 mg/kg/day. This 
conclusion was based on the finding that the morphometric changes, 
although statistically significant, were minimal in nature and, 
therefore, judged not likely to be present at the mid-dose of 1 mg/kg/
day. (Refs. 13, 14, and 15).
    Subsequently, in November of 2006, OPP received data from a 
carbaryl comparative cholinesterase assay study (CCA study) performed 
by EPA's Office of Research and Development. CCA studies are specially 
designed toxicity studies that evaluate comparative sensitivity in 
adult and juvenile rats with respect to inhibition of cholinesterase 
activity. In the case of the carbaryl CCA study, the juvenile rats were 
aged post-natal day 11 and 17 (PND11 and PND17).
    In the carbaryl CCA, a time course study was first conducted to 
determine the time to peak ChE effects followed by a dose-response 
study where rats were dosed by oral gavage with corn oil or 3, 7.5, 15, 
or 30 mg carbaryl/kg body weight. All ages received the same dose so as 
to better compare the effects across ages. The dose was given at 2 ml/
kg. Therefore, the dosing solutions were 0, 1.5, 3.75, 7.5, or 15 mg/
ml. In 2007, EPA conducted a BMD analysis for the carbaryl CCA study, 
using the same modeling methodology used in the N-methyl carbamate 
cumulative risk assessment. This BMD analysis demonstrated sensitivity 
of PND11 and PND17 pups compared to adult ORD ChE data. Previously, in 
2005 and in support of the N-methyl carbamate cumulative risk 
assessment, the Agency also conducted a BMD analysis of brain and RBC 
cholinesterase inhibition in rat oral toxicity studies for adults. 
(Ref. 16, see also Refs. 17 and 18). The BMD10 is the 
estimated benchmark doses that results in 10% cholinesterase inhibition 
(a level generally regarded as not an adverse effect), and the 
BMDL10 is the lower 95% confidence interval on the 
BMD10, for the data evaluated. Generally, the 
BMD10 is used to compare across compartments and across ages 
but the BMDL10 is used as the POD. The results of the study 
are presented in the following table in terms of the BMD10 
and BMDL10:

----------------------------------------------------------------------------------------------------------------
                                                           Brain (mg/kg)                   RBC (mg/kg )
                       Age                       ---------------------------------------------------------------
                                                       BMD10          BMDL10            BMD           BMDL10
----------------------------------------------------------------------------------------------------------------
PND11                                                       1.46            1.14            1.11            0.78
----------------------------------------------------------------------------------------------------------------
PND17                                                       3.00            2.37            1.41            1.05
----------------------------------------------------------------------------------------------------------------
Adults                                                      2.63            2.03            0.96            0.73
----------------------------------------------------------------------------------------------------------------

    As the table shows, juvenile 11-day old (PND11) pups were 1.8 times 
more sensitive to inhibition of brain cholinesterase than adult rats in 
terms of BMDs. The BMD analyses show that the brain BMD for pups is 
protective of adults since the pup BMD values are lower than adult 
values. For the red blood cell cholinesterase (RBC ChE) compartment, 
the RBC BMD10 in PND11 pups is similar to that in adults. 
Although the RBC BMDL10 for PND11 pups is numerically lower 
(0.8 mg/kg) than the BMDL10 for PND11 brain AChE inhibition 
(1.1 mg/kg), the magnitude of this difference is not biologically 
meaningful, particularly in light of the similarity in 
BMD10s, and considering the higher variability typically 
seen in RBC measurements relative to brain. Brain represents the target 
tissue for the N-methyl carbamates as opposed to using a surrogate 
measure (RBC) and the brain BMDL10 of 1.1 mg/kg would be 
protective of both central nervous system and peripheral nervous system 
effects. (Refs. 17 and 18).
    For the carbaryl risk assessment, the BMDL10 for 
inhibition of brain cholinesterase in PND11 juveniles from the CCA 
study was chosen as the most sensitive and appropriate POD for 
calculating a safe dose instead of using an extrapolated NOAEL from the 
DNT study. Several factors were critical to that determination. First, 
the CCA study is considered a sentinel study for the N-methyl 
carbamates as it evaluates the most sensitive endpoint (cholinesterase 
inhibition) in the most sensitive age group (PND11) at the time of peak 
effect. For each N-methyl carbamate with a valid CCA study, this study 
is being used in the risk assessment to inform the children's safety 
factor or the POD. EPA has high confidence in the quality of the data 
from the carbaryl study because it used a broad range of doses and used 
the radiometric method of measuring AChE inhibition. (Ref. 19). The 
radiometric method for assaying

[[Page 56004]]

ACHe inhibition provides the most appropriate method for measuring 
cholinesterase inhibition due to N-methyl carbamate exposure because 
factors (i.e., assay temperature, dilution, and incubation time) which 
promote reversibility are minimized.
    Second, gavage studies, such as the CCA study, are the preferred 
and most sensitive studies for carbaryl. The toxicity profile of 
carbaryl and other N-methyl carbamates is characterized by a rapid 
onset of toxicity with a peak time of effect around 15 to 60 minutes 
and rapid recovery (typical half-lives in adult rats are 1 to 2 hours). 
This pattern of toxicity is shown in Figure 1 for carbaryl.
[GRAPHIC] [TIFF OMITTED] TR15SE10.020

    With N-methyl carbamates, due to rapid recovery, toxicity does not 
accumulate in juveniles or adults with repeated exposures. As such, EPA 
is most concerned about acute effects, particularly those which occur 
at the peak time of effect. The Agency has found for these pesticides 
that acute studies, particularly via gavage administration, provide the 
most sensitive effects (i.e., more health protective) for risk 
assessment. Specifically, acute gavage studies provide more sensitive 
effects than studies administered in the diet, even studies of much 
longer durations. For example, the NOAEL and LOAEL for RBC AChE 
inhibition in the carbaryl dietary 2-year rat chronic/carcinogenicity 
study are 10/12\1\ mg/kg/day and 60.2/78.6 mg/kg/day in adult rats, 
whereas the BMD10/BMDL10 for RBC AChE inhibition 
in adult rats in acute gavage studies are 0.96 and 0.73 mg/kg. Based on 
this comparison, the acute gavage study provides toxicity values almost 
tenfold more sensitive than in the 2-year feeding study.
---------------------------------------------------------------------------

    \1\ Two values are provided for males/females.
---------------------------------------------------------------------------

    This pattern of toxicity is somewhat unique to this class of 
pesticides and can be attributed to the pharmacokinetic and 
pharmacodynamic properties of N-methyl carbamates, like carbaryl. The 
parent active ingredient, carbaryl, is the toxicologically active 
compound. As such, no metabolic activation is required; instead, 
metabolism results in detoxification of carbaryl. As evidenced by the 
rapid onset of toxicity, these pesticides are rapidly absorbed, 
distributed, and cleared from the body.
    For this class of pesticides, neurotoxicity is correlated to peak 
concentrations of carbaryl. Specifically, brain tissue levels and 
inhibition of brain AChE at the time of peak effect are highly 
correlated. In dietary administration studies like the 2-year study and 
the DNT study, rats are exposed to carbaryl over several hours of 
feeding. This is in contrast to a bolus dose in gavage studies where 
the entire dose is given at one time. In the dietary studies, the total 
administered dose of carbaryl consumed may be equal or even higher than 
the gavage dose. However, it is the internal dose of carbaryl at the 
target tissues which is related to the magnitude to toxicity. In the 
dietary studies, due to the rapid metabolism and clearance, carbaryl 
does not reach a peak level like that in gavage studies at the target 
tissues and thus the degree of toxicity in dietary studies is far less 
than that for gavage studies. As a result, acute gavage studies tend to 
be far more sensitive than dietary studies for N-methyl carbamates. 
This is the case for carbaryl as shown by the high quality and 
sensitive data from the CCA study.
    Finally, the changes in brain morphometrics (10 mg/kg) from the DNT 
study originally used in the POD derivation were determined to be a 
marginal effect not consistently seen in carbarmate pesticides. (See 
Unit IV.B.4.b. for a full discussion of EPA's review of the DNT study.) 
Although a 10X uncertainty factor was originally applied to the 
marginal brain morphometric endpoint, the real NOAEL is likely greater 
than 1 mg/kg and less than 10 mg/kg.
    In any event, the extrapolated NOAEL from the DNT study is 
essentially

[[Page 56005]]

equivalent to the BMDL10 for PND11 juveniles in the CCA 
study (i.e., 1 mg/kg/day as compared to 1.1 mg/kg/day). As explained 
below, if the LOAEL from the DNT was used in calculating a safe dose, 
EPA would retain a children's safety factor of no greater than 10X due 
to the lack of a NOAEL in that study. Retention of a children's safety 
factor of 10X would make the extrapolated NOAEL for the DNT study 
essentially equivalent to the BMDL10 for PND11 juveniles in 
the CCA study (i.e., 1 mg/kg/day as compared to 1.1 mg/kg/day).
    b. Children's safety factor. With respect to the children's safety 
factor, in preliminary reviews undertaken in 1999 and 2001, EPA 
initially retained the full 10X safety factor for carbaryl. The reasons 
for retaining the 10X children's safety factor were that EPA was 
missing a two-generation reproduction study for carbaryl and the DNT 
study showed changes in brain morphometric measurements of the 
offspring which raised concerns. The data from the DNT study showed 
that for the first generation pups, there were no treatment-related 
effects on pup weight, pup survival indices, developmental landmarks 
(tooth eruption and eye opening), Functional Observational Battery 
(FOB) measurements or motor activity assessments. There were also no 
treatment related effects on brain weight and gross or microscopic 
pathology. There were, however, changes noted in brain morphometric 
measurements at the high dose (10 mg/kg/day): Bilateral decrease in the 
size of the forebrain in adult males; a bilateral decrease in the 
length of the cerebella in female pups; and a bilateral increase in the 
length of the cerebella in female adults. EPA requested that a 
morphometric analysis of the low-dose and mid-dose groups be conducted, 
but this was not possible because brain samples had not been prepared 
for measurement and the tissues had dried during the preservation 
process. At the time, EPA found these changes at the high dose to be 
significant. (See generally Refs. 20, 21, 22, 23, 24, 25 and 26).
    When new information became available in 2002, EPA removed the 10X 
safety factor for acute dietary and short-and intermediate-term 
exposures. (Refs. 13, 14 and 15). Not only did EPA receive a new two-
generation reproduction study (and therefore no longer had any data 
gaps) but EPA also obtained new brain morphometric measurements from 
the DNT study for the control and high-dose groups. The new 
measurements demonstrated that even at the high dose, the morphometric 
changes, although statistically significant, were minimal in nature. 
This is consistent with the DNT study results for other N-methyl 
carbamates (aldicarb and carbofuran), which did not show any changes in 
morphometrics. In addition, the DNTs available for all three N-methyl 
carbamates have not shown any long-term effects, including effects on 
behavior. The Agency is also not aware of any literature studies that 
have shown any changes in brain histopathology following N-methyl 
carbamate exposure to animals of any age. Based on this information, 
EPA concluded that the brain morphometic effects were not likely to be 
present at the mid-dose. (Refs. 13, 14 and 15). Because the 
developmental effects in the DNT were now well-characterized and the 
evidence strongly indicated that no brain morphometric changes would 
have been present at the mid-dose (1 mg/kg/day), EPA determined that 
the children's safety factor was not needed. In addition, there were no 
concerns or residual uncertainties for pre- and/or postnatal toxicity 
from other carbaryl development studies.
    After EPA received the CCA study in 2006, it modified its decision 
on the children's safety factor slightly. As explained above, the 
BMDL10 for PND11 juveniles from the CCA study was chosen for 
the POD in calculating a safe dose. Because (1) EPA had a complete data 
set for carbaryl including high quality data comparing the relative 
sensitivity of adults and the young, (2) the effects in the young had 
been well-characterized, and (3) the most sensitive effect in the young 
(the BMDL10 from the CCA study) was being used to calculate 
the safe dose (i.e., the BMDL10 was divided by inter- and 
intra-species safety factors), EPA determined that a children's safety 
factor was not needed for risk assessments based on the CCA study. 
Where carbaryl assessments relied on other data not involving the 
testing of juveniles, EPA retained a children's safety factor of 1.8X 
reflecting the degree of sensitivity of the young observed in the CCA 
study.
    c. Calculation of safe dose/aPAD for carbaryl. For dietary risks, 
EPA calculated the aPAD by dividing the dietary POD (the 
BMDL10 for PND11 juveniles in the CCA study) by the inter-
species and intra-species safety factors (100X) to yield a value of 
0.01 mg/kg. For dermal risks, instead of calculating an aPAD, EPA 
assessed risk under a MOE approach. The acceptable or target MOE was 
calculated using a POD of 86 mg/kg. The POD was obtained by multiplying 
the BMDL10 of 30.56 mg/kg from the dermal toxicity study by 
2.8, because in an in vitro dermal absorption study, rat skin was 2.8 
times more permeable than human skin to carbaryl. The target MOE for 
risk assessment is 100 for adults because the inter-species and intra-
species safety factors total 100X. The target MOE for risk assessment 
for infants and children is 180 because, in addition to the 100X, the 
children's safety factor is 1.8X.

V. NRDC Petitions Regarding Carbaryl

    In the underlying petition, NRDC requested, among other things, 
that EPA cancel all carbaryl registrations and revoke all carbaryl 
tolerances. (Ref. 2). NRDC's January 10, 2005 petition was submitted in 
the form of comments on and requests for changes to the Carbaryl 
Interim Reregistration Eligibility Decision published in the Federal 
Register on October 27, 2004, 70 FR 62663. Nonetheless, in the 
introduction to the comments, NRDC included a statement that NRDC was 
also petitioning the Agency to revoke all carbaryl tolerances. Among 
other things, NRDC raised issues with the dietary assessment, and in 
particular, EPA's drinking water assessment that supported the 2004 
IRED decision. NRDC also raised concerns about the data surrounding 
EPA's selection of a children's safety factor. NRDC raised other safety 
factor issues, particularly as they relate to EPA use of the DNT study. 
NRDC's petition also included generic disagreements with how EPA 
conducts its assessments.
    Subsequently, as part of its comments on the N-methyl carbamate 
cumulative assessment dated November 26, 2007, NRDC requested that EPA 
cancel all carbaryl pet collar registrations. (Ref. 3). The basis for 
NRDC's petition to cancel all pet collar registrations rested on issues 
related to EPA's assessment of cumulative effects under the FFDCA. In 
addition, NRDC incorporated by reference its earlier petition to revoke 
all carbaryl tolerances. Accordingly, EPA addressed the exposure issues 
raised in the subsequent pet collar petition as part of its response to 
the earlier petition to revoke all carbaryl tolerances.

VI. EPA's Response to the Petitions to Revoke Carbaryl Tolerances

    On October 29, 2008, EPA denied NRDC's petition to revoke all 
pesticide tolerances for carbaryl under section 408(d) of the FFDCA. 
(73 FR 64229). EPA's Order also constituted a response to NRDC's 
petition dated November 26, 2007, to cancel carbaryl pet collar 
registrations submitted as part of NRDC's comments on the N-methyl 
carbamate cumulative assessment. Again, EPA's response to NRDC's 
petition to cancel pet collar registrations was addressed in that Order 
because the

[[Page 56006]]

basis for the petition to cancel pet collars rested on issues related 
to EPA's assessment of cumulative effects under the FFDCA.

VII. NRDC's Objections and Requests for Hearing

    On December 28, 2008, NRDC filed, pursuant to FFDCA section 
408(g)(2), objections to EPA's denial of its tolerance revocation 
petition and requested a hearing on those objections. As indicated 
above, NRDC's objections and requests for hearing raise two main 
claims: (1) that EPA lacks reliable data to reduce the default tenfold 
safety factor and (2) that EPA's exposure assessment for carbaryl is 
flawed and underestimates the exposure to children from pet collar 
uses.
    NRDC asserts that EPA failed to consider the available 
developmental neurotoxicity data and, therefore, unlawfully lowered the 
10X children's safety factor. Specifically, NRDC argues that the DNT 
study showed adverse developmental abnormalities in juvenile test 
animals at doses that had no effect on adult test