Carbofuran; Final Tolerance Revocations, 23046-23095 [E9-11396]

Agencies

• ENVIRONMENTAL PROTECTION AGENCY

[Federal Register Volume 74, Number 93 (Friday, May 15, 2009)]
[Rules and Regulations]
[Pages 23046-23095]
From the Federal Register Online via the Government Printing Office [www.gpo.gov]
[FR Doc No: E9-11396]



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Part III





Environmental Protection Agency





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40 CFR Part 180



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Carbofuran; Final Tolerance Revocations; Final Rule

Federal Register / Vol. 74, No. 93 / Friday, May 15, 2009 / Rules and 
Regulations

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ENVIRONMENTAL PROTECTION AGENCY

40 CFR Part 180

[EPA-HQ-OPP-2005-0162; FRL-8413-3]


Carbofuran; Final Tolerance Revocations

AGENCY: Environmental Protection Agency (EPA).

ACTION: Final rule.

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SUMMARY: EPA is revoking 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).

DATES: This final rule is effective August 13, 2009. Written 
objections, requests for a hearing, or requests for a stay identified 
by the docket identification (ID) number EPA-HQ-OPP-2005-0162 must be 
received on or before July 14, 2009, and must be filed in accordance 
with the instructions provided in 40 CFR part 178 (see also Unit I.C. 
of the SUPPLEMENTARY INFORMATION).

ADDRESSES: Written objections and hearing requests, identified by the 
docket ID number EPA-HQ-OPP-2005-0162, may be submitted to the Hearing 
Clerk by one of the following methods:
     Mail: U.S. EPA Office of the Hearing Clerk, Mailcode 1900 
L, 1200 Pennsylvania Ave., NW., Washington, DC 20460-0001.
     Delivery: U.S. EPA Office of the Hearing Clerk, 1099 14th 
St., NW., Suite 350, Franklin Court, Washington, DC 20005. Deliveries 
are only accepted during the Office'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 Office's telephone number is (202) 564-6262.
    In addition to filing an objection or hearing request with the 
Hearing Clerk as described in 40 CFR part 178, please submit a copy of 
the filing that does not contain any CBI for inclusion in the public 
docket that is described in ADDRESSES. Information not marked 
confidential pursuant to 40 CFR part 2 may be disclosed publicly by EPA 
without prior notice. Submit this copy, identified by docket ID number 
EPA-HQ-OPP-2005-0162, by one of the following methods:
     Federal eRulemaking Portal: https://www.regulations.gov. 
Follow the on-line instructions for submitting comments.
     Mail: Office of Pesticide Programs (OPP) Regulatory Public 
Docket (7502P), Environmental Protection Agency, 1200 Pennsylvania 
Ave., NW., Washington, DC 20460-0001.
     Delivery: OPP Regulatory Public Docket (7502P), 
Environmental Protection Agency, Rm. S-4400, One Potomac Yard (South 
Bldg.), 2777 S. Crystal Dr., Arlington, VA. Deliveries are only 
accepted during the Docket's normal hours of operation (8:30 a.m. to 4 
p.m., Monday through Friday, excluding legal holidays). Special 
arrangements should be made for deliveries of boxed information. The 
Docket Facility telephone number is (703) 305-5805.
    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 in the electronic docket at https://www.regulations.gov, or, 
if only available in hard copy, at the OPP Regulatory Public Docket in 
Rm. S-4400, One Potomac Yard (South Bldg.), 2777 S. Crystal Dr., 
Arlington, VA. The Docket Facility is open from 8:30 a.m. to 4 p.m., 
Monday through Friday, excluding legal holidays. The Docket Facility 
telephone number is (703) 305-5805.
    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 objection that includes information claimed as 
CBI, a copy of the objection 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.

FOR FURTHER INFORMATION CONTACT: Jude Andreasen, Special Review and 
Reregistration Division (7508P), Office of Pesticide Programs, 
Environmental Protection Agency, 1200 Pennsylvania Ave, NW., 
Washington, DC 20460-0001; telephone number: (703) 308-9342; e-mail 
address: andreasen.jude@epa.gov.

SUPPLEMENTARY INFORMATION: 

I. General Information

A. Does This Action Apply to Me?

    You may be potentially affected by this action if you are an 
agricultural producer, food manufacturer, or pesticide manufacturer. 
Potentially affected entities may include, but are not limited to:
     Crop production (NAICS code 111).
     Animal production (NAICS code 112).
     Food manufacturing (NAICS code 311).
     Pesticide manufacturing (NAICS code 32532).
    This listing is not intended to be exhaustive, but rather provides 
a guide for readers regarding entities likely to be affected by this 
action. Other types of entities not listed in this unit could also be 
affected. The North American Industrial Classification System (NAICS) 
codes have been provided to assist you and others in determining 
whether this action might apply to certain entities. To determine 
whether you or your business may be affected by this action, you should 
carefully examine the applicability provisions in 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. How Can I Access Electronic Copies of This Document?

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

C. What Can I Do if I Wish the Agency To Maintain a Tolerance That the 
Agency Has Revoked?

    Any affected party has 60 days from the date of publication of this 
order to file objections to any aspect of this order with EPA and to 
request an evidentiary hearing on those objections (21 U.S.C. 
346a(g)(2)). A person may raise objections without requesting a 
hearing.
    The objections submitted must specify the provisions of the 
regulation deemed objectionable and the grounds for the objection (40 
CFR 178.25). Each objection must be accompanied by the fee prescribed 
by 40 CFR 180.33(i). If a

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hearing is requested, the objections must include a statement of the 
factual issue(s) on which a hearing is requested, the requestor's 
contentions on such issues, and a summary of any evidence relied upon 
by the objector (40 CFR 178.27).
    Although any person may file an objection, the substance of the 
objection must have been initially raised as an issue in comments on 
the proposed rule. As explained in the July 31, 2008 proposed rule (73 
FR 44864) (FRL-8378-8), EPA will treat as waived any issue not 
originally raised in timely submitted comments. Accordingly, EPA will 
not consider any legal or factual issue presented in objections that 
was not presented by a commenter in response to the proposed rule, if 
that issue could reasonably have been raised at the time of the 
proposal.
    Similarly, if you fail to file an objection to an issue resolved in 
the final rule within the time period specified, you will have waived 
the right to challenge the final rule's resolution of that issue (40 
CFR 178.30(a)). After the specified time, issues resolved in the final 
rule cannot be raised again in any subsequent proceedings on this rule. 
See Nader v EPA, 859 F.2d 747 (9th Cir. 1988), cert denied 490 US 1931 
(1989).
    You must file your objection or request a hearing on this 
regulation in accordance with the instructions provided in 40 CFR part 
178. To ensure proper receipt by EPA, you must identify docket ID 
number EPA-HQ-OPP-2005-0162 in the subject line on the first page of 
your submission. All requests must be in writing, and must be received 
by the Hearing Clerk as required by 40 CFR part 178 on or before July 
14, 2009.
    EPA will review any objections and hearing requests in accordance 
with 40 CFR 178.30, and will publish its determination with respect to 
each in the Federal Register. A request for a hearing will be granted 
only to resolve factual disputes; objections of a purely policy or 
legal nature will be resolved in the Agency's final order, and will 
only be subject to judicial review pursuant to 21 U.S.C. 346a(h)(1), 
(40 CFR 178.20(c) and 178.32(b)(1)). A hearing will only be held if the 
Administrator determines that the material submitted shows the 
following: There is a genuine and substantial issue of fact; there is a 
reasonable probability that available evidence identified by the 
requestor would, if established, resolve one or more of such issues in 
favor of the requestor, taking into account uncontested claims to the 
contrary; and resolution of the issue(s) in the manner sought by the 
requestor would be adequate to justify the action requested (40 CFR 
178.30).

II. Introduction

A. What Action Is the Agency Taking?

    EPA is revoking all of the existing tolerances for residues of 
carbofuran. Currently, tolerances have been established on the 
following crops: Alfalfa, forage; alfalfa, hay; artichoke, globe; 
banana; barley, grain; barley, straw; beet, sugar roots; beet, sugar 
tops; coffee bean, green; corn, forage; corn, grain (including 
popcorn); corn, stover; corn, sweet, kernel plus cob; cotton, 
undelinted seed; cranberry; cucumber; grape; grape raisin; grape, 
raisin, waste; melon; milk; oat, grain; oat, straw; pepper; potato; 
pumpkin; rice, grain; rice, straw; sorghum, forage; sorghum, grain 
grain; sorghum, grain, stover; strawberry; soybean, forage; soybean, 
hay; squash; sugarcane, cane; sunflower, seed; wheat, grain; wheat, 
straw.
    As discussed at greater length in Unit VII., on September 29, 2008, 
the sole registrant of carbofuran pesticide products, FMC Corporation 
requested that EPA cancel certain registrations. Consistent with the 
request, the registrant indicated that it no longer seeks to maintain 
the tolerances associated with the domestic use of carbofuran on the 
eliminated crops, and therefore no longer opposes the revocation of 
those tolerances. No other commenter indicated any interest in 
maintaining these tolerances. EPA is therefore revoking the tolerances 
associated with those domestic uses on two separate grounds. The first 
is that the tolerances will no longer be necessary because the 
registrations for these uses have been canceled (74 FR 11551, March 18, 
2009) (FRL-8403-6). The tolerances that EPA is revoking on this basis 
are: Alfalfa, forage; alfalfa, hay; artichoke, globe; barley, grain; 
barley, straw; beet, sugar roots; beet, sugar tops; corn, fresh 
(including sweet); cotton, undelinted seed; cranberry; cucumber; grape; 
grape raisin; grape, raisin, waste; melon; oat, grain; oat, straw; 
pepper; rice, straw; sorghum, forage; sorghum, grain grain; sorghum, 
grain, stover; strawberry; soybean, forage; soybean, hay; squash; 
wheat, grain; and wheat, straw. The second basis is that EPA also 
finds, that as outlined in its July 31, 2008 proposed rule, revocation 
of these tolerances is warranted on the grounds that aggregate exposure 
to residues from these tolerances do not meet the safety standard of 
section 408(b)(2) of the FFDCA. The Agency is therefore revoking 
tolerances for these crops because aggregate dietary exposure to these 
residues of carbofuran, including all anticipated dietary exposures and 
all other exposures for which there is reliable information, is not 
safe.
    The remaining tolerances the commenters seek to retain are: Banana; 
coffee bean; corn, forage; corn, grain; corn, stover; milk; potato; 
pumpkin; rice, grain; sugarcane, cane; and sunflower, seed. EPA has 
determined that aggregate exposure to carbofuran greater than 0.000075 
milligrams/kilogram/day (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. For the 11 remaining tolerances, based 
on the contribution from food alone, exposure levels are below EPA's 
level of concern. At the 99.9th percentile of exposure, aggregate 
carbofuran dietary exposure from food alone was estimated to range 
between 0.000020 mg/kg/day for children 6 to 12 years old (29% of the 
aPAD) and 0.000058 mg/kg/day (78% of the aPAD) for children 1 to 2 
years old, the population subgroup with the highest estimated dietary 
exposure. However, EPA's analyses show that those individuals--both 
adults and children--who receive their drinking water from sources 
vulnerable to carbofuran contamination are exposed to carbofuran levels 
that exceed EPA's level of concern--in some cases by orders of 
magnitude. This primarily includes those populations consuming drinking 
water from ground water 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 (e.g., from shallow wells associated with sandy 
soils and acidic aquifers) result in significant estimated exceedances. 
The estimates for aggregate food and ground water exposure from such 
sources range between 780% of the aPAD for adults over 50 years, to 
9,400% 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 corn use in Nebraska, range between 330% of the aPAD 
for

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youths 13 to 19 years old and 3,900% of the aPAD for infants.
    Every analysis EPA has performed has shown that estimated exposures 
from drinking water from each remaining domestic use significantly 
exceed EPA's level of concern for children. Accordingly, aggregate 
exposures from food and water significantly exceed safe levels. 
Although the magnitude of the exceedance varies depending on the level 
of conservatism in the assessment, the fact that in each case aggregate 
exposures to residues of carbofuran fail to meet the FFDCA section 
408(b)(2) safety standard, including where EPA relied on highly refined 
estimates of risk, using all relevant data and methods, strongly 
corroborates EPA's conclusion that aggregate exposures to residues of 
carbofuran are not safe.

B. Overview of Final Rule

    EPA's final rule preamble is organized primarily into two sections. 
Following a brief summary of the July 31, 2008 proposed rule, EPA 
summarizes the major comments received on the proposed rule, along with 
the Agency's responses in Unit VII. Because EPA only presents a summary 
of all of the comments received, readers are encouraged to also consult 
EPA's Response to Comments Documents, found in the docket for today's 
action (Refs. 111, 112, 113). These documents contain EPA's complete 
responses to all of the significant comments received on this 
rulemaking, and therefore will contain a more detailed explanation on 
many of the issues presented in Unit VII.
    Unit VIII. presents the results of EPA's analyses of carbofuran's 
dietary risks. This Unit generally describes the bases for the Agency's 
conclusions that carbofuran presents unacceptable dietary risks to 
children. Readers are also encouraged to consult EPA's underlying risk 
assessment support documents, identified in the References section, and 
contained in the docket for today's action, for a more detailed 
presentation of EPA's scientific analyses.
    Each of these units is generally organized consistent with the 
structure of a risk assessment. Each unit begins with a discussion of 
carbofuran's toxicity, and EPA's hazard identification, including a 
discussion of the issues surrounding the selection of the children's 
safety factor EPA has applied to this chemical. EPA then discusses 
issues relating to carbofuran's exposures from food and drinking water. 
The final section of each unit relates to EPA's conclusions regarding 
the risks from carbofuran's aggregate (i.e., food + water) exposures.

C. 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 
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 to 
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 revoking 
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'' (21 
U.S.C. 346a(b)(2)(A)(ii). 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 final 
rule 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\TM\, Version 2.03), 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 a

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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. 19). 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 FIFRA Scientific Advisory 
Panel (SAP) on its draft NOIC. Having considered the comments from the 
SAP, EPA initiated the process to revoke all carbofuran tolerances, 
publishing its proposed revocation on July 31, 2008 (73 FR 44864). The 
comment period for the proposed rule closed on September 29, 2008. 
Having considered all comments received by this date, EPA is now 
finalizing the revocation of all existing carbofuran tolerances. As 
noted above, aggregate exposures from food and water to the U.S. 
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. 71). 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 expeditiously to address the unacceptable dietary risks to 
children. EPA anticipates issuing 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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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 https://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:
     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.
     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).
     An uncertainty factor to address the potential for 
differences in sensitivity in the toxic response across the human 
population (for intraspecies extrapolation).
     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 Population Adjusted 
Dose (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% 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.
    Carbofuran is a member of the class of pesticides called n-methyl 
carbamates (NMCs). The primary toxic effect caused by NMCs, including 
carbofuran, is neurotoxicity resulting from inhibition of the enzyme 
acetylcholinesterase (AChE, See Unit VIII.A.). The toxicity profile of 
these pesticides is characterized by rapid time to onset of effects 
followed by rapid recovery (minutes to hours). Consistent with its 
mechanism of action, toxicity data on AChE inhibition from laboratory 
rats provide the basis for deriving the PoD for carbofuran.

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 by multiple pathways of exposure. EPA uses available data 
and standard analytical methods, together with assumptions designed to 
be protective of public health, 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,

[[Page 23050]]

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 
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. 101). 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 
data comes from federally conducted surveys, including the PDP 
conducted by the USDA. Further, market basket surveys, 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, when EPA believes the information 
will provide more accurate exposure estimates, EPA will rely on field 
trial data (see below in Unit VIII.E.1.).
    EPA uses a computer program known as the DEEM-FCID\TM\ to estimate 
exposure by combining data on human consumption amounts with residue 
values in food commodities. DEEM-FCID\TM\ also compares exposure 
estimates to appropriate RfD or PAD values to estimate risk. EPA uses 
DEEM-FCID\TM\ to estimate exposure for the general U.S. population as 
well as for 32 subgroups based on age, sex, ethnicity, and region. 
DEEM-FCID\TM\ 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\TM\ 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\TM\ 
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). 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\TM\ program to estimate exposure and risk.
    For carbofuran's assessment, EPA used DEEM-FCID\TM\ to calculate 
risk estimates based on a probabilistic distribution. DEEM-FCID\TM\ 
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\TM\ 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 a value selected randomly from the 
concentration data sets. The exposure amounts for the thousands of 
person-days in the CSFII are then collected in a frequency 
distribution. EPA also uses DEEM-FCID\TM\ 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\TM\ 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 1 by randomly selecting residue values for the foods from 
the residue database.
    (3) Repetition of Step 2 one thousand times for each 
person-day.
    (4) Collection of all of the hundreds of thousands of potential 
exposures estimated in Steps  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) (FRL-7355-7). 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 water and surface 
water. Depending on the modeling algorithm (e.g., surface water 
modeling scenarios), daily concentrations can be estimated

[[Page 23051]]

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 for 
surface water is actually a combination of two models: The Pesticide 
Root Zone Model (PRZM) and the Exposure Analysis Model System (EXAMS). 
The second tier model for ground water uses PRZM alone.
    A detailed description of the models routinely used for exposure 
assessment is available from the EPA OPP Water Models web site: https://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 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 take 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 PCA area factors and the Index Reservoir scenario was 
reviewed by the FIFRA SAP in 1999 and 1998, respectively (Refs. 37 and 
38).
    In modeling potential surface water concentrations, EPA attempts to 
model areas of the country that are 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\TM\, 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.
    3. Aggregate exposure analyses. Using probabilistic analyses, EPA 
combines the national food exposures with the exposures derived for 
individual region and crop-specific drinking water scenarios to derive 
estimates of aggregate exposure. 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.
    EPA's standard acute dietary exposure assessment calculates total 
dietary exposure over a 24-hour period; that is consumption over 24 
hours is summed and no account is taken of the fact that eating and 
drinking occasions may spread out exposures over a day. This total 
daily exposure generally provides reasonable estimates of the risks 
from acute dietary exposures, given the nature of most chemical 
endpoints. Due to the rapid recovery associated with carbofuran 
toxicity (AChE inhibition), 24-hour exposure periods may or may not, a 
priori, be appropriate. To the extent that a day's eating or drinking 
occasions leading to high total daily exposure might be found close 
together in time, or to occur from a single eating event, minimal AChE 
recovery would occur between eating occasions (i.e., exposure events). 
In that case, the ``24-hour sum'' approach, which sums eating events 
over a 24-hour period, would provide reasonable estimates of risk from 
food and drinking water. Conversely, to the extent that eating 
occasions leading to high total daily exposures are widely separated in 
time (within 1 day) such that substantial AChE recovery occurs between 
eating occasions, then the estimated risks under any 24-hour sum 
approach may be overstated. In that case, a more sophisticated approach 
- one that accounts for intra-day eating and drinking patterns and the 
recovery of AChE between exposure events -- may be more appropriate. 
This approach is referred to as the ``Eating Occasions Analysis'' and 
it takes into account the fact that the toxicological effect of a first 
dose may be reduced or tempered prior to a second (or subsequent) dose.
    Thus, rather than treating a full day's exposure as a one-time 
``bolus'' dose, as is typically done in the Agency's assessments, the 
Eating Occasion Analysis uses the actual time of eating or drinking 
occasion, and amounts consumed as reported by individuals to the USDA 
CSFII. The actual CSFII-recorded time of each eating event is used to 
``separate out'' the exposures due to each eating occasion; in doing 
so, this ``separation'' allows the Agency to distinguish between each 
intake event and account for the fact that at least some partial 
recovery of AChE inhibition attributable to the first (earlier) 
exposure occurs before the second exposure event. For chemicals for 
which the toxic effect is rapidly reversible, the time between two (or 
more) exposure events permits partial to full recovery from the toxic 
effect from the first exposure and it is this ``partial recovery'' that 
is specifically accounted for by the Eating Occasion Analysis. More 
specifically, an estimated ``persisting dose'' from the first exposure 
event is added to the second exposure event to account for the partial 
recovery of AChE inhibition that occurs over the time between the first 
and second exposures. The ``persisting dose'' terminology, and this 
general approach were originally offered by the FIFRA SAP in the 
context of assessing AChE inhibition from cumulative exposures to 
organophosphorous pesticides (OPs) (Ref. 40).

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

[[Page 23052]]

evaluation, which represents one person out of every 1,000 persons. 
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. 101).

VI. Summary of the Proposed Rule

    EPA proposed to revoke all of the existing tolerances for residues 
of carbofuran on the grounds that aggregate exposure from all uses of 
carbofuran fail to meet the FFDCA section 408 safety standard (73 FR 
44864). Based on the contribution from food alone, EPA calculated that 
dietary exposures to carbofuran exceeded EPA's level of concern for all 
of the more sensitive subpopulations of infants and children. 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. 16). In addition, EPA's analyses showed 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 included those populations consuming drinking water from 
ground water from shallow wells in acidic aquifers overlaid with sandy 
soils that have had crops treated with carbofuran. It also included 
those populations that obtain their drinking water from reservoirs 
located in small agricultural watersheds, prone to runoff, and 
predominated by crops that are treated with carbofuran, although there 
was more uncertainty associated with these exposure estimates. The 
proposal discussed a number of sensitivity analyses the Agency had 
conducted in order to further characterize the potential risks to 
children. Every one of these sensitivity analyses determined that 
estimated exposures significantly exceeded EPA's level of concern for 
children.

VII. Summary of Public Comments and EPA Responses

    This section presents a summary of some of the significant comments 
received on the proposed rule, as well as the Agency's responses. More 
detailed responses to these comments, along with the Agency's responses 
to other comments received can be found in the Response to Comments 
Documents, located in the docket for this rulemaking (Refs. 111, 112, 
and 113).

A. Tolerances Associated With Voluntarily Canceled Uses

    On September 29, 2008, the registrant, FMC Corporation requested 
EPA to eliminate several uses from their end-use products. Consistent 
with this request, the registrant has indicated that it no longer seeks 
to maintain the tolerances associated with the domestic use of these 
products, and therefore no longer opposes the revocation of those 
tolerances. No other commenter indicated any interest in maintaining 
these tolerances. EPA is therefore revoking the tolerances associated 
with those domestic uses, on two separate grounds. The first ground is 
that the tolerances will no longer be necessary because the 
registrations for these uses have been canceled. The tolerances that 
EPA is revoking on this basis are: Alfalfa, forage; alfalfa, hay; 
artichoke, globe; barley, grain; barley, straw; beet, sugar roots; 
beet, sugar tops; corn, fresh (including sweet); corn, popcorn; cotton, 
undelinted seed; cranberry; cucumber; grape; grape raisin; grape, 
raisin, waste; melon; oat, grain; oat, straw; pepper; rice, straw; 
sorghum, forage; sorghum, grain grain; sorghum, grain, stover; 
strawberry; soybean, forage; soybean, hay; squash; wheat, grain; and 
wheat, straw.
    EPA also finds, however, that revocation of these tolerances is 
warranted on the grounds that aggregate exposures to these residues of 
carbofuran do not meet the safety standard of section 408(b)(2) of the 
FFDCA. The Agency is therefore revoking tolerances for these crops 
because aggregate dietary exposures to residues of carbofuran, 
including all anticipated dietary exposures and all other exposures for 
which there is reliable information, are not safe.
    As noted in the proposed rule, based on the contribution from only 
the foods bearing residues resulting from all of these tolerances, 
dietary exposures to carbofuran would 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. 70). In addition, as discussed 
in more detail, both in the proposed rule, and in Unit VIII.E.2. below, 
drinking water residues of carbofuran contribute significantly to 
unsafe aggregate exposures. Accordingly, it has not been shown that 
exposures from these uses would meet the FFDCA safety standard.

B. Comments Relating to EPA's Toxicology Assessment

    1. Comments relating to EPA's PoD. One group of commenters stated 
that the studies clearly support EPA's conclusion that the post-natal 
day (PND)11 brain data on the inhibition of AChE in juvenile rats 
provide the most appropriate PoD for risk assessment. The commenters 
also claimed, however, that ``the specific PoD proposed by EPA is 0.03 
mg/kg/day, but our analysis of the best data for the risk assessment 
are found in the good laboratory practices (GLP) compliant studies and 
those studies support 0.033 as a better value for the PND11 rat.'' This 
group of commenters also described an analysis their consultant had 
conducted. According to the commenters, their consultant calculated the 
value of 0.033 mg/kg/day/day from the BMD10s and 
BMDL10s \3\ in the four FMC studies with first observation 
time equal to 0.25 hours. The BMDs and BMDLs were calculated separately 
for each of these datasets. The results for the four datasets were 
combined, but, unlike EPA's analyses, the datasets themselves were not 
combined.
---------------------------------------------------------------------------

    \3\ BMD is an abbreviation for benchmark dose. The 
BMDL10 is the lower 95% confidence limit on the 
BMD10. The BMD10 is the estimated dose (i.e., 
benchmark dose) to result in 10% AChE inhibition. EPA uses the BMDL, 
not the BMD, as the point of departure.
---------------------------------------------------------------------------

    With respect to using the PND11 rat pup data as the PoD, the Agency 
acknowledges this area of agreement with the commenters. Ultimately, 
the BMDL10 recommended by the commenters differs from the 
EPA's BMDL10 by only 6% (0.031 mg/kg/day vs. 0.033 mg/kg/
day), a difference that is not biologically significant. Moreover, when 
rounded to one significant digit, as is done by typical convention and 
consistent with the dose information provided in the comparative 
cholinesterase (ChE) studies (also called CCA studies), both values 
yield the identical PoD of 0.03 mg/kg/day.
    Moreover, the Agency notes that the value of 0.033 mg/kg/day 
recommended

[[Page 23053]]

by the commenter does not include the 0.5-hr time-point from MRID no. 
47143705 although this dataset yielded the lowest BMDL for individual 
datasets reported by the commenters. As such, the commenter's 
recommended value does not include all of the relevant data collected 
at the time of peak effect. The commenters have provided no rationale 
for why it would be appropriate to selectively exclude data from the 
time frame in this study most relevant to the risk assessment. 
Accordingly, as noted in footnote 115 of the comment, when the 
commenters included the data at 0.5-hr timepoint from MRID no. 
47143705, the BMDL10 was lowered from 0.033 to 0.030 mg/kg/
day--a value almost identical to the Agency's BMDL10 of 
0.031 mg/kg/day.
    Thus, although the commenters are critical of the Agency's 
approach, there is basic consensus between EPA and the commenters that 
the PoD is 0.03 mg/kg/day given the precision of available data in 
deriving the BMDL10.
    The Agency also notes that specific details about the commenter's 
BMD modeling were not provided to the Agency. The Agency is therefore 
unable to fully evaluate the scientific validity of the modeling 
procedure used by the commenter.
    Some commenters claimed that ``EPA's derivation of its PoD, 
however, is not transparent and is not scientifically supported. 
Equally important, based on a recent review of the raw data from the 
Moser study (obtained via a FOIA request originally filed in April 
2008), we believe that the Moser study may not meet minimum criteria 
for scientific acceptability. Critical data are simply unavailable for 
this study, including: a complete protocol, analysis of dosing 
solutions, clinical observations, standardization of brain and red 
blood cell (RBC) AChE results in terms of amount per unit of protein, 
and quality assurance records of inspections for the carbofuran portion 
of the study.'' As a result, the commenters assert that the better 
approach is to use the brain AChE inhibition values calculated from the 
GLP-compliant registrant studies, because the commenters claim that EPA 
has acknowledged them to be valid, and which the commenters claim are 
fully documented. Using EPA's BMD dose-time response model, the 
commenters claim that the correct PoD is 0.033 mg/kg/day.
    The Agency disagrees with the commenters' assertions that the 
derivation of the PoD was not transparent. The Agency's analysis, 
computer code, and data have been placed in the docket for public 
scrutiny. EPA's models have been repeatedly reviewed and approved by 
the FIFRA SAP (Refs. 42, 43, and 44), and, as part of that process, 
been made available to the public. The most recent occasion was as part 
of the February 2008 FIFRA SAP meeting on the draft carbofuran NOIC. As 
EPA has explained numerous times, the Agency has not deviated from its 
standard practice. Most recently, EPA laid out its approach at length 
in the proposed rule. While it is true that EPA may not have repeated 
in this most recent analysis all of the specifics that it has 
previously provided, it is inaccurate for the commenter to claim that 
the information is not available, or that its review has in any way 
been hampered by this so-called lack of transparency. Indeed, given 
that the commenters appear to have been able to duplicate EPA's 
analyses, it seems reasonable to assume that the information was 
available. It is further worth noting that the commenters had 
sufficient access to the Moser data to allow a complete re-analysis 
before the 2008 SAP on the draft carbofuran NOIC, which was months 
before the FOIA request was filed with the Agency. In addition, a 
complete study protocol as well as a report of the quality assurance 
(QA) technical and data reviews of the study were included in the 
documents provided in response to the FOIA request. The Agency further 
notes that although the commenters complain about their perceived lack 
of transparency in EPA's BMD calculations, they did not provide any 
detailed information about the derivation of their proposed value.
    EPA also disagrees with the claim that EPA's PoD is not 
scientifically supported. As an initial matter, EPA notes that the 
commenters' suggested PoD of 0.033 mg/kg/day is not significantly 
different than EPA's PoD of 0.03 mg/kg/day (see Unit VIII.B.). The 
criticisms of the Moser study are also incorrect. The procedures and 
documentation are in accordance with the ORD Quality Assurance 
Management Plan. Concerning standardization of brain and RBC AChE in 
terms of protein, it is interesting to note that, despite their 
complaints that EPA had failed to do this, the registrant also failed 
to do this in their own studies. However, in the Moser study, the AChE 
activity was standardized in terms of tissue weight per ml, so the 
amount of protein was consistent across samples. This is an acceptable 
and widely used practice. Further, abnormal (or ``clinical'') 
observations were recorded when they occurred; however, it is not 
technically possible to observe the animals while they are being tested 
for motor activity. Finally, the registrant is correct that the dosing 
solutions for the CCA study were not analyzed, but this was done for 
the adult studies in McDaniel et al., (2007), and the preparation and 
stability of the carbofuran samples were confirmed therein.
    If, however, the Agency elected to follow the commenters' 
recommendation to not use the ORD data in the risk assessment, there 
would be no high quality RBC AChE inhibition data available in juvenile 
rats. As such, there would be no surrogate data evaluating AChE 
inhibition in the peripheral nervous system (PNS), much less any data 
from the PNS itself. As discussed in Unit VIII.C., with the 
availability of some RBC data from ORD evaluating the effects in the 
PNS, the Agency is able to reduce the children's safety factor from 10X 
to 4X. Without the ORD data, the Agency would be required to retain the 
statutory 10X.
    Some commenters raised concern that EPA's PoD was not sufficiently 
protective. The commenters point to comments from the February SAP 
review of EPA's draft carbofuran NOIC, quoting the following language 
from the report, which indicated concern that the starting point used 
in the risk assessment was not sufficiently protective:

    Some Panel members questioned the assumption that a 10% level of 
brain AChE inhibition (i.e., BMD10) is sufficiently 
harmless to be used as a point of departure in risk assessment. It 
was noted that as more refined brain data become available, we are 
beginning to understand that not all regions of this organ show the 
same level of AChE inhibition. Thus a 10% inhibition for the whole 
brain may imply significantly greater inhibition in a more sensitive 
region.

    The FIFRA SAP report provides conflicting information on the issue 
of the benchmark dose response used by EPA in its BMD calculations. On 
page 53 of the FIFRA SAP report, the text suggests that the available 
data do not support the 10% response level used in BMD modeling and 
that a 20% response level is more appropriate. The text quoted by the 
commenters from the report argues that a 10% response level may not be 
sufficiently health protective, but that a 5% response level may be 
more appropriate. Given the lack of unanimous advice by the Panel in 
this case, and that past SAPs have previously supported the use of a 
10% level in comparable cases, the Agency has concluded that the 
overall weight of the available evidence supports a decision that use 
of a 10% response level will be protective of human health.

[[Page 23054]]

A more detailed response to this issue can be found in the Agency's 
response to the SAP (Ref. 109).
    2. Comments relating to the children's safety factor--a. Reliance 
on RBC to predict effects on the PNS. Some commenters argued that brain 
is a better surrogate for the PNS than RBC, and that therefore reliance 
on the brain data is sufficiently protective that no additional 
children's safety factor is necessary. The commenters claim that the 
carbofuran data on brain AChE inhibition and on clinical signs of 
toxicity indicate that PNS AChE inhibiton is sufficiently modeled by 
brain AChE inhibtion. They note that the available data show that brain 
AChE responds rapidly to carbofuran; it readily passes the blood-brain 
barrier and the data show maximal AChE inhibition within minutes. The 
commenters also alleged that brain and tissue AChE are more similar to 
each other than to RBC AChE. The commenters also point to the fact that 
oral time-course studies by EPA and the registrant show that brain 
cholinesterase responds quickly and recovers promptly. Carbofuran 
clearly reaches the brain quickly. They also cite to the fact that EPA 
has acknowledged that in adults, no difference in sensitivity is seen 
between brain and RBC AChE inhibition.
    The commenters repeatedly mention the rapid speed by which 
carbofuran reaches the brain and the rapid onset and recovery of AChE 
inhibition as support for the notion that reliance on the brain data 
will be adequately protective of PNS toxicity. The Agency agrees with 
the commenters on the rapid nature of carbofuran toxicity. However, 
this rapid toxicity occurs in multiple tissues, not just the brain. 
Moreover, the time course of such toxicity is not relevant to 
determining which tissue is more sensitive. Therefore, these comments 
are not relevant to a discussion of the use of brain versus RBC AChE as 
a surrogate for PNS toxicity.
    The commenters' allegation that brain and tissue AChE are more 
similar to each other than to RBC AChE is not scientifically 
supportable. Radic and Taylor (2006), for example, state, ``In humans 
and most other vertebrate species, only one gene encodes AChE'' (Ref. 
81). Accordingly, if only one gene encodes the enzyme, then the 
structure of the active site is the same throughout the body.
    Responses in adult animals are not necessarily predictive or 
relevant to responses in juveniles since the metabolic capacity of 
juveniles is less than that of adults. As such, juveniles can be more 
sensitive to some toxic agents. Specific to carbofuran, multiple 
studies have shown juvenile rats to be more sensitive than adult rats. 
Thus, comments about responses in adults are less relevant compared to 
data in pups from the carbofuran risk assessment, particularly in the 
evaluation of the children's safety factor.
    One group of commenters argue that there is evidence that RBC AChE 
activity can be inhibited to a greater degree than AChE in peripheral 
organs. For example, Marable et al., (2007), showed that chlorpyrifos 
caused much greater inhi