[Federal Register Volume 73, Number 148 (Thursday, July 31, 2008)]
[Proposed Rules]
[Pages 44864-44892]
From the Federal Register Online via the Government Publishing Office [www.gpo.gov]
[FR Doc No: E8-17660]



[[Page 44863]]

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Part III





Environmental Protection Agency





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40 CFR Part 180



Carbofuran; Proposed Tolerance Revocations; Proposed Rule

Federal Register / Vol. 73, No. 148 / Thursday, July 31, 2008 / 
Proposed Rules

[[Page 44864]]


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ENVIRONMENTAL PROTECTION AGENCY

40 CFR Part 180

[EPA-HQ-OPP-2005-0162; FRL-8373-8]


Carbofuran; Proposed Tolerance Revocations

AGENCY: Environmental Protection Agency (EPA).

ACTION: Proposed rule.

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SUMMARY: EPA is proposing to revoke all tolerances for carbofuran. The 
Agency has determined that the risk from aggregate exposure from the 
use of carbofuran does not meet the safety standard of section 
408(b)(2) of the Federal Food, Drug, and Cosmetic Act (FFDCA). EPA is 
specifically soliciting comment on whether there is an interest in 
retaining any individual tolerance, or group of tolerances, and whether 
information exists to demonstrate that such tolerance(s) meet(s) the 
FFDCA section 408(b)(2) safety standard. EPA encourages interested 
parties to comment on the tolerance revocations proposed in this 
document and on the proposed time frame for tolerance revocation. 
Issues not raised during the comment period may not be raised as 
objections to the final rule, or in any other challenge to the final 
rule.

DATES: Comments must be received on or before September 29, 2008.

ADDRESSES: Submit your comments, identified by docket identification 
(ID) number EPA-HQ-OPP-2005-0162, by one of the following methods:
    <bullet> Federal eRulemaking Portal: http://www.regulations.gov. 
Follow the on-line instructions for submitting comments.
    <bullet> Mail: Office of Pesticide Programs (OPP) Regulatory Public 
Docket (7502P), Environmental Protection Agency, 1200 Pennsylvania 
Ave., NW., Washington, DC 20460-0001.
    <bullet> 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.
    Instructions: Direct your comments to docket ID number EPA-HQ-OPP-
2005-0162. EPA's policy is that all comments received will be included 
in the docket without change and may be made available on-line at 
http://www.regulations.gov, including any personal information 
provided, unless the comment includes information claimed to be 
Confidential Business Information (CBI) or other information whose 
disclosure is restricted by statute. Do not submit information that you 
consider to be CBI or otherwise protected through regulations.gov or e-
mail. The Federal regulations.gov website is an ``anonymous access'' 
system, which means EPA will not know your identity or contact 
information unless you provide it in the body of your comment. If you 
send an e-mail comment directly to EPA without going through 
regulations.gov, your e-mail address will be automatically captured and 
included as part of the comment that is placed in the docket and made 
available on the Internet. If you submit an electronic comment, EPA 
recommends that you include your name and other contact information in 
the body of your comment and with any disk or CD-ROM you submit. If EPA 
cannot read your comment due to technical difficulties and cannot 
contact you for clarification, EPA may not be able to consider your 
comment. Electronic files should avoid the use of special characters, 
any form of encryption, and be free of any defects or viruses.
    Docket: All documents in the docket are listed in the docket index. 
Although listed in the index, some information is not publicly 
available, e.g., CBI or other information whose disclosure is 
restricted by statute. Certain other material, such as copyrighted 
material, is not placed on the Internet and will be publicly available 
only in hard copy form. Publicly available docket materials are 
available either in the electronic docket at http://www.regulations.gov, or, if only available in hard copy, at the OPP 
Regulatory Public Docket in Rm. S-4400, One Potomac Yard (South 
Building), 2777 S. Crystal Drive, 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 telephone number is (703) 
305-5805.

FOR FURTHER INFORMATION CONTACT: Jude Andreasen Special Review and 
Reregistration Division (7508C), Office of Pesticide Programs, 
Environmental Protection Agency, 1200 Pennsylvania Ave, NW., 
Washington, DC 20460-0001; telephone number: (703) 305-0076; e-mail 
address: <a href="/cdn-cgi/l/email-protection#debfb0baacbbbfadbbb0f0b4abbabb9ebbaebff0b9b1a8"><span class="__cf_email__" data-cfemail="2f4e414b5d4a4e5c4a4101455a4b4a6f4a5f4e01484059">[email protected]</span></a>.

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:
    <bullet> Crop production (NAICS code 111).
    <bullet> Animal production (NAICS code 112).
    <bullet> Food manufacturing (NAICS code 311).
    <bullet> 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 [Unit II.A]. 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. What Should I Consider as I Prepare My Comments for EPA?

    1. Submitting CBI. Do not submit this information to EPA through 
regulations.gov or e-mail. Clearly mark the part or all of the 
information that you claim to be CBI. For CBI information in a disk or 
CD ROM that you mail to EPA, mark the outside of the disk or CD ROM as 
CBI and then identify electronically within the disk or CD ROM the 
specific information that is claimed as CBI. In addition to one 
complete version of the comment that includes information claimed as 
CBI, a copy of the comment that does not contain the information 
claimed as CBI must be submitted for inclusion in the public docket. 
Information so marked will not be disclosed except in accordance with 
procedures set forth in 40 CFR part 2.
    2. Tips for preparing your comments. When submitting comments, 
remember to:
    i. Identify the document by docket ID number and other identifying 
information (subject heading, Federal Register date and page number).
    ii. Follow directions. The Agency may ask you to respond to 
specific questions or organize comments by referencing a

[[Page 44865]]

Code of Federal Regulations (CFR) part or section number.
    iii. Explain why you agree or disagree; suggest alternatives and 
substitute language for your requested changes.
    iv. Describe any assumptions and provide any technical information 
and/or data that you used.
    v. If you estimate potential costs or burdens, explain how you 
arrived at your estimate in sufficient detail to allow for it to be 
reproduced.
    vi. Provide specific examples to illustrate your concerns and 
suggest alternatives.
    vii. Explain your views as clearly as possible, avoiding the use of 
profanity or personal threats.
    viii. Make sure to submit your comments by the comment period 
deadline identified.

C. What Can I Do if I Wish the Agency to Maintain a Tolerance that the 
Agency Proposes to Revoke?

    This proposed rule provides a comment period of 60 days for any 
interested person to submit comments on the Agency's proposal. EPA 
issues a final rule after considering comments that are submitted in 
response to this proposed rule. Comments should be limited only to the 
pesticide and tolerances subject to this proposed notice.
    EPA's finding that aggregate exposure from all existing uses of 
carbofuran is not safe does not necessarily mean that no individual 
tolerance or group of tolerances could meet the FFDCA 408(b)(2) safety 
standard and be maintained. For example, in its Interim Reregistration 
Eligibility Decision (IRED), EPA concluded that the Agency could 
maintain import tolerances for bananas, coffee, rice, and sugarcane, 
because dietary risks from the food residues from the import tolerances 
are below the Agency's level of concern when considered together with 
the food residues from the phase-out crops, but with no other domestic 
uses (Ref. 35). However, as discussed in more detail below, EPA can 
only maintain tolerances that it can determine will be ``safe'' within 
the meaning of section 408(b)(2)(A)(ii). Accordingly, commenters 
interested in retaining any tolerance or group of tolerances should 
consider submitting information to demonstrate that the tolerance(s) 
meet the statutory standard, rather than merely indicating an interest 
in retaining the tolerance. Commenters should also be aware that even 
if EPA determines that any carbofuran tolerance(s) meet the safety 
standard, those tolerances can only be maintained if EPA can also 
determine that the cumulative effects from those tolerances, when 
considered with the exposures from other N-methyl carbamate pesticide 
chemicals, will meet the FFDCA 408(b)(2) safety standard. EPA will not 
respond to any comments on subjects that do not relate to the 
evaluation or safety of the pesticide tolerances subject to this 
proposed notice.
    After consideration of comments, EPA will issue a final regulation 
determining whether revocation of the tolerances is appropriate and 
making a final finding on whether these tolerances are ``safe'' within 
the meaning of section 408(b)(2)(A)(ii). Such regulation will be 
subject to objections pursuant to section 408(g) (21 U.S.C. 346a(g)).
    In addition to submitting comments in response to this proposal, 
you may also submit an objection at the time of the final rule. If you 
anticipate that you may wish to file objections to the final rule, you 
must raise those issues in your comments on this proposal. EPA will 
treat as waived, any issue not originally raised in comments on this 
proposal. Similarly, if you fail to file an objection to the final rule 
within the time period specified, you will have waived the right to 
raise any issues resolved in the final rule. After the specified time, 
issues resolved in the final rule cannot be raised again in any 
subsequent proceedings on this rule.

II. Introduction

A. What Action is the Agency Taking?

    EPA is proposing to revoke all of the existing tolerances for 
residues of carbofuran. Currently, tolerances have been established on 
the following crops: alfalfa, fresh; alfalfa, hay; artichoke, globe; 
banana; barley, grain; barley, straw, sugar beet; sugar beet, tops; 
coffee bean; corn, forage; corn, fresh (including sweet corn); corn, 
grain (including popcorn); corn, stover; cotton, undelinted seed; 
cranberry; cucumber; grape; grape (raisin); melon; milk; oat, grain; 
oat, straw; pepper; potato; pumpkin; raisins, waste; rice, grain; rice, 
straw; sorghum, fodder; sorghum, forage; sorghum, grain; strawberry; 
soybean; soybean, forage; soybean, hay; squash; sugarcane, cane; 
sunflower, seed; wheat, grain; wheat, straw. The Agency is proposing to 
revoke tolerances for these crops because aggregate dietary exposure to 
residues of carbofuran, including all anticipated dietary exposures and 
all other exposures for which there is reliable information, is not 
safe.
    EPA has determined that aggregate exposure to carbofuran greater 
than 0.000075 mg/kg/day (i.e., greater than the acute Population 
Adjusted Dose (aPAD)) does not meet the safety standard of section 
408(b)(2) of the FFDCA. Based on the contribution from food alone, the 
more sensitive children's subpopulations receive unsafe exposures to 
carbofuran. At the 99.9th percentile of exposure, aggregate carbofuran 
dietary exposure from food alone was estimated to range between 
0.000121 mg/kg/day for children 6-12 (160% of the aPAD) and 0.000156 
mg/kg/day (210% of the aPAD) for children 3-5 years old, the population 
subgroup with the highest estimated dietary exposure. In addition, 
EPA's analyses show that those individuals-both adults and children--
who receive their drinking water from vulnerable sources are also 
exposed to levels that exceed EPA's level of concern--in some cases by 
orders of magnitude. This primarily includes those populations 
consuming drinking water from groundwater from shallow wells in acidic 
aquifers overlaid with sandy soils that have had crops treated with 
carbofuran. Aggregate exposures from food and from drinking water 
derived from ground water in vulnerable areas (i.e., from shallow wells 
associated with sandy soils and acidic aquifers, such as are found in 
the Delmarva Peninsula of Delaware, Maryland, and Virginia) result in 
even higher estimated exceedances. The aggregate estimates for food and 
ground water exposure range between 1100% of the aPAD for adults over 
50 years, to over 10,000% of the aPAD for infants. Similarly, EPA 
analyses show substantial exceedances for those populations that obtain 
their drinking water from reservoirs (i.e., surface water) located in 
small agricultural watersheds, prone to runoff, and predominated by 
crops that are treated with carbofuran, even though there is more 
uncertainty associated with these exposure estimates. For example, 
estimated aggregate exposures from food and drinking water derived from 
surface water, based on the corn use in Nebraska, range between 340% of 
the aPAD for youths 13-19, and 3900% of the aPAD for infants.
    Every sensitivity analysis EPA has performed has shown that 
estimated exposures (both for food alone as well as for food and water) 
significantly exceed EPA's level of concern for children. Although the 
magnitude of the exceedance varies depending the level of conservatism 
in the assessment, the fact that in each case aggregate exposures from 
carbofuran fail to meet the FFDCA section 408(b)(2) safety standard, 
including where EPA relied on highly refined estimates of risk,

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using all relevant data and methods, strongly corroborates EPA's 
conclusion that aggregate exposures from carbofuran are not safe.

B. What is the Agency's authority for Taking this Action?

    EPA is taking this action, pursuant to the authority in FFDCA 
sections 408(b)(1)(b), 408(b)(2)(A), and 408(e)(1)(A). 21 U.S.C. 
346a(b)(1)(b), (b)(2)(A), (e)(1)(A).

III. Statutory and Regulatory Background

    A ``tolerance'' represents the maximum level for residues of 
pesticide chemicals legally allowed in or on raw agricultural 
commodities (including animal feed) and processed foods. Section 408 of 
the FFDCA, 21 U.S.C. 346a, as amended by the Food Quality Protection 
Act (FQPA) of 1996, Public Law 104-170, authorizes the establishment of 
tolerances, exemptions from tolerance requirements, modifications in 
tolerances, and revocation of tolerances for residues of pesticide 
chemicals in or on raw agricultural commodities and processed foods. 
Without a tolerance or exemption, food containing pesticide residues is 
considered to be unsafe and therefore ``adulterated'' under section 
402(a) of the FFDCA, 21 U.S.C. 342(a). Such food may not be distributed 
in interstate commerce (21 U.S.C. 331(a)). For a food-use pesticide to 
be sold and distributed, the pesticide must not only have appropriate 
tolerances under the FFDCA, but also must be registered under the 
Federal Insecticide Fungicide and Rodenticide Act (FIFRA) (7 U.S.C. 136 
et seq.). Food-use pesticides not registered in the United States must 
have tolerances in order for commodities treated with those pesticides 
to be imported into the United States.
    Section 408(e) of the FFDCA, 21 U.S.C. 346a(e), authorizes EPA to 
modify or revoke tolerances on its own initiative. EPA is proposing to 
revoke these tolerances to implement the Agency's findings made during 
the reregistration and tolerance reassessment processes. As part of 
these processes, EPA is required to determine whether each of the 
existing tolerances meets the safety standard of section 408(b)(2) (21 
U.S.C. 346a(b)(2)). Section 408(b)(2)(A)(i) of the FFDCA requires EPA 
to modify or revoke a tolerance if EPA determines that the tolerance is 
not ``safe.'' (21 U.S.C. 346a(b)(2)(A)(i)). Section 408(b)(2)(A)(ii) of 
the FFDCA defines ``safe'' 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.'' This 
includes exposure through drinking water and in residential settings, 
but does not include occupational exposure.
    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 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 proposal 
as the ``children's safety factor.''

IV. Carbofuran Background and Regulatory History

    In July 2006, EPA completed a refined acute probabilistic dietary 
risk assessment for carbofuran as part of the reassessment program 
under section 408(q) of the FFDCA. The assessment was conducted using 
Dietary Exposure Evaluation Model-Food Commodity Intake Database (DEEM-
FCID<SUP>(TM)</SUP>, Version 200-2.02), which incorporates consumption 
data from the United States Department of Agriculture's (USDA's) 
Nationwide Continuing Surveys of Food Intake by Individuals (CSFII), 
1994-1996 and 1998, as well as carbofuran monitoring data from USDA's 
Pesticide Data Program\1\ (PDP), estimated percent crop treated 
information, and processing/cooking factors, where applicable. The 
assessment was conducted applying an additional 500-fold safety factor 
that included a 5X children's safety factor, pursuant to section 
408(b)(2)(C). That refined assessment showed acute dietary risks from 
carbofuran residues in food above EPA's level of concern (Ref 15). 
Since 2006, EPA has evaluated additional data submitted by the 
registrant, FMC Corporation, and has further refined its original 
assessment by incorporating more recent 2005/2006 PDP data, and by 
conducting additional analyses. In January 2008, EPA published a draft 
Notice of Intent to Cancel (NOIC) all carbofuran registrations, based 
in part on carbofuran's dietary risks. As mandated by FIFRA, EPA 
solicited comments from the Scientific Advisory Panel (SAP) on its 
draft NOIC. Having considered the comments from the SAP, EPA is 
initiating the process to revoke all carbofuran tolerances. As noted 
above, aggregate exposures from food and water to the US population at 
the upper percentiles of exposure substantially exceed the safe daily 
levels and thus are ``unsafe'' within the meaning of FFDCA section 
408(b)(2) (Ref 12). It is particularly significant that under every 
analysis EPA has conducted, the levels of carbofuran exceed the safe 
daily dose for children, even when EPA used the most refined data and 
models available. Based on these findings, EPA has decided to move as 
expeditiously as possible to address the unacceptable dietary risks to 
children. EPA still expects to issue the NOIC subsequent to undertaking 
the activities required to revoke the carbofuran tolerances.
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    \1\ USDA's Pesticide Data Program monitors for pesticides in 
certain foods at the distribution points just before release to 
supermarkets and grocery stores.
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    In May 2008, FMC Corporation, the sole U.S. registrant, submitted a 
conditional request to cancel use of carbofuran on certain crops and to 
add use restrictions intended to mitigate ground and surface water 
contamination from use on other crops (Ref. 32). The tolerances that 
would have been affected by that proposal are: alfalfa, fresh; alfalfa, 
hay; artichoke, globe; barley, grain; barley, straw; sugar beet, tops; 
cranberry; cucumber; grape; grape (raisin); oat, grain; oat, straw; 
pepper; sorghum, fodder; sorghum, forage; sorghum, grain; strawberry; 
soybean; soybean, forage; soybean, hay; squash; wheat, grain; wheat, 
straw. FMC, however, conditioned the request on receiving assurance 
from EPA that the Agency would permit the retention of several uses 
that do not meet the FFDCA 408(b)(2) safety standard or the FIFRA 
registration standard (Id.). EPA, therefore, could not accept the 
request, and FMC has withdrawn it (Id.). The tolerances that FMC would 
have sought to retain under that proposal were:

[[Page 44867]]

banana, coffee bean; corn, forage; corn, fresh; corn, grain (including 
popcorn); corn, stover; cotton, undelinted seed; melon; milk; potato; 
rice, grain; rice, straw; sugarcane, cane; and sunflower, seed. Based 
on the contribution from these foods alone, dietary exposures to 
carbofuran would still be unsafe for the more sensitive children's 
subpopulations. At the 99.9th percentile, carbofuran dietary exposure 
from food alone was estimated at 0.000082 mg/kg/day (110% of the aPAD) 
for children 3-5 years old, the population subgroup with the highest 
estimated dietary exposure (Ref. 12). In addition, as discussed in more 
detail in Refs 18 and 54, although FMC's proposed groundwater 
restrictions would have protected against further contamination in the 
most vulnerable locations, the Agency could not conclude that the 
restrictions would be protective of all vulnerable groundwater. EPA 
also has substantial questions about the efficacy of FMC's proposed 
surface water restrictions to reduce drinking water exposure in 
vulnerable reservoirs (Refs. 18 and 54). Accordingly, it has not been 
shown that drinking water residues of carbofuran would no longer 
contribute significantly to unsafe aggregate exposures, nor that such 
exposures would meet the FFDCA safety standard.

V. EPA's Approach to Dietary Risk Assessment

    EPA performs a number of analyses to determine the risks from 
aggregate exposure to pesticide residues. A short summary is provided 
below to aid the reader. For further discussion of the regulatory 
requirements of section 408 of the FFDCA and a complete description of 
the risk assessment process, see http://www.epa.gov/fedrgstr/EPA-PEST/1999/January/Day-04/p34736.htm.
    To assess the 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: (1) identification of 
the toxicological hazards posed by a pesticide; (2) determination of 
the exposure ``level of concern'' for humans; (3) estimation of human 
exposure; and (4) characterization of human risk based on comparison of 
human exposure to the level of concern.

A. Hazard Identification and Selection of Toxicological Endpoint

    Any risk assessment begins with an evaluation of a chemical's 
inherent properties, and whether those properties have the potential to 
cause adverse effects (i.e., a hazard identification). EPA then 
evaluates the hazards to determine the most sensitive and appropriate 
adverse effect of concern, based on factors such as the effect's 
relevance to humans and the likely routes of exposure.
    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 evaluating a chemical's 
dietary risks EPA uses a reference dose (RfD) approach, which involves 
a number of considerations including:
    <bullet> A `point of departure'(PoD) -- the value from a dose-
response curve that is at the low end of the observable data and that 
is the toxic dose that serves as the `starting point' in extrapolating 
a risk to the human population;
    <bullet> An uncertainty factor to address the potential for a 
difference in toxic response between humans and animals used in 
toxicity tests (i.e., interspecies extrapolation);
    <bullet> An uncertainty factor to address the potential for 
differences in sensitivity in the toxic response across the human 
population (for intraspecies extrapolation); and
    <bullet> The need for an additional safety factor to protect 
infants and children, as specified in FFDCA section 408(b)(2)(C).
    EPA uses the chosen PoD to calculate a safe dose or RfD. The RfD is 
calculated by dividing the chosen PoD by all applicable safety or 
uncertainty factors. Typically in EPA risk assessments, a combination 
of safety or uncertainty factors providing at least a hundredfold 
(100X) margin of safety is used: 10X to account for interspecies 
extrapolation and 10X to account for intraspecies extrapolation. 
Further, in evaluating the dietary risks for pesticide chemicals, an 
additional safety factor of 10X is presumptively applied to protect 
infants and children, unless reliable data support selection of a 
different factor. In implementing FFDCA section 408, EPA also 
calculates a variant of the RfD referred to as a PAD. A PAD is the RfD 
divided by any portion of the children's safety factor that does not 
correspond to one of the traditional additional uncertainty/safety 
factors used in general Agency risk assessment. 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 acute assessments, the risk is expressed as a 
percentage of a maximum acceptable dose or the acute PAD (i.e., the 
acute dose which EPA has concluded will be ``safe''). As discussed 
below in Unit V.C., dietary exposures greater than 100 percent of the 
acute PAD are generally cause for concern and would be considered 
``unsafe'' within the meaning of FFDCA section 408(b)(2)(B). Throughout 
this document general references to EPA's calculated safe dose are 
denoted as an acute PAD, or aPAD, because the relevant point of 
departure for carbofuran is based on an acute risk endpoint.

B. Estimating Human Dietary Exposure Levels

    Pursuant to section 408(b) of the FFDCA, EPA has evaluated 
carbofuran's dietary risks based on ``aggregate exposure'' to 
carbofuran. By ``aggregate exposure,'' EPA is referring to exposure to 
carbofuran alone by multiple pathways of exposure. EPA uses available 
data, together with assumptions designed to be protective of public 
health and standard analytical methods, to produce separate estimates 
of exposure for a highly exposed subgroup of the general population, 
for each potential pathway and route of exposure. For acute risks, EPA 
then calculates potential aggregate exposure and risk by using 
probabilistic\2\ techniques to combine distributions of potential 
exposures in the population for each route or pathway. For dietary 
analyses, the relevant sources of potential exposure to carbofuran are 
from the ingestion of residues in food and drinking water. The Agency 
uses a combination of monitoring data and predictive models to evaluate

[[Page 44868]]

environmental exposure of humans to carbofuran.
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    \2\ Probabilistic analysis is used to predict the frequency with 
which variations of a given event will occur. By taking into account 
the actual distribution of possible consumption and pesticide 
residue values, probabilistic analysis for pesticide exposure 
assessments ``provides more accurate information on the range and 
probability of possible exposure and their associated risk values.'' 
(Ref. 58). In capsule, a probabilistic pesticide exposure analysis 
constructs a distribution of potential exposures based on data on 
consumption patterns and residue levels and provides a ranking of 
the probability that each potential exposure will occur. People 
consume differing amounts of the same foods, including none at all, 
and a food will contain differing amounts of a pesticide residue, 
including none at all.
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    1. Exposure from food. Data on the residues of carbofuran in foods 
are available from a variety of sources. One of the primary sources of 
the data comes from federally-conducted surveys, including the PDP 
conducted by the USDA. Further, market basket studies, which are 
typically performed by registrants, can provide additional residue 
data. These data generally provide a characterization of pesticide 
residues in or on foods consumed by the U.S. population that closely 
approximates real world exposures because they are sampled closer to 
the point of consumption in the chain of commerce than field trial 
data, which are generated to establish the maximum level of legal 
residues that could result from maximum permissible use of the 
pesticide. In certain circumstances, EPA will rely on field trial data, 
as it can provide more accurate exposure estimates (see below in Unit 
VI.E.1).
    EPA uses a computer program known as the DEEM-FCID to estimate 
exposure by combining data on human consumption amounts with residue 
values in food commodities. DEEM-FCID also compares exposure estimates 
to appropriate RfD or PAD values to estimate risk. EPA uses DEEM-FCID 
to estimate exposure for the general U.S. population as well as for 32 
subgroups based on age, sex, ethnicity, and region. DEEM-FCID allows 
EPA to process extensive volumes of data on human consumption amounts 
and residue levels in making risk estimates. Matching consumption and 
residue data, as well as managing the thousands of repeated analyses of 
the consumption database conducted under probabilistic risk assessment 
techniques, requires the use of a computer.
    DEEM-FCID contains consumption and demographic information on the 
individuals who participated in the USDA's CSFII in 1994-1996 and 1998. 
The 1998 survey was a special survey required by the FQPA to supplement 
the number of children survey participants. DEEM-FCID also contains 
``recipes'' that convert foods as consumed (e.g., pizza) back into 
their component raw agricultural commodities (e.g., wheat from flour, 
or tomatoes from sauce, etc.). This is necessary because residue data 
are generally gathered on raw agricultural commodities rather than on 
finished ready-to-eat food. Data on residue values for a particular 
pesticide and the RfD or PADs for that pesticide are inputs to the 
DEEM-FCID program to estimate exposure and risk.
    For carbofuran's assessment, EPA used DEEM-FCID to calculate risk 
estimates based on a probabilistic distribution. DEEM-FCID combines the 
full range of residue values for each food with the full range of data 
on individual consumption amounts to create a distribution of exposure 
and risk levels. More specifically, DEEM-FCID creates this distribution 
by calculating an exposure value for each reported day of consumption 
per person (``person/day'') in CSFII, assuming that all foods 
potentially bearing the pesticide residue contain such residue at the 
chosen value. The exposure amounts for the thousands of person/days in 
the CSFII are then collected in a frequency distribution. EPA also uses 
DEEM-FCID to compute a distribution taking into account both the full 
range of data on consumption levels and the full range of data on 
potential residue levels in food. Combining consumption and residue 
levels into a distribution of potential exposures and risk requires use 
of probabilistic techniques.
    The probabilistic technique that DEEM-FCID uses to combine 
differing levels of consumption and residues involves the following 
steps:
    (1) Identification of any food(s) that could bear the residue in 
question for each person/day in the CSFII;
    (2) Calculation of an exposure level for each of the thousands of 
person/days in the CSFII database, based on the foods identified in 
Step <greek-i>1, by randomly selecting residue values for the foods 
from the residue database;
    (3) Repetition of Step <greek-i> 2 one thousand times for each 
person/day; and
    (4) Collection of all of the hundreds of thousands of potential 
exposures estimated in Steps <greek-i><greek-i> 2 and 3 in a frequency 
distribution.
    The resulting probabilistic assessment presents a range of 
exposure/risk estimates.
    2. Exposure from water. EPA may use field monitoring data and/or 
simulation water exposure models to generate pesticide concentration 
estimates in drinking water. Monitoring and modeling are both important 
tools for estimating pesticide concentrations in water and can provide 
different types of information. Monitoring data can provide estimates 
of pesticide concentrations in water that are representative of the 
specific agricultural or residential pesticide practices in specific 
locations, under the environmental conditions associated with a 
sampling design (i.e., the locations of sampling, the times of the year 
samples were taken, and the frequency by which samples were collected). 
Although monitoring data can provide a direct measure of the 
concentration of a pesticide in water, it does not always provide a 
reliable basis for estimating spatial and temporal variability in 
exposures because sampling may not occur in areas with the highest 
pesticide use, and/or when the pesticides are being used and/or at an 
appropriate sampling frequency to detect high concentrations of a 
pesticide that occur over the period of a day to several days.
    Because of the limitations in most monitoring studies, EPA's 
standard approach is to use simulation water exposure models as the 
primary means to estimate pesticide exposure levels in drinking water. 
Modeling is a useful tool for characterizing vulnerable sites, and can 
be used to estimate peak pesticide water concentrations from 
infrequent, large rain events. EPA's computer models use detailed 
information on soil properties, crop characteristics, and weather 
patterns to estimate water concentrations in vulnerable locations where 
the pesticide could be used according to its label. (69 FR 30042, 
30058-30065 (May 26, 2004)). These models calculate estimated water 
concentrations of pesticides using laboratory data that describe how 
fast the pesticide breaks down to other chemicals and how it moves in 
the environment at these vulnerable locations. The modeling provides an 
estimate of pesticide concentrations in ground and surface water. 
Depending on the modeling algorithm (e.g., surface water modeling 
scenarios), daily concentrations can be estimated continuously over 
long periods of time, and for places that are of most interest for any 
particular pesticide.
    EPA relies on models it has developed for estimating pesticide 
concentrations in both surface water and ground water. Typically EPA 
uses a two-tiered approach to modeling pesticide concentrations in 
surface and ground water. If the first tier model suggests that 
pesticide levels in water may be unacceptably high, a more refined 
model is used as a second tier assessment. The second tier model is 
actually a combination of two models: the Pesticide Root Zone Model 
(PRZM) and the Exposure Analysis Model System (EXAMS).
    A detailed description of the models routinely used for exposure 
assessment is available from the EPA OPP Water Models web site: http://www.epa.gov/oppefed1/models/water/index.htm. These models provide a 
means for EPA to estimate daily pesticide concentrations in surface 
water sources of drinking water (a reservoir) using local soil, site, 
hydrology, and weather

[[Page 44869]]

characteristics along with pesticide application and agricultural 
management practices, and pesticide environmental fate and transport 
properties. Consistent with the recommendations of the FIFRA SAP, EPA 
also considers regional percent cropped area factors (PCA) which takes 
into account the potential extent of cropped areas that could be 
treated with pesticides in a particular area. The PRZM and EXAMS models 
used by EPA were developed by EPA's Office of Research and Development 
(ORD), and are used by many international pesticide regulatory agencies 
to estimate pesticide exposure in surface water. EPA's use of the 
percent cropped area factors and the Index Reservoir scenario was 
reviewed by the FIFRA SAP in 1999 and 1998, respectively (Refs. 25 and 
26).
    In modeling potential surface water concentrations, EPA attempts to 
model areas of the country that are highly vulnerable to surface water 
contamination rather than simply model ``typical'' concentrations 
occurring across the nation. Consequently, EPA models exposures 
occurring in small highly agricultural watersheds in different growing 
areas throughout the country, over a 30 year period. The scenarios are 
designed to capture residue levels in drinking water from reservoirs 
with small watersheds with a large percentage of land use in 
agricultural production. EPA believes these assessments are likely 
reflective of a small subset of the watersheds across the country that 
maintain drinking water reservoirs, representing a drinking water 
source generally considered to be more vulnerable to frequent high 
concentrations of pesticides than most locations that could be used for 
crop production.
    EPA uses the output of daily concentration values from tier two 
modeling as an input to DEEM-FCID, which combines water concentrations 
with drinking water consumption information in the daily diet to 
generate a distribution of exposures from consumption of drinking water 
contaminated with pesticides. These results are then used to calculate 
a probabilistic assessment of the aggregate human exposure and risk 
from residues in food and drinking water.

C. Selection of Acute Dietary Exposure Level of Concern

    Because probabilistic assessments generally present a realistic 
range of residue values to which the population may be exposed, EPA's 
starting point for estimating exposure and risk for such aggregate 
assessments is the 99.9th percentile of the population under 
evaluation. When using a probabilistic method of estimating acute 
dietary exposure, EPA typically assumes that, when the 99.9th 
percentile of acute exposure is equal to or less than the aPAD, the 
level of concern for acute risk has not been exceeded. By contrast, 
where the analysis indicates that estimated exposure at the 99.9th 
percentile exceeds the aPAD, EPA would generally conduct one or more 
sensitivity analyses to determine the extent to which the estimated 
exposures at the high-end percentiles may be affected by unusually high 
food consumption or residue values. To the extent that one or a few 
values seem to ``drive'' the exposure estimates at the high end of 
exposure, EPA would consider whether these values are reasonable and 
should be used as the primary basis for regulatory decision making (Ref 
58).

VI. Aggregate Risk Assessment and Conclusions Regarding Safety

    Consistent with section 408(b)(2)(D) of FFDCA, EPA has reviewed the 
available scientific data and other relevant information in support of 
this action. EPA's assessment of exposures and risks associated with 
carbofuran use follows:

A. Toxicological Profile

    Carbofuran is an N-methyl carbamate (NMC) pesticide. Like other 
pesticides in this class, the primary toxic effect seen following 
carbofuran exposure is neurotoxicity resulting from inhibition of the 
enzyme acetylcholinesterase (AChE). AChE breaks down acetylcholine 
(ACh), a compound that assists in transmitting signals through the 
nervous system. Carbofuran inhibits the AChE activity in the body. When 
AChE is inhibited at nerve endings, the inhibition prevents the ACh 
from being degraded and results in prolonged stimulation of nerves and 
muscles. Physical signs and symptoms of carbofuran poisoning include 
headache, nausea, dizziness, blurred vision, excessive perspiration, 
salivation, lacrimation (tearing), vomiting, diarrhea, aching muscles, 
and a general feeling of severe malaise. Uncontrollable muscle 
twitching and bradycardia (abnormally slow heart rate) can occur. 
Severe poisoning can lead to convulsions, coma, pulmonary edema, muscle 
paralysis, and death by asphyxiation. Carbofuran poisoning also may 
cause various psychological, neurological and cognitive effects, 
including confusion, anxiety, depression, irritability, mood swings, 
difficulty concentrating, short-term memory loss, persistent fatigue, 
and blurred vision (Refs. 15 and 16).
    The most sensitive and appropriate effect associated with the use 
of carbofuran is its toxicity following acute exposure. Acute exposure 
is defined as an exposure of short duration, usually characterized as 
lasting no longer than a day. EPA classifies carbofuran as Toxicity 
Category I, the most toxic category, based on its potency by the oral 
and inhalation exposure routes. The lethal potencies of chemicals are 
usually described in terms of the ``dose'' given orally or the 
``concentration'' in air that is estimated to cause the death of 50 
percent of the animals exposed (abbreviated as LD<INF>50</INF> or 
LC<INF>50</INF>). Carbofuran has an oral LD<INF>50</INF> of 7.8-6.0 mg/
kg, and an inhalation LC<INF>50</INF> of 0.08 mg/l (Refs. 12, 16 and 
48). The lethal dose and lethal concentration levels for the oral and 
inhalation routes fall well below the limits for the Toxicity Category 
I, < 50 mg/kg and < 0.2 mg/l, respectively (40 CFR 156.62).
    Carbofuran has a steep dose-response curve. In other words, a 
marginal increase in administered doses of carbofuran can result in a 
significant change in the toxic effect. For example, carbofuran data in 
juvenile rats (postnatal day 11 and 17) demonstrate that small 
differences in carbofuran doses (0.1 mg/kg to 0.3 mg/kg) can change the 
measured effect from significant brain and red blood cell (RBC) AChE 
inhibition without clinical signs (0.1 mg/kg) to significant AChE 
inhibition, and resultant tremors, and decreased motor activity (0.3 
mg/kg) (Refs. 31 and 46). In other words there is a slight difference 
in exposure levels that produce no noticeable outward effects and the 
level that causes adverse effects. This means that small differences in 
human exposure levels can have significant adverse consequences for 
large numbers of individuals. For example, as discussed in greater 
detail in Unit VI.E.1.b below, the difference between the amount of 
food with carbofuran residues that can be safely consumed without 
adverse effect, and the amount that provides a dose that exceeds safe 
levels is minimal. Children who consume typical amounts of watermelon 
(i.e., 8 grams) containing carbofuran residues of 0.009 ppm-a residue 
level detected in PDP data--receive a safe daily dose, but those 
consuming the same amount of watermelon with a PDP residue level of 
0.013 receive an exposure of 130% of the safe daily dose.

[[Page 44870]]

B. Deriving Carbofuran's point of departure

    EPA uses a weight of evidence approach to determine the toxic 
effect that will serve as the appropriate PoD for a risk assessment for 
AChE inhibiting pesticides, such as carbofuran (Ref. 61). The 
neurotoxicity that carbofuran causes can occur in both the central 
(brain) and peripheral nervous systems (PNS). In its weight of the 
evidence analysis, EPA reviews data, such as AChE inhibition data from 
the brain, peripheral tissues and blood (e.g., 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.). Due to technical 
difficulties regarding dissection of peripheral nerves and the rapid 
nature of carbofuran toxicity, measures of AChE inhibition in the PNS 
are very rare for NMC pesticides. 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.
    AChE inhibition in brain and the PNS is the initial adverse 
biological event which results from exposure to carbofuran, and with 
sufficient levels of inhibition leads to other effects such as tremors, 
dizziness, as well as gastrointestinal and cardiovascular effects, 
including bradycardia (Ref. 16). Thus, AChE inhibition provides the 
most appropriate effect to use in risk extrapolation for derivation of 
RfDs and PADs. Protecting against AChE inhibition ensures that the 
other adverse effects mentioned above do not occur.
    EPA has relied on a benchmark dose approach for deriving the PoD 
from the available rat toxicity studies. A benchmark dose, or BMD, is a 
point estimate along a dose-response curve that corresponds to a 
specific response level. For example, a BMD<INF>10</INF> represents a 
10% change from the background or typical value for the response of 
concern. 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 carbofuran, inhibition of AChE is 
the toxic effect of concern. Following exposure to carbofuran, the 
normal biological activity of the AChE enzyme is decreased (i.e., the 
enzyme is inhibited). Thus, when evaluating BMDs for carbofuran, the 
Agency is interested in a decrease in AChE activity compared to normal 
activity levels, which are also termed ``background'' levels. 
Measurements of ``background'' AChE activity levels are usually 
obtained from animals in experimental studies that are not treated with 
the pesticide of interest (i.e., ``negative control'' animals).
    In addition to the BMD, a ``confidence limit'' was also 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. From the PoD, EPA 
calculates the RfD and aPAD.
    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 no-observed-adverse-effect levels (NOAELs) or lowest-
observed-adverse-effect-levels (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. 27, 28, 29 and 57). 
Specific to carbofuran and other NMCs, the FIFRA SAP has reviewed and 
supported the statistical methods used by the Agency to derive BMDs and 
BMDLs on two occasions, February 2005 and August 2005 (Refs. 28 and 
29). Recently, in reviewing EPA's draft NOIC, the SAP again unanimously 
concluded that the Agency's approach in using a benchmark dose to 
derive the PoD from carbofuran brain AChE data in juvenile rats is 
``state of the art science and the Panel strongly encouraged the Agency 
to follow this approach for all studies where possible'' (Ref. 30).
    There are laboratory data on carbofuran for cholinesterase activity 
in plasma, RBC, and brain. EPA evaluated the quality of the AChE data 
in all the available studies. In this review, particular attention was 
paid to the methods used to assay AChE inhibition in the laboratory 
conducting the study. Because of the nature of carbofuran inhibition of 
AChE, care must be taken in the laboratory such that experimental 
conditions do not promote enzyme reactivation (i.e., recovery) while 
samples of blood and brain are being processed and analyzed. If this 
reactivation occurs during the assay, the results of the experiment 
will underestimate the toxic potential of carbofuran (Refs. 33, 37, 43, 
66 and 67). Through its review of available studies, the Agency 
identified problems and irregularities with the RBC AChE data from both 
FMC supported studies. These problems are described in detail in the 
Agency's study review (Refs. 19 and 20). As such, the Agency determined 
that the RBC AChE inhibition data from both FMC studies were unreliable 
and not useable in extrapolating human health risk. In addition, RBC 
data from a study performed at EPA ORD did not provide doses low enough 
to adequately characterize the full dose-response in postnatal day 11 
(PND11) rats. In the recent SAP review of the draft carbofuran NOIC, 
the Panel unanimously agreed with the Agency's conclusion, remarking 
that ``[t]he Agency is well-justified in taking the position that the 
data on AChE inhibition in rat RBC, particularly with regard to the 
PND11 pups, are not acceptable for the purpose of predicting health 
risk from carbofuran'' (Ref. 30). By contrast, the brain AChE data from 
the FMC and EPA-ORD studies are acceptable and have been used in the 
Agency's BMD analysis.
    In EPA's BMD dose analysis to derive PoDs for carbofuran, the 
Agency used a response level of 10% brain AChE inhibition and thus 
calculated BMD<INF>10</INF>s and BMDL<INF>10</INF>s based on the 
available carbofuran brain data. These values (the central estimate and 
lower confidence bound, respectively) represent the estimated dose 
where AChE is inhibited by 10% compared to untreated animals. In the 
last few years EPA has used this 10% value to regulate AChE inhibiting 
pesticides, including organophosphate pesticides and NMCs including 
carbofuran. For a variety of toxicological and statistical reasons, EPA 
chose 10%

[[Page 44871]]

brain AChE inhibition as the response level for use in BMD and BMDL 
calculations. EPA analyses have demonstrated that 10% is a level that 
can be reliably measured in the majority of rat toxicity studies; is 
generally at or near the limit of sensitivity for discerning a 
statistically significant decrease in AChE activity across the brain 
compartment; and is a response level close to the background AChE level 
(Refs. 28 and 29)
    The Agency used a meta-analysis to calculate the BMD<INF>10</INF> 
and BMDL<INF>10</INF> for pups and adults; this analysis includes brain 
data from studies where either adult or juvenile rats or both were 
exposed to a single oral dose of carbofuran. The Agency used a dose-
time-response exponential model where benchmark dose and half-life to 
recovery can be estimated together. This model and the statistical 
approach to deriving the BMD<INF>10</INF>s, BMDL<INF>10</INF>s, and 
half-life to recovery have been reviewed and supported by the FIFRA SAP 
(Refs. 28 and 29). The meta-analysis approach offers the advantage over 
using single studies by combining information across multiple studies 
and thus provides a robust PoD.
    There are three studies available which compare the effects of 
carbofuran on PND11 rats with those in young adult rats (herein called 
`comparative AChE studies') (Refs. 1, 2 and 46). Two of these studies 
were submitted by FMC, the registrant, and one was performed by EPA-
ORD. An additional study conducted by EPA-ORD involved PND17 rats (Ref. 
45). Although it is not possible to directly correlate ages of juvenile 
rats to humans, PND11 rats are believed to be close in development to 
newborn humans. PND17 rats are believed to be closer developmentally to 
human toddlers (Ref. 9). Other studies in adult rats used in the 
Agency's analysis included additional data from EPA-ORD (Refs 44 and 
46).
    Using quality brain AChE data from the three studies (2 FMC, 1 EPA-
ORD) conducted with PND11 rats, in combination, provides data to 
describe both low and high doses. By combining the three studies in 
PND11 animals together in a meta-analysis, the entire dose-response 
range is covered (see Figure 1 in Unit VI.C. below). The Agency 
believes the BMD analysis for the PND11 brain AChE data is the most 
robust analysis for purposes of PoD selection.
    The studies in juvenile rats show a consistent pattern that 
juvenile rats are more sensitive than adult rats to the effects of 
carbofuran. These effects include inhibition in AChE in addition to 
incidence of clinical signs of neurotoxicity such as tremors. This 
pattern has also been observed for other NMC pesticides, which exhibit 
the same mechanism of toxicity as carbofuran (Ref. 63). It is not 
unusual for juvenile rats, or indeed, for infants or young children, to 
be more sensitive to chemical exposures as metabolic detoxification 
processes in the young are still developing. Because juvenile rats, 
called `pups' herein, are more sensitive than adult rats, data from 
pups provide the most relevant information for evaluating risk to 
infants and young children and are thus used to derive the PoD. In 
addition, typically (and is the case for carbofuran) young children 
(ages 0-5) tend to be the most exposed age groups because they tend to 
eat larger amounts of food per their body weight than do teenagers or 
adults. As such, the focus of EPA's analysis of carbofuran's dietary 
risk from residues in food and water is on young children (ages 0-5). 
Since these age groups experience the highest levels of dietary risk, 
protecting these groups against the effects of carbofuran will, in 
turn, also protect other age groups.
    Using data from PND11 pup brain AChE levels, the estimated oral 
dose that will result in 10% brain AChE inhibition (BMD<INF>10</INF>) 
is 0.04 mg/kg. The lower 95% confidence limit on the BMD<INF>10</INF> 
(BMDL<INF>10</INF>) is 0.03 mg/kg--this BMDL<INF>10</INF> of 0.03 mg/kg 
provides the PoD.
    As noted, although EPA does not consider RBC AChE inhibition as an 
adverse effect in its own right, in the absence of data from peripheral 
tissues, RBC AChE inhibition data are a critical component to 
determining that a selected PoD will be sufficiently protective of PNS 
effects. Because of the problems discussed previously with the 
available RBC AChE inhibition data, there remains uncertainty 
surrounding the dose-response relationship for RBC AChE inhibition in 
pups, which the EPA-ORD data clearly show to be a more sensitive 
endpoint than brain AChE. Consequently, EPA cannot reliably estimate 
the BMD<INF>10</INF> and BMDL<INF>10</INF> for RBC AChE data in pups. 
Furthermore, given that the EPA-ORD data clearly show RBC AChE to be 
more sensitive than brain AChE, EPA cannot conclude that reliance on 
the pup brain data as the PoD would be sufficiently protective of PNS 
effects in pups. This uncertainty provides the scientific basis, in 
part, for retention of the children's safety factor as described below.

C. Safety Factor for Infants and Children

    1. In general. Section 408 of the FFDCA provides that EPA shall 
apply an additional tenfold margin of safety for infants and children 
in the case of threshold effects to account for prenatal and postnatal 
toxicity and the completeness of the data base on toxicity and exposure 
unless EPA determines that a different margin of safety will be safe 
for infants and children. Margins of safety are incorporated into EPA 
assessments either directly through use of a margin of exposure 
analysis or through using uncertainty (safety) factors in calculating a 
dose level that poses acceptable risk to humans.
    In applying the children's safety factor provision, EPA has 
interpreted the statutory language as imposing a presumption in favor 
of applying an additional 10X safety factor (Ref. 60). Thus, EPA 
generally refers to the additional 10X factor as a presumptive or 
default 10X factor. EPA has also made clear, however, that 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.).
    2. Prenatal and postnatal sensitivity. As noted in the previous 
section, there are several studies in juvenile rats that show they are 
more sensitive than adult rats to the effects of carbofuran. These 
effects include inhibition of brain AChE in addition to the incidence 
of clinical signs of neurotoxicity (such as tremors) at lower doses in 
the young rats. The SAP concurred with EPA that the data clearly 
indicate that the juvenile rat is more sensitive than the adult rat 
with regard to brain AChE (Ref. 30). However, the Agency does not have 
AChE data for cabofuran in the peripheral tissue of adult or juvenile 
animals; nor does the Agency have adequate RBC AChE inhibition data at 
low doses relevant to risk assessment to serve as a surrogate in pups. 
As previously noted the RBC AChE data from both FMC supported studies 
are not reliable and thus are not appropriate for use in risk 
assessment. Although the EPA studies did provide reliable RBC data, 
they did not include data at the low end of the dose-response curve, 
which is the area on the dose-response curve most relevant for risk 
assessment (see Figure 1).
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    There is indication in a toxicity study where pregnant rats were 
exposed to carbofuran that effects on the PNS are of concern; 
specifically, chewing motions or mouth smacking was observed in a clear 
dose-response pattern immediately following dosing each day (Ref. 64). 
Based on this study, the California Department of Pesticide Regulation 
calculated a BMD<INF>05</INF> and BMDL<INF>05</INF> of 0.02 and 0.01 
mg/kg/day, and established the acute PoD (Refs. 11 and 30). These BMD 
estimates are notable as they are close to the values EPA has 
calculated for brain AChE inhibition and being used as the PoD for 
extrapolating risk to children. It is important to note that these 
clinical signs have been reported for at least one other cholinesterase 
inhibiting pesticide at doses producing only blood, not brain, AChE 
inhibition (Ref. 38). Thus, although RBC AChE inhibition is not an 
adverse effect, per se, blood measures are used as surrogates in the 
absence of peripheral tissue data. Assessment of potential for 
neurotoxicity in peripheral tissues is a critical element of hazard 
characterization for NMCs, like carbofuran. The lack of an appropriate 
surrogate to assess the potential for RBC AChE inhibition is a key 
uncertainty in the carbofuran toxicity database. Thus, EPA cannot 
conclude that reliance on the pup brain data solely as the PoD will be 
protective of PNS effects in pups.
    To account for the lack of RBC data in pups at the low end of the 
response curve, and for the fact that RBC AChE inhibition appears to be 
a more sensitive point of departure compared to brain AChE inhibition 
(and is considered an appropriate surrogate for the peripheral nervous 
system), EPA is retaining a portion of the children's safety factor. On 
the other hand, there are data available, albeit incomplete, which 
characterize the toxicity of carbofuran in juvenile animals, and the 
Agency believes the weight of the evidence supports reducing the 
statutory factor of 10X to a value lower than 10X. This results in a 
children's safety factor that is less than 10 but more than 1.
    This modified safety factor should take into account the greater 
sensitivity of the RBC AChE. The preferred approach to comparing the 
relative sensitivity of brain and RBC AChE inhibition would be to 
compare the BMD<INF>10</INF> estimates. However, as described above, 
BMD<INF>10</INF> estimates from the available RBC AChE inhibition data 
are not reliable due to lack of data at the low end of the dose 
response curve (Figure 1). As an alternative approach, EPA has used the 
ratio of brain to RBC AChE inhibition at the BMD<INF>50</INF>, since 
there are quality data at or near the 50% response level such that a 
reliable estimate can be calculated. There is, however, an assumption 
associated with using the 50% response level--namely that the magnitude 
of difference between RBC and brain AChE inhibition is constant across 
dose. In other words, EPA is assuming the RBC and brain AChE dose 
response curves are parallel. There are currently no data to test this 
assumption for carbofuran.
    The Agency has recommended the application of a children's safety 
factor of 4X, based on a weight-of-evidence approach. This safety 
factor is calculated using the difference in RBC and brain AChE 
inhibition, using the data on administered dose for the animals from 
the EPA-ORD studies and the FMC studies combined. In other words, EPA 
estimated the BMD<INF>50</INF> for PND11 animals from each quality 
study and used the ratio from the combined analysis, resulting in a 
BMD<INF>50</INF> ratio of 4.1X\3\. EPA also compared the 
BMD<INF>50</INF> ratios for PND17 pups (who are slightly less sensitive 
than 11-day olds; see Figure 2) in the EPA-ORD study, resulting in a 
BMD<INF>50</INF> of 3.3 X. Conceptually, the RBC to brain potency ratio 
could be estimated using two different approaches: 1) EPA's data for 
RBC (the only reliable RBC data in PND11 animals for carbofuran) and 
all available data in PND11 animals for brain; or 2) using only EPA's 
data in PND11 animals for both RBC and brain. The former procedure, the 
approach used by EPA, yields a ratio of about fourfold, while the 
latter gives a twofold ratio for carbofuran. EPA has elected to use the 
4X factor as the more health protective choice. This selection was made 
based on: 1) uncertainty regarding lack of an appropriate measure of 
peripheral toxicity (i.e., lack of RBC AChE inhibition data at the low 
end of the dose response curve), and 2) the RBC to brain AChE ratio at 
the BMD<INF>50</INF> for PND17 animals of 3.3X which suggests that a 
factor of 2X would not be protective of PND11 pups.
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    \3\ EPA made a mathematical error when it originally calculated 
the children's safety factor, which resulted in a factor of 5X (Ref. 
50). Correcting the mathematical error results in a 4X actor.

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    EPA recently presented its dietary risk assessment of carbofuran to 
the FIFRA SAP, and requested comment on the Agency's approach to 
selecting the point of departure and the children's safety factor. 
Overall, the Agency believes that the Panel's responses support the 
Agency's approach with regard to carbofuran's hazard identification and 
hazard characterization. For example, the Agency notes that the Panel 
``unanimously'' agreed with the Agency with regard to the conclusion 
that the second FMC comparative cholinesterase (ChE) study provides 
reliable brain, but not RBC, AChE data. The Panel further remarked 
that, ``EPA is well-justified in taking the position that the data on 
AChE inhibition in rat RBC, particularly with PND11 pups, are not 
acceptable for the purpose of predicting health risk from carbofuran'' 
(Ref. 30). The Panel went on to concur with the Agency that the brain 
AChE inhibition data from the FMC and EPA-ORD studies show ``good 
concordance.'' With regard to the use of a benchmark dose approach to 
derive a PoD from brain AChE data in pups, the Panel stated that the 
Agency's approach is ``state-of-the-art science and the Panel strongly 
encouraged the Agency to follow this approach for all studies where 
possible'' (Id.).
    The Panel provided five `scenarios' or options for applying the 
children's safety factor and/or PoD. Four of the five scenarios 
included the application of a children's safety factor. Because the 
Panel report stated that the Panel was ``not in agreement regarding the 
magnitude of a [children's] safety factor,'' it is reasonable to 
conclude that a majority did not support any one of the five scenarios, 
including the one advocating removal of the children's safety factor 
(Ref. 30). It follows that a majority of the Panel agreed with the 
Agency that at least a portion of the safety factor should be retained; 
however, recommendations for the appropriate factor ranged between a 2X 
and 10X. Two of the scenarios were consistent with the Agency's 
approach in which the magnitude of the safety factor is derived based 
on the differences in RBC and brain AChE responses, quantified by the 
administered dose. The remaining two scenarios were based on retention 
of the 10X safety factor. Those Panel members supporting retention of 
the 10X safety factor did so on the basis that the statutory 
requirement that EPA may use a different factor ```only if, on the 
basis of reliable data, such margin will be safe for infants and 
children.' Given the uncertainty in the data and in its interpretation 
for risk assessment by the entire Panel, these Panel members believes 
that this standard for change had not been met'' (Id.). EPA believes 
that, on balance, the application of a 4X children's safety factor is 
consistent with the SAP's advice. Additional detail on the SAP's advice 
and EPA's responses can be found at Ref. 23.
    In sum, EPA has concluded that there is reliable data to support 
the application of a 4X safety factor and has therefore applied this 
safety factor in its dietary risk estimates. However, in light of the 
disagreement among the SAP panelists on the appropriate factor to 
apply, the Agency solicits comment on this issue.

D. Hazard Characterization and Point of Departure Conclusions

    The doses and toxicological endpoints selected and Margins of 
Exposures for various exposure scenarios are summarized in Table 1 
below.

                                     Table 1--Toxicology Endpoint Selection
----------------------------------------------------------------------------------------------------------------
                                                                    FQPA factor and
          Exposure Scenario               Dose Used in Risk        Endpoint for Risk     Study and Toxicological
                                            Assessment, UF             Assessment                Effects
----------------------------------------------------------------------------------------------------------------
Acute Dietary Infants and Children     BMDL 10 = 0.03 mg/kg/    Children's SF = 4X       Comparative AChE
                                        day                     aPAD = 0.000075 mg/kg/    Studies in PND11 rats
                                       UF = 100...............   day.                     (FMC and EPA-ORD)
                                       Acute RfD = 0.0003 mg/                            BMD10 = 0.04 mg/kg/day
                                        kg/day.                                          BMDL10 = 0.03 mg/kg/
                                                                                          day, based on brain
                                                                                          AChE inhibition of
                                                                                          postnatal day 11
                                                                                          (PND11) pups
----------------------------------------------------------------------------------------------------------------
Acute Dietary Youth (13 and older)     BMDL10 = 0.02 mg/kg/day  Children's SF = 1X       Comparative AChE Study
 and Adults                            UF = 100...............  aRfD = 0.0002 mg/kg/day   (EPA-ORD), Padilla et
                                       Acute RfD = 0.00024 mg/                            al (2007), McDaniel et
                                        kg/day.                                           al (2007)
                                                                                         BMD10 = 0.06 mg/kg/day
                                                                                         BMDL10 = 0.02 mg/kg/
                                                                                          day, based on RBC AChE
                                                                                          inhibition in adult
                                                                                          rat
----------------------------------------------------------------------------------------------------------------

E. Dietary Exposure and Risk Assessment

    1. Dietary exposure to carbofuran (food)--a. EPA methodology and 
background. EPA conducted a refined (Tier 3) acute probabilistic 
dietary risk assessment for carbofuran residues in food. Carbofuran is 
registered for use on the following crops: alfalfa, artichokes, banana, 
barley, corn, cranberry, cucumber, grapes, melons, milk, oats, peppers, 
potatoes, pumpkin, rice, sorghum, soybean, spinach, squash, strawberry, 
sugar beets, sugar cane, sunflower seed, and wheat. To conduct the 
assessment, EPA relied on DEEM-FCID, Version 2.00-2.02, which uses food 
consumption data from the USDA's CSFII from 1994-1996 and 1998.
    Using data on the percent of the crop actually treated with 
carbofuran and data on the level of residues that may be present on the 
treated crop, EPA developed estimates of combined anticipated residues 
of carbofuran and 3-hydroxycarbofuran on food. 3-Hydroxycarbofuran is a 
degradate of carbofuran and is assumed to have toxic potency equivalent 
to carbofuran (Refs. 12, 16 and 48). Anticipated residues of carbofuran 
for most foods were derived using USDA PDP monitoring data from recent 
years (through 2006 for all available commodities). In some cases, 
where PDP data were not available for a particular crop, EPA translated 
PDP monitoring data from surrogate crops based on the characteristics 
of the crops and the use patterns. For example, PDP data for 
cantaloupes were used to derive anticipated residues for casaba and 
honeydew.
    USDA PDP provides the most comprehensive sampling design, and the 
most extensive and intensive sampling procedures for pesticide residues 
of the various data sources available to EPA. Additionally, the intent 
of PDP's sampling design is to provide statistically representative 
samples of food commodities eaten by the U.S. population specifically 
for the purpose of performing dietary risk assessments for pesticides. 
The program focuses on high-consumption foods for

[[Page 44876]]

children and reflects foods typically available throughout the year. A 
complete description of the PDP program (including all data through 
2006) is available online.
    The PDP analyzed for parent carbofuran and its metabolite of 
concern, 3-hydroxycarbofuran. Most of the samples analyzed by the PDP 
were measured using a high Level of Detection (LOD) and contained no 
detectable residues of carbofuran or 3-hydroxycarbofuran. Consequently, 
the acute assessment for food assumed a concentration equal to [frac12] 
of the LOD for PDP monitoring samples with no detectable residues, and 
0.00 ppm carbofuran to account for the percent of the crop not treated 
with carbofuran.
    An additional source of data on carbofuran residues was provided by 
a market basket survey of NMC pesticides in single-serving samples of 
fresh fruits and vegetables collected in 1999-2000 (Ref. 14), which was 
sponsored by the Carbamate Market Basket Survey Task Force. EPA relied 
on these data to construct the residue distribution files for 2 crops 
(bananas and grapes) because the use of these data resulted in more 
refined exposure estimates. The combined Limits of Quantitation (LOQs) 
for carbofuran and its metabolite in the Market Basket Survey (MBS) 
were between tenfold and twentyfold lower than the combined LODs in the 
PDP monitoring data.
    For certain crops where PDP data were not available (sugar beets, 
sugarcane, and sunflower seed), anticipated residues were based on 
field trial data. EPA also relied on field trial data for particular 
food commodities that are blended during marketing (barley, field corn, 
popcorn, oats, rice, soybeans and wheat), as use of PDP data can result 
in significant overestimates of exposure when evaluating blended foods. 
Field trial data are typically considered to overestimate the residues 
that are likely to occur in food as actually consumed because they 
reflect the maximum application rate and shortest preharvest interval 
allowed by the label. However, for crops that are blended during 
marketing, such as corn or wheat, use of field trial data can provide a 
more refined estimate than PDP data, by allowing EPA to better account 
for the percent of the crop actually treated with carbofuran.
    EPA used average and maximum percent crop treated (PCT) estimates 
for most crops, following the guidance provided in HED SOP 99.6 
(Classification of Food Forms with Respect to level of Blending; 8/20/
99), and available processing and/or cooking factors. The maximum PCT 
estimates were used to refine the acute dietary exposure estimates. 
Maximum PCT ranged from <1 to 35%. The estimated percent of the crop 
imported was applied to crops with tolerances currently maintained 
solely for import purposes (cranberry, rice, strawberry).
    b. Acute dietary exposure (food alone) results and conclusions. The 
estimated acute dietary exposure from carbofuran residues in food alone 
(i.e., assuming no additional carbofuran exposure from drinking water), 
exceeds EPA's level of concern for all but one of the children's 
population subgroups at the 99.9th percentile of exposure. Carbofuran 
dietary exposure at the 99.9th percentile was estimated at 0.000156 mg/
kg/day (210% of the aPAD) for children 3-5 years old, the population 
subgroup with the highest estimated dietary exposure. Estimated dietary 
exposure to carbofuran also exceeds EPA's level of concern for children 
1-2 years old and 6-12 years at the 99.9th percentile of exposure. (See 
results Table 2 below).

                       Table 2--Results of Acute Dietary Exposure Analysis for Food Alone
----------------------------------------------------------------------------------------------------------------
                                                                   99th Percentile          99.9th Percentile
                                                 aPAD (mg/kg/---------------------------------------------------
              Population Subgroup                    day)       Exposure                  Exposure
                                                              (mg/kg/day)     % aPAD    (mg/kg/day)     % aPAD
----------------------------------------------------------------------------------------------------------------
All Infants (< 1 year old)                          0.000075     0.000025           33     0.000070           93
----------------------------------------------------------------------------------------------------------------
Children 1-2 years old                              0.000075     0.000045           60     0.000152          200
----------------------------------------------------------------------------------------------------------------
Children 3-5 years old                              0.000075     0.000036           48     0.000156          210
----------------------------------------------------------------------------------------------------------------
Children 6-12 years old                             0.000075     0.000024           32     0.000121          160
----------------------------------------------------------------------------------------------------------------

    Exposure estimates for all of the major food contributors were 
based on PDP monitoring data adjusted to account for the percent of the 
crop treated with carbofuran and, therefore, may be considered highly 
refined.
    As noted previously, because most of the PDP samples contained no 
detectable residues of carbofuran or its 3-hydroxy metabolite, the 
acute assessment for food assumed a concentration equal to [frac12] of 
the LOD for PDP monitoring samples with no detectable residues, with 
0.00 ppm carbofuran incorporated to account for the percent of the crop 
not treated with carbofuran. In accordance with OPP policy for 
analyzing commodities with non-detectable residues, EPA performed 
additional analyses to determine the impact of using [frac12] the LOD 
to estimate exposure (Ref. 56).
    In the first analysis (Sensitivity Analysis <greek-i>1), those 
commodities that had no detectable residues at all in either the 
monitoring data or field trials were eliminated from the assessment. 
The commodities that were eliminated included barley, coffee, corn, 
cranberry, oats, potato, raisin, rice, soybean, spinach, strawberry, 
sugar beet, sunflower, winter squash, and wheat. For the remaining 
commodities, on which carbofuran was detected, EPA continued to 
substitute the [frac12] LOD values for the percent of the crop treated 
with carbofuran, with 0.00 ppm carbofuran incorporated to account for 
the remaining untreated percent of the crop. This analysis resulted in 
estimated exposures that were still above EPA's level of concern for 
children 1-2 at the 99.9th percentile (115% of the aPAD; see Table 3 
below).
    To further understand the extent to which the [frac12] LODs from 
the PDP monitoring data were affecting the risk assessment, EPA 
conducted an additional sensitivity analysis, (Sensitivity Analysis 
<greek-i>2) that excluded the crops for which PDP and MBS data were not 
available and assigned 0.00 ppm carbofuran for all non-detected 
residues in commodities sampled in the PDP or MBS. In other words, an 
analysis using only detectable residues from residue monitoring 
programs was conducted. In this analysis, estimated dietary exposures 
at the 99.9th percentile of exposure remained above EPA's level of 
concern for children 1-2 yrs. old (114% of the aPAD). The

[[Page 44877]]

results of these sensitivity analyses at the 99.9th percentile of 
exposure are compared to the results using [frac12] LOD for non-
detectable residues in Table 3 below.

                          Table 3--Impact of Using [frac1s2] LOD for Non-Detectable Residues on Estimated Exposure From Food\1\
--------------------------------------------------------------------------------------------------------------------------------------------------------
                                                                                     Analysis Assuming     Sensitivity Analysis    Sensitivity Analysis
                                                                                  [frac1s2] LOD for Non-       <greek-i>1\2\           <greek-i>2\3\
                                                                     aPAD (mg/kg/   Detectable Residues  -----------------------------------------------
                        Population Subgroup                              day)    ------------------------
                                                                                    Exposure                Exposure     % aPAD     Exposure     % aPAD
                                                                                  (mg/kg/day)    % aPAD   (mg/kg/day)             (mg/kg/day)
--------------------------------------------------------------------------------------------------------------------------------------------------------
All Infants (< 1 year old)                                              0.000075     0.000070         93     0.000044         58     0.000043         57
--------------------------------------------------------------------------------------------------------------------------------------------------------
Children 1-2 years old                                                  0.000075     0.000152        200     0.000086        115     0.000086        114
--------------------------------------------------------------------------------------------------------------------------------------------------------
Children 3-5 years old                                                  0.000075     0.000156        210     0.000066         88     0.000065         87
--------------------------------------------------------------------------------------------------------------------------------------------------------
Children 6-12 years old                                                 0.000075     0.000121        160     0.000039         52     0.000038         51
--------------------------------------------------------------------------------------------------------------------------------------------------------
\1\ At the 99.9th Percentile of Exposure.
\2\ Non-detectable PDP residues assumed to be zero only for commodities having no detectable residues at all in the PDP monitoring data and field trials
  (i.e., these commodities were eliminated from the analysis). Crops without PDP data and detectable residues in field trials were included, based on
  the distribution of residues from field trial studies.
\3\ Non-detectable residues assumed to be zero for all commodities. Commodities without PDP or Market Basket data were excluded from the analysis.

    The major contributors in Sensitivity Analysis <greek-i>2, to the 
estimated dietary exposure of children are listed in Table 4 below.

 Table 4--Major Contributors to Carbofuran Acute Exposure at the 99.9th
     Percentile in Sensitivity Analysis <Register>2 (Expressed as an
                 Approximate Percent of Total Exposure)
------------------------------------------------------------------------
                                                Children, 1- Children, 3-
               Food                Infants, <1  2 Years Old  5 Years Old
                                     year old
------------------------------------------------------------------------
Cantaloupe                                   9           18           20
------------------------------------------------------------------------
Squash                                      10            2            1
------------------------------------------------------------------------
Grape                                       15           10            5
------------------------------------------------------------------------
Cucumbers                                    2           20           29
------------------------------------------------------------------------
Milk                                        32           <1            1
------------------------------------------------------------------------
Watermelon                                  29           39           41
------------------------------------------------------------------------

    EPA's evaluation of these two sensitivity analyses and other 
information on carbofuran residue levels yields three conclusions. 
First, the results of the sensitivity analyses indicate that the 
dietary risk assessment for carbofuran is sensitive to the assumed 
concentrations (i.e., [frac12] LOD) for non-detectable residues in the 
PDP monitoring data. This sensitivity appears to be more of a factor 
for commodities with no detections because the main difference between 
the Sensitivity Analyses <greek-i>1 and <greek-i>2 was substituting 
0.00 ppm for [frac12] LODs for commodities with detects in the second 
analysis yet that analysis yielded similar results to the first 
sensitivity analysis. On the other hand, both sensitivity analyses were 
approximately 2X lower than the analysis that used [frac12] LOD for all 
treated commodities. The finding that the use of a [frac12] LOD 
assumption had a noticeable impact on the risk estimate is contrary to 
EPA's experience in conducting pesticide risk assessments. Generally, 
risk estimates do not show noticeable differences whether non-detects 
are treated as true zeros or [frac12] LODs. In all likelihood, this is 
a factor of the relatively insensitive level of the carbofuran method's 
LOD.
    Second, given that there are data showing that carbofuran is found 
at levels below the LOD when a more sensitive method was used, EPA 
finds that use of either of the approaches in the sensitivity analyses 
will understate carbofuran risk. The available information demonstrates 
that carbofuran residues are present; when a lower level of detection 
was utilized, both in the most recent PDP milk analyses and in the 
Carbamate MBS data; residues of carbofuran and 3-hydroxycarbofuran were 
detected in commodities that previously had no detections. Moreover, 
detected residues ranged between levels below and above [frac12] LOD. 
Thus, unlike the circumstance where a relatively sensitive method of 
detection is used and there is some uncertainty as to whether a non-
detect may mask an actual exposure, with cabofuran there is no question 
- treating all non-detects as zero clearly would mask actual exposures 
to carbofuran. Thus, these sensitivity analyses do not provide a basis 
for concluding that EPA has overestimated risk.
    Third, and most important, EPA would call attention to the fact 
that these sensitivity analyses, although clearly underestimating 
actual carbofuran exposure and risk, still indicate that one group of 
children will have exposures exceeding the safe level.
    Because it appears that carbofuran's dietary risks to children are 
driven by

[[Page 44878]]

relatively low residues in a small percentage of commodities, and to 
try to gain further insight into the potential impact of using [frac12] 
LOD in this case, EPA conducted a third sensitivity analysis to 
evaluate whether its estimates that food only and aggregate carbofuran 
exposure results in risks of concern were overstated. EPA combined 
actual residue values measured in the food supply (from PDP and MBS 
data) with the typical (50th percentile) and high-end (90th percentile) 
amounts of a single commodity that a child would be expected to 
consume, and compared that to the aPAD, without considering the 
likelihood that a child would be exposed to that residue value. The 
results one of these analyses are summarized in Table 5 below.

                                  Table 5--Risk to Children Consuming Typical or High-End Amounts of Fresh (Uncooked) Cucumbers Containing Carbofuran Residues
------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------
                                                                                      Typical: 50th Percentile of Consumption                     High-End: 90th Percentile of Consumption
                                                                        ------------------------------------------------------------------------------------------------------------------------
                   Food                         Population Subgroup                                       PDP       Exposure                                     PDP       Exposure
                                                                            Consumption (g/kg bw)      Residue\1\    (mg/kg      % aPAD     Consumption (g/   Residue\1\    (mg/kg      % aPAD
                                                                                                         (ppm)        bw)                        kg bw)         (ppm)        bw)
------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------
Cucumbers (Uncooked) DEEM food form 110    Children 1-2                  1.0                                0.005   0.000005            7              4.3         0.005   0.000022           29
                                                                                                     --------------------------------------                 ------------------------------------
                                                                                                            0.029   0.000029           39                          0.029   0.000125          170
                                                                                                     --------------------------------------                 ------------------------------------
                                                                                                            0.063   0.000063           84                          0.063   0.000271          360
                                                                                                     --------------------------------------                 ------------------------------------
                                                                                                            0.117   0.000117          160                          0.117   0.000503          670
                                                                                                     --------------------------------------                 ------------------------------------
                                                                                                            0.137   0.000137          180                          0.137   0.000589          790
                                                                                                     --------------------------------------                 ------------------------------------
                                                                                                            0.147   0.000147          200                          0.147   0.000632          840
                                                                                                     --------------------------------------                 ------------------------------------
                                                                                                            0.437   0.000437          580                          0.437   0.001879        2,500
                                                                                                     --------------------------------------                 ------------------------------------
                                                                                                            0.537   0.000537          720                          0.537   0.002309        3,100
                                          ======================================================================================================================================================
                                           Children 3-5                  0.8                                0.005   0.000004            5              5.1         0.005   0.000026           34
                                                                                                     --------------------------------------                 ------------------------------------
                                                                                                            0.029   0.000023           31                          0.029   0.000148          200
                                                                                                     --------------------------------------                 ------------------------------------
                                                                                                            0.063   0.000050           67                          0.063   0.000321          430
                                                                                                     --------------------------------------                 ------------------------------------
                                                                                                            0.117   0.000094          120                          0.117   0.000597          800
                                                                                                     --------------------------------------                 ------------------------------------
                                                                                                            0.137   0.000110          150                          0.137   0.000699          930
                                                                                                     --------------------------------------                 ------------------------------------
                                                                                                            0.147   0.000118          160                          0.147   0.000750        1,000
                                                                                                     --------------------------------------                 ------------------------------------
                                                                                                            0.437   0.000350          470                          0.437   0.002229        3,000
                                                                                                     --------------------------------------                 ------------------------------------
                                                                                                            0.537   0.000430          570                          0.537   0.002739        3,700
------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------
\1\ The PDP detected residues of carbofuran in 11 of 1479 cucumber samples at levels ranging from 0.005 ppm to 0.537 ppm.

    Detectable residues of carbofuran and/or 3-hydroxycarbofuran were 
found in only a few samples of cucumber in monitoring data (11 out of 
1479 or less than one percent). However, if young children aged 1 to 5 
consume moderate amounts of cucumber (i.e., the median or 50th 
percentile of consumption, corresponding to approximately 1 gram per kg 
of body weight of cucumber) that contain actual levels of carbofuran 
measured in the food supply, the percent of the aPAD that would be 
utilized ranges from about 7% of the safe daily dose for the lower 
observed residue values to 720% of the safe daily dose for the higher 
observed values. For children who consume larger amounts of cucumber 
(i.e., the 90th percentile of consumption, corresponding to 5 grams per 
kg of body weight of cucumber or roughly [frac12] cup), exposure 
increases approximately tenfold (29% to over 3700% of the aPAD). Many 
of these values significantly exceed the Agency's level of concern 
based on the consumption of a single daily serving of one commodity.
    Additional analyses are summarized in Table 6 below, and analyses 
on additional foods can be found in Ref. 12. EPA focused on children in 
making these calculations, because children have the highest estimated 
dietary exposure to carbofuran; however, it is reasonable to assume 
that adult exposures from a single treated food item could also exceed 
EPA's level of concern, particularly at the high end of consumption.

[[Page 44879]]



                                   Table 6--Risk to Children Consuming Typical or High-End Amounts of Cantaloupe or Watermelon Containing Carbofuran Residues
------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------
                                                                  Typical: 50th Percentile of Consumption                                 High-End: 90th Percentile of Consumption
                                                ------------------------------------------------------------------------------------------------------------------------------------------------
              Population Subgroup                                                   PDP Residue    Exposure                 Consumption (g/kg                       Exposure
                                                       Consumption (g/kg bw)           (ppm)      (mg/kg bw)     % aPAD            bw)         PDP Residue (ppm)   (mg/kg bw)        % aPAD
------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------
                                                                                           Cantaloupe
------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------
Children 1-2                                     Approx. 6g                               0.009    0.0000531           71        Approx. 12 g              0.009    0.0001035                140
                                                                                   ----------------------------------------                   --------------------------------------------------
                                                                                           0.01     0.000059           79                                   0.01     0.000115                150
                                                                                   ----------------------------------------                   --------------------------------------------------
                                                                                           0.02     0.000118          160                                   0.02      0.00023                310
                                                                                   ----------------------------------------                   --------------------------------------------------
                                                                                           0.06     0.000354          470                                   0.06      0.00069                920
                                                                                   ----------------------------------------                   --------------------------------------------------
                                                                                          0.085    0.0005015          670                                  0.085    0.0009775              1,300
                                                                                   ----------------------------------------                   --------------------------------------------------
                                                                                          0.357    0.0021063        2,800                                  0.357    0.0041055              5,500
================================================================================================================================================================================================
Children 3-5                                     approx. 5g                               0.009    0.0000441           59      approx. 15g or              0.009    0.0001368                180
                                                                                                                                [frac1s2] cup
                                                                                   ----------------------------------------                   --------------------------------------------------
                                                                                           0.01     0.000049           65                                   0.01     0.000152                200
                                                                                   ----------------------------------------                   --------------------------------------------------
                                                                                           0.02     0.000098          130                                   0.02     0.000304                400
                                                                                   ----------------------------------------                   --------------------------------------------------
                                                                                           0.06     0.000294          390                                   0.06     0.000912              1,200
                                                                                   ----------------------------------------                   --------------------------------------------------
                                                                                          0.085    0.0004165          560                                  0.085     0.001292              1,700
                                                                                   ----------------------------------------                   --------------------------------------------------
                                                                                          0.357    0.0017493        2,300                                  0.357    0.0054264              7,200
================================================================================================================================================================================================
                                                                                           Watermelon
------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------
Children 1-2                                     approx. 8g                              0.0057   0.00004332           58       less than 30g             0.0057   0.00014706                200
                                                                                   ----------------------------------------                   --------------------------------------------------
                                                                                          0.009    0.0000684           91                                  0.009    0.0002322                310
                                                                                   ----------------------------------------                   --------------------------------------------------
                                                                                         0.0132   0.00010032          130                                 0.0132   0.00034056                450
                                                                                   ----------------------------------------                   --------------------------------------------------
                                                                                          0.014    0.0001064          140                                  0.014    0.0003612                480
                                                                                   ----------------------------------------                   --------------------------------------------------
                                                                                          0.062    0.0004712          630                                  0.062    0.0015996              2,100
                                                                                   ----------------------------------------                   --------------------------------------------------
                                                                                          0.081    0.0006156          820                                  0.081    0.0020898              2,800
                                                                                   ----------------------------------------                   --------------------------------------------------
                                                                                          0.205     0.001558        2,100                                  0.205     0.005289              7,100
================================================================================================================================================================================================
Children 3-5                                     approx. 12g                             0.0057   0.00007125           95         approx. 35g             0.0057   0.00019893                270
                                                                                   ----------------------------------------                   --------------------------------------------------
                                                                                          0.009    0.0001125          150                                  0.009    0.0003141                420
                                                                                   ----------------------------------------                   --------------------------------------------------
                                                                                         0.0132     0.000165          220                                 0.0132   0.00046068                610
                                                                                   ----------------------------------------                   --------------------------------------------------
                                                                                          0.014     0.000175          230                                  0.014    0.0004886                650
                                                                                   ----------------------------------------                   --------------------------------------------------
                                                                                          0.062     0.000775        1,000                                  0.062    0.0021638              2,900
                                                                                   ----------------------------------------                   --------------------------------------------------
                                                                                          0.081    0.0010125        1,400                                  0.081    0.0028269              3,800
                                                                                   ----------------------------------------                   --------------------------------------------------
                                                                                          0.205    0.0025625        3,400                                  0.205    0.0071545              9,500
------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------


[[Page 44880]]

    The analyses in Tables 5 and 6 demonstrate three significant 
points. First, the fact that individual children, consuming typical 
amounts of a single food item receive unsafe levels of carbofuran, 
based on actual residue levels measured in the food supply, strongly 
supports EPA's findings that aggregate exposures to carbofuran are 
unsafe. It is true that the results described in Tables 5 and 6, as 
well as the additional analyses in Ref. 12, do not describe the 
probability that an individual child will receive those residues on the 
foods they consume. By contrast, EPA's analyses in Tables 2 and 3 
account for the probability that a particular level of residues will be 
present on a food item, as well as the likelihood that an individual 
will consume a particular food. It is EPA's typical approach, as was 
done with carbofuran, to conduct its estimates of exposure across the 
entire population, generally assuming that as long as the 99.9th 
percentile of the estimated daily exposure is equal to or less than the 
aPAD, there is a reasonable certainty of no harm to the general 
population, including all significant subpopulations (Ref. 58). In 
practice, this can mean that if only a small portion of the population 
reported eating the commodity, or if the residues are infrequently 
detected, individual high-end risks may fall above EPA's usual 
benchmark of the 99.9th percentile, or in other words, fall in the 
``tail end'' of the distribution curve. Admittedly, some of the results 
described in Tables 5 and 6 would be expected to fall within this tail 
end, given the relatively infrequent detections of carbofuran in 
sampled commodities. However, taking into account the analysis of the 
risk drivers in Table 4 above, it is clear that some of these values do 
fall within the 99.9th percentile.
    In any event, given all of the facts, it is just as appropriate for 
EPA to evaluate whether the eating occasions that drive a conclusion 
that risks at the 99.9th percentile yield unacceptable risks are 
realistic, as it is for EPA to examine whether eating occasions in the 
tail of a distribution curve are examples of consumption events the 
Agency should be concerned about. In this regard, it is notable that 
even the high-end consumption values described in Tables 5 and 6 are 
extremely likely to be valid reported consumption events--or in other 
words, consumption of the amounts at the 90th percentile are quite 
realistic. For example, a child between 3-5 years, who consumes a 
[frac12] cup of cantaloupe would receive a dose ranging between 180% 
and 7,200% of the aPAD. Accordingly, this analysis by itself supports a 
conclusion that the carbofuran tolerances are not safe and certainly 
buttresses EPA's conclusions that exposures from carbofuran in food or 
water alone or from carbofuran residues in food and water aggregated 
when assessed at the 99.9th percentile are not safe.
    Additionally, because of the uncertainty surrounding carbofuran's 
exposure potential, investigation of individual children's risks, even 
if in the ``tail end,'' is particularly relevant. There are a number of 
reasons that significant uncertainty remains with respect to 
carbofuran's exposure potential. One primary consideration stems from 
the high LOD for carbofuran and consequent large numbers of non-detects 
in the PDP data. The LOD for most commodities is tenfold to twentyfold 
higher than the more precise methods used for the CMS and some of the 
more recent PDP data. Generally, EPA would consider use of [frac12] LOD 
as a conservative way of addressing non-detects but that may not be the 
case where the LOD is relatively insensitive and the risk of concern is 
an acute exposure. For acute risks, the higher values in a 
probabilistic risk assessment are often driven by relatively high 
values in a few commodities rather than relatively lower values in a 
greater number of commodities. This is due to the fact that an acute 
assessment looks at a narrow window of exposure where there are 
unlikely to be a great variety of foods consumed. Thus, to the extent 
that there is a high exposure it will be more likely due to a high 
residue value in a single commodity. However, assuming [frac12] LOD for 
non-detects does not reflect that the non-detects actually will bear a 
range of values from close to or near zero to close to or near the LOD. 
Importantly, those commodities bearing residues only slightly below the 
LOD may result in an exceedance of the aPAD where assuming [frac12] LOD 
would not. In this way, the [frac12] LOD analysis may actually 
understate risk. In these circumstances, reliance on [frac12] LOD can 
skew the distribution of residues, which in turn masks the true ``tail 
end'' of exposures. In other words, to the extent that the [frac12] LOD 
underestimates exposures for some individual commodities, it 
effectively decreases the probability of receiving higher residues, 
thereby shifting those values with greater risks to the tail end of the 
distribution curve, above the 99.9th percentile.
    The second important point from these tables is that the 
exceedances from both the 50th and 90th percentile consumer are quite 
large--sometimes orders of magnitude above safe doses. The size of 
these exceedances gives rise to concerns that the exceedances are more 
likely to result in actual harm to exposed individuals, particularly if 
they are also consuming carbofuran-contaminated drinking water. 
Additionally worrisome in this regard is that carbofuran is a highly 
potent (i.e., has a very steep dose-response curve), acute toxicant, 
and therefore any aPAD exceedances are more likely to have greater 
significance in terms of the potential likelihood of actual harm.
    Finally, that Tables 5 and 6 show large exceedances across several 
crops for which relatively more residue data are available suggests 
these results are not unique to the specific crops for which precise 
residues have been detected in PDP and MBS. In other words, crops for 
which such residue data are not available may be posing similar risks.
    In sum, these results strongly support EPA's conclusion that its 
dietary exposure assessment for carbofuran has not overstated exposure 
and risk. Further, serious questions remain as to the extent to which 
similar exceedances exist for all crops, but which remain undetected, 
because, as result of the high LOD, EPA lacks precise residue levels 
for the majority of crops.
    2. Drinking water exposures. EPA's drinking water assessment uses 
both monitoring data for carbofuran and modeling methods, and takes 
into account contributions from both surface water and groundwater 
sources (Refs. 3, 4, 13, 36 and 47). Concentrations of carbofuran in 
drinking water, as with any pesticide, are in large part determined by 
the amount, method, timing and location of pesticide application, the 
chemical properties of the pesticide, the physical characteristics of 
the watersheds and/or aquifers in which the community water supplies or 
private wells are located, and other environmental factors, such as 
rainfall, which can cause the pesticide to move from the location where 
it was applied. While there is a considerable body of monitoring data 
that has measured carbofuran residues in surface and groundwater 
sources, the locations of sampling and the sampling frequencies 
generally are not sufficient to capture peak concentrations of the 
pesticide in a watershed or aquifer where carbofuran is used. Capturing 
these peak concentrations is particularly important for assessing risks 
from carbofuran because the toxicity end-point of concern results from 
single-day exposure (acute effects). Because pesticide loads in surface 
water tend to move in relatively quick pulses in

[[Page 44881]]

flowing water, frequent targeted sampling is necessary to reliably 
capture peak concentrations for surface water sources of drinking 
water. Pesticide concentrations in ground water, however, are generally 
the result of longer-term processes and less frequent sampling can 
better characterize peak ground water concentrations. However, such 
data must be targeted at vulnerable aquifers in locations where 
carbofuran applications are documented in order to capture peak 
concentrations. As a consequence, monitoring data for both surface and 
groundwater tends to underestimate exposure for acute endpoints. 
Simulation modeling complements monitoring by making estimations at 
vulnerable sites and can be used to represent daily concentration 
profiles, based on a distribution of weather conditions. Thus, modeling 
can account for the cases when a pesticide is used in drinking water 
watersheds at any rate and is applied to a substantial proportion of 
the crop. It can also account for stochastic processes, such as 
rainfall represented by 30 years of existing weather data maintained by 
the National Oceanic and Atmospheric Administration.
    a. Exposure to carbofuran from drinking water derived from ground 
water sources. Drinking water taken from shallow wells is particularly 
vulnerable to contamination in areas where carbofuran is used around 
sandy, highly acidic soil. Some areas with these characteristics 
include Long Island, parts of Florida, and the Atlantic coastal plain, 
in addition to other areas of the country. Exposure estimates for this 
assessment are drawn primarily from (1) the results of a prospective 
groundwater (PGW) study developed by the registrant in the early 1980s; 
and (2) additional groundwater modeling conducted as part of the NMC 
cumulative assessment in 2007. The results of the PGW study are 
consistent with a number of other targeted groundwater studies 
conducted in the 1980s showing that high concentrations of carbofuran 
can occur in vulnerable areas; the results of these studies as well as 
the PGW study are summarized in (Refs. 13 and 47). For example, a study 
in Manitoba, Canada assessed the movement of carbofuran into tile 
drains and groundwater from the application of liquid carbofuran to 
potato and corn fields. The application rates ranged between 0.44-0.58 
pounds a.i./acre, and the soils at the site included fine sand, loamy 
fine sand, and silt loam, with pH ranging between 6.5-8.3. 
Concentrations of carbofuran in groundwater samples ranged between 0 
(non-detect) and 158 ppb, with a mean of 40 ppb (Refs. 13 and 47).
    While there have been additional groundwater monitoring studies 
that included carbofuran as an analyte since that time, there has been 
no additional monitoring targeted to carbofuran use in areas where 
aquifers are vulnerable. Accordingly, EPA believes the PGW study 
continues to be the most relevant monitoring data for assessing 
drinking water exposures from private wells at vulnerable sites. 
Because this study was conducted over only one growing season, however, 
and was conducted at use rates that now exceed current label maximum 
rates for the use being studied (3 lb ai/acre vs. the current 2 lb ai/
acre for corn), EPA has scaled the results to represent impacts from 
carbofuran use over a long-term period (25 years) at current label 
rates. Temporal scaling was necessary because the PGW study represents 
water quality impacts from a single application rather than repeated 
years of use. Based on EPA's assessment, the maximum 90-day average 
carbofuran concentrations in vulnerable groundwater for various 
application rates were estimated to range from a low of 11 parts per 
billion (ppb) based on a 1 pound per acre application rate, to a high 
of 34 ppb, based on a 3 pound per acre application rate. The peak 
concentration measured in the PGW study was 65 ppb. Because the 
degradate 3-hydroxycarbofuran, which is assumed to be of equal potency 
with the parent compound, was not measured in this study, exposure was 
not estimated. Although the failure to include the degradate is 
expected to underestimate exposure to some degree, the extent to which 
it would contribute to exposure is unclear.
    EPA conducted additional groundwater modeling for the NMC 
cumulative risk assessment, and developed a time series of exposures at 
locations selected based on potential for exposure to a combination of 
carbamate insecticides relevant for cumulative exposure assessment for 
use in probabilistic dietary assessments using DEEM. EPA estimated 
carbofuran groundwater concentrations associated with two possible use 
scenarios: potatoes in northeastern Florida and cucurbits on the 
Delmarva Peninsula in the Mid-Atlantic region. While the modeled potato 
use scenario in Florida did not show concentrations of carbofuran of 
concern, estimated carbofuran concentrations associated with the 
cucurbit use in the Delmarva Peninsula - a region with shallow, acidic 
groundwater and acidic, sandy soils - are consistent with EPA's 
assessment of the PGW study discussed above. Specifically, the 
assessment indicated that at an application rate of 1.25 pounds a.i. 
per acre, on cucurbits, maximum concentrations were 38.5 ppb (Ref. 63). 
EPA does not believe the results of this assessment are particularly 
conservative, since the application rate used in this assessment was 
less than the maximum rate of 1.94 lb/acre that growers can use. Also, 
concentrations of the degradate, 3-hydroxycarbofuran were not included 
in modeling simulations, which would tend to underestimate exposure to 
some degree.
    Based on these estimates, EPA compiled a distribution of estimated 
carbofuran concentrations in water that could be used to generate 
probabilistic assessments of the potential exposures from drinking 
water derived from vulnerable ground water sources. The results of 
EPA's probabilistic assessments are represented below in Table 7. As 
discussed in the previous section, it is important to remember that the 
aPAD for carbofuran is quite low, hence, relatively low concentrations 
of carbofuran monitored or estimated in vulnerable groundwater can have 
a significant impact on the aPAD utilized.

      Table 7--Results of Acute Dietary (Ground Water Only) Exposure Analysis Using DEEM FCID and Incorporating the Delmarva Ground Water Scenario
                                                              (Representing Private Wells)
--------------------------------------------------------------------------------------------------------------------------------------------------------
                                                                                      95th Percentile         99th Percentile        99.9th Percentile
                                                                     aPAD (mg/kg/-----------------------------------------------------------------------
                        Population Subgroup                              day)       Exposure                Exposure                Exposure
                                                                                  (mg/kg/day)    % aPAD   (mg/kg/day)    % aPAD   (mg/kg/day)    % aPAD
--------------------------------------------------------------------------------------------------------------------------------------------------------
All Infants (< 1 year old)                                              0.000075     0.003800      5,100     0.006006      8,000     0.010030    >10,000
--------------------------------------------------------------------------------------------------------------------------------------------------------
Children 1-2 years old                                                  0.000075     0.001612      2,100     0.002732      3,600     0.004628      6,200
--------------------------------------------------------------------------------------------------------------------------------------------------------

[[Page 44882]]

 
Children 3-5 years old                                                  0.000075     0.001459      1,900     0.002405      3,200     0.004613      5,600
--------------------------------------------------------------------------------------------------------------------------------------------------------
Children 6-12 years old                                                 0.000075     0.001018      1,360     0.001710      2,300     0.002792      3,700
--------------------------------------------------------------------------------------------------------------------------------------------------------
Youth 13-19 years old                                                     0.0002     0.000809        400     0.001441        720     0.002919      1,500
--------------------------------------------------------------------------------------------------------------------------------------------------------
Adults 20-49 years old                                                    0.0002     0.000955        480     0.001632        820     0.003073      1,500
--------------------------------------------------------------------------------------------------------------------------------------------------------
Adults 50+ years old                                                      0.0002     0.000884        440     0.001345        670     0.002271      1,100
--------------------------------------------------------------------------------------------------------------------------------------------------------

    While the registrant has attempted to address drinking water 
exposure from ground water sources by including on current carbofuran 
product labeling an advisory statement warning growers against 
application in vulnerable areas, this language does not prohibit use in 
such areas. In addition, EPA does not believe that the available 
information demonstrates that even the additional restrictions that FMC 
included on its labels submitted in May, 2008 would adequately mitigate 
the risk of contaminating all vulnerable ground water (Refs. 18 and 
54). For example, those restrictions were based on the use of a 
particular methodology to evaluate the characteristics in the site used 
in the PGW study in the Delmarva Penninsula. Using that as a surrogate 
to identify sites with vulnerability to ground water contamination, FMC 
identified counties that had higher vulnerability scores than the site 
used for the PGW study in the Delmarva Penninsula, and proposed label 
restrictions to preclude use in such areas. While EPA agrees in 
principle that precluding use in sites vulnerable to leaching can 
mitigate the risks, and even presuming that the methodology used by FMC 
adequately identifies those sites, sites less vulnerable than the PGW 
site would still be vulnerable to contamination, and the proposed 
restrictions in no way addressed the less sensitive, but still 
vulnerable, sites (Refs. 18 and 54). Accordingly, EPA continues to 
believe that its assessment of drinking water from groundwater sources 
based on current labels is a realistic assessment of potential 
exposures to those portions of the population consuming drinking water 
from shallow wells in highly vulnerable areas.
    b. Exposure from drinking water derived from surface water sources. 
EPA's evaluation of environmental drinking water concentrations of 
carbofuran from surface water, as with its evaluation of groundwater, 
takes into account the results of both surface water monitoring and 
modeling.
    Data compiled in 2002 by EPA's Office of Water show that carbofuran 
was detected in treated drinking water at a few locations. Based on 
samples collected from 12, 531 ground water and 1,394 surface water 
source drinking water supplies in 16 states, carbofuran was found at no 
public drinking water supply systems at concentrations exceeding 40 ppb 
(the MCL). Carbofuran was found at one public ground water system at a 
concentration of greater than 7 ppb and in two ground water systems and 
one surface water public water system at concentrations greater than 4 
ppb (measurements below this limit were not reported). Sampling is 
costly and is conducted typically four times a year or less at any 
single drinking water facility. The overall likelihood of collecting 
samples that capture peak exposure events is, therefore, low. For 
chemicals with acute risks of concern, such as carbofuran, higher 
concentrations and resulting risk is primarily associated with these 
peak events, which are not likely to be captured in monitoring unless 
the sampling rate is very high.
    Unlike drinking water derived from private groundwater wells, 
public water supplies (surface water or ground water source) will 
generally be treated before it is distributed to consumers. An 
evaluation of laboratory and field monitoring data indicate that 
carbofuran may be effectively removed (60 - 100%) from drinking water 
by lime softening and activated carbon; other treatment process are 
less effective in removing carbofuran (Ref. 63). The detections between 
4 and 7 ppb, reported above, represent concentrations in samples 
collected post-treatment. As such, these levels are of particular 
concern to the Agency. An infant who consumes a single 8 ounce serving 
of water with a concentration of 4 ppb, as detected in the monitoring, 
would receive 121% of the aPAD. An infant who consumes a single 8 ounce 
serving of water with the higher detected concentration of 7 ppb, as 
detected in the monitoring, would receive 210% of the aPAD.
    To further characterize carbofuran concentrations in surface water 
(e.g., streams or rivers) that may drain into drinking water 
reservoirs, EPA analyzed the extensive source of national water 
monitoring data for pesticides, the United States Geological Survey 
National Water Quality Assessment (USGS NAWQA) program. The NAWQA 
program focuses on ambient water rather than on drinking water sources, 
is not specifically targeted to the high use area of any specific 
pesticide, and is sampled at a frequency (generally weekly or bi-weekly 
during the use season) insufficient to provide reliable estimates of 
peak pesticide concentrations in surface water. For example, 
significant fractions of the data may not be relevant to assessing 
exposure from carbofuran use, as there may be no use in the basin above 
the monitoring site. Unless ancillary usage data are available to 
determine the amount and timing of the pesticide applied, it is 
difficult to determine whether non-detections of carbofuran were due to 
a low tendency to move to water or from a lack of use in the basin. The 
program, rather, provides a good understanding on a national level of 
the occurrence of pesticides in flowing water bodies that can be useful 
for screening assessments of potential drinking water sources. A 
detailed description of the pesticide monitoring component of the NAWQA 
program is available on the NAWQA Pesticide National Synthesis Project 
(PNSP) web site (http://ca.water.usgs.gov/pnsp/).
    A summary of the first cycle of NAWQA monitoring from 1991 to 2001 
indicates that carbofuran was the most frequently detected carbamate 
pesticide in streams and ground water in agricultural areas. Overall, 
where

[[Page 44883]]

carbofuran was detected, these non-targeted monitoring results 
generally found carbofuran at levels below 0.5 ppb. In the NMC 
assessment, EPA summarized NAWQA monitoring for carbofuran between 1991 
and 2004. Maximum surface-water concentrations exceeded 1 ppb in 
approximately nine agricultural watershed-based study units, with 
detections in the sub-ppb range reported in additional watersheds (Ref. 
63). The highest concentrations of carbofuran are reported from at a 
sampling station on Zollner Creek, in Oregon. Zollner Creek, located in 
the Molalla-Pudding sub-basin of the Willamette River, is not directly 
used as a drinking water source. This creek is a low-order stream and 
its watershed is small (approximately 40 km2) and intensively farmed, 
with a diversity of crops grown, including plant nurseries. USGS 
monitoring at that location from 1993 to 2006 detected carbofuran 
annually in 40-100 % of samples. Although the majority of 
concentrations detected there are also in the sub-part per billion 
range, concentrations have exceeded 1 ppb in 8 of the 14 years of 
sampling. The maximum measured concentration was 32.2 ppb, observed in 
the spring of 2002. The frequency of detections generally over a 14-
year period suggests that standard use practices rather than 
aberrational misuse incidents in the region are responsible for high 
concentration levels at this location.
    While available monitoring from other portions of the country 
suggests that the circumstances giving rise to high concentrations of 
carbofuran may be rare, overall, the national monitoring data indicate 
that EPA cannot dismiss the possibility of detectable carbofuran 
concentrations in some surface waters under specific use and 
environmental conditions. Even given the limited utility of the 
available monitoring data, there have been relatively recent measured 
concentrations of carbofuran in surface water systems at levels above 4 
ppb (concentrations of 4-7 ppb would result in exposures of 121-210% of 
the aPAD for an infant consuming 8 oz of water) and levels of 
approximately 1 to 30 ppb measured in streams representative of those 
in watersheds that support drinking water systems (Ref. 63). Based on 
this analysis, and since monitoring programs have not been sampling at 
a frequency sufficient to detect daily-peak concentrations that are 
needed to assess carbofuran's acute risk, the available monitoring 
data, in and of themselves, are not sufficient to establish the risks 
posed by carbofuran in surface drinking water are below thresholds of 
concern. Nor can this data be reasonably used to establish a lower 
bound of potential carbofuran risk through this route of exposure.
    To further characterize carbofuran risk through drinking water 
derived from surface water sources, EPA modeled estimated daily 
drinking water concentrations of carbofuran using PRZM to simulate 
field runoff processes and EXAMS to simulate receiving water body 
processes. These models were summarized in Unit V.B.2.
    There are sources of uncertainty associated with estimating 
exposure of carbofuran in surface water source drinking water. Several 
of the most significant of these are the effect of treatment in 
removing carbofuran from finished drinking water before it is delivered 
to the consumer supply system, the impact of percent crop treated 
assumptions, and the variation in pH across the landscape. The effect 
of the percent crop treated assumption in the case of carbofuran is 
discussed in detail in EPA's assessment of additional data submitted by 
the registrant (Refs. 18 and 54) and summarized below. Available data 
on the degree to which carbofuran may be removed from treatment systems 
was summarized previously and is discussed in more detail in Appendix 
E-3 of the Revised NMC Cumulative Assessment (Ref. 63). Although EPA is 
aware of the mitigating effects of specific treatment processes, the 
processes employed at public water supply utilities across the country 
vary significantly both from location to location and throughout the 
year, and therefore are difficult to incorporate quantitatively in 
drinking water exposure estimates. Therefore, EPA assumes that there is 
no reduction in carbofuran concentrations in surface water source 
drinking water due to treatment, which is a source of conservatism in 
surface water exposure estimates used for human health risk assessment. 
While it is well established that carbofuran will degrade at higher 
rates when the pH is above 7, and lower rates when below pH 7, due to 
the high variation of pH across the country a neutral pH (pH 7) default 
value was used to estimate water concentrations. Finally, available 
environmental fate studies do not show formation of 3-hydroxycarbofuran 
through most environmental processes except soil photolysis, where in 
one study it was detected in very low amounts. Although 3-
hydroxycarbofuran was not explicitly considered as a separate entity in 
the drinking water exposure assessment, it is unclear whether it would 
significantly add to exposure estimates.
    EPA compiled a distribution of estimated carbofuran concentrations 
in surface water in order to conduct probabilistic assessments of the 
potential exposures from drinking water. For the IRED, EPA modeled 
crops representing 80 percent of total carbofuran use at locations that 
would be considered among the more vulnerable where the crops are 
grown. Modeling was conducted at a range of application rates and 
included adjustments to reflect different regional levels for 
agricultural intensity, resulting in estimated 1-in-10-year (peak) 
concentrations of 0.11-75 ppb (Refs. 5 and 36). For corn, carbofuran 
concentration estimates assuming different rates and regional percent 
cropped area (PCA) factors reflective of corn intensity nationally 
resulted in a range of peak concentrations of 4 - 26 ppb. For the 
dietary risk assessment, EPA generated distributions for 13 different 
scenarios representing all labeled uses of carbofuran treated at 
maximum label rates and adjusted with PCA factors (Refs. 3, 13 and 47). 
Peak concentrations for these distributions ranged from 3.2 to 168 ppb 
(excluding use on bananas), with the corn use at 26 ppb (Refs. 3 and 
47).
    EPA has subsequently conducted several rounds of modeling to refine 
estimates for specific uses and agricultural practices. One set of 
refinements addressed use of carbofuran on corn at typical rather than 
maximum label rates and application practices that assume the only use 
of carbofuran in a watershed is on corn. Simulations included those 
specific to control European corn borer, a rescue treatment for corn 
rootworm, and an in-furrow application at plant. The assessment also 
included estimates resulting from treatment at the maximum label rate, 
for comparative purposes. The peak concentrations estimated ranged from 
3.9 to 16.6 ppb for the refined analyses, compared to 32.9 ppb at the 
maximum application rate (Ref. 4). The range of 3.9 to 16.6 ppb is 
approximately 1 to 4 times the values of the 4 ppb detected in finished 
water from a surface water drinking plant, as summarized previously, 
and approximately twofold to tenfold lower than the maximum peak 
concentration of 32.2 ppb reported in the USGS-NAWQA data set.
    Additional refined modeling assessments were based on a proposed 
label submitted by FMC in May 2008. The refinements focused on two uses 
currently allowed on the existing label that would have remained under 
the withdrawn label: a corn rootworm rescue treatment, evaluated at 7 
representative sites, and an at-plant

[[Page 44884]]

treatment for melons evaluated at 4 additional sites. EPA developed 5 
additional corn scenarios representing use in states with extensive 
carbofuran usage at locations more vulnerable than most in each state 
in areas corn is grown. Using measured rainfall values, and assuming 
typical rather than maximum use rates, these assessments focused on the 
corn rescue treatment (Ref. 4). Peak concentrations for the corn rescue 
treatments simulated for Illinois, Iowa, Indiana, Kansas, Minnesota, 
Nebraska, and Texas ranged from 16.6 - 36.7 ppb. For refinement of 
estimates for the other use, melons, EPA developed 3 additional melon 
scenarios representing states with extensive carbofuran usage at 
locations more vulnerable than most in each state in areas melons are 
grown. EPA used measured rainfall values and a wide row spacing to 
simulate an application rate less than half of what is allowed as the 
maximum rate for melons (0.65 versus 1.94 lb/A). Peak concentrations 
resulting from a single ground application of carbofuran at plant in 
Florida, Michigan, Missouri, and New Jersey resulted in peak 
concentrations from 4.2 - 24.4 ppb (Id.). Additional details on these 
assessments can be found at Ref. 4. Consistent with the analysis 
summarized above these predicted carbofuran water concentrations are 
similar to or lower than the peak concentrations reported in the USGS-
NAWQA monitoring data and similar to or not more than tenfold higher 
than the 4 ppb reported in finished water from a surface water drinking 
plant.
    There are few surface water field-scale studies targeted to 
carbofuran use that could be compared with modeling results. Most of 
these studies were conducted in fields that contain tile drains, which 
is a common practice throughout midwestern states to increase drainage 
in agricultural fields (Ref. 13). Drains are common in the upper 
Mississippi river basin (Illinois, Iowa, and the southern part of 
Minnesota), and the northern part of the Ohio River Basin (Indiana, 
Ohio, and Michigan) (Ref. 42). Although it is not possible to directly 
correlate the concentrations found in most of the studies with drinking 
water concentrations, these studies confirm that carbofuran use under 
such circumstances can contaminate surface water, as tile drains have 
been identified as a pathway for contamination of surface water. For 
example, one study conducted in the United Kingdom in 1991 and 1992 
looked at concentrations in tile drains and surface water treated at a 
rate of 2.7 lbs a.i. per acre (granular formulation). Resulting 
concentrations in surface water downstream of the field ranged from 
49.4 ppb almost two months after treatment to 0.02 ppb 6 months later, 
and were slightly lower than concentrations measured in the tile 
drains, which were a transport pathway. Even with the factors that 
limit the study's relevance to the majority of current carbofuran use--
the high use rate and granular formulation--the study clearly confirms 
that tile drains can serve as a source of significant surface water 
contamination. Although EPA's models do not account for tile drain 
pathways, and acknowledging the uncertainties in comparing carbofuran 
monitoring data to the concentrations predicted from the exposure 
models, as noted previously, estimated (model-derived) peak 
concentrations of carbofuran are similar to peak concentrations 
reported in stream monitoring studies and are no more than tenfold 
higher than a value reported from a drinking water plant where it is 
unlikely the sample design would have ensured that water was sampled on 
the day of the peak concentration.
    EPA conducted dietary exposure analyses based on the modeling 
scenarios for the current label as well as scenarios comparable to the 
uses on FMC's proposed label of May 2008. Exposures from all modeled 
scenarios substantially exceeded EPA's level of concern (Ref. 12). For 
example, an Illinois corn scenario, assuming 2 foliar applications at a 
typical 1-lb a.i. per acre use rate, estimated a 1-in-10-year peak 
carbofuran water concentration of 26 ppb. Exposures at the 99.9th 
percentile based on this modeled distribution ranged from 860% of the 
aPAD for youths 13-19 to greater than 10,000% of the aPAD for infants. 
This scenario is intended to be representative of highly vulnerable 
sites on which corn could be grown on a national basis, and is used as 
a screen for corn on a national basis. Similarly, exposures based on an 
Idaho potato scenario, and using a 3 lb a.i. acre rate, ranged from 
230% of the aPAD for children 6-12 to 890% of the aPAD for infants, 
with a1-in-10-year peak carbofuran concentration of 10 ppb. Although 
other crop scenarios resulted in higher exposures, estimates for these 
two crops are presented here, as they are major crops on which a large 
percentage of carbofuran use occurs. More details on these assessments, 
as well as the assessments EPA conducted for other crop scenarios, can 
be found in Refs. 4, 12 and 47.
    Table 8 below presents the results of one of EPA's refined exposure 
analyses that addresses a use comparable to one in FMC's proposed May 
2008 label. This example is based on a Nebraska corn rootworm ``rescue 
treatment'' scenario, and assumes a single aerial application at a 
typical rate of 1 pound a.i. per acre. To simulate an application made 
post-plant, at or near rootworm hatch, EPA modeled an application of 
carbofuran 30 days after crop emergence. EPA used a crop specific PCA 
of 0.46 which is the maximum proportion of corn acreage in a Hydrologic 
Unit Code 8-sized basin in the United States. (The U.S. Geological 
Survey has classified all watersheds in the US into basins of various 
sizes, according to hydrologic unit codes, in which the number of 
digits indicates the size of the basin). The full distribution of daily 
concentrations over a 30-year period was used in the probabilistic 
dietary risk assessment. The 1-in-10-year peak concentration of the 
distribution of values for the Nebraska corn rescue treatment was 22.3 
ppb. More details on these assessments, as well as the assessments EPA 
conducted for other crop scenarios, can be found in Refs. 4, 12 and 47.

            Table 8--Results of Acute Dietary (Surface Water Only) Exposure Analysis Incorporating the Nebraska Corn Rootworm Rescue Scenario
--------------------------------------------------------------------------------------------------------------------------------------------------------
                                                                                      95th Percentile         99th Percentile        99.9th Percentile
                                                                     aPAD (mg/kg/-----------------------------------------------------------------------
                        Population Subgroup                              day)       Exposure                Exposure                Exposure
                                                                                  (mg/kg/day)    % aPAD   (mg/kg/day)    % aPAD   (mg/kg/day)    % aPAD
--------------------------------------------------------------------------------------------------------------------------------------------------------
All Infants (< 1 year old)                                              0.000075     0.000444        590     0.001236      1,650     0.002912      3,900
--------------------------------------------------------------------------------------------------------------------------------------------------------
Children 1-2 years old                                                  0.000075     0.000190        250     0.000517        690     0.001267      1,700
--------------------------------------------------------------------------------------------------------------------------------------------------------
Children 3-5 years old                                                  0.000075     0.000177        240     0.000473        630     0.001144      1,500
--------------------------------------------------------------------------------------------------------------------------------------------------------

[[Page 44885]]

 
Children 6-12 years old                                                 0.000075     0.000122        160     0.000329        440     0.000801      1,100
--------------------------------------------------------------------------------------------------------------------------------------------------------
Youth 13-19 years old                                                     0.0002     0.000091         45     0.000255        130     0.000671        340
--------------------------------------------------------------------------------------------------------------------------------------------------------
Adults 20-49 years old                                                    0.0002     0.000118         60     0.000313        160     0.000766        380
--------------------------------------------------------------------------------------------------------------------------------------------------------
Adults 50+ years old                                                      0.0002     0.000125         60     0.000307        150     0.000671        340
--------------------------------------------------------------------------------------------------------------------------------------------------------

    The populations described in the ``Nebraska corn'' assessments are 
those people who consume water from a reservoir located in a small 
watershed predominated by corn production (with the assumption that 
treatment does not reduce carbofuran concentrations). The only crop 
treated by carbofuran in the watershed is corn, and all of that crop is 
assumed treated with carbofuran at the rate of 1 lb per acre. To the 
extent a drinking water plant drawing water from the reservoir normally 
treats the raw intake water with lime softening or activated carbon 
processes the finished water concentrations could be reduced from 60 to 
100% with the resultant aPADs ranging from approximately 460 to 102% of 
the aPAD to 0% of the aPAD, respectively, at the 99.9th percentile of 
exposure.
    As discussed in the previous sections, it is important to remember 
that carbofuran's aPAD is quite low, hence relatively low 
concentrations of carbofuran monitored or estimated in surface water 
can have a significant impact on the percent of the aPAD utilized. 
Thus, while the refined carbofuran water concentrations for the corn 
``rescue'' treatment in the range of approximately 16.6 to 36.7 ppb are 
comparable to maximum peak concentrations reported in the monitoring 
studies, these concentrations can result in very significant 
exceedences of the aPAD for various age groups, primarily because 
carbofuran is inherently very toxic.
    FMC has criticized EPA's assessment for failing to account more 
fully for the percent of the crop treated (PCT) in its modeling. 
Uncertainty associated with PCT assumptions can be a major factor in 
EPA's drinking water exposure assessment for surface-water sources. 
Estimates of the percent of major crops (for example, corn) that are 
treated with pesticides are available at the state level, but are 
generally not available on a smaller scale suitable for estimating 
drinking water exposure in a watershed. In addition, the PCT should be 
assessed at a watershed-scale, aggregating all crops treated with the 
pesticide in a watershed. If state-scale estimates are used to account 
for PCT it will underestimate the risk for some of the drinking water 
facilities in the state as the state-wide estimate represents an 
average: values for individual facilities will be both lower and higher 
than the state-wide estimate. In some cases, the underestimate can be 
substantial if the application pattern tends to form cluster or pockets 
of high usage. Insecticides like carbofuran are particularly prone to 
this use pattern, as insect outbreaks often tend to be locally intense, 
rather than widespread. In addition, marginal use practice changes in a 
given watershed can substantially affect the percentage of the crop 
treated, and such changes are effectively impossible to track. Without 
data collected at a finer spatial scale, it is not possible to know 
whether pesticide usage is evenly dispersed through the state or is 
locally clustered. This results in large uncertainty in the drinking 
water exposure assessments when percent crop treated is moderate or 
low. Consequently, EPA does not typically include such information in 
its surface-water exposure assessments.
    However, in response to FMC's concerns, EPA performed a sensitivity 
analysis of an exposure assessment using a PCT in the watershed to 
determine the extent to which some consideration of this factor could 
meaningfully affect the outcome of the risk assessment. The registrant 
has at different times, suggested the application of a 5 or 10% crop 
treated based on county sales data. While substantial questions remain 
as to the support for these percentages for a given basin where 
carbofuran may be used, EPA used the upper figure for the purpose of 
conducting a sensitivity analysis. The results suggest that, even at 
levels below 10% crop treated, exposures from drinking water derived 
from surface waters can contribute significantly to the aggregate 
dietary risks, particularly for infants and children. For example, 
applying a 10% crop treated figure to the Nebraska corn scenario 
described above, in addition to the corn-PCA of 0.46 incorporated into 
that scenario, results in estimated exposures from water alone, ranging 
from 110% of the aPAD for children 6-12 to 390% of the aPAD for 
infants, assuming water treatment processes do not affect 
concentrations in drinking water consumed. Details on the assessments 
EPA conducted for other crop scenarios, which showed higher 
contributions from drinking water, can be found in Refs. 12, 13 and 47. 
Accordingly, these assessments suggest that EPA's use of PCA alone, 
rather than in conjunction with PCT, will not meaningfully affect the 
carbofuran risk assessment, as aggregate exposures would still exceed 
100% of the aPAD.
    In conclusion, the large difference between concentrations seen in 
the monitoring data on the low side, and the simulation modeling on the 
high side, is an indication of the uncertainty in the assessment for 
surface-water source drinking water exposure. The majority of drinking 
water concentrations resulting from use of carbofuran are likely to be 
occurring at higher concentrations than those measured in most 
monitoring studies, but below those estimated with simulation modeling; 
however the exact values are highly uncertain. However, the monitoring 
data show a consistent pattern of low concentrations, with the 
occasional, infrequent spike of high concentrations. Those infrequent 
high concentrations are consistent with EPA's modeling, which is 
intended to capture the exposure peaks. For a chemical with an acute 
risk, like carbofuran, the spikes or peaks in exposures, even though 
infrequent, are the most relevant for assessing the risks. And, as 
previously noted, the available monitoring has its own limitations for 
estimating exposure for risk assessment.
    Further, the results of the modeling analyses provide critical 
insights

[[Page 44886]]

regarding locations in the country where the potential for carbofuran 
contamination to surface water and associated drinking water sources 
are more likely. These locations include areas with soils prone to 
runoff (such as those high in clay or containing restrictive layers), 
in regions with intensive agriculture with crops on which carbofuran is 
used (e.g. corn), which have high rainfall amounts and/or are subject 
to intense storm events in the spring around the times applications are 
being made. Drinking water facilities with small basins tend to be more 
vulnerable, as it is more likely that a large proportion of the crop 
acreage will be treated in small basins.
    Apparently FMC also has determined that some drinking water 
facilities associated with surface source waters are vulnerable to 
carbofuran exposure. In the now withdrawn labels FMC proposed to 
require buffer zones around surface waters in certain locations of the 
country, presumably to protect surface water. The proposed buffers were 
for fields where soils were considered to be highly erodible. Buffers 
were to be 66 feet wide and were to be vegetated with ``crop, seeded 
with grass, or other suitable crop''. In 2000, EPA participated in the 
development of a guidance document on how to reduce pesticide runoff 
using conservation buffers (Ref. 55). Results of this effort found that 
properly designed buffers can reduce runoff of weakly absorbed 
pesticides like carbofuran by increasing filtration so that the 
pesticide can be trapped and degraded in the buffer. However, it is of 
critical importance that sheet flow be maintained across the buffer in 
order for this to occur. To ensure sheet flow, buffers need to be 
specifically designed for that purpose and they must be well-
maintained, as over time sediment trapped in the buffer causes flow to 
become more channelized and the buffer then becomes ineffective. The 
guidance concludes that un-maintained, un-vegetated buffers around 
water bodies, often referred to a `setback,' are ineffective in 
reducing pesticide movement to surface water.
    3. Aggregate dietary exposures (food and drinking water). EPA 
conducted a number of probabilistic analyses to combine the national 
food exposures with the exposures from the individual region and crop-
specific drinking water scenarios. Although food is distributed 
nationally, and residue values are therefore not expected to vary 
substantially throughout the country, drinking water is locally derived 
and concentrations of pesticides in source water fluctuate over time 
and location for a variety of reasons. Pesticide residues in water 
fluctuate daily, seasonally, and yearly as a result of the timing of 
the pesticide application, the vulnerability of the water supply to 
pesticide loading through runoff, spray drift and/or leaching, and 
changes in the weather. Concentrations are also affected by the method 
of application, the location and characteristics of the sites where a 
pesticide is used, the climate, and the type and degree of pest 
pressure. Consequently, EPA conducted several estimates of aggregate 
dietary risks by combining exposures from food and drinking water. All 
of these estimates showed that aggregate exposures to carbofuran 
residues are unsafe. More details on the individual aggregate 
assessments presented below, as well as the assessments EPA conducted 
for other regional and crop scenarios, can be found in Refs. 12 and 13.
    Table 9 below reflects the results of aggregate exposures from food 
and from drinking water derived from ground water in vulnerable areas 
(i.e., from shallow wells associated with sandy soils and acidic 
aquifers, such as are found in the Delmarva Peninsula). The estimates 
range between 1,100% of the aPAD for adults, to over 10,000% of the 
aPAD for infants.

                  Table 9--Results of Acute Dietary (Food and Water) Exposure Analysis Incorporating the Delmarva Ground Water Scenario
--------------------------------------------------------------------------------------------------------------------------------------------------------
                                                                                      95th Percentile         99th Percentile        99.9th Percentile
                                                                     APAD (mg/kg/-----------------------------------------------------------------------
                        Population Subgroup                              day)       Exposure                Exposure                Exposure
                                                                                  (mg/kg/day)    % aPAD   (mg/kg/day)    % aPAD   (mg/kg/day)    % aPAD
--------------------------------------------------------------------------------------------------------------------------------------------------------
All Infants (< 1 year old)                                              0.000075     0.003799      5,100     0.006026      8,000     0.010011    >10,000
--------------------------------------------------------------------------------------------------------------------------------------------------------
Children 1-2 years old                                                  0.000075     0.001622      2,200     0.002740      3,700     0.004644      6,200
--------------------------------------------------------------------------------------------------------------------------------------------------------
Children 3-5 years old                                                  0.000075     0.001465      2,000     0.002414      3,200     0.004273      5,700
--------------------------------------------------------------------------------------------------------------------------------------------------------
Children 6-12 years old                                                 0.000075     0.001026      1,400     0.001715      2,300     0.002825      3,800
--------------------------------------------------------------------------------------------------------------------------------------------------------
Youth 13-19 years old                                                     0.0002     0.000813        410     0.001442        720     0.002921      1,500
--------------------------------------------------------------------------------------------------------------------------------------------------------
Adults 20-49 years old                                                    0.0002     0.000958        480     0.001638        820     0.003091      1,500
--------------------------------------------------------------------------------------------------------------------------------------------------------
Adults 50+ years old                                                      0.0002     0.000888        440     0.001351        680     0.002278      1,100
--------------------------------------------------------------------------------------------------------------------------------------------------------

    The peak concentration estimates in the Delmarva groundwater 
scenario time series are consistent with monitoring data from wells in 
vulnerable areas where carbofuran was used. For example, the maximum 
water concentration from the time series is 38.5 ppb while maximum 
values from a targeted ground water monitoring study at the same site 
was 65 ppb, with studies at other sites having similar or higher peak 
concentrations (Refs. 13 and 47). For studies with multiple 
measurements at each well, central tendency estimates were also in the 
same range as the time series. For example, the mean carbofuran 
concentration from wells under no-till agriculture in Queenstown, MD 
was 7 ppb, while the median for the modeling was 15.5 ppb. The 90-day 
average concentration, based on the registrant's PGW study conducted on 
corn in the Delmarva (adjusted for current maximum application rates) 
is 22 ppb.
    Table 10 below presents the results of aggregate exposure from food 
and derived from surface water using the Nebraska corn surface water 
scenario. This table reflects the risks only for those people in 
drinking watersheds with characteristics similar to that used in the 
scenario, and assuming that water treatment does not remove carbofuran.

[[Page 44887]]

As discussed previously, the estimated water concentrations are 
comparable to the maximum peak concentrations reported in monitoring 
studies that were not designed to detect peak, daily concentrations of 
carbofuran in vulnerable locations.

                  Table 10--Results of Acute Dietary (Food and Water) Exposure Analysis Using the Nebraska Corn Surface Water Scenario
--------------------------------------------------------------------------------------------------------------------------------------------------------
                                                                                      95th Percentile         99th Percentile        99.9th Percentile
                                                                     aPAD (mg/kg/-----------------------------------------------------------------------
                        Population Subgroup                              day)       Exposure                Exposure                Exposure
                                                                                  (mg/kg/day)    % aPAD   (mg/kg/day)    % aPAD   (mg/kg/day)    % aPAD
--------------------------------------------------------------------------------------------------------------------------------------------------------
All Infants (< 1 year old)                                              0.000075     0.000448        600     0.001240      1,700     0.002899      3,900
--------------------------------------------------------------------------------------------------------------------------------------------------------
Children 1-2 years old                                                  0.000075     0.000200        270     0.000533        710     0.001326      1,800
--------------------------------------------------------------------------------------------------------------------------------------------------------
Children 3-5 years old                                                  0.000075     0.000187        250     0.000486        650     0.001190      1,600
--------------------------------------------------------------------------------------------------------------------------------------------------------
Children 6-12 years old                                                 0.000075     0.000128        170     0.000336        450     0.000824      1,100
--------------------------------------------------------------------------------------------------------------------------------------------------------
Youth 13-19 years old                                                     0.0002     0.000095         48     0.000264        130     0.000685        340
--------------------------------------------------------------------------------------------------------------------------------------------------------
Adults 20-49 years old                                                    0.0002     0.000122         61     0.000318        160     0.000785        390
--------------------------------------------------------------------------------------------------------------------------------------------------------
Adults 50+ years old                                                      0.0002     0.000129         65     0.000312        160     0.000689        340
--------------------------------------------------------------------------------------------------------------------------------------------------------

    Typically, EPA's food and water exposure assessments sum exposures 
over a 24-hour period, and EPA used this 24-hour total in developing 
its acute dietary risk assessment for carbofuran. Because of the rapid 
nature of carbofuran toxicity and recovery, EPA considered that it 
might be appropriate to consider durations of exposure less than 24 
hours. EPA has developed an analysis using information about external 
exposure, timing of exposure within a day, and half-life of AChE 
inhibition from rats to estimate risk to carbofuran at durations less 
than 24 hours. Specifically, EPA has evaluated individual eating and 
drinking occasions and used the AChE half-life information to estimate 
the residual effects from carbofuran from previous exposures within the 
day. The carbofuran analyses are described in the July 2008 aggregate 
(dietary) memo (Ref. 12).
    EPA has used two approaches for considering the impact of rapid 
reversibility on exposure estimates in the food and drinking water risk 
assessments. EPA previously used these approaches in the cumulative 
risk assessment of the NMC pesticides and/or risk assessments for other 
NMC pesticides (e.g., methomyl and aldicarb) (Ref. 63).
    Incorporating eating occasion analysis and either the 150 minute or 
300 minute recovery half life for carbofuran into the food only 
analysis does not significantly change the risk estimates when compared 
to baseline levels (for which a total daily consumption basis - and not 
eating occasion - was used). From this, it is apparent that modifying 
the analysis such that information on eating (i.e. food) occasions and 
carbofuran half life is incorporated results in only minor reductions 
in estimated risk.
    The food analysis showed that over 70% of exposures at the top 0.2 
percentile for children ages 1-2 and 3-5 are from a single eating event 
of carbofuran indicating that carbofuran's food risk is not 
substantively overstated. Moreover, when incorporating half-life to 
recovery information, risks from summing exposures over 24 hours are 
similar to those when incorporating half-life to recovery of 150 or 300 
minutes. Regarding drinking water exposure, accounting for drinking 
water consumption throughout the day and using the half-life to 
recovery information, risk is reduced by approximately 2-3X.
    Consequently, risk estimates for which food and drinking water are 
jointly considered and incorporated (i.e, Food + Drinking Water) are 
reduced considerably--by a factor of two or more in some cases--
compared to baseline. This is not unexpected, as infants receive much 
of their exposures from indirect drinking water in the form of water 
used to prepare infant formula. But even though the risk estimates from 
aggregate exposure are reduced, they nonetheless still substantially 
exceed EPA's level of concern for infants and children. Using drinking 
water derived from the surface water from the New Jersey melon 
scenario, which estimated one of the lower exposure distributions, 
aggregate exposures ranged from a low of 280% of the aPAD for infants, 
based on a 150-minute half-life, to a high of 370% of the aPAD for 
infants, based on a 300-minute half-life.
    The two approaches discussed above are used to evaluate the extent 
to which the Agency's 24-hour approach to dietary risk assessment 
overestimates risk from carbofuran exposure. The results of both 
approaches indicate that the risk to carbofuran is indeed not 
substantively overestimated using the current exposure models and the 
24-hour approach. This is due to the fact that exposure to carbofuran 
occurs predominantly through single eating events and not from multiple 
events that occur throughout the day. Based on these analyses, the 
Agency concludes that the current exposure assessment methods used in 
the carbofuran dietary assessment provide realistic and high confidence 
estimates of risk to carbofuran exposure through food.
    The result of all of these analyses clearly demonstrate that 
aggregate exposure from all uses of carbofuran fail to meet the FFDCA 
section 408 safety standard, and revocation of the associated 
tolerances is warranted. Based on the contribution from food alone, 
dietary exposures to carbofuran exceed EPA's level of concern for all 
of the more sensitive subpopulations of infants and children. In 
addition, EPA's analyses show that those individuals-both adults as 
well as children--who receive their drinking water from vulnerable 
sources are also exposed to levels that exceed EPA's level of concern--
in some cases by orders of magnitude. This primarily includes those 
populations consuming drinking water from groundwater from shallow 
wells in acidic aquifers overlaid with sandy soils that have had crops 
treated with carbofuran. It could also include those populations that 
obtain their

[[Page 44888]]

drinking water from reservoirs located in small agricultural 
watersheds, prone to runoff, and predominated by crops that are treated 
with carbofuran, although there is substantially more uncertainty 
associated with these exposure estimates. Every sensitivity analysis 
EPA has performed has shown that estimated exposures significantly 
exceed EPA's level of concern for children. Although the magnitude of 
the exceedance varies depending the level of conservatism in the 
assessment, the fact that in each case, aggregate exposures from 
dietary exposures of carbofuran fail to meet the FFDCA section 408 
safety standard strongly corroborates EPA's conclusion that aggregate 
exposures from all uses of carbofuran are not safe.

VII. When Do These Actions Become Effective?

    The Agency is proposing that the revocations of the tolerances for 
all commodities except artichoke and sunflower seed become effective 60 
days after a final rule is published. EPA is also proposing to 
establish an extended effective date for artichokes and sunflower seed, 
to allow growers of these crops additional time to transition to 
alternative compounds. The revocation for these two tolerances will 
become effective two years after a final rule or order is published. 
The Agency believes that these revocation dates will allow users to 
exhaust stocks of carbofuran currently in their possession. However, if 
EPA is presented with information during the comment period on this 
proposal that end-users may need additional time to utilize carbofuran 
stocks currently in their possession, and that information is verified, 
the Agency will consider extending the expiration date of the 
tolerance. If you have comments regarding the effective date, or if you 
have comments on how long it would take you to utilize the carbofuran 
stocks currently in your possession, please submit comments as 
described under SUPPLEMENTARY INFORMATION.
    Any commodities listed in this proposal treated with the pesticide 
subject to this proposal, and in the channels of trade following the 
tolerance revocations, shall be subject to FFDCA section 408(1)(5), as 
established by FQPA. Under this section, any residues of these 
pesticides in or on such food shall not render the food adulterated so 
long as it is shown to the satisfaction of the Food and Drug 
Administration that:
    1. The residue is present as the result of an application or use of 
the pesticide at a time and in a manner that was lawful under FIFRA, 
and
    2. The residue does not exceed the level that was authorized at the 
time of the application or use to be present on the food under a 
tolerance or exemption from tolerance. Evidence to show that food was 
lawfully treated may include records that verify the dates when the 
pesticide was applied to such food.

VIII. Are the Proposed Actions Consistent with International 
Obligations?

    The tolerance revocations in this proposal are not discriminatory 
and are designed to ensure that both domestically-produced and imported 
foods meet the food safety standard established by the FFDCA. The same 
food safety standards apply to domestically produced and imported 
foods.
    EPA is working to ensure that the U.S. tolerance reassessment 
program under FQPA does not disrupt international trade. EPA considers 
Codex Maximum Residue Limits (MRLs) in setting U.S. tolerances and in 
reassessing them. MRLs are established by the Codex Committee on 
Pesticide Residues, a committee within the Codex Alimentarius 
Commission, an international organization formed to promote the 
coordination of international food standards. It is EPA's policy to 
harmonize U.S. tolerances with Codex MRLs to the extent possible, 
provided that the MRLs achieve the level of protection required under 
FFDCA. EPA's effort to harmonize with Codex MRLs is summarized in the 
tolerance reassessment section of individual Reregistration Eligibility 
Decision documents. EPA has developed guidance concerning submissions 
for import tolerance support (65 FR 35069, June 1, 2000) (FRL-6559-3). 
This guidance will be made available to interested persons. Electronic 
copies are available on the internet at http://www.epa.gov/. On the 
Home Page select ``Laws, Regulations, and Dockets,'' then select 
Regulations and Proposed Rules and then look up the entry for this 
document under ``Federal Register--Environmental Documents.'' You can 
also go directly to the ``Federal Register'' listings at http://www.epa.gov/fedrgstr/.

IX. Statutory and Executive Order Reviews

    In this proposed rule, EPA is proposing to revoke specific 
tolerances established under FFDCA section 408. The Office of 
Management and Budget (OMB) has exempted this type of action (e.g., 
tolerance revocation for which extraordinary circumstances do not 
exist) from review under Executive Order 12866, entitled Regulatory 
Planning and Review (58 FR 51735, October 4, 1993). Because this 
proposed rule has been exempted from review under Executive Order 12866 
due to its lack of significance, this proposed rule is not subject to 
Executive Order 13211, Actions Concerning Regulations That 
Significantly Affect Energy Supply, Distribution, or Use (66 FR 28355, 
May 22, 2001). This proposed rule does not contain any information 
collections subject to OMB approval under the Paperwork Reduction Act 
(PRA), 44 U.S.C. 3501 et seq., or impose any enforceable duty or 
contain any unfunded mandate as described under Title II of the 
Unfunded Mandates Reform Act of 1995 (UMRA) (Public Law 104-4). Nor 
does it require any special considerations as required by Executive 
Order 12898, entitled Federal Actions to Address Environmental Justice 
in Minority Populations and Low-Income Populations (59 FR 7629, 
February 16, 1994); or OMB review or any other Agency action under 
Executive Order 13045, entitled Protection of Children from 
Environmental Health Risks and Safety Risks (62 FR 19885, April 23, 
1997). This action does not involve any technical standards that would 
require Agency consideration of voluntary consensus standards pursuant 
to section 12(d) of the National Technology Transfer and Advancement 
Act of 1995 (NTTAA), Public Law 104-113, section 12(d) (15 U.S.C. 272 
note). In addition, the Agency has determined that this action will not 
have a substantial direct effect on States, on the relationship between 
the national government and the States, or on the distribution of power 
and responsibilities among the various levels of government, as 
specified in Executive Order 13132, entitled Federalism (64 FR 43255, 
August 10, 1999). Executive Order 13132 requires EPA to develop an 
accountable process to ensure ``meaningful and timely input by State 
and local officials in the development of regulatory policies that have 
federalism implications.'' ``Policies that have federalism 
implications'' is defined in the Executive order to include regulations 
that have ``substantial direct effects on the States, on the 
relationship between the national government and the States, or on the 
distribution of power and responsibilities among the various levels of 
government.'' This proposed rule directly regulates growers, food 
processors, food handlers and food retailers, not States. This

[[Page 44889]]

action does not alter the relationships or distribution of power and 
responsibilities established by Congress in the preemption provisions 
of section 408(n)(4) of the FFDCA. For these same reasons, the Agency 
has determined that this proposed rule does not have any ``tribal 
implications'' as described in Executive Order 13175, entitled 
Consultation and Coordination with Indian Tribal Governments (65 FR 
67249, November 6, 2000). Executive Order 13175, requires EPA to 
develop an accountable process to ensure ``meaningful and timely input 
by tribal officials in the development of regulatory policies that have 
tribal implications.'' ``Policies that have tribal implications'' is 
defined in the Executive order to include regulations that have 
``substantial direct effects on one or more Indian tribes, on the 
relationship between the Federal Government and the Indian tribes, or 
on the distribution of power and responsibilities between the Federal 
Government and Indian tribes.'' This proposed rule will not have 
substantial direct effects on tribal governments, on the relationship 
between the Federal Government and Indian tribes, or on the 
distribution of power and responsibilities between the Federal 
Government and Indian tribes, as specified in Executive Order 13175. 
Thus, Executive Order 13175 does not apply to this proposed rule.
    The Regulatory Flexibility Act (RFA) of 1980, as amended by the 
Small Business Regulatory Enforcement Fairness Act of 1996 (SBREFA), 5 
USC 601 et.seq, generally requires an agency to prepare a regulatory 
flexibility analysis of any rule subject to notice and comment 
rulemaking requirements under the Administrative Procedures Act or any 
other statute. This is required unless the agency certifies that the 
rule will not have a significant economic impact on a substantial 
number of small entities. Small entities include small businesses, 
small organizations, and small governmental jurisdictions. The Agency 
has determined that no small organizations or small governmental 
jurisdictions are impacted by today's rulemaking.
    For purposes of assessing the impacts of today's determination on 
businesses, a small business is defined either by the number of 
employees or by the annual dollar amount of sales/revenues. The level 
at which an entity is considered small is determined for each North 
American Industry Classification System (NAICS) code by the Small 
Business Administration (SBA). Farms are classified under NAICS code 
111, Crop Production, and the SBA defines small entities as farms with 
total annual sales of $750,000 or less.
    The Agency has examined the potential effects today's proposed rule 
may have on potentially impacted small businesses. Based on this 
analysis, EPA concludes that the Agency can certify that revoking the 
food tolerances for carbofuran will not have a significant economic 
impact on a substantial number of small entities (No SISNOSE) for 
alfalfa, artichoke, banana, chili pepper, coffee, cotton, cucurbits 
(cucumber, melons, pumpkin, and squash), grape, grains (barley, flax, 
oats, and wheat), field corn, potato, soybean, sorghum, sugarbeet, 
sugarcane, sunflower, and sweet corn. Even in a worst-case scenario, in 
which a grower obtains income only from a single crop and his/her 
entire acreage is affected, the impact generally amounts to less than 
2% of gross income and would be felt by fewer than 3% of affected small 
producers. Estimates of impacts to corn growers were refined to account 
for the sporadic nature of need for carbofuran while still maintaining 
some assumptions that would bias the estimates upward. Refined 
estimates were also made for artichoke and sunflower, which consider 
the diversity in growers' revenue. The largest impact may be felt by 
artichoke growers, with impacts as high as 5% of gross revenue, but 
fewer than five growers are likely to be affected. EPA could not 
quantify the impacts to banana, sugarcane, and sweet corn producers, 
but the number of impacted farms is less than 2% of the farms subject 
to the action. Additional detail on the analyses EPA conducted in 
support of this certification can be found in Ref. 49.

X. References

    EPA has established an official record for this rulemaking. The 
official record includes all information considered by EPA in 
developing this proposed rule including documents specifically 
referenced in this action and listed below, any public comments 
received during an applicable comment period, and any other information 
related to this action, including any information claimed as CBI. This 
official record includes all information physically CAlocated in docket 
ID number EPA-HQ-OPP-2005-0162, as well as any documents that are 
referenced in the documents listed below or in the docket. The public 
version of the official record does not include any information claimed 
as CBI.
    1. Acute oral (gavage) dose range-finding study of cholinesterase 
depression from carbofuran technical in juvenile (day 11) rats. 
Hoberman, 2007. MRID 47143703 (unpublished FMC study) EPA-HQ-OPP-2007-
1088-0062.
    2. Acute oral (gavage) time course study of cholinesterase 
depression from carbofuran technical in adult and juvenile (day 11 
postpartum) rats. Hoberman, 2007. MRID 47143704 (unpublished FMC study) 
EPA-HQ-OPP-2007-1088-0063.
    3. Additional chemographs for potatoes and cucurbits for drinking 
water exposure assessment in support of the reregistration of 
carbofuran (PC Code 090601) (R. David Jones, 10/23/07 D345729). EPA-HQ-
OPP-2005-0162-0486.
    4. Additional refinements of the drinking water exposure assessment 
for the use of carbofuran on corn and melons (PC code 090601)(R. David 
Jones, 06/2008 D353714).
    5. An In-Depth Investigation to Estimate Surface Water 
Concentrations of Carbofuran within Indiana Community Water Supplies. 
Performed by Waterborne Environmental, Inc., Leesburg, VA, Engel 
Consulting, and Fawcett Consulting. Submitted by FMC. Corporation, 
Philadelphia, PA. WEI No 528.01, FMC Report No. PC-0378. MRID 47221603. 
EPA-HQ-OPP-2007-1088-0023.
    6. An Investigation into the Potential for Carbofuran Leaching to 
Ground Water Based on Historical and Current Use Practices. Submitted 
by FMC. Corporation, Philadelphia, PA. Report No. PC-0363. MRID 
47221602. EPA-HQ-OPP-2007-1088-0022.
    7. An Investigation into the Potential for Carbofuran Leaching to 
Ground Water Based on Historical and Current Use Practices: 
Supplemental Report on Twenty-one Additional States. Submitted by FMC 
Corporation, Philadelphia, PA. Report No. PC-0383. MRID 47244901. EPA-
HQ-OPP-2007-1088-0025.
    8. Benchmark dose analysis of cholinesterase inhibition data in 
neonatal and adult rats (MRID no. 46688914) following exposure to 
carbofuran (A.Lowit, 1/19/06, D325342, TXR no. 0054034). EPA-HQ-OPP-
2007-1088-0045.
    9. Benjamins, J.A. and McKhann, G.M. (1981) Development, 
regeneration, and aging of the brain. In: Basic Neurochemistry, 3rd 
edition. Edited by Siegel, G.J., Albers, R.W., Agranoff, B.W., and 
Katzman, R. Little, Brown and Co., Boston. pp 445-469; Dobbing, J. and 
Smart, J.L. (1974) Vulnerability of developing brain and behaviour. 
British Medical Bulletin. 30:164-168; Davison, A.N. and Dobbing, J. 
(1966) Myelination as a vulnerable period in brain development. British 
Medical Bulletin. 22:40-44.

[[Page 44890]]

    10. Best Management Practices to Reduce Carbofuran Losses to Ground 
And Surface Water. Submitted by FMC. Corporation, Philadelphia, PA. 
Report No. PC-0362. MRID 47279201. EPA-HQ-OPP-2005-0162-0464.
    11. California Department of Pesticide Regulation. Risk 
Characterization Document for Carbofuran. January 23, 2006. 219 pgs.
    12. Carbofuran Acute Aggregate Dietary (Food and Drinking Water) 
Exposure and Risk Assessments for the Reregistration Eligibility 
Decision (T. Morton, 7/22/08, D351371).
    13. Carbofuran Environmental Risk Assessment and Human Drinking 
Water Exposure Assessment for IRED. March 2006. EPA-HQ-OPP-2005-0162-
0080.
    14. Carringer, 2000. Carbamate Market Basket Survey. Reviewed by S. 
Piper, D267539, 8/8/02. (MRID 45164701 S. Carringer, 5/12/00).
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Eligibility Decision (RED) Document (Phase 6). (PC 090601) D 330541, 
July 26, 2006. EPA-HQ-OPP-2005-0162-0307.
    16. Carbofuran. HED Revised Risk Assessment for the Notice of 
Intent to Cancel. (PC 090601) D 347038, January 2007. EPA-HQ-OPP-2007-
1088-0034.
    17. Cholinesterase depression in juvenile (day 11) and adult rats 
following acute oral (gavage) dose of carbofuran technical. Hoberman, 
2007. MRID 47143705 (unpublished FMC study). EPA-HQ-OPP-2007-1088-0066.
    18. Context Document for Carbofuran Risk Assessment Issues not 
Specifically Addressed in the FIFRA SAP Charge Questions (M. Panger, C. 
Salice, R. David Jones, E. Odenkirchen, I. Sunzenauer, 1/08 D348292). 
EPA-HQ-OPP-2007-1088-0071.
    19. Data Evaluation Record for Acute dose-response study of 
carbofuran technical administered by gavage to adult and postnatal day 
11 male and female CD[reg](Sprague-Dawley) rats. MRID 46688914. EPA-HQ-
OPP-2007-1088-0045.
    20. Data Evaluation Record for Cholinesterase depression in 
juvenile (day 11) and adult rats following acute oral (gavage) dose of 
carbofuran technical. MRID 47143705.
    21. Dose-time response modeling of rat brain AChE activity: 
carbofuran gavage dosing 10/5/07 (Carbofuran-RatBrainDR.pdf) EPA-HQ-
OPP-2007-1088-0053.
    22. Dose-time response modeling of rat RBC-AChE activity: 
carbofuran gavage dosing 10/23/07 (RatRBC--DR.pdf). EPA-HQ-OPP-2007-
1088-0029.
    23. EPA Response to the Transmittal of Meeting Minutes of the FIFRA 
Scientific Advisory Panel Meeting Held February 5-8 2008 on the 
Agency's Proposed Action under FIFRA 6(b) Notice of Intent to Cancel 
Carbofuran (E.Reaves, A. Lowit, J. Liccione 7/2008 D352315).
    24. Estimated Drinking Water Concentrations (email communication 
D.Young to D.Drew, 3/8/06).
    25. FIFRA SAP (1998) ``A set of Scientific Issues Being Considered 
by the Agency in Connection with Proposed Methods for Basin-scale 
Estimation of Pesticide Concentrations in Flowing Water and Reservoirs 
for Tolerance Reassessment.'' Final Report from the FIFRA Scientific 
Advisory Panel Meeting of July 29-30, 1998 (Report dated September 2, 
1998). Available at: http://www.epa.gov/scipoly/sap/meetings/1998/july/final1.pdf.
    26. FIFRA SAP (1999) ``Sets of Scientific Issues Being Considered 
by the Environmental Protection Agency Regarding Use of Watershed-
derived Percent Crop Areas as a Refinement Tool in FQPA Drinking Water 
Exposure Assessments for Tolerance Reassessment.'' Final Report from 
the FIFRA Scientific Advisory Panel Meeting of February 5-7, 2002 
(Report dated May 25, 1999). SAP Report 99-03C. Available at: http://www.epa.gov/scipoly/sap/meetings/1999/may/final.pdf.
    27. FIFRA SAP. (2002). ``Methods Used to Conduct a Preliminary 
Cumulative Risk Assessment for Organophosphate Pesticides.'' Final 
Report from the FIFRA Scientific Advisory Panel Meeting of February 5-
7, 2002 (Report dated March 19, 2002). FIFRA Scientific Advisory Panel, 
Office of Science Coordination and Policy, Office of Prevention, 
Pesticides and Toxic Substances, U.S. Environmental Protection Agency. 
Washington, DC. SAP Report 2002-01.
    28. FIFRA Science Advisory Panel (SAP). 2005a. ``Final report on N-
Methyl Carbamate Cumulative Risk Assessment: Pilot Cumulative 
Analysis.'' Final Report from the FIFRA Scientific Advisory Panel 
Meeting of February , 2005 (Report dated September 2, 1998). Available 
at: http://www.epa.gov/scipoly/sap/2005/february/minutes.pdf .
    29. FIFRA Science Advisory Panel (SAP). 2005b. ``Final report on 
Preliminary N-Methyl Carbamate Cumulative Risk Assessment.'' Final 
Report from the FIFRA Scientific Advisory Panel Meeting of July 29-30, 
1998 (Report dated September 2, 1998). Available at: http://www.epa.gov/scipoly/sap/2005/august/minutes.pdf.
    30. FIFRA Science Advisory Panel (SAP). 2008. ``Final report on the 
Agency's Proposed Action under FIFRA 6(b) Notice of Intent to Cancel 
Carbofuran.'' Report from the FIFRA Scientific Advisory Panel Meeting 
of February , 5-8 2008 (Report dated September 2, 1998). Available at: 
http://www.epa.gov/scipoly/sap/meetings/2008/february/carbofuransapfinal.pdf.
    31. Final report on cholinesterase inhibition study of carbofuran: 
PND17 rats. MRID 47167801 (ORD study). EPA-HQ-OPP-2007-1088-0064.
    32. FMC Letter Requesting Proposed Label Amendments and Voluntary 
Cancellations. Dated May 9, 2008. EPA-HQ-OPP-2005-0162-0496 and -0497. 
Email Communication from John Cummings to Steven Bradbury, dated June 
10, 2008. EPA-HQ-OPP-2005-0162-0499.
    33. Hunter, D.L., Marshall, R.S., and Padilla, S. (1997). Automated 
instrument analysis of cholinesterase activity in tissues from 
carbamate-treated animals: A cautionary note. Toxicology Mechanisms and 
Methods, 7:43-53.
    34. Interim Reregistration Eligibility Decision for Carbofuran. D. 
Edwards. 2006. Regulations.gov document number: EPA-HQ-OPP-2005-0162-
0304.
    35. IPCS World Health Organization. 2005. Chemical Specific 
Adjustment factors for Interspecies Differences and Human Variability: 
Guidance Document for use of Data in Dose/Concentration-Response 
Assessment.
    36. Issue Paper for the FIFRA SAP Meeting on Carbofuran: Human 
Health Risk Assessment Reregistration Eligibility Science Chapter for 
Carbofuran, Environmental Fate and Effects Chapter. March 2006. EPA-HQ-
OPP-2007-1088-0031.
    37. Johnson, C.D. and Russell, R.L. (1975) A rapid, simple 
radiometric assay for cholinesterase, suitable for multiple 
determinations. Analytical Biochemistry. 64:229-238.
    38. McDaniel K.L. and Moser V.C. (2004) Differential profiles of 
cholinesterase inhibition and neurobehavioral effects in rats exposed 
to fenamiphos or profenofos. Neurotoxicology and Teratology. 26:407-
415.
    39. McDaniel K.L., Padilla S., Marshall R.S., Phillips P.M., 
Podhorniak L., Qian Y., Moser V.C. (2007) Comparison of acute 
neurobehavioral and cholinesterase inhibitory effects of N-methyl 
carbamates in rats. Toxicology Sciences. 98, 552-560.
    40. Moser V.C. (1995) Comparisons of the acute effects of 
cholinesterase inhibitors using a neurobehavioral

[[Page 44891]]

screening battery in rats. Neurotoxical and Teratology 17: 617-625.
    41. National Assessment of the Relative Vulnerability of Community 
Water Supply Reservoirs in Carbofuran Use Areas. Performed by 
Waterborne Environmental Inc., Leesburg, VA and Engel Consulting, West 
Lafayette, IN. Submitted by FMC Corporation, Philadelphia, PA. WEI 
Report No. 528.01-B, FMC Report No. PC-0387. MRID 47272301. EPA-HQ-OPP-
2007-1088-0024.
    42. National Resources Inventory 1992, cited in USGS 2002, 
``Herbicide Concentrations in the Mississippi River Basin--the 
importance of chloracetanilide degradates.'' R.A. Rebich, R.H. Coupe, 
E.M.Thurman.
    43. Nostrandt, A.C., Duncan, J.A., and Padilla, S. (1993). A 
modified spectrophotometric method appropriate for measuring 
cholinesterase activity in tissues from carbaryl-treated animals. 
Fundamentals of Applied Toxicology. 21:196-203.
    44. Padilla S., Marshall R.S., Hunter D.L., and Lowit A. 2007. Time 
course of cholinesterase inhibition in adult rats treated acutely with 
carbaryl, carbofuran, formetanate, methomyl, methiocarb, oxamyl, or 
propoxur. Toxicology and Applied Pharmacology, 219; 202-209.
    45. PND17 BMDs and BMDLs and recovery half-lives for the effects of 
carbofuran on brain and blood AChE (PND17--DR.pdf). EPA-HQ-OPP-2007-
1088-0047.
    46. Report on cholinesterase sensitivity study of carbofuran: Adult 
and PND11 MRID 47289001 (ORD study). EPA-HQ-OPP-2007-1088-0065.
    47. Revised Drinking Water Assessment in Support of the 
Reregistration of Carbofuran (PC Code 090601) (R. David Jones, 9/5/07 
D3424057). EPA-HQ-OPP-2005-0162-0485.
    48. Revised HED Product Chemistry and Residue Chemistry Chapter of 
the RED (D. Drew, 1/13/05, D306796). EPA-HQ-OPP-2005-0162-0028.
    49. Screening Level analysis of the small business impacts of 
revoking carbofuran tolerances. (Wyatt, T.J. July 2008) 28 pgs.
    50. Setzer W. 2008 Carbofuran: Updated Statistical Analysis of the 
FQPA Factor Based on the BMD<INF>50</INF> ratio of Adult/Pup RBC Data. 
7 pgs.
    51. Setzer W. October 23, 2007. Dose-time response modeling of rat 
RBC AChE activity: Carbofuran gavage dosing. 47 pgs. EPA-HQ-OPP-2007-
1088-0029.
    52. Setzer W. October 25, 2007. PND17 BMDs and BMDLs and recovery 
half-lives for the effect of Carbofuran on brain and blood AChE. 12 
pgs. EPA-HQ-OPP-2007-1088-0047.
    53. Setzer W. October 5, 2007. Dose-time response modeling of rat 
brain AChE activity: Carbofuran gavage dosing. 64 pgs. EPA-HQ-OPP-2007-
1088-0053.
    54. Summary Evaluation of Recently Submitted FMC Water Exposure 
Studies. (PC Code 090601) (R. David Jones, 12/26/07 D347901), 12 pgs. 
EPA-HQ-OPP-2007-1088-0016.
    55. USDA NRCS. Conservation Buffer to Reduce Pesticide Losses. 
Natural Resources Conservation Service, Fort Worth, TX, 21 pp.
    56. USEPA (2000) ``Assigning Values to Nondetected/Nonquantified 
Pesticide Residues in Human Health Dietary Exposure Assessments.'' 
March 23, 2000. Available at: http://www.epa.gov/pesticides/trac/science/trac3b012.pdf.
    57. USEPA. (2000b). ``Benchmark Dose Technical Guidance Document.'' 
Draft report. Risk Assessment Forum, Office of Research and 
Development, U.S. Environmental Protection Agency. Washington, DC. EPA/
630/R-00/001.
    58. USEPA. (2000) ``Choosing a Percentile of Acute Dietary Exposure 
as a Threshold of Regulatory Concern.'' March 16, 2000. Available at: 
http://www.epa.gov/pesticides/trac/science/trac2b054.pdf .
    59. USEPA. (2001). Memorandum from Marcia Mulkey to Lois Rossi. 
``Implementation of the Determinations of a Common Mechanism of 
Toxicity for N-Methyl Carbamate Pesticides and for Certain 
Chloroacetanilide Pesticides.'' July 12, 2001. Available at: http://www.epa.gov/oppfead1/cb/csb_page/updates/carbamate.pdf.
    60. USEPA. (2002). ``Office of Pesticide Programs' Policy on the 
Determination of the Appropriate FQPA Safety Factor(s) For Use in 
Tolerance Assessment.'' Available at: http://www.epa.gov/oppfead1/trac/science/determ.pdf.
    61. USEPA. (2000). ``The Use of Data on Cholinesterase Inhibition 
for Risk Assessments of Organophosphorous and Carbamate Pesticides.'' 
August 18, 2000. Available at: http://www.epa.gov/pesticides/trac/science/cholin.pdf.
    62. USEPA. (2005). ``Preliminary N-Methyl Carbamate Cumulative Risk 
Assessment.'' Available at: http://www.epa.gov/oscpmont/sap/2005/index.htm#august.
    63. USEPA (2007). ``Revised N-Methyl Carbamate Cumulative Risk 
Assessment U.S. Environmental Protection Agency, Office of Pesticide 
Programs,'' September 24, 2007. Available at: http://www.epa.gov/oppsrrd1/REDs/nmc_revised_cra.pdf.
    64. WARF, 1978. Rao, G.N.; Davis, G.J.; Giesler, P.; et al. (1978) 
Teratogenicity of Carbofuran in Rats: ACT 184.33. (Unpublished study 
received Dec 5, 1978 under 275-2712; prepared by WARF Institute, Inc., 
submitted by FMC Corp., Philadelphia, Pa.; CDL:236593-A).
    65. Watershed Regressions for Pesticides (WARP) Model Estimates for 
Carbofuran in Illinois Watershed. Performed by Waterborne 
Environmental, Inc., Leesburg, VA. WEI 362.07. Submitted by FMC 
Corporation, Philadelphia, PA. Report No. P-3786. MRID 46688915. EPA-
HQ-OPP-2007-1088-0021.
    66. Williams, C.H. and Casterline, J.L., Jr. (1969). A comparison 
of two methods for measurement of erythrocyte cholinesterase inhibition 
after carbamate administration to rats. Food and Cosmetics Toxicology. 
7:149-151.
    67. Winteringham, F.P.W. and Fowler, K.S. (1966) Substrate and 
dilution effects on the inhibition of acetylcholinesterase by 
carbamates. Biochemical Journal. 101:127-134.

List of Subjects in 40 CFR Part 180

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


    Dated: July 23, 2008.
Debra Edwards,
Director, Office of Pesticide Programs.

    Therefore, it is proposed that 40 CFR chapter I be amended as 
follows:

PART 180--[AMENDED]

    1. The authority citation for part 180 continues to read as 
follows:

    Authority: 21 U.S.C. 321(q), 346a and 371.

    2. Section 180.254 is amended by revising the table in paragraph 
(a) and the table in paragraph (c), and by removing paragraph (d) to 
read as follows.


Sec.  180.254  Carbofuran; tolerances for residues.

    (a) * * *

------------------------------------------------------------------------
                                                             Expiration/
                   Commodity                     Parts per    Revocation
                                                  million        Date
------------------------------------------------------------------------
Sunflower, seed (of which no more than 0.2 ppm          1.0     10/31/10
 is carbamate)
------------------------------------------------------------------------

* * * * *
    (c) * * *

[[Page 44892]]



------------------------------------------------------------------------
                                                             Expiration/
                   Commodity                     Parts per    Revocation
                                                  million        Date
------------------------------------------------------------------------
Artichoke, globe (of which no more than 0.2             0.4     10/31/10
 ppm is carbamate)
------------------------------------------------------------------------


[FR Doc. E8-17660 Filed 7-29-08; 1:15 pm]
BILLING CODE 6560-50-S


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