23046 Federal Register / Vol. 74, No. 93 / Friday, May 15, 2009 / Rules and Regulations 

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. 

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: http:// 

www.regulations.gov. Follow the on-line 

instructions for submitting comments. 

• Mail: Office of Pesticide Programs 

(OPP) Regulatory Public Docket (7502P), 

Environmental Protection Agency, 1200 

Pennsylvania Ave., NW., Washington, 

DC 20460–0001. 

• Delivery: OPP Regulatory Public 

Docket (7502P), Environmental 

Protection Agency, Rm. S-4400, One 

Potomac Yard (South Bldg.), 2777 S. 

Crystal Dr., Arlington, VA. Deliveries 

are only accepted during the Docket’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 http://www.regulations.gov, 

or, if only available in hard copy, at the 

OPP Regulatory Public Docket in Rm. S– 

4400, One Potomac Yard (South Bldg.), 

2777 S. Crystal Dr., Arlington, VA. The 

Docket Facility is open from 8:30 a.m. 

to 4 p.m., Monday through Friday, 

excluding legal holidays. The Docket 

Facility telephone number is (703) 305– 

5805. 

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; email 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 http:// 

www.regulations.gov, you may access 

this Federal Register document 

electronically through the EPA Internet 

under the ‘‘Federal Register’’ listings at 

http://www.epa.gov/fedrgstr. You may 

also access a frequently updated 

electronic version of EPA’s tolerance 

regulations at 40 CFR part 180 through 

the Government Printing Office’s pilot 

e-CFR site at http://www.gpoaccess.gov/ 

ecfr. 

C. 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 

Federal Register / Vol. 74, No. 93 / Friday, May 15, 2009 / Rules and Regulations 23047 

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 

23048 Federal Register / Vol. 74, No. 93 / Friday, May 15, 2009 / Rules and Regulations 

1USDA’s Pesticide Data Program monitors for 

pesticides in certain foods at the distribution points 

just before release to supermarkets and grocery 

stores. 

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-FCIDTM, 

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 Program1 (PDP), 

estimated percent crop treated 

information, and processing/cooking 

factors, where applicable. The 

assessment was conducted applying a 

Federal Register / Vol. 74, No. 93 / Friday, May 15, 2009 / Rules and Regulations 23049 

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. 

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: 

• 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, 

23050 Federal Register / Vol. 74, No. 93 / Friday, May 15, 2009 / Rules and Regulations 

2Probabilistic 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. 

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. 

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-FCIDTM to estimate 

exposure by combining data on human 

consumption amounts with residue 

values in food commodities. DEEMFCIDTM also compares exposure 

estimates to appropriate RfD or PAD 

values to estimate risk. EPA uses DEEMFCIDTM to estimate exposure for the 

general U.S. population as well as for 32 

subgroups based on age, sex, ethnicity, 

and region. DEEM-FCIDTM 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-FCIDTM 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-FCIDTM 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-FCIDTM program 

to estimate exposure and risk. 

For carbofuran’s assessment, EPA 

used DEEM-FCIDTM to calculate risk 

estimates based on a probabilistic 

distribution. DEEM-FCIDTM 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, DEEMFCIDTM 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 persondays in the CSFII are then collected in 

a frequency distribution. EPA also uses 

DEEM-FCIDTM 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-FCIDTM 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 

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

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-FCIDTM, 

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 CSFIIrecorded 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 

23052 Federal Register / Vol. 74, No. 93 / Friday, May 15, 2009 / Rules and Regulations 

3BMD 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. 

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 enduse 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. 

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 

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

23054 Federal Register / Vol. 74, No. 93 / Friday, May 15, 2009 / Rules and Regulations 

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 inhibition of AChE in RBC than 

in diaphragm, left atrium, and 

quadriceps, as well as in brain. 

Similarly, Padilla et al., (2005), reported 

a greater inhibition of AChE in RBC 

than in diaphragm or brain. Bretaud et 

al., (2000), showed that carbofuran 

caused significant inhibition of AChE in 

brain tissues but not in muscle in 

goldfish. The commenters claim that 

these results demonstrate that RBC 

AChE activity does not reflect AChE 

activity in peripheral organs. 

The commenters mention three 

references: Padilla et al., 2005; Marable 

et al., 2007; Bretaud et al., 2000. Two of 

these studies involve testing with 

chlorpyrifos in rats (Refs. 65 and 77) 

and the third involves testing fish with 

carbofuran (Ref. 14). Quantitative 

extrapolation of RBC and peripheral 

AChE inhibition differences from fish to 

mammals is highly uncertain because 

distribution of carbofuran across fish 

and mammalian tissues may be quite 

different. The Padilla et al., (2005) and 

Marable et al., (2007) references include 

testing with chlorpyrifos, an OP whose 

primary mode of action is also AChE 

inhibition (Refs. 65 and 77). Exposure to 

OP and NMC insecticides results in 

inhibition of AChE. The Agency 

assumes it is this similarity in 

mechanism of toxicity, which provides 

the basis for inclusion of these 

chlorpyrifos references by the 

commenters. 

The Agency believes that direct 

comparison between the results of 

studies with chlorpyrifos and 

carbofuran should be done with great 

caution. OP and NMC insecticides have 

different time courses of effects, which 

lead to toxicity profiles that are 

somewhat different. The studies cited 

by the commenters (Padilla et al., 2005, 

Marable et al., 2007) involve long-term 

treatment (chronic exposure) in adult 

animals where blood, brain and 

peripheral tissue AChE inhibition were 

at steady-state. The time course and 

AChE inhibition in various tissues at 

steady state is distinctly different from 

acute AChE inhibition at the time of 

peak effect, like that in the carbofuran 

studies. In the case of acute toxicity 

with NMCs, the time course of 

inhibition and reactivation of the AChE 

is rapid (minutes to hours). In the case 

of OPs, when steady state inhibition is 

achieved in adults, recovery is slow 

(days to weeks) and is influenced by 

synthesis of new AChE protein. In 

addition, as stated above, responses in 

adults are not adequate for drawing 

conclusions in the young. As such, the 

Agency views the Padilla et al., (2005) 

and Marable, et al., (2007) references as 

providing limited useful information for 

the carbofuran risk assessment. 

Although the Agency is cautious 

about direct comparisons between OPs 

and NMCs, it must be noted in this case 

that: (1) The commenters have provided 

an incomplete review of the literature 

and ignored more relevant studies; and 

(2) the chlorpyrifos literature does, in 

fact, generally support the Agency’s 

conclusions with respect to carbofuran. 

The commenters state specifically that 

‘‘[t]here is also evidence that RBC AChE 

activity can be inhibited to a greater 

degree than AChE in peripheral organs.’’ 

The assertion that RBC AChE activity 

can be more inhibited than peripheral 

tissues ignores relevant chlorpyrifos 

data. For example, Richardson and 

Chambers (2003) showed that lung 

AChE can be more sensitive than serum 

and brain AChE in rat fetuses (Ref. 82). 

EPA’s response to comments 

document provides a more extensive 

review of chlorpyrifos studies (those 

that include data in peripheral tissue) 

than that discussed by the commenters 

(Ref. 112). While there are many studies 

that have measured AChE inhibition 

with chlorpyrifos, the Agency has 

limited its discussion here only to those 

in pregnant rats and fetuses which 

provide peripheral AChE data (e.g., 

heart, lung, and liver) as they are the 

most relevant to the present issues 

raised by the commenters. Several 

chlorpyrifos studies in pregnant dams 

and/or their fetuses show that 

peripheral AChE is more sensitive than 

brain AChE. For example, a study 

conducted by Dow AgroSciences 

showed that a dose of 1 mg/kg results 

in 4–6 fold more inhibition in heart 

AChE than in brain tissues (Refs. 66 and 

67). Similarly, Hunter et al., (1999) 

showed that in pregnant dams at doses 

of 3 mg/kg liver AChE was inhibited 

84% when brain tissues were inhibited 

by only 41% (Ref. 51). Fetuses evaluated 

at or near the peak time of effect in the 

Hunter et al., (1999) study showed 2–8 

fold more AChE inhibition in liver than 

in brain. (Id.). Although there is some 

variation among studies, the 

preponderance of data supports the 

Federal Register / Vol. 74, No. 93 / Friday, May 15, 2009 / Rules and Regulations 23055 

conclusion that peripheral tissues are 

more sensitive to chlorpyrifos exposure 

than brain tissues. Thus, the 

chlorpyrifos data in fetuses and 

pregnant rats supports the Agency’s 

concern that sole reliance on brain data 

may not be protective of the PNS 

following carbofuran exposure. 

Chlorpyrifos data in post-natal pups are 

described in the Agency’s Response to 

Comments on the proposed tolerance 

revocation (Ref. 112). 

Although OPs and NMCs both inhibit 

AChE, the chemical reaction at the 

active site differs. This difference leads 

to different time courses of toxicity and 

recovery. As such, comparisons, 

particularly quantitative ones, between 

chlorpyrifos and carbofuran should be 

done with care. However, in general, 

review of these data supports the 

Agency’s conclusion for carbofuran that 

in the absence of high quality data that 

is relevant for risk assessment in either 

peripheral tissue or a surrogate (i.e., 

RBCs), the Agency cannot be certain 

that brain AChE inhibition is protective 

of potential peripheral toxicity 

following carbofuran exposure. 

Therefore, the chlorpyrifos data support 

the Agency’s conclusion that at least a 

portion of the children’s safety factor 

must be retained for carbofuran given 

the lack of peripheral AChE data and 

lack of RBC AChE (as a surrogate for 

peripheral AChE) at the low end of the 

dose-response curve. 

b. Comments relating to EPA’s 

approach to deriving the 4X factor. One 

group of commenters argued that EPA’s 

approach to calculating its 4X 

Children’s Safety Factor was flawed. 

According to the commenters, it would 

be more plausible and straightforward to 

compare the RBC and brain AChE levels 

at the same time in the same rat when 

these rats are exposed to carbofuran. 

Based on an analysis of the RBC and 

brain AChE inhibition data, the 

commenters’ claim that the percentage 

reduction in RBC AChE in a rat is 

almost the same as the percentage 

reduction in brain AChE in that same 

rat. The commenters summarize a 

statistical evaluation of the 

experimental data on AChE inhibitions 

in RBC and brain in rats due to 

carbofuran exposure conducted by their 

contractor, and claim that this 

evaluation shows that the percentage 

inhibition of RBC AChE in a rat 

compared to the percentage inhibition 

of brain AChE in the rat is no more than 

1.5X—a difference that they claim is not 

meaningful from a physiological 

perspective and does not warrant 

imposition of a 4X FQPA safety factor. 

EPA notes that the commenters 

recommended this approach of 

comparing the degree of inhibition for 

each animal as part of their presentation 

to the Carbofuran SAP. EPA also 

addressed this approach, comparing 

RBC to brain in the same animals, at the 

SAP and in the responses to the SAP 

report (Ref. 109). It is notable that the 

SAP did not endorse this approach. 

EPA’s analyses of the commenters’ 

approach identified several significant 

deficiencies. First, the comparison 

suggested by the commenter means that 

EPA would need to ignore existing data. 

This is because only EPA’s study of 

PND11 animals contains both brain and 

RBC data, so the comparisons suggested 

by the commenter can only be made 

using that dataset. However, the dose 

levels in that study were so high that the 

lower portion of the dose-response 

curve was missed. At these higher 

doses, there is little difference between 

the levels of brain and RBC inhibition. 

This phenomenon, namely the relative 

sensitivity of RBC compared to brain 

appears smaller at higher doses. This 

phenomenom is also shown in multiple 

chlorpyrifos studies, where blood or 

peripheral measures of AChE inhibition 

are more sensitive than brain at low to 

mid doses but the tissues appear to be 

similar at higher doses. 

Second, the commenters’ approach is 

fundamentally flawed. The commenters’ 

suggested alternative relies exclusively 

on comparisons between the degree of 

inhibition in the treated animals 

without any regard to the doses at 

which the effects occurred. For 

example, one animal may have shown, 

on average, 10% inhibition in the brain, 

when it demonstrated 20% RBC 

inhibition. Under this approach, what 

would be relevant would simply be the 

ratio of 1:2. But the Agency believes it 

is critical to focus on the ratios of 

potency, which is the ratio of the doses 

in the data that cause the same level of 

AChE inhibition. The Agency’s 

approach of comparing potencies is 

more directly relevant for regulatory 

purposes than comparisons of average 

inhibition. This is because dose 

corresponds more directly to potential 

exposures, which is what EPA regulates 

(i.e., how much pesticide residue does 

a child ingest). By comparison, the 

commenters’ suggested reliance purely 

on the average degree of inhibition 

provides no information that 

corresponds to a practical basis for 

regulation. 

Finally, the range of ratios of effects 

that the commenters propose as an 

alternative is consistent with range of 

potencies that EPA has calculated at the 

higher doses in the available data, so the 

commenters’ results do not ultimately 

contradict EPA’s assessment, which 

tries to account for what occurs at lower 

doses. Briefly, if the dose-responses for 

RBC and brain inhibition were linear, 

ratios of inhibition would equal ratios of 

BMDs. However, these dose-responses 

are not at all linear, and the available 

data demonstrate that brain and blood 

dose-responses have somewhat different 

shapes. Thus, estimates of relative 

effects at particular, relatively high, 

doses are not relevant to the problem of 

estimating potency ratios at lower doses. 

The dose-response curves level off at 

about the same level of inhibition, so, at 

high doses, there is no difference 

between the ratio of inhibitions. Except 

at the lowest dose, where the ratio is 

slightly greater than 2, the remaining 

ratios are only slightly greater than 1. 

Given the inevitable statistical noise in 

these measures, it is clear that the ratios 

expected from EPA’s modeling are 

substantially similar to what the 

commenter finds in its comparison 

between individuals. Accordingly, the 

commenter’s suggested comparisons at 

higher doses provide no evidence of 

what occurs at lower doses; and thus 

provides no evidence that demonstrates 

that EPA’s modeling results at lower 

doses is inaccurate. 

One group of commenters claimed 

that the statistical comparisons that 

support EPA’s selection of a 4X 

children’s safety factor are flawed. The 

commenters claim that, even assuming 

that RBC values are relevant, EPA’s 

conclusion that RBC effects in the 

relevant studies were four times more 

sensitive than brain effects is not 

mathematically supportable. The 

commenters reference statistical 

analyses performed for them by a 

contractor, which they claim show that 

EPA’s calculation of the 4X children’s 

safety factor is simply incorrect. The 

commenters complain that the datasets 

EPA used for brain differ not only 

because they were from different 

studies, but also because the data were 

taken at different times ranging from 15 

minutes to 4 hours after dosing. The 

commenters also raise the concern that 

EPA’s decision to combine data for 

different strains of rats, sexes, 

experiments, laboratories, dates, dose 

preparations, rat ages, and times 

between dosing and AChE 

measurement, is problematic, claiming 

that these differences in study design 

severely limit the validity of EPA’s 

comparisons. In addition, the 

commenters claim to have found a 

number of errors and inconsistencies in 

how the modeling was conducted. 

Correcting for these errors, the 

commenters claim, shows that the 

23056 Federal Register / Vol. 74, No. 93 / Friday, May 15, 2009 / Rules and Regulations 

BMDs for brain and RBC data are 

essentially the same. 

As discussed at length below, and in 

EPA’s Response to Comments 

document, EPA disagrees that its 

statistical modeling was in any way 

flawed (Ref. 112). 

In general, EPA believes that 

consideration of all available data is the 

scientifically more defensible approach, 

rather than the selective exclusion of 

reliable data. The Agency’s Draft BMD 

Guidance says the following: ‘‘Data sets 

that are statistically and biologically 

compatible may be combined prior to 

dose response modeling, resulting in 

increased confidence, both statistical 

and biological, in the calculated BMD’’ 

(Ref. 100). The Agency’s carbofuran 

analysis has included all available, valid 

data in its analysis. Further regarding 

combining data from multiple strains, 

the SAP was fully aware that the 

Agency was planning to derive BMD 

estimates from data sets using different 

strains of rats (Ref. 43). 

By contrast, the commenters’ 

suggested analysis ignores relevant, 

scientifically valid data. The FMC 

analysis left out the 30–minute data 

from MRID no. 47143705. The 

commenters have provided no rationale 

as to why it would be appropriate to 

selectively exclude data from the time 

frame in this study most relevant to the 

risk assessment (i.e., peak AChE 

inhibition). The commenters’ analysis of 

the individual datasets from MRID no. 

47143705, showed that at 30 minutes 

the females and males provide BMDL10s 

of 0.009 mg/kg/day and 0.014 mg/kg/ 

day, respectively. When the datasets 

were combined, inclusion of the 30– 

minute timepoint from MRID no. 

47143705 decreased the BMDL10 from 

0.033 mg/kg/day to 0.030 mg/kg/day. 

EPA has used a sophisticated analysis 

of multiple studies and datasets to 

develop the PoD for the carbofuran risk 

assessment. However, instead of this 

analysis, EPA could simply have 

followed the general approach laid out 

in its BMD policy (Ref. 100), which is 

used in the majority of risk assessments. 

Under this general approach, EPA 

would regulate using the most sensitive 

effect, study, and/or dataset. If the 

Agency chose not to combine the data 

in its analyses, as the commenters’ 

suggested, data collected at or near the 

peak time of effect (i.e., 30 minutes) 

would in fact provide the more relevant 

datasets. If this more simple approach 

were taken, in accordance with BMD 

guidance, EPA would select the lowest 

BMDL10. Assuming the commenters’ 

values were used, EPA would have 

selected a PoD of 0.009 mg/kg/day, 

instead of 0.03 mg/kg/day, which is the 

value EPA is currently using in its risk 

assessment. 

Further, the commenters complain 

that EPA’s approach of combining data 

across multiple studies is scientifically 

inappropriate. The commenters have, 

however, combined the results of 

analysis from four datasets. It is notable 

that most of the issues cited by the 

commenters also apply equally to the 

commenter’s own analysis, as described 

in more detail in EPA’s Response to 

Comments document (Ref. 112). 

EPA has addressed all of the 

commenters’ claimed inconsistencies in 

its Response to Comments document 

(Ref. 112). The majority of these claimed 

flaws and inconsistencies were either 

misunderstandings by the commenters 

or areas where it was the commenters 

who were incorrect, not EPA. However, 

in response to some of their allegations, 

EPA conducted new analyses to 

determine whether the suggested 

alternative approaches would make any 

significant difference in EPA’s modeling 

outcomes. For example, in response to 

one of their comments, EPA used the 

dose-time-response model to extrapolate 

BMD50s to develop a common point of 

comparison between all studies. 

Specifically, EPA extrapolated the 

PND11 brain analysis to estimate BMD50

for 40 minutes after dosing for 

comparison with the existing PND11 

RBC BMD50, and extrapolated the 

PND11 RBC BMD50 to 15 minutes after 

dosing for a range of assumed recovery 

half-lives, for comparison to the existing 

PND11 brain BMD50 (Refs. 30 and 31). 

In either approach, the estimate of the 

RBC to brain potency ratio in PND11 

animals is increased, and EPA’s safety 

factor would correspondingly increase 

to reflect that larger difference. For 

example, when the PND11 brain BMD50

is extrapolated to 40 minutes, the RBC 

to brain potency ratio grows to 4.7 (Ref. 

30), and when the PND11 RBC BMD50

is extrapolated to 15 minutes, using a 

range of estimates for the recovery halflife of the RBC endpoint, the RBC to 

brain potency ratio ranges from 4.2 to 

4.6 (Ref. 31). The commenter’s approach 

would therefore support a children’s 

safety factor of 5X rather than 4X. 

Similarly, in response to the 

complaint that EPA should have 

generated a new dose-response model in 

order to calculate the BMD50s for brain 

and RBC, EPA conducted the suggested 

calculation (Ref. 112). The ratio of brain 

to RBC BMD50s in this new analysis is 

the same as that calculated by EPA 

using the mathematical expression. Both 

provide a ratio of brain to RBCs BMD50

of 4X. Specifically, the values are for 

PND11 brain BMD50 0.35 and for RBC, 

0.086, resulting in a ratio of 4.09 (Ref. 

112). 

Several commenters disagreed with 

the Agency’s decision to apply a 4X, 

arguing that the high bar set by the 

statute for lessening the tenfold safety 

factor has not been achieved because 

‘‘important data gaps exist.’’ These 

commenters raised the concern that key 

data on carbofuran toxicity and 

exposure for the very young are 

inadequate. Examples include: No data 

were presented for pre-natal sensitivity 

as would have been desirable for 

addressing the need to protect 

developing individuals; BMD10

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. The commenters also 

highlighted EPA’s assumption that the 

RBC and brain AChE dose response 

curves are parallel, noting that there are 

currently no data to test this assumption 

for carbofuran. One commenter raised 

the concern that ‘‘EPA has no 

substantial research on alternate 

mechanisms of carbofuran toxicity. EPA 

has acknowledged but failed to 

incorporate in its assessment the 

potential for lasting adverse effects from 

transient exposures during fetal and 

newborn life-stages, and EPA has 

acknowledged that there are 

uncertainties in the available data (as 

raised by the SAP).’’ The commenters 

concluded that the Agency does not 

have the requisite ‘‘completeness of 

data’’ required by law to lessen the 

safety factor,’’ and urged the Agency to 

reinstate the default 10X safety factor. 

Section 408(b)(2)(C) of the FFDCA 

requires that EPA consider the 

‘‘completeness of data with respect to 

exposure and toxicity to infants and 

children’’ when evaluating whether 

retention of the default 10X safety factor 

is appropriate. The Agency has 

concluded that available exposure 

information is sufficient for purposes of 

developing its human health risk 

assessment, and has adequately 

accounted for the lack of certain hazard 

information with the retention of a 4X 

children’s safety factor. Moreover, the 

Agency has concluded that the exposure 

assessment does not substantially 

underestimate food or water exposure. 

The completeness of the hazard 

database and the interpretation of 

available toxicity studies were described 

elsewhere in this final rule preamble. 

The Agency continues to believe that a 

4X children’s safety factor is appropriate 

for carbofuran. 

Several commenters alleged that 

application of a 4X children’s safety 

factor, rather than a 10X, is inconsistent 

with the SAP’s advice. These 

Federal Register / Vol. 74, No. 93 / Friday, May 15, 2009 / Rules and Regulations 23057 

commenters argued that the SAP report 

reflected strong support, if not 

unanimity, among panel members for a 

safety factor of at least fivefold, and 

pointed to the statement in the report 

that ‘‘some Panel members considered it 

reasonable to retain the full 10X 

[children’s] safety factor (Panel Scenario 

5). Given the uncertainty in the data and 

in its interpretation for risk assessment 

by the entire Panel, these Panel 

members believed that this standard for 

change had not been met.’’ 

As described in detail in the Agency’s 

response to the SAP report (Ref. 109), 

the Agency believes there was a general 

consensus that a children’s safety factor 

of 2X or greater was necessary. The 

Agency does note that one Panel 

member thought a 1X was appropriate 

and at least two believed a 2X was 

appropriate. Given that the Panel did 

not take a vote on the record and the 

report notes that the Panel did not 

endorse a particular approach, any 

conclusions about the possible 

‘‘unanimity’’ of the Panel is speculation. 

However, as described in the Agency’s 

response to the SAP and in the July 

2008 proposed rule, EPA believes that 

on balance, its reliance on the data 

derived factor of 4X is consistent with 

the SAP’s advice, as a whole. 

Several commenters raised concern 

that EPA’s application of a 4X children’s 

safety factor did not adequately account 

for the differences between children and 

adults. The commenters raised several 

reasons that children are more 

vulnerable than adults to carbofuran. 

These include the following: 

(1) Children are growing. Pound for 

pound, children eat more food, drink 

more water and breathe more air than 

adults. Thus, the commenters conclude, 

they are likely to be more exposed to 

substances in their environment than 

are adults. Children have higher 

metabolic rates than adults and are 

different from adults in how their 

bodies absorb, detoxify and excrete 

toxicants. 

(2) Children’s bodies, including their 

nervous, reproductive, digestive, 

respiratory and immune systems, are 

developing. This process of 

development creates periods of 

vulnerability. Exposure to toxicants at 

such times may result in irreversible 

damage when the same exposure to a 

mature system may result in little or no 

damage. 

(3) Children behave differently than 

adults, leading to a different pattern of 

exposures to the world around them. 

For example, they exhibit hand-tomouth behavior, ingesting whatever 

substances may be on their hands, toys, 

household items, and floors. Children 

play and live in a different space than 

do adults. For example, very young 

children spend hours close to the 

ground where there may be more 

exposure to toxicants in dust, soil, and 

carpets as well as low-lying vapors. 

(4) The recovery time from carbofuran 

exposure for the very young is more 

than four times that of adults, as the 

SAP noted. 

Carbofuran does not have any 

residential uses. As such, comments 

about the breathing rate of children and 

hand-to-mouth behavior do not apply to 

carbofuran’s risk assessment. The 

Agency agrees with the commenters that 

infants and children represent a 

potentially susceptible lifestage to 

carbofuran exposure. Accordingly, the 

Agency has taken steps to incorporate 

lifestage specific information in its risk 

assessment. For example, the Agency’s 

hazard assessment has used data from 

PND11 rat pups as the PoD in 

extrapolating human risk. 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 (Refs. 5, 12, and 26). 

The Agency’s food exposure assessment 

relies on DEEM-FCIDTM, which uses the 

CSFII database, including the 1998 

supplemental survey of children. As 

such, the Agency’s aggregate risk 

assessment accounts for the decreased 

metabolic capacity of juveniles in 

addition to age-specific behaviors in 

eating and drinking. 

One commenter noted that while they 

agreed that the use of brain and RBC 

AChE inhibition data is an appropriate 

endpoint for use in EPA’s risk 

assessment, they did not believe that it 

is sufficiently health-protective to only 

rely on this endpoint without an 

uncertainty factor because it has not 

been established scientifically that 

AChE inhibition is the most sensitive 

endpoint. The commenter noted that 

one SAP member argued for retaining a 

10X children’s safety factor because of 

uncertainty in both the dosimetry in 

subtle developmental effects and also 

the available data on related pesticides 

suggesting effects on nerve outgrowth at 

cholinesterase inhibition levels of 20% 

or less, and some effects at less than 

10%. The commenter asserted that ‘‘this 

position is supported by published 

studies on the toxicity of a related 

family of pesticides, the OPs, reporting 

that exposures during fetal and newborn 

life-stages affect diverse cellular 

functions by mechanisms of toxicity 

that are independent of cholinesterase 

inhibition, and may occur at exposures 

that elicit less than 20% inhibition 

(Refs. 1, 2, 32, and 91). This is important 

because while the systemic toxicity that 

results from cholinesterase inhibition is 

reasonably well characterized, it does 

not explain why rodents exposed preand post-natally seem to recover from 

cholinesterase inhibition relatively 

rapidly, yet display persistent and more 

severe damage to the central nervous 

system’’ (Ref. 90). The commenter also 

pointed to what they assert is a 

‘‘growing body of science for OPs 

demonstrating that non-cholinergic 

mechanisms of toxicity may be acting to 

disrupt multiple brain targets’’ (Ref. 80). 

According to the commenter, experts 

have warned that ‘‘the fact that 

alterations in neurodevelopment occur 

with OPs below the threshold for 

cholinesterase inhibition reinforces the 

inadequacy of this biomarker 

[cholinesterase inhibition] for assessing 

exposure or outcome related to 

developmental neurotoxicity’’ (Ref. 92). 

When reviewing the EPA assessment of 

the OPs, the commenter asserted that 

the FIFRA SAP in 2002 had raised the 

same concern, stating that ‘‘reliance on 

a single biochemical assay to measure 

brain damage may become problematic’’ 

(Ref. 41). 

The Agency is aware of the available 

studies noted by the commenters on the 

OPs and has recently developed a draft 

issue paper on many such studies as 

part of its on-going review of 

chlorpyrifos. The Agency cautions the 

commenters against extrapolating these 

studies to the NMCs. The Agency is not 

aware of any studies in laboratory 

animals where long-term behavioral or 

other effects were noted with exposure 

to NMCs. Moreover, the Agency is not 

aware of any epidemiology study that 

has associated NMC exposure with 

adverse birth or neurodevelopmental 

outcomes in children. Although OPs 

and NMCs both inhibit AChE, the 

chemical reaction at the active site 

differs. This difference leads to different 

time courses of toxicity and recovery. 

Time to peak effect and time to recovery 

for the NMCs is very rapid in 

comparison to OPs. Moreover, once 

reactivation of the AChE occurs, the 

parent compound is no longer active. As 

such, NMCs may not be present in the 

body long enough to cause the types of 

outcomes associated with OP exposure. 

The Agency concludes that there are no 

data which link NMC exposure, 

including studies with carbofuran, at 

relatively low doses to long-term 

outcomes in juvenile animals or 

children. Therefore, the Agency further 

concludes that the OP studies noted by 

the commenters have limited relevance 

to the carbofuran human health risk 

assessment. 

c. Comments regarding consistency in 

approach. One group of commenters 

23058 Federal Register / Vol. 74, No. 93 / Friday, May 15, 2009 / Rules and Regulations 

claimed that the derivation of 

carbofuran’s PoD and children’s safety 

factor was inconsistent with EPA’s 

analyses for other NMCs, including 

aldicarb and carbaryl. 

The commenters are incorrect. The 

Agency’s recent hazard assessments of 

carbaryl and aldicarb are each 

consistent with OPP policies and 

practice, as well as with the Agency’s 

approach to the assessment of 

carbofuran. 

The commenters’ assertions regarding 

aldicarb were based on an earlier 

assessment. At the time the Agency 

conducted the assessment to which the 

commenters refer, the Agency was 

unaware of the differences in sensitivity 

between PND17 and PND11 animals. 

Since EPA became aware of the 

differences, EPA has required the 

aldicarb registrant to conduct a CCA 

study in PND11 rats; the Agency 

anticipates the receipt of this study and 

the companion range-finding and time 

course studies in 2009. In the absence 

of these data, EPA will apply the 

statutory default children’s safety factor 

to account for the additional sensitivity 

of PND11 animals, because the Agency 

lacks any data that could be used to 

derive a reduced factor that EPA could 

determine will be ‘‘safe for infants and 

children.’’ 

Carbaryl was not evaluated any 

differently than carbofuran. EPA’s 

typical practice which was used in both 

the carbofuran and carbaryl risk 

assessments, is to use the central 

estimate on the BMD to provide an 

appropriate measure for comparing 

chemical potency and to use the lower 

limit on the central estimate (i.e., 

BMDL) to provide an appropriate 

measure for extrapolating risk. This 

approach is also consistent with the 

NMC cumulative risk assessment (CRA) 

and single chemical risk assessments for 

multiple OPs. 

In the case of carbaryl, the 

commenters inappropriately focused on 

the BMDL10s, instead of the BMD10s. 

The more appropriate comparison is 

between the BMD10s; the carbaryl brain 

BMD10 is 1.46 mg/kg/day compared 

with the RBC BMD10 of 1.11 mg/kg/day. 

As such, the brain to RBC ratio is 1.3X. 

Therefore, for carbaryl, the brain and 

RBC AChE data are similarly sensitive, 

and, when the tissues are similarly 

sensitive, the Agency prefers to use data 

from the nervous system tissue (i.e., 

brain) over data from a surrogate tissue 

(i.e., RBC) (Ref. 108). Thus, for carbaryl, 

the RBC AChE inhibition (a surrogate 

for PNS AChE inhibition) and brain 

AChE inhibition were basically 

equivalent. This contrasts with the 

situation with carbofuran where a 

significant difference in AChE 

inhibition between the two is noted. 

With regard to the carbaryl children’s 

safety factor, the available brain and 

RBC dose-response data in PND11 pups 

include data from the lower end of the 

dose-response curves. ORD’s 

comparative AChE data with carbaryl 

show that at the lowest dose at or near 

20% inhibition in brain and RBC AChE 

was observed. Although not ideal, the 

carbaryl data provide information closer 

to the benchmark response of 10%, 

which allows for a reasonable 

estimation of the BMD10 and BMDL10. 

This is distinctly different from ORD’s 

data with carbofuran in PND11 and 

PND17 pups where 50% or greater RBC 

AChE inhibition was observed at the 

lowest dose. 

C. Comments Relating to EPA’s 

Exposure Assessment 

1. Food exposures. One group of 

commenters alleged that it is more 

appropriate to apply USDA PDP residue 

monitoring data from winter squash to 

pumpkins, rather than residue data from 

cantaloupes. 

The Agency agrees with the 

commenters. An appropriate residue 

assignment has been made in the latest 

dietary exposure assessment (Ref. 71). 

The results of this assessment are 

discussed below in Unit VIII.E.1.b. 

One group of commenters asserted 

that the measurable residues of 

carbofuran in milk obtained by the 

USDA PDP program should be 

‘‘adjusted to a lower level because a 

significant proportion of the milk 

residues in the PDP database are due to 

carbofuran use on alfalfa, which is no 

longer permitted under the carbofuran 

label.’’ The same commenters discussed 

the results of an exposure assessment 

that they apparently conducted, in 

which they have reduced the residues 

anticipated to be found in milk by some 

unspecified amount. 

Based on the commenters’ results, 

their adjustments to milk residues 

appear to have about a 50% reduction 

on the risk estimates for the food only 

results. While the commenters appeared 

to have made the adjustments to milk 

residues in most of their food-only 

assessments, as well as their food+water 

assessment, they did not: (1) Describe 

the amount by which residues were 

reduced; (2) present the DEEM-FCIDTM

input files detailing the residue inputs 

used in their assessment; or (3) provide 

to the Agency related data to support 

any such reduction factor—information 

that the Agency would need to accept 

such an adjustment. Because of the lack 

of any explanation or rationale, the 

Agency attempted to determine how the 

commenters made the ‘‘adjustment to 

residues’’ to account for the cancellation 

of use on alfalfa. As described in the 

Agency’s Response to Comments, EPA 

was not able to reproduce the 

commenters’ results, but did 

approximate their reported results after 

reducing milk residues by 77% (Ref. 

112). 

In actuality, it is difficult to ascertain 

how the recent cancellation of 

carbofuran use on alfalfa may affect 

future residues found on milk (from 

dairy feed items associated with corn, 

potatoes or sunflowers). This is 

especially true for milk since it is a 

blended commodity. That is, milk may 

be obtained from dairy cows from 

multiple farms (i.e., a dairy 

cooperative). The milk in any particular 

PDP sample may have come from dairy 

cows that might have had a diet that 

contained substantial amounts of alfalfa, 

or a diet that contained predominately 

corn, or from multiple farms using 

various combinations of feed that may 

or may not have been treated with 

carbofuran. In any case, the aggregate 

pesticide use statistics do not support 

the contention that most residues in 

milk are (or have been) due to 

carbofuran use on alfalfa—the USDA 

and Proprietary use data indicate that 

field corn has historically had a greater 

overall amount of total carbofuran use 

than alfalfa. Potatoes and sunflowers 

rank 3rd and 4th. 

The Agency included a summary of 

dietary burdens for dairy cattle in the 

dietary exposure analysis memorandum 

documenting the higher dietary burden 

involved with field corn feed stuffs 

(Refs. 70 and 71). These two diets 

represent a corn-based diet and an 

alfalfa-based diet, accounting for 

appropriate amounts of roughage and 

protein. Based on these dietary burdens, 

milk from dairy cows having a cornbased diet may have higher 

concentrations of carbofuran than milk 

from cows having an alfalfa-based diet 

(Refs. 70 and 71). 

The Agency notes that 3-hydroxy 

carbofuran was detected in about 7.5% 

of all PDP milk samples analyzed in 

2004 and 2005 (7.5% = 110 detects in 

1,485 samples). 

Considering all of the various factors 

involved with the PDP milk samples– 

e.g., uncertainty regarding mixture of 

feeds, pesticide use and corresponding 

residues—the Agency finds no basis for 

applying estimated reduction factors to 

actual measured concentrations of 

carbofuran residues found by the PDP 

program in milk based on the 

cancellation of alfalfa uses. In the 

absence of supporting data the Agency 

has no scientific basis for making the 

Federal Register / Vol. 74, No. 93 / Friday, May 15, 2009 / Rules and Regulations 23059 

commenters’ recommended changes to 

the dietary exposure assessment with 

regard to carbofuran residues in milk. 

Certainly, the commenters’ have failed 

to provide any scientific justification for 

their position. Moreover, since the 

Agency was unable to reproduce the 

commenters’ results, EPA could not 

make the suggested adjustment, even if 

they had provided details on the exact 

adjustment figure they wanted EPA to 

apply. 

One group of commenters raised 

concern that PCT estimates used by the 

Agency for bananas, potatoes, and milk 

are conservatively high. 

In response to those comments, the 

Agency reviewed its PCT estimates for 

the two crops and revised its PCT 

estimates for bananas from 78% to 25%. 

The Agency also developed a regional 

PCT estimate for potatoes of 5% based 

on projected limited use in the 

Northwest, and has applied these 

estimates in its revised dietary risk 

assessment (Ref. 71). The Agency also 

applied a 5% CT for milk, based on the 

PCT for potatoes, which is the feed stuff 

with the highest PCT. Further 

discussion regarding the Agency’s 

previous and revised PCT estimates can 

be found in References 71 and 122. As 

discussed below in Unit VIII.E.1.b., 

these adjustments had relatively modest 

effects on the dietary exposure 

assessment of those crops the registrant 

now seeks to maintain. 

Some commenters claimed that the 

Agency acted inconsistently in the way 

in which it conducted its ‘‘Eating 

Occasion Analyses’’ to account for the 

extent to which individuals recover 

from AChE inhibition between exposure 

events. The commenters claimed that 

the Agency analyzed aldicarb and 

carbofuran differently, and came to 

different conclusions concerning the 

effects of reversibility for these two 

compounds. 

The commenter’s assertion that the 

Agency came to different conclusions 

concerning the effects of reversibility for 

aldicarb and carbofuran is incorrect. 

EPA discusses the Eating Occasion 

Analysis it conducted for carbofuran in 

greater detail in Unit VIII.E.3. below and 

in its Response to Comments document 

(Ref. 112). 

The Agency concurs with the 

commenter that ‘‘there is no basis for 

treating aldicarb-treated potatoes 

differently from carbofuran treated 

potatoes.’’ The commenters’ assertions 

regarding what the Agency has or has 

not done with respect to the Eating 

Occasion Analysis (i.e., ‘‘reversibility’’) 

to some extent reflects confusion 

resulting from the several assessments 

the Agency has produced since 2006. 

Since that period, EPA has conducted 

several risk assessments, based on the 

tolerances FMC has variously indicated 

that it wished EPA to retain. EPA notes, 

for clarity, that for the proposed rule, 

EPA conducted a risk assessment of ‘‘all 

registered carbofuran uses’’ that did 

incorporate the concept of reversibility 

(i.e., ‘‘persisting dose’’). The proposed 

rule also contained an assessment of the 

subset of ‘‘6 domestic uses’’ that EPA 

believed the registrant primarily wished 

to retain, which did not incorporate this 

concept because these were not the only 

crops on which carbofuran was legally 

permitted to be used. However, now 

that the registrant has cancelled all but 

four domestic food uses, the Agency’s 

risk assessment of all the remaining uses 

accounts for reversibility, performed 

using the same DEEM-based Eating 

Occasion Analyses previously used for 

both carbofuran and aldicarb. 

In support of their contention, the 

commenters took an observation in the 

aldicarb IRED that exposures did not 

pass at the per capita 99.9th percentile, 

but were equal to the aPAD at a lower 

percentile—out of context, and used 

that statement to infer that the Agency 

regulates at this lower percentile. This 

is incorrect. The aldicarb registrant 

agreed to a number of risk mitigation 

measures that brought the aggregate 

risks to below the aPAD at the 99.9th 

per capita percentile. The registrant 

agreed to modify the aldicarb label to 

require a 500–foot well set back for 

aldicarb use on peanuts (GA soil type), 

since aggregate exposure at the per 

capita 99.9th percentile for infants 

continued to exceed the level of concern 

even after reversibility was accounted 

for in the Eating Occasions Analyses 

under the 300–foot well set back 

scenario. 

In summary, the Agency did not 

analyze aldicarb exposure and risk any 

differently than it analyzed carbofuran 

exposure and risk; the ‘‘persisting dose’’ 

concept was used in both assessments. 

Mathematically and conceptually, the 

calculations of the adjustment for 

reversibility are the same for both 

exposure assessments. Any differences 

in the conclusions EPA drew from the 

analyses are attributable purely to the 

factual differences between the two 

compounds. The reduction in 

‘‘persisting dose’’ is slightly greater for 

aldicarb due to its quicker recovery 

times (2–hour half-life for aldicarb), but 

in both cases, the Agency applied the 

same procedure to account for 

reversibility. The qualitative results for 

the food only and food + water 

scenarios presented in Unit VIII.E., 

produce similar qualitative results: in 

both cases, accounting for reversibility 

between eating occasions for food alone 

results in relatively modest reductions 

in the ‘‘persisting dose’’ at the per capita 

99.9th percentile, and a relatively large 

effect on exposure for water alone, or 

food+water, when water is the 

predominant contributor (73 FR 44864). 

These Eating Occasion Analyses support 

the Agency’s position that reversibility 

has a relatively greater effect for 

drinking water exposures than for food 

exposures. 

One group of commenters claimed 

that the Agency should have calculated 

the effects of carbofuran exposure based 

on the ‘‘persisting dose’’ over the 1,440 

person-minutes rather than on the 

person-days that are currently used by 

the Agency. 

In effect, the commenters suggest that 

the ‘‘persisting dose’’ should be 

calculated over the entire 1,440 minutes 

of each modeled person-day (1,440 

minutes/day = 24 hrs × 60 minutes/hr). 

EPA has rejected this approach for a 

number of reasons. While the 

commenters’ person-minute approach 

may be an attempt to capture multiple 

measures with one statistic, it does not 

properly capture the Agency’s concern 

regarding peak inhibition, and the 

commenters’ assertion that the Agency 

should use all person-minutes to 

calculate the per capita 99.9th 

percentile is misguided at best since: (1) 

It does not reflect a comparison to peak 

inhibition which is what the Agency 

believes is the most appropriate and 

relevant toxicological measure and (2) it 

produces risk estimates that are entirely 

dependent upon the time of day at 

which consumption occurs. Hence, this 

approach will obtain different values 

depending upon the reported time of 

consumption even if exposure occurs on 

a single eating occasion. The 

commenters suggested approach does 

not appear to capture peak inhibition, or 

other temporal aspects of cholinesterase 

inhibition (e.g., duration over which 

inhibtion exceeds 10%). EPA’s 

Response to Comments document 

provides a further explanation of this 

issue and details why the Agency’s 

approach is consistent with the 

identified endpoint (peak inhibition) 

and the corresponding point of 

departure (BMDL10 that serves as the 

basis for calculating a %aPAD (Ref. 

112). 

2. Drinking water exposures. As part 

of their comments on the proposed 

tolerance revocation, FMC submitted a 

revised label with use restrictions 

intended to address drinking water 

contamination. These measures include 

eliminating a number of crop uses, 

prohibiting use in a broad swath of areas 

with potentially vulnerable soils, and 

23060 Federal Register / Vol. 74, No. 93 / Friday, May 15, 2009 / Rules and Regulations 

requiring application buffers in other 

areas. In addition to these label 

modifications, the registrant, along with 

two other commenters, submitted 

comments summarizing the results of 

risk assessments they had previously 

submitted, and the results of new risk 

assessments they claim to have 

conducted. The commenters did not 

provide to the Agency either the new 

risk assessments they claim to have 

conducted, or the underlying support 

documents for those assessments, 

including the ‘‘national leaching 

assessment’’ or the ‘‘crop-specific 

evaluation of use patterns and the 

registrant’s proposed non-application 

buffers using the PRZM-EXAMS 

model.’’ FMC concludes that their label 

revisions have a pronounced effect on 

dietary risk and result in ‘‘exposure that 

even fit within the risk cup that EPA has 

proposed.’’ 

EPA has reviewed the September 

2008 proposed label modifications, and 

a synopsis of the Agency’s conclusions 

are summarized below in this Unit. 

More detailed analyses can be found in 

EPA’s Response to Comments (Ref. 111). 

In addition, EPA’s revised risk 

assessment, discussed below in Unit 

VIII.E., is based on this revised label. 

The label revisions leave two national 

food uses on the label, corn and 

sunflowers, and two regional food uses, 

potatoes in the northwest and pumpkins 

in the southeast. EPA has assessed the 

impact of all of these remaining uses, 

taking into consideration all label 

restrictions, and has concluded that 

remaining uses may result in 

concentrations in some locations that 

are similar in magnitude to those 

estimated previously (Refs. 57, 58, 60, 

and 62). 

a. Comments relating to EPA’s ground 

water analyses. One group of 

commenters alleged that ‘‘[g]roundwater 

sources are vulnerable to carbofuran 

leaching only under certain conditions, 

namely where permeable soils (e.g., 

areas with soils greater than 90% sand 

and less than 1% organic matter), acidic 

soil and water conditions, and shallow 

water tables predominate (e.g., where 

ground water is less than 30 feet).’’ The 

commenters claim that these conditions 

are rare in areas where carbofuran is 

used. They further assert that in ‘‘most 

states where carbofuran is used, less 

than 2% of the entire surface areas 

possess sandy soil texture’’ and that 

‘‘low pH conditions are not found in 

carbofuran use areas allowed under the 

registrant’s amended label’’. 

EPA disagrees that the commenter’s 

specific criteria define 100% of 

conditions where ground water sources 

are vulnerable to carbofuran leaching. 

No comprehensive analysis was 

provided evaluating how they reached 

this conclusion. Although these criteria 

appear on the revised carbofuran label 

restricting use, the spatial extent of the 

label restrictions is not provided. As 

discussed in greater detail in EPA’s 

Response to Comments, the information 

provided as part of FMC’s comments 

(primarily maps depicting areas 

identified as vulnerable) is not sufficient 

to allow the Agency to evaluate their 

claim (Ref. 111). For example, water 

table depth can vary with the time of the 

year, depending on such factors as the 

amount of rainfall that has occurred in 

the recent past, and how much 

irrigation has been removed from the 

aquifer. It is difficult to determine how 

the depth to the water table varies 

throughout fields, and the definition of 

a ‘‘shallow’’ water table is indeterminate 

(e.g., less than 30 feet). Furthermore, the 

vulnerability associated with depth 

varies with location; for example, 

deeper aquifers may be more vulnerable 

in areas with greater precipitation and 

rapid recharge. 

While the assertion regarding percent 

sand is in part true, it is misleading. 

While many states have only small areas 

of sandy soils, some states have quite 

extensive areas. For example, according 

to FMC’s own assessment of high use 

states (Ref. 8), Texas had 4.2% sand, 

Michigan had 21.3% and Nebraska had 

26.3%. In addition, this statement 

implies that soils that are sandy 

textured define the universe of soil 

textures that are vulnerable to leaching. 

It is possible that more fine-textured 

soils, for example sandy loams or silt 

loams, could also be sufficiently 

permeable to result in carbofuran 

leaching as it has not been established 

how much of a reduction in leaching 

might occur as texture becomes finer. 

Furthermore, finer textured soils tend to 

have more cracks and root channels and 

thus are more prone to preferential flow. 

EPA also disagrees that the 

commenters have provided sufficient 

information to support their general 

claim that only high pH conditions (pH 

above 7) exist in all the areas in which 

carbofuran could be used under FMC’s 

September 2008 revised label. There is 

considerable spatial variability in pH 

conditions for both the subsurface and 

surface environments. The pH has a 

large effect on the persistence of 

carbofuran as, for more acidic 

conditions, the hydrolysis half-life 

increases from 28 days at pH 7 to years 

or more at pHs less than 6. Further, the 

results of EPA’s corn ground water 

simulations (bounded by the high and 

low pH values of the aquifer system 

underlying the scenario location) 

showed that a relatively small (0.5) 

decrease in pH from 7 to 6.5 resulted in 

an increase by 4 orders of magnitude in 

the 1–in–10–year peak concentration of 

carbofuran. EPA has presented its 

assessment of the newly submitted label 

in its Response to Comments document 

and these issues are addressed in more 

detail there (Ref. 111). 

Accordingly, the criteria the 

commenters suggest are not sufficient to 

prohibit use in all areas that could 

reasonably be expected to be vulnerable 

to ground water contamination from 

carbofuran use. EPA’s assessment 

identifies an example of one area where 

carbofuran use would still be permitted 

on the proposed labels; an additional 

scenario for the updated ground water 

modeling provided in Reference 111 

was based on this location in the southcentral region of Wisconsin. This 

scenario is in no way unique; EPA 

expects that other similar sites exist in 

other locations where carbofuran could 

still be used across the United States. 

One group of commenters claimed 

that the most recent label modifications 

‘‘has ensured that carbofuran use will 

not occur in these vulnerable areas by 

removing them from the label.’’ They 

support this by reference to a map of the 

carbofuran use areas in 2005, that 

identifies counties with DRASTIC 

scores as high as that of the location of 

the prospective ground water study 

(PGW study) conducted by FMC in 

Maryland, defining that combination as 

vulnerable. 

DRASTIC is a USEPA model that was 

developed as a screening tool to identify 

ground water resources that are 

‘‘generally vulnerable to the release of 

contaminants at the surface * * *.’’ 

(Ref. 6). The commenters indicate that 

the map provided in their comments 

shows counties ‘‘identified as 

vulnerable,’’ based on DRASTIC scores 

that exceed 185, and 2005 carbofuran 

usage, although the map’s level of 

resolution is insufficient to provide 

more than a general impression of the 

location of ground water classified as 

vulnerable. In FMC’s September 2008 

label revisions, FMC expanded the areas 

where carbofuran cannot be applied, 

apparently because of ground water 

concerns. The specific criteria that FMC 

used to determine these further 

locations were not provided to the 

Agency. Nevertheless, EPA does agree 

that ground water in the Atlantic 

Coastal Plain is vulnerable, and that 

FMC has restricted use in those areas. 

However, EPA does not agree with the 

premise that only locations with 

DRASTIC scores as high as that of the 

location of the Maryland PGW study are 

those that require mitigation. DRASTIC 

Federal Register / Vol. 74, No. 93 / Friday, May 15, 2009 / Rules and Regulations 23061 

scores as high as those identified by the 

commenters would indicate that the site 

is located in a generally sensitive or 

vulnerable area. The Agency agrees that 

the DRASTIC tool can be used to 

generally identify areas that may be 

vulnerable to pesticide contamination. 

However, DRASTIC is somewhat dated 

(1987), and better methods currently 

exist that can take advantage of 

geospatial data at a more refined level 

than the county level used here. FMC 

apparently agrees with this criticism 

since they subsequently developed the 

‘‘National Leaching Assessment’’ as part 

of their comments on the proposed 

tolerance revocation, to replace their 

earlier DRASTIC assessment. 

Importantly, EPA believes that FMC 

has used an inappropriate criterion for 

determining whether a site is 

vulnerable–that it has the same or 

greater vulnerability (based on a 

DRASTIC score greater than 185) as that 

of the Maryland PGW study site. The 

maximum concentration at the 

Maryland PGW site, adjusted to 

simulate an application rate of 1 lb/acre, 

was 21 μg/L this exceeds acceptable 

exposure thresholds by factors of 10 to 

20 (Ref. 71). Thus, sites that are less 

vulnerable (e.g., deeper aquifer, high 

soil sand content, higher organic 

matter), with lower DRASTIC scores, 

could still be prone to have carbofuran 

concentrations exceeding acceptable 

exposures. 

Further, the commenters provide no 

detail on the specific data used to 

generate their DRASTIC estimates. In 

footnote 39 of their comments they 

indicate that ‘‘Data to support these 

[DRASTIC] inputs were primarily 

collected from state-wide, statistically 

designed studies conducted by state and 

federal agencies (primarily the National 

Water Quality Assessment Program 

(‘‘NAWQA’’), but also state surveys and 

other state and federal agricultural data, 

where NAWQA data were not 

available.’’) Given EPA’s general 

reservations about their approach, EPA 

cannot conclude that the commenters’ 

assessment is scientifically supportable 

or useful, without information on the 

sources of the data, the geographic scale 

of the data, or how that input data was 

prepared for the analysis. 

One group of commenters assert that 

their ‘‘assessments revealed that the 

soils and water pHs are generally higher 

in those states in the Midwest and 

Northwest where most carbofuran is 

used, providing further confirmation 

that conditions that favor carbofuran 

leaching in those areas do not exist.’’ 

Since the commenters have not 

provided all of the assessments they 

appear to have conducted, EPA is 

unable to confirm whether their 

assessments do in fact support their 

contention. However, as a general 

matter, none of the previously 

submitted assessments provided a 

comprehensive analysis of the 

distribution of soil and water pHs for 

the Midwest, Northwest or any other 

region of the country where carbofuran 

use would be permitted on the 

September 2008 label, nor have the 

commenters provided such an analysis 

with their most recent comments. 

Further, the available scientific 

information does not support their 

contention. 

EPA examined readily available data 

with respect to ground water and soil 

pH in order to evaluate the spatial 

variability of pH. Data from the United 

States Geological Survey (USGS) and 

other readily available sources do not 

necessarily encompass the entire range 

of ground water pH values present 

within a state. This is especially true for 

shallow ground water systems, where 

local conditions can greatly affect the 

quality and characteristics of the water. 

Also, pH in a water body can be higher 

or lower than the tabulated average 

values. In addition, average ground 

water pH values for a given area do not 

truly characterize the area’s temporal 

and especially spatial heterogeneity. 

This can be seen by comparing 

differences in pH values between 

counties within a state, and noting that 

even within a county individual wells 

will consistently yield ground water 

with either above- or below-average pH 

values for that county. The ground 

water simulations in Reference 111 

Appendix I reflect variability in pH by 

modeling carbofuran leaching in four 

different soil and subsurface pH 

conditions (pH 5.25, 6.5, 7.0, and 8.7), 

representing the range in the aquifer 

system in that area. This range also 

approximates the pH range of natural 

waters in general. The results of the 

ground water simulations for corn use 

showed that a relatively small (0.5) 

decrease in pH from 7 to 6.5 resulted in 

an increase in the 1–in–10–year peak 

concentrations of carbofuran in ground 

water of 4 orders of magnitude. 

FMC summarized the results of their 

‘‘National Leaching Assessment’’ which 

used PRZM and ‘‘databases specifically 

created to provide access to all 

necessary inputs for a national scale 

PRZM modeling.’’ They claim that after 

accounting for the use prohibitions on 

their September 2008 label, the 

maximum 1–in–10–year peak 

concentrations in all potential 

carbofuran use areas is 1.2–1.3 ppb, 

while expected concentrations in most 

areas covered by this assessment are 

below 1.0 ppb. They claim to have 

modeled a single application to corn at 

1 lb/acre—which is the application rate 

on the September 2008 labels applicable 

to the rescue treatment on corn—and 

simulated ground water recharge and 

lateral flow. They assert that their 

estimate that 1–in–10–year peak 

carbofuran concentrations will not 

exceed ‘‘~1 ppb’’ is consistent with 

EPA’s NMC CRA. 

Neither the ‘‘National Leaching 

Assessment,’’ nor the ‘‘National 

Pesticide Assessment Tool’’ upon which 

the assessment appears to have been 

based, were submitted to EPA for 

review, therefore EPA cannot comment 

further on the methodology for reaching 

these conclusions, or indeed, whether 

the assessment actually supports their 

claims. Based on the information 

provided, EPA cannot confirm or negate 

the assertion that there is no overlap 

between use and all potentially 

vulnerable ground water, as the 

information provided does not enable 

the Agency to evaluate this claim. 

EPA’s assessment of the impacts of 

FMC’s September 2008 label differs 

significantly from the commenters’ 

summary conclusions; these differences 

are addressed more completely in EPA’s 

Response to Comments document, and 

are based on application by FMC of 

unsupported factors (Ref. 111). 

Part of EPA’s assessment of ground 

water exposure for the proposed 

tolerance revocation was based on 

simulation modeling using PRZM for 

corn grown on the Delmarva Peninsula 

in Maryland receiving an annual 

application of 1.0 lb/acre-1. The 1–in– 

10–year peak estimated drinking water 

concentration (EDWC) was 30.8 μg/L. 

FMC’s assessment of the same label 

resulted in their estimate of 

concentrations up to 22.7 μg/L. The 

September 2008 labels prohibit 

application at sites in the Atlantic 

Coastal Plain with similar vulnerability 

to the Delmarva site. However, EPA 

believes that the study and the resulting 

scenario derived from this study remain 

relevant for other areas with similar 

conditions, where use remains. Based 

on the September 2008 labels, EPA has 

concluded that there are locations in the 

United States where carbofuran could 

still be applied, and in which ground 

water concentrations are estimated to be 

high enough to cause concern. For 

example, simulations of corn grown the 

central sands region of Wisconsin had 

an estimated 1–in–10–year peak 

concentration of 16 μg/L at pH 6.5 and 

284 μg/L at pH 5.25, both of which are 

in the pH range for aquifers in this area 

(Ref. 115). For higher pH’s in that area, 

23062 Federal Register / Vol. 74, No. 93 / Friday, May 15, 2009 / Rules and Regulations 

estimated carbofuran concentrations 

were generally close to zero. 

As noted the ‘‘National Leaching 

Assessment’’ has not been provided to 

EPA for review, and consequently, the 

Agency cannot determine model input 

parameters or check model algorithms. 

In many cases, model inputs cannot be 

directly inferred from values in the 

available weather and soil databases 

(e.g., NOAA SAMSON weather datasets, 

NRCS Soil Datamart) (Refs. 75 and 93). 

Methods used by FMC to select or 

calculate values for model input from 

these databases were not described. The 

only model output provided was in map 

format. While maps are useful for 

interpreting results, maps alone are 

insufficient for a thorough evaluation of 

the assessment, in part because of their 

spatial resolution. Further, the maps 

provided by FMC do not represent all 

carbofuran use patterns. For example, 

Figure IV-2 on page 42 of FMC’s 

comments does not address the granular 

use patterns and proposed label 

prohibitions. 

FMC contends that their results are 

consistent with the NMC CRA, but this 

is untrue. The NMC CRA examined 

carbofuran at two sites, northeast 

Florida and the Delmarva Peninsula. In 

Florida, concentrations were found to be 

below levels of concern because of high 

pH, but in Delmarva, both in corn and 

in melon scenarios EPA estimated that 

90% of daily concentrations could be as 

high as 20.5 and 25.6 μg/L, respectively. 

These values are greater than the 1 μg/ 

L that FMC claims is the maximum 

expected 1–in–10–year peak 

concentration. The claim that EPA’s 

modeling fails to address use patterns 

‘‘changing naturally over time’’ is 

ambiguous, and EPA cannot evaluate 

any inputs included by FMC to address 

this in their own modeling, if indeed 

they did so. Because of these 

deficiencies, EPA is unable to verify or 

evaluate the results of FMC’s analysis 

and can reach no conclusion on its 

validity or utility. 

FMC asserts that ‘‘EPA’s approach is 

not consistent with the Agency’s 

treatment of other carbamates. For 

example, in the aldicarb assessment, 

EPA used monitoring data to develop 

eight different region-specific scenarios, 

‘based on broad similarity in compound 

usage, crop type or soil conditions’, and 

taking a ‘single maximum sample result 

detected within [each] region during the 

last 5 to 10 years to represent ground 

water concentrations within that entire 

region.’ The Agency estimated drinking 

water concentrations for risk assessment 

purposes by accounting for the effect of 

ground water mitigation measures (i.e., 

setbacks).’’ In footnote 53 of their 

comments, FMC apparently quotes from 

the aldicarb IRED ‘‘[H]igher residue 

values that may have resulted from 

historical use if aldicarb in vulnerable 

areas were excluded.’’ 

EPA disagrees with FMC’s assertion 

that the carbofuran drinking water 

exposure assessment was not consistent 

with other carbamates, particularly 

aldicarb. In both cases, Tier 2 modeling, 

using the PRZM and EXAMS models, 

was used to characterize surface water 

exposure and in both cases available 

monitoring data were summarized. For 

carbofuran, ground water exposure was 

characterized using a combination of 

targeted and non-targeted monitoring 

data, a PGW study, and Tier 2 modeling, 

through the course of two RED chapters 

and several post-RED drinking water 

exposure assessments. For aldicarb, two 

different ground water exposure 

assessments were conducted for the 

initial and the final IRED chapters. In 

the comment quoted above, FMC has 

described the process used for the 

aldicarb risk assessment supporting the 

initial aldicarb IRED dated May 12, 

2006. 

The second aldicarb ground water 

exposure assessment supported the 

revised dietary exposure assessment in 

February 2007 (Ref. 48). This is a more 

refined assessment, which relies on 

simulation modeling for ground water 

using PRZM in places vulnerable to 

ground water leaching where aldicarb 

was used. While FMC has correctly 

quoted ‘‘[H]igher residue values that 

may have resulted from historical use of 

aldicarb in vulnerable areas were 

excluded,’’ the implication that this is 

different from EPA’s evaluation of 

carbofuran is not correct. For example, 

the carbofuran IRED describes 

monitoring in New York where 

carbofuran use was canceled in 1984, 

and where detections of carbofuran 

continue. The carbofuran IRED did not 

use the high concentrations of 

carbofuran measured in drinking water 

wells in that study, up to 178 ppb, 

which resulted from historical use of 

carbofuran. In both cases, historical 

monitoring data were described (Refs. 

10 and 47), but endpoints used for 

ground water exposure assessment were 

only based on monitoring relevant to 

use patterns current at the time of the 

assessment. For aldicarb, the Agency 

utilized retrospective monitoring data 

collected after 1990. For carbofuran, the 

most relevant monitoring data set was 

the Maryland PGW study. Because of 

the design of that study, results could be 

adjusted to represent current use 

patterns. 

The aldicarb assessment took into 

account the impact of well setbacks on 

estimated concentrations in ground 

water modeling conducted in 2007. The 

carbofuran modeling in EPA’s most 

recent assessment also took into account 

the impact of well setbacks on estimated 

concentrations in ground water. 

Previous carbofuran assessments did not 

assess the impact of well setbacks, as 

setbacks were not included on a 

proposed carbofuran label until 

September 2008. 

In summary, both assessments for 

aldicarb and carbofuran used a 

combination of monitoring data and 

simulation modeling for the drinking 

water exposure assessments, simulating 

the impact of mitigation measures on 

the labels. 

b. Comments relating to EPA’s surface 

water assessment. One group of 

commenters summarized conclusions 

based on a previously submitted surface 

water assessment based in Indiana. 

Specifically, they claim that: (1) EPA’s 

standard index reservoir scenario 

overestimates surface water 

concentrations compared with 

‘‘expected concentrations in actual 

Indiana community water system (CWS) 

where carbofuran is used,’’ (2) ‘‘Indiana 

CWSs bracket the Index Reservoir 

scenario (i.e., some reservoirs are more 

sensitive and others are less); however, 

in each instance the expected 

concentrations in the Indiana CWSs 

were significantly less than those 

estimated by the Index Reservoir 

scenario.’’ 

EPA has reviewed the Indiana surface 

water assessment submitted by the 

registrant previously, and has provided 

comments on that submission (Ref. 59). 

FMC’s first major conclusion from this 

study is that ‘‘EPA’s standard index 

reservoir scenario overestimates surface 

water concentrations compared with 

expected concentrations in actual 

Indiana CWS where carbofuran is 

used.’’ The Index Reservoir is designed 

to be used as a screen, and as such, 

represents watersheds more vulnerable 

than most of those which support a 

drinking water facility. It is thus 

protective of most drinking water on a 

national basis. That, however, does not 

mean that EPA believes this scenario 

overestimates concentrations for all 

drinking water reservoirs. While EPA 

agrees that it is an appropriate 

refinement to simulate local and 

regional watersheds, and has in fact 

done so (Refs. 58, 60, 61, 62, and 111), 

EPA does not believe that FMC’s 

assessment refutes the concern for 

carbofuran occurrence in Indiana 

surface water source drinking water. 

Even accepting the Indiana surface 

water assessment at face value (which 

we do not), FMC estimated 1–in–10– 

Federal Register / Vol. 74, No. 93 / Friday, May 15, 2009 / Rules and Regulations 23063 

year peak concentrations at some 

facilities as high as 6.88 μg/L, and these 

concentrations substantially exceed the 

concentration they now claim represent 

reasonable estimates. 

FMC’s second major conclusion has 

two parts: (1) That the vulnerability of 

the Indiana CWSs ‘‘bracket’’ the Index 

Reservoir, and (2) that the 

concentrations they estimated for these 

locations are significantly less than EPA 

estimates. Regarding the vulnerability of 

the CWS, FMC’s assessment describes 

their approach for modifying the 

parameters of the Index Reservoir 

scenario to represent 15 reservoir-based 

watersheds in Indiana cropped in corn. 

FMC indicates they have included data 

that, based on our review of these 

submissions, are not available at the 

appropriate scale to determine all sitespecific parameters. FMC modified 

some of the parameters based on 

available data to represent more 

localized conditions that are more or 

less vulnerable than for the Index 

Reservoir. From FMC’s description, 

their approach is similar to the methods 

that EPA uses to develop new scenarios, 

in that soil and weather data are varied 

in order to represent different locations. 

However, for other parameters, EPA 

believes FMC’s modifications are 

inconsistent with fundamental 

assumptions upon which the modeling 

is based. In submissions made to the 

Agency, FMC has described that they 

have made modifications to scenarios to 

reflect local conditions of each CWS in 

Indiana by modifying the soil, and 

weather data and altering the ratio of 

watershed drainage area to the reservoir 

capacity (Ref. 120). EPA agrees that soils 

and weather data can be modified to 

reflect conditions at local watersheds. 

However, other modifications FMC 

made cannot reasonably be justified for 

all scales without contradicting the 

assumptions upon which the modeling 

relies (uniformity of soils, equal and 

simultaneous movement of runoff to the 

reservoir, and uniform weather across 

the watershed). 

FMC also calculated their own PCAs 

for this assessment. The PCA is the 

fraction of the drinking water watershed 

that is used to grow a particular crop. 

EPA uses the maximum PCA calculated 

for any HUC8 (8-digit hydrologic unit 

code) watershed in exposure estimates. 

HUC8s are cataloging units for a 

watershed developed by the USGS and 

are used as surrogates for drinking water 

watersheds. The process by which PCAs 

were developed and how they are used 

by the Agency has been vetted with the 

FIFRA SAP (Refs. 37 and 38). The 

Agency has developed PCAs for four 

major crops, corn, soybeans, wheat, and 

cotton, and uses a default PCA based on 

all agricultural land for characterizing 

other crops. The Agency has also 

calculated regional default PCAs for use 

in charactering regional differences in 

drinking water exposure. EPA limited 

further development of PCAs for 

additional crops, as a result of FIFRA 

SAP peer review comments, which 

concluded that data were not available 

at the appropriate scale to do so. In their 

assessment, FMC estimated PCAs for 

specific watersheds in Indiana. FMC did 

not provide sufficient detail in their 

descriptions of how they calculated 

PCAs to enable EPA to assess their 

validity. 

Regarding FMC’s statement that the 

concentrations they estimated for these 

locations in Indiana are significantly 

less than EPA estimates, EPA has 

determined that FMC has included an 

adjustment factor to account for the 

percent of a crop that is treated with 

carbofuran. As discussed in more detail 

below, although EPA does evaluate such 

factors in conducting ‘‘sensitivity 

analyses’’ to understand the impact that 

various PCT assumptions may have, 

EPA does not believe that it is 

appropriate to base its aggregate risk 

estimates on PCT within watersheds. 

This is because data and/or methods are 

not available that would allow EPA to 

develop PCT at the watershed scale with 

the necessary level of confidence to 

allow EPA to make a safety finding. The 

PCT factors that FMC generated would 

lead to significantly lower 

concentrations than those estimated by 

EPA. 

One group of commenters reiterated 

conclusions from a previously 

submitted surface water assessment, the 

‘‘Nationwide CWS Assessment.’’ Based 

on this assessment, the commenters 

allege that: ‘‘use intensity in the 

majority (~ 75%) of carbofuran use 

areas is less than 2.1 lbs a.i./sq. mi,’’ and 

that based on this use intensity, the 

commenters’ modeling results in surface 

water concentrations ‘‘that are not above 

the applicable level of concern.’’ The 

commenters also claim that, because 

areas with historical use intensities 

greater than 2.1 lbs. a.i./sq. mi may be 

more sensitive to carbofuran, the 

registrant proposed no-application 

buffers which effectively mitigate the 

risks in these areas. 

EPA has reviewed FMC’s 

‘‘Nationwide CWS Assessment’’ 

previously and has provided a response 

to the submission (Ref. 59). It is worth 

noting that FMC only assessed use 

intensity for reservoir-based systems 

and excluded use intensity for all 

stream- or river-based systems from 

their assessment. 

Similar to the Indiana CWS study 

discussed in the previous response, this 

study relied on county-level usage 

estimates to estimate use intensity. This 

value was subsequently used in 

modeling to draw their second major 

conclusion, which FMC states formed 

the basis for their decisions to propose 

no-application buffers to mitigate risks 

in those areas, their third conclusion. To 

respond to this comment, therefore, it is 

important to understand how FMC 

arrived at these use intensities. Their 

methods have been poorly described in 

statements, but EPA was able to piece 

together a general sense of the methods 

from the various reports FMC provided 

to EPA. 

To summarize, for FMC’s National 

CWS Assessment, the registrant relied 

on sales data to generate its use 

intensity estimates, but these data were 

not provided to EPA. The method FMC 

used to generate the county-level use 

estimates from the sales data is not 

described. The actual county level use 

estimates used in the use intensity 

calculations were not provided. There is 

a limited description indicating only 

that the county level use estimates were 

apportioned to different crops, but the 

method FMC used to do this was not 

provided. FMC used an objective 

method to group the county-level use 

estimates into 5 classes, but the method 

is only briefly described. Thus, because 

EPA cannot determine how use 

intensity was estimated, the Agency 

cannot determine if the conclusions 

made in the National CWS Assessment 

are justified by the underlying data. 

Since carbofuran sales data used for 

FMC’s assessment were not provided in 

the document submitted to EPA, or with 

the comments to the SAP (Ref. 33), or 

with the comments on the proposed 

tolerance revocation, it was not possible 

for EPA to determine if FMC’s claim 

that 75% of the use areas have a 

carbofuran use intensity of less than 2.1 

lbs a.i./sq. mi., is accurate. Use intensity 

data in maps provided in their 

comments appear to indicate that 

carbofuran use varies year by year, 

however, it is also not clear for which 

year or years FMC is making this 

conclusion. 

EPA agrees that using lower rates of 

carbofuran will result in lower 

exposure. But EPA does not agree that 

it has been demonstrated that a use 

intensity below 2.1 lbs a.i./sq. mile will 

assure that surface water concentrations 

will be below the applicable level of 

concern. The National CWS Assessment 

does not justify such a finding, nor has 

any other assessment that has been 

submitted to date. The Agency modeled 

use rates for carbofuran on corn based 

23064 Federal Register / Vol. 74, No. 93 / Friday, May 15, 2009 / Rules and Regulations 

on the label proposed in September 

2008 and results are described in Unit 

VIII. and in Reference 111. 

EPA is equally unable to confirm the 

claims that the no-application buffers on 

the September 2008 labels will 

adequately mitigate the risks ‘‘in areas 

with historical use intensities greater 

than 2.1 lbs a.i./sq. mi.’’ On the 

September 2008 labels, FMC included 

buffers of 300 feet on water bodies in 

Kansas, and 66 feet around water bodies 

in other places, but EPA cannot evaluate 

how these buffers relate to areas where 

carbofuran use intensities exceeded a 

specific value, for all of the reasons 

stated above. EPA did, however, model 

the effects from the buffers proposed on 

the September 2008 labels and found 

that these buffers reduce exposure by 

5.1% (33.5 to 31.8 μg/L) for corn in 

Kansas with a 300 foot spray drift buffer 

and 4.7% (29.9 to 28.5 μg/L) for corn in 

Texas with a 66 foot spray drift buffer. 

These results are described in more 

detail in Reference 111, Appendix I. 

One group of commenters claimed 

that EPA’s modeling assumptions are 

‘‘implausible for most surface water 

systems across the country.’’ They 

specifically criticize the following 

assumptions: (i) ‘‘a lack of inflow to or 

meaningful outflow from the CWS; (ii) 

instantaneous and homogeneous mixing 

throughout the entire CWS; (iii) all 

receiving water directly abut the treated 

field and there are no buffers; and (iv) 

a lack of variation in pH across water 

bodies in the United States.’’ 

All of the commenters’ claims are 

incorrect. Their first contention, that 

EPA assumes that there is a lack of 

inflow to or meaningful outflow from 

the CWS, is incorrect. EPA’s modeling 

assumes the inflow to the reservoir is 

equivalent to the mean annual runoff 

into the reservoir. Since the EXAMS 

model is a steady state model, outflow 

will equal inflow to the reservoir. 

Assuming that outflow equals inflow 

and that mixing occurs instantaneously 

throughout the reservoir are reasonable 

assumptions; the commenters made the 

same assumptions in their modeling. 

Secondly, the commenters believe the 

assumption that there is instantaneous 

and homogeneous mixing throughout 

the entire reservoir supporting the 

community water supply is implausible. 

This is a reasonable assumption for 

small, un-stratified reservoirs like the 

Index Reservoir. Also, the commenters 

made the same modeling assumption in 

their modeling in the Indiana CWS 

study, and apparently in the modeling 

done in support of their submitted 

comments on the proposed tolerance 

revocation. Thirdly, the commenters 

believe it is implausible to assume that 

all receiving water directly abuts the 

treated field, and there are no buffers. 

This claim is also not accurate. Until the 

September 2008 label, carbofuran labels 

did not require buffers, thus, EPA did 

not have reason to assess the impact of 

buffers. EPA’s assessment of FMC’s 

September 2008 labels considered the 

impact of the buffers (see Ref. 111, 

Appendix I). Finally, FMC contends that 

EPA’s assumption of pH was 

implausible. EPA disagrees; EPA’s 

assessment was based on the middle of 

the range of pH occurring in natural 

waters. In addition, as a sensitivity 

analysis, EPA assessed exposure 

assuming a high pH, representative of a 

high end pH of waters in Western 

Kansas, as well as the high end of 

natural waters in general. 

One group of commenters summarizes 

conclusions from a previously 

submitted assessment based on the 

Watershed Regression for Pesticides 

(WARP) (Ref. 117) model. They claim, 

based on this assessment that ‘‘[t]he 

maximum 1–in–10 day estimated 

concentrations of carbofuran at the 90th 

percentile level in Illinois, Indiana. 

Iowa, and Nebraska (where a majority of 

current carbofuran is located) will be 

less than or equal to 0.3687 ppb.’’ They 

claim that WARP’s 1–in–10–day 

estimates are a reasonable surrogate for 

the 1–in–10–year peak concentrations 

typically relied on by the Agency 

because ‘‘the extreme nature of a 1–in– 

10–year event (i.e., severe rain) would 

result in dilution effects that cancel out 

any increased loading.’’ They also allege 

that the differences in surface water 

concentrations estimates in their 

assessment and EPA’s modeling are due 

to their use of ‘‘actual county-level 

usage data.’’ 

EPA has reviewed the WARP 

assessment previously and has provided 

comments on the submission (Refs. 59 

and 117). The WARP model has not 

been fully evaluated for quantitative use 

in exposure estimation by the Agency, 

although it has been preliminarily 

reviewed by the SAP (Ref. 39). EPA 

used WARP to select monitoring sites 

for the herbicide atrazine, based on 

predicted vulnerability of watersheds to 

atrazine runoff within the corn/sorghum 

growing regions. EPA presented its 

approach to the FIFRA SAP in 

December 2007. The SAP report 

concluded that ‘‘WARP appears to be a 

logical approach to identify the areas of 

high vulnerability to atrazine exposure,’’ 

endorsing EPA’s use of this tool only for 

atrazine, and for the limited purpose of 

designing a monitoring program. The 

SAP noted that the most important 

explanatory value with WARP was use 

intensity, and underscored the 

importance of having the most accurate 

data for this parameter. 

WARP is a regression model 

developed by the USGS to estimate 

concentrations of the pesticide atrazine 

in rivers and streams. As a regression 

model, it is based on monitoring data, 

in this case from 112 USGS National 

Ambient Water Quality Assessment 

(NAWQA) monitoring locations. WARP 

does not directly estimate daily 

concentrations, but predicts the percent 

of the time in a randomly selected year 

that concentrations of the pesticide are 

less than a specified value, with a 

specified level of confidence. USGS 

attempted to develop an approach to 

estimate annual time series for other 

pesticides, and concluded that ‘‘further 

data collection and model development 

may be necessary to determine whether 

the model should be used for areas for 

which fewer historical data are available 

* * * Because of the relative simplicity 

of the time-series model and because of 

the inherent noise and unpredictability 

of pesticide concentrations, many 

limitations of the model need to be 

considered before the model can be 

used to assess long-term pesticide 

exposure risks.’’ (Ref. 126). 

The commenter’s conclusion that the 

‘‘maximum 1–in–10–day estimated 

concentrations of carbofuran at the 90th 

percentile level in Illinois, Indiana, 

Iowa, and Nebraska [* * *] will be less 

than or equal to 0.3687 ppb,’’ is 

erroneous. WARP does not provide 

direct estimates of return frequency, i.e., 

1–in–10 days, but rather percentiles of 

the expected distribution of 

measurements. This may be similar but 

not identical to the return frequency 

expressed as a percentile, depending on 

the number of measurements used to 

support the regression. EPA lacked the 

information necessary to determine 

whether FMC’s contractor calibrated the 

model correctly. However, taking the 

conclusion at face value, the value FMC 

predicted using WARP, 0.3687 ppb, 

appears to represent the maximum of 

the estimated values of the annual 90th 

percentile among all the sites evaluated. 

Such a site would be expected to have 

higher concentrations than 0.3687 ppb 

about 37 days a year (10% of the year). 

Generally, the 90% prediction intervals 

tend to be about plus or minus an order 

of magnitude. Thus, roughly 5% of such 

sites could have about 37 days a year 

greater than about 3.7 ppb. 

The Agency also disagrees that the 

differences between FMC and EPA 

estimates are only due to FMC’s use of 

county-level usage data. Most 

importantly, the Agency does not 

concur that 1–in–10–day estimates are a 

reasonable surrogate the for the 1–in– 

Federal Register / Vol. 74, No. 93 / Friday, May 15, 2009 / Rules and Regulations 23065 

10–year peak concentrations estimates 

used routinely by EPA. 1–in–10–day 

concentrations are not the measurement 

endpoint EPA uses for human health 

risk assessment and are not appropriate 

for estimating drinking water exposure. 

The Agency uses 1–in–10–year peak 

concentrations for screening level 

assessments, and the full time series 

(typically 30 years) of daily 

concentration values for refined 

assessments. For example, EPA’s 

estimate of the 1–in–10–year peak 

concentration from the simulation of 

corn in Kansas with a 300 ft buffer was 

31.8 μg/L. EPA’s estimate of the 1–in– 

10–day concentration from the same 

simulation was 4.5 μg/L. The 

measurement endpoint used by EPA, 

which has been subject to peer review 

by the FIFRA SAP, is the 1–in–10–year, 

peak concentration. A concentration 

that occurs 1–in–10 days occurs 350 

times as often as a 1–in–10–year event. 

Assuming this statistic instead of the 

one EPA used would result in a 

significantly lower estimates of 

pesticide water concentration and 

human exposure. Such an approach 

would be inconsistent with the SAP’s 

advice and EPA’s typical practice, as 

well as with EPA’s statutory 

requirement to protect human health. 

EPA disagrees with FMC’s claim that 

‘‘the extreme nature of a 1–in–10–year 

event would result in dilution effects 

that cancel out any increased loading.’’ 

The Index Reservoir scenario has been 

validated against monitoring collected 

at the site it was designed to represent, 

Shipman City Lake in Illinois (Ref. 56). 

This assessment showed that the 1–in– 

10–year event EPA modeled was similar 

in magnitude to the peak value of the 

pesticide concentrations shown in 5 

years of monitoring data collected at 

that site. The 1–in–10–year peak 

concentration calculated for that 

pesticide (not carbofuran), using the 

Index Reservoir was 33 μg/L, while the 

peak value from 5 years of monitoring 

was 34 μg/L. 

EPA cannot comment on the use 

intensities assumed for FMC’s 

assessment. The source of county level 

use data was not described. Based on 

the comments submitted to the SAP by 

FMC (Ref. 33) the source is likely to be 

sales data at the distributor level. 

However, the method chosen to estimate 

county level use estimates from the 

sales data was not provided. The county 

level estimates used in the assessment 

for 2002 to 2004 for Illinois were 

provided in a table. These estimates for 

each county were averaged over the 3 

years for input to the model. A summary 

description of how watershed-scale use 

estimated from county level use data 

was provided, but because the sales data 

and method that was used to generate 

county level estimates were not 

available, this validity of this 

assessment cannot be evaluated. 

Several commenters criticize the 

Agency for the assumption that 100% of 

the cropped area in a watershed is 

treated. These commenters claim that 

actual carbofuran sales data on a county 

basis confirm that the actual carbofuran 

PCT is less that 5%, with most PCTs 

less than 1%. The commenters claim 

that these county level sales data either 

were provided to EPA as part of reports 

prepared by their consultants, or would 

be provided to EPA. They further claim 

that ‘‘how these data were analyzed, 

interpreted, and applied’’ was provided 

to EPA in a report on best management 

practices. 

While the Agency typically uses PCT 

in developing estimates of pesticide 

residues in food, this is entirely 

different than developing estimates of 

the percent of a watershed that is treated 

for purposes of estimating drinking 

water exposures. Food is generally 

randomly distributed across the nation 

without regard to where it is grown. 

This tends to even out any PCT 

variations that may arise on local levels. 

By contrast, the source of water 

consumption (and consequently 

exposure) is localized, either in a 

private well or a community water 

system. The PCT in any watershed will 

therefore directly impact the residues to 

which people living in that watershed 

will be exposed. 

For this reason, among others, for 

drinking water exposure estimation, the 

Agency assumes that 100% of the 

cropped area (or 100% PCT) is treated. 

EPA also makes this assumption due to 

the large uncertainties in the actual PCT 

on a watershed-by-watershed basis. EPA 

developed an extensive discussion of 

the uncertainties in PCT and how they 

impact drinking water exposure 

assessment in its proposed rule (73 FR 

44834) and in a background document 

provided to the SAP considering the 

draft carbofuran NOIC (Ref. 59). Because 

usage is often not evenly distributed 

across the landscape, due to differences 

in factors like pest pressure, local 

consultant recommendations and 

weather, it may be much higher in some 

areas. Further, temporal uncertainties 

can result in changes in use that might 

be driven by weather, changes in insect 

resistance over time, and changes in 

agronomic practices. To date, methods 

that account for this uncertainty, given 

the nature of the available data, have not 

been developed. Consequently, EPA 

cannot accurately estimate a drinkingwater watershed scale PCT that, when 

used in a quantitative risk assessment 

on a national or regional basis, standing 

alone, provides the necessary level of 

certainty to allow the Agency to 

confidently conclude that exposures 

will meet the FFDCA 408 safety 

standard. 

In most cases, EPA agrees that it is 

unlikely that 100% of the crop will be 

treated in most watersheds, particularly 

in larger watersheds. However, for small 

watersheds, it is reasonable to assume 

that an extremely high percentage of the 

crops in the watershed may be treated. 

Moreover, EPA has an obligation to 

evaluate all legally permitted use 

practices under the label, and to ensure 

that all such use meets the requisite 

statutory standards, not simply to base 

its decisions on the practices the 

majority might typically use. The 

September 2008 proposed label imposes 

no restriction on the application of 

carbofuran related to whether a 

particular percent of the watershed has 

been treated. Thus, even with the 

restrictions on FMC’s September 2008 

labels, it remains legally permissible for 

100% of the watershed to be treated 

with carbofuran. 

Nor is EPA aware of an enforceable 

mechanism to ensure that farmers 

applying pesticide to their individual 

fields will have the ability to determine 

whether a particular percentage of the 

watershed has been treated. There are 

significant practical difficulties inherent 

in implementing such label directions, 

as they force individual growers to have 

continual knowledge of the variances of 

the behavior of other farmers across the 

entire watershed. While for small 

watersheds that involve only one or two 

farms it might be feasible for neighbors 

to coordinate applications with respect 

to adjacent fields, for larger watersheds, 

the practical difficulties increase 

significantly. 

However, in the proposed rule, EPA 

conducted a sensitivity analysis to 

explore the impact of PCT assumption 

on dietary risk using an assumed 10% 

PCT, a figure proposed previously by 

FMC (73 FR 48864). The results of that 

analysis demonstrated that even at these 

low percentages, which may 

significantly underestimate exposures, 

particularly in small watersheds, 

carbofuran exposures from drinking 

water contribute significantly to 

children’s dietary risks. EPA conducted 

a similar sensitivity analysis for this 

final rule, discussed below in Unit 

VIII.E.3., which demonstrates that even 

assuming that a low percentage of a 

watershed is treated, exposures will be 

unsafe for infants. 

23066 Federal Register / Vol. 74, No. 93 / Friday, May 15, 2009 / Rules and Regulations 

FMC has submitted three assessments 

that relied in part on what they refer to 

as ‘‘county-level usage data’’ (Refs. 36, 

96, and 120). The description that EPA 

has been able to piece together from the 

registrant’s various submissions 

indicates that the original source of the 

‘‘county-level usage data’’ is sales data, 

apparently collected at the distributor 

level. FMC claims to have augmented 

these sales data in an unspecified 

manner, by incorporating information 

from the distributor, which FMC used to 

allocate carbofuran usage at the county 

level. FMC has provided maps 

representing county level and 

watershed-scale use estimates, but has 

not provided the actual usage estimates 

in any clearly understandable format. 

Nor, as of the close of the comment 

period, has any commenter provided 

either the ‘‘actual sales data’’ FMC used 

to develop these estimates, or the 

methods used to estimate county level 

usage from the sales data. FMC has 

provided only a limited description of 

how these data were collected and no 

description of how they were actually 

analyzed or validated; what FMC 

characterizes as ‘‘careful and proven 

techniques to capture this data’’ were 

not described. The method FMC used to 

attribute carbofuran sales to counties 

was not described. In the absence of the 

data or analyses described above, EPA is 

unable to verify or evaluate the results 

of any analyses that rely on these data 

and can reach no conclusion on its 

validity or utility. 

The Agency agrees that county-level 

use data would be useful in generating 

reasonable estimates of PCT that could 

be used in drinking water assessments. 

However, as discussed in the previous 

responses, FMC has only provided 

county-level use estimates (not the 

underlying data nor the analyses that 

presumably are the basis for the 

estimates) for Illinois; county-level 

estimates to support other risk 

assessments have not been submitted by 

FMC as of the end of the comment 

period. The underlying sales data (i.e., 

measurements) used to make the 

county-level estimates and the methods 

FMC used to estimate county level use 

from them have also not been 

submitted. FMC has provided limited 

characterization of the source data, 

noting that these data were derived from 

FMC billings and ‘‘EDI data’’, which 

they did not define, and that the sales 

data had been adjusted to reflect 

different use patterns and by removing 

use for patterns which they no longer 

support (e.g., alfalfa). However, FMC 

did not provide adequate details on the 

methodology they used to make these 

adjustments. 

A major problem with the method 

FMC seemingly used is that it does not 

appear to account for uncertainties due 

to variation in time and space and the 

potential for use to be locally 

concentrated due to pest pressures. The 

method FMC summarily describes as 

having been used to allocate countylevel usage estimates to watersheds 

appears to be similar to a method that 

has been used by others for calculating 

‘‘best-estimate’’ county-level PCT (Ref. 

95) to map nation-scale pesticide usage. 

However, these methods are not 

appropriate for calculating PCTs for 

surface drinking water sources or 

watersheds that drain to CWSs, because 

they do not adequately account for the 

uncertainty in the data at the 

appropriate spatial scale. This 

methodology produces an estimate that 

is a measure of central tendency and, as 

such, roughly half the estimated values 

will underestimate the PCT. 

Furthermore, because, pesticide use 

varies from year to year, and can in 

some cases be patchy, with high levels 

of use in small areas and little use in 

most areas, the underestimates of PCT 

can be substantial in small watersheds. 

As previously noted, methods for 

calculating PCT that account for these 

uncertainties have not been developed. 

Several commenters allege that 

carbofuran use will not concentrate in 

areas due to pest pressure. One 

commenter criticizes EPA for failing to 

support its conclusion that the pest 

pressure and infestation patterns could 

result in concentrated usage that could 

occur within vulnerable watersheds, 

and claims that EPA ignored the countylevel sales data provided by the 

registrant which can be used both to 

determine whether carbofuran usage is 

evenly dispersed or locally clustered (an 

assessment [FMC’s contractor] expressly 

undertook) and the probability of 

concentrated usage within vulnerable 

watersheds. 

Two commenters claim that, because 

‘‘more than 60% of the total corn 

acreage is made up of rootworm 

resistant GMO corn, which vary rarely 

requires treatment,’’ and the remaining 

acreage ‘‘is refugia acreage for GMO 

fields which is widely distributed 

geographically,’’ it is a ‘‘virtual 

impossibility’’ that all corn acreage in a 

particular watershed will require a 

rescue treatment in any given year. 

Another commenter made similar 

allegations for sunflower acreage. The 

commenter claims that ‘‘[s]unflowers 

are a specialty crop that is only grown 

on a small proportion of agricultural 

acreage generally, particularly in states 

where carbofuran is used (i.e., Nebraska, 

Colorado, Kansas, and Texas).’’ 

According to the commenter, the 

available data suggests that sunflowers 

are only used on 25% of total cropped 

area, and that carbofuran is not used on 

all of these acres. As further support for 

this point, another commenter cites to 

the sunflower PCAs they calculated for 

Nebraska, Kansas, Colorado, and 

Texas,’’ which they claim is 2.12%. 

The Agency agrees that the true PCT 

is not likely to be 100%. However, as 

discussed in several places throughout 

this preamble, the Agency is certain that 

PCT is higher in some cases than values 

calculated by the commenter. The 

degree of spatial correlation, however, is 

unknown, and thus is a major 

uncertainty. FMC’s own analysis of 

carbofuran use in watersheds in Indiana 

suggests that carbofuran use is indeed 

localized, as carbofuran use was found 

in watersheds of only 12 of the 35 

community water supplies that they 

considered in the state (Ref. 120). This 

suggests that when pest pressure occurs 

it is not unreasonable to assume it will 

be localized. Other factors, such as 

market pressures, consultant 

recommendations, or local availability 

may also be driving disparate levels of 

use in different locations. Since there is 

no method to account for this 

uncertainty in estimating PCT, it cannot 

be estimated in this assessment with the 

degree of confidence consistent with the 

statutory requirement of a reasonable 

certainty of no harm. 

The commenters raise several valid 

points that, taken together, reduce the 

probability that carbofuran usage will be 

concentrated over large geographical 

areas. However, the commenters failed 

to rebut EPA’s conclusion that 

carbofuran’s use patterns could be 

concentrated in certain locations, such 

that a large percentage of a small 

watershed is treated. Their first 

observation that carbofuran is applied as 

a rescue treatment on 0.27% of all U.S. 

corn acreage is true at the national level. 

However, the commenters failed to note 

that there are regional differences in 

carbofuran use, and as the scale 

becomes smaller, one would expect 

these differences to become even 

greater, precisely because use of 

carbofuran is sporadic in both time and 

space. Large areas would not be treated, 

but smaller areas, such as some drinking 

water watersheds considered by EPA 

may have a significantly higher 

proportion of their acreage treated than 

compared to national estimates. 

The commenters’ point that control 

failures are more likely to occur on 

biotech corn refugia is valid and will 

tend to prevent treatment of large 

Federal Register / Vol. 74, No. 93 / Friday, May 15, 2009 / Rules and Regulations 23067 

contiguous areas of corn. However, not 

all farmers plant biotech corn. Further, 

farmers who do grow biotech corn do 

not locate their refugia universally in 

one part of the field, and there is no 

requirement that farmers in contiguous 

fields coordinate the location of their 

respective refugia. Consequently, the 

possibility that several contiguous corn 

fields could be simultaneously treated 

in any given year is not precluded. It is 

worth noting in this context that the 

September 2008 labels do not restrict 

application to the refugia. Moreover, in 

those areas where carbofuran is applied 

aerially, such as Nebraska, it is 

frequently easier for applicators to treat 

an entire field, rather than restricting 

their application to only select portions 

of the field. This is particularly true in 

smaller fields. Finally, because usage is 

often not evenly distributed across the 

landscape due to differences in factors 

like pest pressure, local consultant 

recommendations and weather, it may 

be much higher in some areas, and 

methods that account for this 

uncertainty, given the nature of the data, 

have not been developed. 

EPA agrees that the 87% default PCA 

that has been used for EPA’s drinking 

water exposure assessments is likely a 

conservative estimate of sunflower 

acreage in a watershed. However, EPA 

has not developed PCAs for specific 

crops other than for corn, wheat, and 

cotton, consistent with guidance 

provided by the FIFRA SAP (Ref. 38). 

Nevertheless, the sunflower growers’ 

own estimate of sunflower PCAs range 

as high as 25%, which certainly cannot 

support a PCA of 2.12% as one of the 

commenters suggested. 

One commenter complained that as 

part of the NMC CRA, EPA relied on 

actual ‘‘county-or multi-county level 

pesticide use information, based on 

agricultural chemical use surveys’’ to 

develop its estimates of potential 

exposure, rather than assuming 100% 

PCT.’’ The commenter compares their 

surface water estimations to those 

developed by EPA for the NMC 

cumulative assessment, and claims that 

the two are consistent. 

While it is true that in the NMC 

assessment, EPA used PCT numbers to 

estimate the cumulative exposure from 

the contamination of such pesticides in 

surface water, this was done in order to 

more accurately account for the 

likelihood of pesticide co-occurrence at 

a single drinking water facility. But this 

does not mean that use of PCT is 

appropriate in conducting an 

assessment of aggregate exposure from 

carbofuran residues in surface water. 

This difference in approach between the 

assessment of a single chemical’s 

aggregate exposure, and the assessment 

of the cumulative exposures from 

several chemicals, stems from the 

differences in the purpose and scope of 

the two assessments. These differences 

inevitably require the application of 

different methodologies. 

In evaluating the acute risks 

associated with a single chemical’s 

contamination of drinking water, EPA 

must consider all of the variations 

permitted under the label. Drinking 

water exposures are driven by uniquely 

local factors; not only is the source of 

drinking water local (i.e. a person drinks 

water from his or her local water system 

not from a combination of water systems 

from across the United States), but the 

likelihood and degree of contamination 

of any particular, local drinking water 

source, whether it is a reservoir or well, 

varies widely based on local conditions 

(e.g, from local pest pressures, weather). 

Given this local variability, EPA must 

evaluate how all of the practices 

permitted under the label will affect 

drinking water exposures, because all 

are legally allowed, and farmers may 

choose any of them based on their 

particular individual local conditions. 

This means that even if typically 

growers, on a national or regional basis, 

do not frequently use a particular 

practice, EPA must still evaluate 

whether aggregate exposures from that 

practice would be safe because the 

practice is legally permissible and may 

be used due to local conditions. Thus, 

for example, even if most growers tend 

to apply the chemical only to a portion 

of the field, or typically only apply onehalf of the maximum application rate, 

EPA must determine whether use by all 

or some growers to the entire field or at 

the maximum rate in a local watershed 

would result in unsafe drinking water 

concentrations. 

By contrast, it is not feasible to 

conduct the identical analysis for a 

cumulative assessment of related 

chemicals. Since the potential 

combinations of variations in pesticide 

use practices for the group of pesticides 

to be assessed are essentially infinite, 

even with computer modeling it would 

be impossible to model or evaluate all 

of the combinations allowed under the 

labels. EPA therefore needed to narrow 

its evaluation of the possible 

combinations to those deemed ‘‘likely’’ 

to occur. In contrast to the single 

chemical assessment, a cumulative 

assessment is intended to develop a 

snapshot in time of what is likely 

occurring at the moment. Moreover, the 

purpose of a cumulative assessment is 

to identify major sources of risk that 

could potentially accrue due to the 

concurrent use of several pesticides that 

act through a common mechanism of 

toxicity. Thus, EPA is primarily 

interested in the subset of circumstances 

in which residues from such pesticides 

occur concurrently (or co-occur). 

In addition, one of the important 

attributes of a cumulative risk 

assessment is that its scope and 

complexity can potentially lead to 

inflated estimates of risk due to 

compounding conservatisms, which 

would reduce the interpretability and 

ultimately the utility of the assessments. 

Because many data sets need to be 

combined, reducing the impact and 

likelihood of compounding conservative 

assumptions and over-estimation bias 

becomes very important in constructing 

a reasonable cumulative risk 

assessment. 

When little or no information is 

available to inform potential sources of 

exposure, such as a reasonable or 

maximum watershed scale PCT, it is 

both scientifically and legally 

reasonable for a single chemical 

assessment to incorporate conservative 

assumptions to reflect reasonable worstcase exposure estimates. But in a 

cumulative risk assessment, the 

incorporation of such conservative 

assumptions would imply multiple 

simultaneous reasonable worst-case 

exposure estimates for each individual 

chemical. This is so unlikely that the 

results would no longer represent even 

a reasonable worst-case estimate of the 

likely risks. Consequently, some of the 

conservative assumptions appropriately 

used in the single chemical risk 

assessments are not appropriate or 

reasonable for use in a cumulative risk 

assessment, and vice versa. 

As a result, EPA chose in the NMC to 

work with those data that most closely 

reflect ‘‘representative’’ exposures, and 

developed ‘‘representative’’ estimates of 

PCT in regional watersheds. However, 

to be clear, the PCT values used in the 

NMC assessment do not represent 

estimates of 50% of watersheds, or even 

the ‘‘average’’ watershed; rather, they 

represent values that are expected to be 

as likely to be accurate as not, based on 

a random selection of watersheds. A 

comparable example is the statistic that 

the average American family has 

approximately 2 children; this may or 

may not be true for any individual 

family, but there is an equally good 

chance that it will be accurate for any 

randomly selected family, as that it will 

not be accurate. For the cumulative 

assessment, EPA is able accept this level 

of uncertainty in these estimates, 

precisely because it has confidence that 

aggregate exposures from the individual 

chemicals will be safe, based on the 

level of conservatism in the single 

23068 Federal Register / Vol. 74, No. 93 / Friday, May 15, 2009 / Rules and Regulations 

chemical assessments. But given the 

statute’s mandate to ensure a 

‘‘reasonable certainty of no harm,’’ EPA 

could not rely on the approach used 

under the cumulative assessment in the 

absence of the more conservative singlechemical assessment that evaluates the 

full range of exposures permitted by the 

registration. 

Nevertheless, as discussed in Unit 

VIII.E.3., 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 results 

suggest that, even at levels below 10% 

CT, exposures from drinking water 

derived from surface waters can 

contribute significantly to the aggregate 

dietary risks, particularly for infants and 

children. Accordingly, these 

assessments suggest that use of a 

reasonably conservative PCT estimate, 

even if one could be developed, would 

not meaningfully affect the carbofuran 

risk assessment, as aggregate exposures 

would still exceed 100% of the aPAD. 

One commenter raised the concern 

that USGS monitoring found that 

concentrations of carbofuran in 

agricultural streams ranged from nondetect to 7 ppb (with a 95th percentile 

concentration of 0.044 ppb), noting that 

the monitoring strategy used by USGS 

for this program is likely to 

underestimate peak contamination 

levels (Ref. 114). The commenter argued 

that the USGS monitoring program is 

not designed to target waterways where 

carbofuran is in high use, or timed to 

coincide with predicted peak levels of 

pesticide runoff into waterways. 

Moreover, the frequency of sampling is 

normally weekly or bi-weekly, not 

enough to reliably sample the sporadic 

peaks that are predicted to be associated 

with pesticide application days or heavy 

runoff following rains. This monitoring 

strategy is more likely to capture the 

trends in chronic pollutants, but miss 

peak events such as pesticide runoff 

following rain. The sampling strategy 

biases towards the null; that is, it is 

likely to underestimate contamination 

by missing peak events when they 

occur, but will not over-represent nondetects. The commenter alleged that the 

fact that these data show routine 

detections of carbofuran in streams from 

agricultural land use areas suggests that 

there are likely to be peak events that go 

undetected. These data further support 

EPA’s decision to cancel carbofuran and 

support rejecting FMC’s proposal to 

restrict its use only in a limited number 

of watersheds. Because carbofuran is 

detected in streams across the nation, 

FMC’s spatially limited mitigation plan 

would fail to protect many waterways 

from contamination. 

One commenter argued that FMC’s 

proposal to restrict uses of carbofuran in 

the most vulnerable watersheds, to limit 

ground water contamination, would fail 

to provide adequate protection. The 

commenter noted ‘‘substantial 

monitoring data showing that 

carbofuran has been detected by the 

USGS in 10.4% of over 2,000 streamwater samples taken from 83 

agricultural streams monitored from 

1992–2001, demonstrating that it is a 

widespread water pollutant and that 

geographically limited mitigation 

measures are not likely to be adequately 

protective.’’ (Ref. 114). 

EPA agrees with the commenters that 

the risks of surface water contamination 

from carbofuran are significant, and that 

FMC’s September 2008 labels do not 

mitigate the risks sufficiently. 

3. Aggregate exposures. One group of 

commenters presented a summary of 

some of the results of their own 

aggregate exposure assessment. 

According to these commenters, the 

results of their risk assessment 

demonstrate that carbofuran residues 

from the four domestic food uses, 

imports, and drinking water are ‘‘safe.’’ 

EPA notes that the commenters 

merely provided summaries of the 

results of this assessment, and describe 

their methodology in only the most 

general terms, but chose not to provide 

the actual risk assessment to the 

Agency. Nor did the commenters 

provide any of their input files. 

Consequently, EPA was unable to fully 

evaluate the scientific adequacy of this 

assessment. 

The Agency’s analyses result in food 

only exposures comparable to some of 

those reported by the commenters (e.g., 

exposures from the four import 

tolerances). But the remaining scenarios 

could not be verified since the 

commenters did not elaborate on the 

methods by which the detected 

concentrations found in the PDP milk 

samples were adjusted. Nor could EPA 

replicate the commenters’ reported 

results. As discussed in more detail in 

Unit VIII.E.1., the Agency’s assessment 

for this subset of foods differs slightly 

from the commenters due to PCT 

estimates (bananas), and more 

significantly, in the treatment of milk 

residues detected by the PDP program. 

Those differences cause the 

commenters’ food only scenario 

(without accounting for any reversibility 

of AChE inhibition) to be slightly lower 

than the Agency’s revised estimates 

(67% vs 78%). 

EPA was also unable to replicate the 

commenters’ results for drinking water 

exposures, or for aggregated exposures 

from food and drinking water. The 

commenters report that in their water 

only scenario, the DEEM results were 

350% aPAD, assuming a 5% crop 

treated value. However, as discussed 

previously VII.C.2.b., EPA believes that 

it lacks sufficient basis to assume that 

only 5% of the crop in a watershed will 

be treated. 

The commenters presented the results 

of their ‘‘Eating Occasions Analyses’’ for 

only one aggregate scenario, which was 

based on a Kansas corn drinking water 

scenario, and only for the infant 

subpopulation. It is based on this 

scenario that the commenters claim that 

aggregate exposure to carbofuran 

residues will be safe. The commenters 

appear to have also developed some 

other scenarios for corn, sunflowers, 

and potatoes that produce similar 

predicted drinking water 

concentrations; some of which have 

slightly higher peak concentrations. 

However, they did not present any 

results for those scenarios, nor provide 

any of the analyses to the Agency as part 

of their comments. As noted, EPA was 

unable to replicate these results. But as 

discussed below in Unit VIII.E., EPA 

disagrees that aggregate exposures to 

carbofuran residues are safe. 

One commenter raised the concern 

about the numbers of people exposed to 

unsafe levels of carbofuran. The 

commenter stated that EPA has 

determined that the aggregate exposures 

to carbofuran from food and water at 

doses greater than 0.000075 mg/kg/day/ 

day, the aPAD, will not meet the safety 

standard of FFDCA section 408(b)(2). At 

the 99.9th percentile of exposure, 

aggregate dietary exposure from food 

alone exceeds the aPAD by 160% for 

children 6–12 years (approximately 

36,000 kids), and 210% for children 3– 

5 years old. The commenter stated that 

when these estimates are aggregated 

with ground water sources of drinking 

water from vulnerable areas, the 

predicted exposure exceeds the aPAD 

by 1,100% for adults over 50 years 

(approximately 71,000 people) and over 

10,000% for infants at the 99.9th 

percentile (approximately 4,000 

infants). According to the commenter 

there are approximately 24,000,000 

children under 5 years old in the United 

States, so 0.1% of this age group would 

mean leaving approximately 24,000 

children at risk, using the 99.9th 

percentile exposure estimates. 

According to the commenter, no reading 

of the statute will support any approach 

that allows thousands of children to be 

Federal Register / Vol. 74, No. 93 / Friday, May 15, 2009 / Rules and Regulations 23069 

exposed to a pesticide at levels that 

exceed the aPAD. 

EPA agrees that aggregate exposures 

to carbofuran do not meet the FFDCA’s 

safety standard. The precise figures 

calculated by the commenter were based 

on exposures from all of the registered 

uses assessed in EPA’s proposed rule; as 

many of those uses have been canceled, 

the number of affected children is 

expected to be lower. However, EPA 

agrees that based on its revised 

estimates, allowing children to continue 

to be exposed to carbofuran would not 

be consistent with the statute. 

D. Comments Relating to Legal or Policy 

Issues 

A number of commenters raised 

concern that EPA had proposed to 

revoke all carbofuran tolerances before 

taking action against the pesticide 

registrations under FIFRA ‘‘in the 

absence of an imminent health hazard.’’ 

Several of these commenters raised 

concern that EPA had failed to comply 

with FFDCA section 408(l)’s 

requirement to ‘‘coordinate action 

[under the FFDCA] with any related 

necessary action under the [FIFRA]. 

EPA has determined with respect to 

carbofuran both that the tolerances 

established for that chemical fail to meet 

the safety standard set forth in section 

408 of the FFDCA and must therefore be 

revoked under that statute, and that the 

pesticide registrations fail to meet the 

relevant standard under FIFRA, and 

must therefore be canceled under that 

statute. Section 408(l)(1) of the FFDCA 

provides that ‘‘[t]o the extent practicable 

and consistent with the review 

deadlines in subsection (q), in issuing a 

final rule that suspends or revokes a 

tolerance or exemption for a pesticide 

chemical residue in or on food, the 

Administrator shall coordinate such 

action with any related necessary action 

under [FIFRA].’’ 21 U.S.C. 346a(l)(1). 

Nothing in this provision establishes a 

predetermined order for how the 

Agency is to proceed to resolve dietary 

risks. Nor does FIFRA include any 

provision that imposes a requirement 

that the Agency act first under FIFRA 

before it may act under the FFDCA in 

a situation such as carbofuran, where 

pesticide registrations and tolerances 

fail to meet the relevant legal standards 

of FIFRA and the FFDCA. Accordingly, 

there is no support for the notion that, 

as a matter of law, the Agency lacks the 

legal authority to revoke pesticide 

tolerances under the FFDCA that do not 

meet the safety standard of that statute 

unless the Agency has first canceled 

associated pesticide registrations under 

FIFRA. 

Coordination is defined as ‘‘to place 

or arrange in proper order or position, 

to combine in harmonious relation or 

action.’’ Thus, the requirement to 

‘‘coordinate’’ is a direction to ensure 

that the substance of actions taken 

under the two statutes are consistent, 

and that the Agency make a 

determination as to the proper order of 

action under the two statutes. This 

cannot be read as a requirement that 

actions under FIFRA precede actions 

under the FFDCA, or that any particular 

order is necessarily required. Indeed, to 

the extent that this provision offers any 

direction with respect to the order of 

preference, the language actually 

suggests that the order in which EPA 

has proceeded is entirely appropriate. 

Section 408(l)(1) requires EPA to 

proceed ‘‘consistent with the review 

deadlines in subsection (q).’’ 21 U.S.C. 

346a(l)(1). 

One commenter raised concern that 

the FFDCA requires EPA to harmonize 

actions under FFDCA and FIFRA ‘‘to the 

extent practicable.’’ The commenter 

alleges that there is no excuse for not 

‘‘harmonizing action under both 

statutes’’ in the absence of an 

‘‘imminent hazard.’’ According to the 

commenter, ‘‘harmonization would 

allow the key science issues to be 

resolved in an orderly manner before 

hasty action is taken, would avoid 

needless disruption and confusion of 

agriculture and the channels of trade, 

and would allow the benefits of the 

pesticide to be properly taken into 

account.’’ 

As explained in the previous 

response, the comment is based on a 

misconstruction of FFDCA section 

408(l)(1). As a preliminary matter, EPA 

interprets the commenter’s phrase 

‘‘harmonizing action under both 

statutes’’ to mean either: (1) Pursuing 

action to cancel registrations under 

FIFRA prior to revoking tolerances or (2) 

holding a hearing pursuant to FIFRA 

and the FFDCA simultaneously. Section 

408(l)(1) does not require EPA to do 

this; as discussed previously EPA is 

merely required to ‘‘coordinate’’ action 

under the two statutes, ‘‘to the extent 

practicable and consistent with the 

review deadlines.’’ Nor is there any 

basis in either FIFRA or the FFDCA for 

the commenter’s alleged requirement 

that EPA determine that a pesticide 

presents an ‘‘imminent hazard,’’ as that 

term is defined in FIFRA, prior to taking 

action to resolve dietary risks under the 

FFDCA. 

EPA chose to initially take action 

exclusively under the FFDCA to resolve 

carbofuran’s dietary risks for a number 

of reasons. First and foremost, this was 

determined to be the quickest way to 

resolve acute dietary risks to children. 

In addition, the fact that this would 

resolve the issues most quickly would 

be beneficial to all parties, including the 

registrant and growers, since it would 

reduce costs and uncertainty for all by 

resolving the question of carbofuran’s 

dietary risks. 

An additional consideration was the 

belief that this route would be more 

transparent, and would ensure that 

there would be no confusion as to the 

appropriate standard that would be used 

to resolve dietary risk concerns. The 

Agency was concerned that holding a 

hearing under FIFRA would lead 

growers to misunderstand the role that 

benefits could play in the ultimate 

decision. Indeed, the commenter’s claim 

that ‘‘harmonization would allow the 

benefits of the pesticide to be properly 

taken into account’’ confirms that EPA’s 

concern was justified. 

Whether under FIFRA or the FFDCA, 

a pesticide’s benefits are irrelevant in 

determining whether a pesticide 

presents an unacceptable dietary risk. 

Section 408(b)(2) clearly provides that 

the only standard is whether the 

pesticide chemical residues will be 

‘‘safe.’’ 21 U.S.C. 346a (b)(2). Nor is the 

evaluation of a pesticide’s ‘‘benefits’’ 

included among the factors to be 

considered in determining whether 

residues will be ‘‘safe.’’ 21 U.S.C. 346a 

(b)(2)(B). FIFRA section 2(bb) 

incorporates the FFDCA’s standard 

explicitly and without modification, 

clearly distinct from the provisions that 

relate to consideration of the benefits of 

the pesticide. Thus, in any FIFRA 

hearing, if it is determined that use of 

a pesticide fails to meet the FFDCA 

section 408 safety standard, the 

pesticide must be canceled, irrespective 

of whether the benefits outweigh the 

ecological and occupational risks. But 

since under FIFRA, all issues are 

addressed in one hearing, the potential 

existed for confusion on the part of the 

members of the public, who might have 

an interest in the proceedings. 

Finally, EPA disagrees that it has 

failed to proceed in an orderly manner 

or that it has taken hasty action. By the 

time these tolerance revocations will be 

effective, EPA will have provided 

numerous opportunities for public 

comment, obtained peer review of the 

key science issues from the SAP, and 

will, if appropriate, hold a hearing on 

remaining issues of material fact. 

Further, notwithstanding the statutory 

deadlines in section 408(q) for 

identifying and resolving dietary risks, 

the registrant had 8 additional months 

to generate data to rebut the Agency’s 

conclusions in the IRED. In total, the 

registrant and the public will have been 

23070 Federal Register / Vol. 74, No. 93 / Friday, May 15, 2009 / Rules and Regulations 

granted numerous opportunities and 

well over 2 years to comment on the key 

science issues. Given that carbofuran 

presents acute dietary risks to children, 

and the clear statutory deadline in 

FFDCA section 408(q), EPA believes it 

would be difficult to characterize its 

action as ‘‘hasty.’’ 

Some commenters objected to EPA’s 

revocation of tolerances on the grounds 

that it was poor public policy because 

the action ‘‘sets up farmers and food 

producers for unanticipated, 

unwarranted, and unfair enforcement 

action and penalties for presence of 

residues in food from otherwise legally 

treated crops.’’ 

EPA shares the concerns that farmers’ 

crops not be subject to unfair or 

unwarranted penalties based on the 

Agency’s choice to resolve carbofuran’s 

dietary risks before proceeding with a 

cancellation. EPA has taken a number of 

measures in response to these concerns, 

to ensure that growers will not be 

unfairly penalized by the Agency’s 

action. 

First, EPA has established delayed 

effective dates for all of the tolerance 

revocations, to provide growers with 

sufficient time to use up stocks of 

carbofuran that they currently have on 

hand. These dates are well after the end 

of the current growing season. These 

delayed effective dates also ensure that 

growers have sufficient notice of when 

these requirements will be applicable to 

allow them to factor this into their 

purchasing and application decisions. 

By the time the rule is scheduled to 

become effective, growers will have 

been informed of EPA’s intentions well 

over a year in advance; this should be 

more than sufficient time to allow 

growers to plan around the final 

revocation dates. Finally, EPA has 

initiated discussions with FDA, and will 

continue to coordinate with FDA, to 

ensure that food that was treated before 

the effective date of the tolerance 

revocations will continue to be allowed 

to be sold. 

Late comments. EPA received a 

number of submissions after the close of 

the comment period. The majority of 

these were from FMC, the registrant of 

carbofuran. These submissions included 

a request to stay the effective date of the 

tolerance revocation, as well as requests 

that EPA consider additional issues and 

factual information in this final rule. In 

addition, one timely submitted 

comment questioned the legal basis for 

the statement in the proposed rule that 

failure to raise issues during the 

comment period would constitute a 

waiver of those issues, asserting that 

‘‘EPA’s requirement. . .does not appear 

to be legally binding.’’ 

Sections 408(e)–(g) of the FFDCA 

provides a multi-step process for the 

establishment and revocation of 

tolerances, that provides ample 

opportunities for those with an interest 

in the tolerance to protect those 

interests. The process essentially 

consists of informal rulemaking, 

supplemented as appropriate with an 

administrative hearing. See, 21 U.S.C. 

321a(e)–(g). As an informal rulemaking, 

the process is governed by section 553 

of the Administrative Procedures Act, 

(APA) except to the extent section 408 

provides otherwise, or to the extent the 

FFDCA falls within one of the APA’s 

exceptions. Accordingly, the legal basis 

for the Agency’s statement that issues 

not raised during the comment period 

on the proposed tolerance revocation 

may not be raised as objections or in any 

future proceeding, stems directly from 

the requirements of section 553 of the 

APA, and the case law interpreting 

these requirements. In this regard, it is 

well established that the failure to raise 

factual or legal issues during the 

comment period of a rulemaking, 

constitutes waiver of the issues in futher 

proceedings, [e.g., Forest Guardians v 

US Forest Service, 495 F.3d 1162, 1170– 

1172 (10th Cir. 2007)] (Claim held 

waived where comments ‘‘failed to 

present its claims in sufficient detail to 

allow the agency to rectify the alleged 

violation’’); Nuclear Energy Institute v 

EPA, 373 F.3d 1251, 1290–1291 (D.C. 

Cir. 2004) (‘‘To preserve a legal or 

factual argument, we require its 

proponent to have given the agency a 

‘fair opportunity’ to entertain it in the 

administrative forum before raising it in 

the judicial forum.’’) Native Ecosystems 

Council v Dombeck, 304 F.3d 886, 889- 

900 (9th Cir. 2002) (Purpose of 

requirement that issues not presented at 

administrative level are deemed waived 

is to avoid premature claims and ensure 

that agency be given a chance to bring 

its expertise to bear to resolve a claim); 

Kleissler v. U.S. Forest Service, 183 F.3d 

196, 202 (3d Cir. 1999) (Policy 

underlying exhaustion requirement is 

that ‘‘objections and issues should first 

be reviewed by those with expertise in 

the contested subject area’’); National 

Association of Manufacturers v US DOI, 

134 F.3d 1095, 1111 (D.C. Cir. 1998) 

(‘‘We decline to find that scattered 

references to the services concept in a 

voluminous record addressing myriad 

complex technical and policy matters 

suffices to provide an agency like DOI 

with a ‘fair opportunity’ to pass on the 

issue.’’) Linemaster Switch Corporation 

v EPA, 938 F.2d 1299, (D.C.Cir. 1991) 

(declining to consider in challenge to 

final rule, data alluded to in comments, 

but not submitted during the comment 

period, and information submitted to 

EPA office that was not developing the 

rule). And nothing in the language or 

structure of the FFDCA alters this. As 

such, this is indisputably a binding legal 

requirement. 

The fact that section 408 of the 

FFDCA in certain limited circumstances 

supplements the informal rulemaking 

with a hearing, does not change the 

fundamental nature of the process. In 

other words, the addition of further 

process, through the availability of an 

administrative hearing to resolve certain 

factual disputes, does not 

fundamentally alter the requirements 

applicable to informal rulemakings. To 

this end, EPA interprets the notice and 

comment rulemaking portion of the 

process as inextricably linked to the 

administrative hearing. The point of the 

rulemaking is to resolve the issues that 

can be resolved, and to identify and 

narrow any remaining issues for 

adjudication. Accordingly the 

administrative hearing does not 

represent an unlimited opportunity to 

supplement the record, particularly 

with information that was available 

during the comment period, but that 

commenters have chosen to withhold. 

To read the statute otherwise would be 

to render the rulemaking portion of the 

process entirely duplicative of the 

hearing, and thus, ultimately 

meaningless. See, e.g., FDA v. Brown & 

Williamson Tobacco, 529 U.S. 120, 132– 

133 (2000) (Court must interpret statute 

as a symmetrical and coherent 

regulatory scheme, and fit, if possible, 

all parts into an harmonious whole.) 

APW, AFL-CIO v Potter, 343 F.3d 619, 

626 (2nd Cir. 2003) (‘‘A basic tenet of 

statutory construction. . .[is] that a text 

should be construed so that effect is 

given to all its provisions, so that no 

part will be inoperative or superfluous, 

void or insignificant, and so that one 

section will not destroy another...’’), 

quoting, Silverman v Eastrich Mulitple 

Investor Fund, 51 F.3d 28, 31 (3rd Cir. 

1995). The equities of this construction 

are particularly strong, where, as here, 

the information was (or should have 

been) available during the comment 

period. See, Kleissler, 183 F.3d at 202 

(‘‘[A]dministrative proceedings should 

not be a game or a forum to engage in 

unjustified obstructionism by making 

cryptic and obscure reference to matters 

that ‘‘ought to be’’ considered and then, 

after failing to do more to bring the 

matter to the agency’s attention, seeking 

to have that agency determination 

vacated’’) citing Vermont Yankee 

Nuclear Power Corp. v. N RDC, 435 U.S. 

519, 553–54 (1978). 

Federal Register / Vol. 74, No. 93 / Friday, May 15, 2009 / Rules and Regulations 23071 

Accordingly, in this final rule, EPA 

has not considered any of the 

information submitted after the close of 

the comment period. 

VIII. 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 NMC pesticide. Like 

other pesticides in this class, the 

primary toxic effect seen following 

carbofuran exposure is neurotoxicity 

resulting from inhibition of the enzyme 

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. 19 and 20). 

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 LD50 or LC50). 

Carbofuran has an oral LD50 of 7.8-6.0 

mg/kg, and an inhalation LC50 of 0.08 

mg/l (Refs. 16 and 20). 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 (PND11 

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 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. 45 and 83). 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. 

B. Deriving Carbofuran’s Point of 

Departure 

There are laboratory data on 

carbofuran for ChE activity in plasma, 

RBC, and brain from studies in multiple 

laboratory animals (rat, mouse, and 

dog). These studies have been submitted 

to EPA as part of pesticide registration 

and include a variety of durations of 

exposure and types of toxic effects 

(neurotoxicity, developmental toxicity, 

cancer, etc). Consistent with its mode of 

action, data on AChE inhibition provide 

the most sensitive effects for purposes of 

deriving a RfD or PAD. 

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. 102). Neurotoxicity resulting from 

carbofuran exposures can occur in both 

the central (brain) and 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). Due to the 

rapid nature of NMC pesticide toxicity, 

measures of AChE inhibition in the PNS 

are very rare for NMC pesticides. 

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). EPA and other 

state and national agencies such as 

California, Washington, Canada, the 

European Union, as well as the World 

Health Organization (WHO), across the 

world use blood measures in human 

health risk assessment and/or worker 

safety monitoring programs as 

surrogates for peripheral AChE 

inhibition. 

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. 20). 

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 associated with cholinergic 

toxicity, mentioned above, do not occur. 

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. 3, 4, 5, and 83). 

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. 79). 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 (Refs. 12, 26, and 27). 

Other studies in adult rats used in the 

Agency’s analysis included additional 

data from EPA-ORD (Refs. 69, 78, and 

83). 

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. 107). 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 

23072 Federal Register / Vol. 74, No. 93 / Friday, May 15, 2009 / Rules and Regulations 

for evaluating risk to infants and young 

children and are thus used to derive the 

PoD. In addition, typically (and this is 

the case for carbofuran) young children 

(ages 0–5 years) 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 to 5 years). 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. 

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. 50, 55, 76, 119, and 

123). Through its review of available 

studies, the Agency identified problems 

and irregularities with the RBC AChE 

data from both FMC supported 

comparative ChE studies. These 

problems are described in detail in the 

Agency’s study review (Refs. 24 and 25). 

As such, the Agency determined that 

the RBC AChE inhibition data from the 

two FMC comparative ChE 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 

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. 44). 

By contrast, the brain AChE data from 

the FMC and EPA-ORD studies are 

acceptable and have been used in the 

Agency’s dose-response analysis. 

EPA has relied on a BMD approach 

for deriving the PoD from the available 

rat toxicity studies. A BMD is a point 

estimate along a dose-response curve 

that corresponds to a specific response 

level. For example, a BMD10 represents 

a 10% change from the background; 

10% is often used as a typical value for 

the response of concern (Ref. 100). 

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-observedadverse-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. 40, 42, 43, and 

100). 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. 42 and 43). 

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. 44). 

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 BMD10s 

and BMDL10s 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 OPs and NMCs 

including carbofuran. For a variety of 

toxicological and statistical reasons, 

EPA chose 10% 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 (Ref. 107) 

The Agency used a meta-analysis to 

calculate the BMD10 and BMDL10 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 dosetime-response exponential model where 

benchmark dose and half-life to 

recovery can be estimated together. This 

model and the statistical approach to 

deriving the BMD10s, BMDL10s, and 

half-life to recovery have been reviewed 

and supported by the FIFRA SAP (Refs. 

42, 43, and 44). The meta-analysis 

approach offers the advantage over 

using single studies by combining 

information across multiple studies and 

thus provides a robust PoD. 

Using quality brain AChE data from 

the three studies (two FMC, one EPAORD) 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. The 

Agency believes the BMD analysis for 

the PND11 brain AChE data is the most 

robust analysis for purposes of PoD 

selection. 

The results of the BMD analysis for 

PND11 pup brain AChE data provide a 

BMD10 of 0.04 mg/kg/day and BMDL10

Federal Register / Vol. 74, No. 93 / Friday, May 15, 2009 / Rules and Regulations 23073 

of 0.03 mg/kg/day—this BMDL10 of 0.03 

mg/kg/day provides the PoD (Ref. 89). 

Some commenters provided extensive 

critique with regard to the BMD 

modeling conducted by the Agency. 

However, 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, both 

approaches yield the identical PoD of 

0.03 mg/kg/day. Thus, although the 

commenters are critical of the Agency’s 

approach, there is basic consensus that 

the PoD is approximately 0.03 mg/kg/ 

day. 

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 inhibition. Consequently, EPA 

cannot reliably estimate the BMD10 and 

BMDL10 for RBC AChE data in pups. 

Furthermore, given that the EPA-ORD 

data clearly show pup RBC AChE to be 

more sensitive than pup brain AChE, 

EPA cannot conclude that reliance on 

the pup brain data as the PoD would be 

sufficiently protective of PNS effects in 

pups. As a result of this uncertainty 

EPA must retain some portion of the 

children’s safety factor as described 

below. 

C. Safety Factor for Infants and Children 

1. In general. Section 408 of 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, based on reliable data, 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. 105). 

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 preand 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.). The Agency’s approach to 

evaluating whether sufficient ‘‘reliable’’ 

data exist to support the reduction or 

removal of the statutory default 10X is 

described below in Figure 1. 

23074 Federal Register / Vol. 74, No. 93 / Friday, May 15, 2009 / Rules and Regulations 

2. Prenatal and postnatal sensitivity. 

Prenatal developmental toxicity studies 

with carbofuran in rat and rabbit, in 

addition to the reproductive toxicity 

and developmental neurotoxicity (DNT) 

studies do not provide evidence for 

developmental or reproductive effects 

from in utero exposure. Moreover, 

effects noted in these studies are less 

sensitive than AChE inhibition. Postnatal exposure to juvenile rat pups 

provides the most sensitive lifestage in 

available animal toxicology studies with 

NMCs, including carbofuran (Refs. 19, 

107, 108, and 124). 

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. 

44). However, the Agency does not have 

AChE data for carbofuran 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. 

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 


er15my09.000</GID>
Federal Register / Vol. 74, No. 93 / Friday, May 15, 2009 / Rules and Regulations 23075 

4One commenter noted that EPA had 

inadvertently failed in its BMD analysis of the 

PND17 data, to convert the units from hours to 

minutes. EPA has corrected its error, and has 

recalculated the BMD50s for the PND17 animals, 

using the corrected times. The BMD50 ratio for brain 

and RBC is now 2.6, rather than the 3.3 originally 

estimated based on its original oversight. 

or mouth smacking was observed in a 

clear dose-response pattern immediately 

following dosing each day (Ref. 116). 

Based on this study, the California 

Department of Pesticide Regulation 

calculated a BMD05 and BMDL05 of 0.02 

and 0.01 mg/kg/day, and established the 

acute PoD (Refs. 15 and 44). These BMD 

estimates are notable as they are close 

to the values EPA has calculated for 

brain AChE inhibition and which are 

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. 68). 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 at low doses 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 data in the 

PNS and/or a surrogate (i.e., RBC AChE 

inhibition 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 PNS), 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 children’s 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 BMD10 estimates. However, as 

described above, BMD10 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. As 

an alternative approach, EPA has used 

the ratio of brain to RBC AChE 

inhibition at the BMD50, 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 determined that a 

children’s safety factor of 4X is 

appropriate based on a weight-ofevidence approach. This safety factor is 

calculated using the ratio of RBC and 

brain AChE inhibition, using the data on 

administered dose for the PND11 

animals from the EPA-ORD studies and 

the FMC studies combined. In other 

words, EPA estimated the BMD50 for 

PND11 animals for RBC and brain from 

each quality study and used the ratio 

from the combined analysis, resulting in 

a BMD50 ratio of 4.1X. EPA estimated 

the RBC to brain potency ratio using 

EPA’s data for RBC (the only reliable 

RBC data in PND11 animals for 

carbofuran) and all available data in 

PND11 animals for brain. 

EPA also compared the BMD50 ratios 

for PND17 pups (who are slightly less 

sensitive than 11-day olds; see Figure 2) 

in the EPA-ORD study, to confirm that 

the differences in sensitivity between 

RBC and brain were not unique to the 

PND11 data. The result of EPAs 

modeling shows a BMD50 ratio of 2.64 X 

between brain and RBC in the PND17 

pups. 

On the basis of the available data, 

EPA believes that application of a 4X 

factor will be ‘‘safe’’ for infants and 

children. This selection was made based 

on: (1) The remaining 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 

BMD50 for PND11 animals of 4.1X. 

23076 Federal Register / Vol. 74, No. 93 / Friday, May 15, 2009 / Rules and Regulations 

EPA presented its dietary risk 

assessment of carbofuran to the FIFRA 

SAP, and requested comment on the 

Agency’s approach to selecting the PoD 

and the children’s safety factor. As 

described in the proposal, the Agency 

believes that the Panel’s responses 

unambiguously support the Agency’s 

approach with regard to carbofuran’s 

hazard identification and hazard 

characterization (73 FR 44864). In 

addition, 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 Reference 34. 

EPA received the greatest number of 

comments for the proposed tolerance 

revocation on the children’s safety 

factor. However, none of the 

commenters provided any new data nor 

information that changes the Agency’s 

major conclusions with regard to the 

uncertainty factor, and the methodology 

used to assess risks as a result of dietary 

exposures to carbofuran. 

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. 

D. Hazard Characterization and Point of 

Departure Conclusions. 

The doses and toxicological endpoints 

selected and Margins of Exposures for 

various exposure scenarios are 

summarized below. 

TABLE 1.—TOXICOLOGY ENDPOINT SELECTION TABLE

Exposure Scenario Dose Used in Risk Assessment, UF FQPA factor and Endpoint 

for Risk Assessment Study and Toxicological Effects 

Acute Dietary Infants 

and Children 

BMDL10 = 0.03 mg/kg/day 

UF = 100 

Acute RfD = 0.0003 mg/kg/day 

Children’s SF = 4X 

aPAD = 0.000075 mg/kg/ 

day 

Comparative AChE Studies in PND11 rats 

(FMC and EPA-ORD) 

BMD10 = 0.04 mg/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) and 

Adults 

BMDL10 = 0.02 mg/kg/day 

UF = 100 

Acute RfD = 0.00024 mg/kg/day 

aRfD = 0.0002 mg/kg/day Comparative AChE Study (EPA-ORD), Padilla 

et al (2007), McDaniel et al (2007) 

BMD10 = 0.06 mg/kg/day 

BMDL10 = 0.02 mg/kg/day, based on RBC 

AChE inhibition in adult rat 


er15my09.001</GID>
Federal Register / Vol. 74, No. 93 / Friday, May 15, 2009 / Rules and Regulations 23077 

E. Dietary Exposure and Risk 

Assessment 

1. Dietary exposure to carbofuran— 

Food—a. EPA methodology and 

background. As noted earlier, in their 

September 29, 2008 comments on the 

Agency’s risk assessment, FMC 

requested cancellation of a large number 

of domestic food uses, including, among 

other uses, artichokes, peppers, and all 

cucurbits except pumpkins. EPA 

granted the request, and accordingly, 

conducted a refined (Tier 3) acute 

probabilistic dietary risk assessment for 

the remaining carbofuran residues in 

food. The remaining sources of ‘‘food’’ 

exposures are from the domestic uses of 

field corn, potato, sunflower, pumpkins, 

as well as milk (indirect residues 

through use on corn, potatoes and 

sunflower), and from four import 

tolerances (bananas, coffee, sugarcane, 

and rice). To conduct the assessment, 

EPA relied on DEEM-FCID(TM), Version 

2.03, 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. 

16 and 20). 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 winter squash were used to 

derive anticipated residues for 

pumpkins. 

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 one-half of the 

LOD for PDP monitoring samples with 

no detectable residues, and zero 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. 18), which was sponsored by the 

Carbamate Market Basket Survey Task 

Force. EPA relied on these data to 

construct the residue distribution files 

for bananas 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 (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 (field corn and rice), 

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 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 10%. The estimated 

percent of the crop imported was 

applied to crops with tolerances 

currently maintained solely for import 

purposes (banana, coffee, sugarcane, 

and rice). 

b. Acute dietary exposure (food alone) 

conclusions. The estimated acute 

dietary exposure from carbofuran 

residues in food alone (i.e., assuming no 

additional carbofuran exposure from 

drinking water), are below EPA’s level 

of concern for the U.S. Population and 

all population subgroups. Children 1 to 

2 years of age (78% aPAD) were the 

most highly exposed population 

subgroup when food only was included. 

The major driver of the acute dietary 

exposure risk (food only) for Children 1 

to 2 years is milk at greater than 90% 

of the exposure. (See results from Table 

2 below). 

TABLE 2.—RESULTS OF ACUTE DIETARY EXPOSURE ANALYSIS FOR FOOD ALONE

Population Subgroup aPAD (mg/ 

kg/day) 

99th Percentile 99.9th Percentile 

Exposure 

(mg/kg/day) % aPAD Exposure (mg/kg/day) % aPAD 

All Infants (< 1 year old) 0.000075 0.000013 18 0.000039 52 

Children 1–2 years old 0.000075 0.000024 32 0.000058 78 

Children 3–5 years old 0.000075 0.000015 20 0.000034 45 

Children 6–12 years old 0.000075 0.000010 13 0.000022 29 

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, in response to 

comments, the Agency revised its PCT 

estimates for the bananas from 78% to 

25%. The Agency also developed a 

regional PCT estimate for potatoes of 

5% based on projected limited use in 

the Northwest, and has applied that 

estimate in its revised dietary risk 

assessment (Ref. 71). Based on the 

estimated 5% crop treated for potato, 

which is the highest PCT of any feed 

stuff that can be treated with carbofuran, 

EPA estimated a 5% CT for milk. 

23078 Federal Register / Vol. 74, No. 93 / Friday, May 15, 2009 / Rules and Regulations 

The Agency notes that these PCT 

changes on bananas, potatoes and milk 

had relatively modest effects on the 

dietary exposure estimates. The PCT 

estimates are used by the Agency to 

account for the fact that not all samples 

are treated, and that some fraction of 

samples (specifically, the complement 

to the PCT fraction) actually have 

residues of zero. This allows the Agency 

to incorporate a residue concentration of 

zero (a true zero) for that fraction of the 

crop which is not treated and a residue 

concentration of c the analytical limit of 

detection for that portion of the crop 

which is treated, but show no detectable 

residues because of insufficient 

sensitivity of the analytical method. 

Specifically in this case, if one were to 

assume for banana, potatoes, and milk 

that all samples without detectable 

residues were not treated and are thus 

‘‘true zeroes,’’ then exposure at the per 

capita 99.9th percentile falls only 

slightly: from 77.8% to 75.2% of the 

aPAD for children 1 to 2 years old, and 

from 45.4% to 44.1% of the aPAD for 

children 3-5 years old. 

The relative insensitivity of exposure 

estimates to PCT found under EPA’s 

most recent risk assessment based on 

the September 2008 revised label, is 

counter to earlier sensitivity analyses 

that the Agency performed that indicate 

exposures at the per capita 99.9th 

percentile fall by about 50% when all 

non-detects were set at 0 ppm (Ref. 70). 

Those effects were due to the 

watermelons and other commodities 

(cucumbers, cantaloupes) that were the 

primary source of unacceptable single 

exposures. The Half LODs for the four 

domestic uses that the commenters 

currently are interested in retaining, and 

milk, are relatively low, such that 

exposures from residues at Half LOD 

concentrations produce nominal 

contributions to high-end exposures. 

As a further consequence of the 

cancellation of the use on melons and 

cucmbers, the risk assessment now 

shows that single exposures from food 

alone are not expected to be the source 

of unacceptable single eating events. 

However, as discussed in Unit VIII.E.2. 

below, concerns still remain that 

children will receive unacceptable 

exposures from a single consumption of 

contaminated drinking water. Further, 

even after accounting for carbofuran’s 

reversibility throughout the day and the 

fact that drinking water can be 

consumed over multiple occasions 

during the day, EPA has concluded that 

carbofuran exposures through the 

drinking water pathway exceed the 

Agency’s level of concern for infants 

and children. 

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 ground water sources (Refs. 

17, 54, 58, 61, and 84). 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 ground water 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 endpoint of concern results from single-day 

exposure (acute effects). Because 

pesticide loads in surface water tend to 

move in relatively quick pulses in 

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 ground water 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 

NOAA. 

a. Exposure to carbofuran from 

drinking water derived from ground 

water sources. Drinking water taken 

from shallow wells is highly vulnerable 

to contamination in areas where 

carbofuran is used around sandy, highly 

acidic soil, although sites that are less 

vulnerable (e.g., deeper aquifer, higher 

organic matter) could still be prone to 

have concentrations exceeding 

acceptable exposures. The results of the 

ground water modeling simulations 

from the South-Central Wisconsin 

scenario show that the persistence of 

carbofuran in ground water is 

dependent on soil and water pH, and 

what might appear as relatively small 

variations in soil pH can have a 

significant impact on estimates of 

carbofuran in ground water. Estimated 

1–in–10-year peak ground water 

concentrations at pH 7 are 1.6 x 10-3 μg/ 

L; however, the estimated 1–in–10-year 

peak ground water concentration at pH 

6.5 is 16 μg/L, nearly 4 orders of 

magnitude greater. Because of 

carbofuran’s sensitivity to pH, EPA has 

concerns that any given set of mitigation 

measures will not successfully protect 

ground water source drinking water. 

Data indicate that pH varies across an 

agricultural field, and also with depth 

(Ref. 64). In particular, the pH can be 

different in ground water than in the 

overlying soil. The upper bound of the 

carbofuran concentrations estimated by 

EPA at pH 6.5 is much greater than the 

concentrations FMC report in their 

comments. 

In EPA’s revised assessment, ground 

water concentrations were estimated for 

all remaining crops on carbofuran 

labels, and used two new Tier 2 

scenarios. Based on a new corn 

scenario, representative of potentially 

vulnerable areas in the upper Midwest, 

EPA estimated 1–in–10-year 

concentrations for ground water source 

drinking water of 16 to 1.6 x 10-3 μg/ 

L, for pH 6.5 and 7, respectively. A 

potato scenario representing use in the 

Northwest estimated no measurable 

concentrations of carbofuran in ground 

water. Other remaining uses were 

modeled using a Tier 1 ground water 

model (Screening Concentration inGroundwater) with estimated peak 90– 

day concentrations of 48 – 178 μg/L, 

depending on application rate. Well 

setback prohibitions of 50 feet were 

proposed on the new label for the 

flowable and granular formulations in 

select counties in Kentucky (seven 

counties), Louisiana (one county), 

Minnesota (one county), and Tennessee 

(one county). Analysis of the impact of 

these setbacks for the use on corn 

indicated that the setbacks would not 

reduce concentrations significantly at 

locations where exposure to carbofuran 

in ground water is of concern because 

Federal Register / Vol. 74, No. 93 / Friday, May 15, 2009 / Rules and Regulations 23079 

5Although higher estimates were generated at a 

pH of 5.25, use should be precluded in such sites 

based on the September 2008 labels. 

at acid pHs, carbofuran does not 

degrade sufficiently during the travel 

time from the application site to the 

well to substantially reduce the 

concentration. 

Exposure estimates for this 

assessment are drawn primarily from 

EPA’s modeling. To conduct its 

modeling, EPA examined readily 

available data with respect to ground 

water and soil pH to evaluate the spatial 

variability of pH. Ground water pH 

values can span a wide range; this is 

especially true for shallow ground water 

systems, where local conditions can 

greatly affect the quality and 

characteristics of the water (higher or 

lower pHs compared to average values). 

Thus, average ground water pH values 

for a given area do not truly characterize 

the (temporal and especially spatial) 

heterogeneity common in most areas. 

This can be seen by comparing 

differences in pH values between 

counties within a state, and noting that 

even within each county specific area, 

wells will consistently yield ground 

water with either above- or belowaverage pH values for that county. The 

ground water simulations reflect 

variability in pH by modeling 

carbofuran leaching in four different pH 

conditions (pH 5.25, 6.5, 7.0, and 8.7), 

representing the range in the Wisconsin 

aquifer system. The upper and lower 

bound of pH values that EPA chose for 

this assessment were measured values 

from the aquifer, and the remaining two 

values were chosen to reflect common 

pH values between the measured values. 

The Idaho potato scenario is 

representative of areas where ground 

water is relatively deep and the soils 

have a relatively alkaline pH. The 

results from the Idaho potato ground 

water simulation estimated no 

measurable concentrations of carbofuran 

in ground water. This is consistent with 

EPA’s findings above, as soils where 

potatoes are typically grown are more 

alkaline. 

The results of EPA’s revised corn 

modeling, based on a new scenario in 

Wisconsin, are consistent with the 

results of the PGW study developed by 

the registrant in Maryland in the early 

1980s. Using higher use rates than 

currently permitted, the peak 

concentration measured in the PGW 

study was 65 ppb; when scaled to 

current use rates, the estimated peak 

concentration was 11 ppb. EPA’s 

modeling is also consistent with a 

number of other targeted ground water 

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 

References 17 and 84. For example, a 

study in Manitoba, Canada assessed the 

movement of carbofuran into tile drains 

and ground water 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 ground water samples 

ranged between 0 (non-detect) and 158 

ppb, with a mean of 40 ppb (Refs. 17 

and 84). 

While there have been additional 

ground water 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. 

However, as discussed in the next 

section, 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 

supplies in 16 states, carbofuran was 

found at one public ground water 

system at a concentration of greater than 

7 ppb and in two ground water systems 

at concentrations greater than 4 ppb 

(measurements below this limit were 

not reported). An infant receiving these 

concentrations receive 220% of the 

aPAD or 130% aPAD, respectively, 

based on a single 8 ounce serving of 

water. As this monitoring was not 

targeted to carbofuran, the likelihood is 

low that these samples capture peak 

concentrations. Given the lack of 

targeted monitoring, EPA has primarily 

relied on modeling to develop estimates 

of carbofuran residues in ground water 

sources of drinking water. 

Based on EPA’s assessment, the 

maximum 1–in–10–year peak 

carbofuran concentrations in vulnerable 

ground water for a single application on 

corn in Wisconsin, at a rate of 1 pound 

per acre were estimated to range from a 

low of less than 1 ppb based on a pH 

of 7 or higher, to a high of 16 ppb, based 

on a pH of 6.55. Because the degradate, 

3-hydroxycarbofuran, which is assumed 

to be of equal potency with the parent 

compound, was not measured in the 

PGW study, and key environmental fate 

data are not available to use in 

modeling, 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 compiled a distribution of 

estimated carbofuran concentrations in 

water based on these estimates that were 

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 3. 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 ground water can have a 

significant impact on the aPAD utilized. 

TABLE 3.—RESULTS OF ACUTE DIETARY (GROUND WATER ONLY) EXPOSURE ANALYSIS USING DEEM-FCID(TM) AND

INCORPORATING THE WISCONSIN GROUND WATER SCENARIO, PH OF 6.5 (REPRESENTING PRIVATE WELLS) 

Population Subgroup aPAD (mg/ 

kg/day) 

95th Percentile 99th Percentile 99.9th Percentile 

Exposure 

(mg/kg/day) % aPAD Exposure (mg/kg/day) % aPAD Exposure (mg/kg/day) % aPAD 

All Infants (< 1 year old) 0.000075 0.001602 2,100 0.003536 4,700 0.007078 9,400 

Children 1–2 years old 0.000075 0.000677 900 0.001481 2,000 0.003163 4,200 

Children 3–5 years old 0.000075 0.000623 830 0.001345 1,800 0.002845 3,800 

23080 Federal Register / Vol. 74, No. 93 / Friday, May 15, 2009 / Rules and Regulations 

TABLE 3.—RESULTS OF ACUTE DIETARY (GROUND WATER ONLY) EXPOSURE ANALYSIS USING DEEM-FCID(TM) AND

INCORPORATING THE WISCONSIN GROUND WATER SCENARIO, PH OF 6.5 (REPRESENTING PRIVATE WELLS)—Continued 

Population Subgroup aPAD (mg/ 

kg/day) 

95th Percentile 99th Percentile 99.9th Percentile 

Exposure 

(mg/kg/day) % aPAD Exposure (mg/kg/day) % aPAD Exposure (mg/kg/day) % aPAD 

Children 6–12 years old 0.000075 0.000431 570 0.000934 1,200 0.002015 2,700 

Youth 13–19 years old 0.0002 0.000334 170 0.000756 380 0.001743 870 

Adults 20–49 years old 0.0002 0.000414 210 0.000893 450 0.001890 950 

Adults 50+ years old 0.0002 0.000413 210 0.000852 430 0.001546 770 

While the registrant has attempted to 

address drinking water exposure from 

ground water sources by including 

additional restrictions on their 

September 2008 proposed labels, EPA’s 

analyses show that these do not 

sufficiently reduce exposures to 

acceptable levels. The proposed labels 

include well setback prohibitions at 50– 

foot-distances for the flowable and 

granular formulations in a select set of 

counties in Kentucky, Louisiana, 

Minnesota, and Tennessee. The impact 

of the well setbacks was modeled for the 

corn use using the approach developed 

for the NMC cumulative assessment 

(Ref. 107), resulting in reductions in 

concentrations that vary with pH (to 

account for degradation of the 

compound in subsurface flow from the 

application site to a private well down 

gradient). At acid pHs the slow 

degradation rate reduced the 

effectiveness of a 50–foot well setback at 

the well head (1–in–10–year peak 

concentration of 16 to 14 μg/L, a 

reduction factor of 0.73 at pH 6.5). 

Additional setback distances (100, and 

300 ft) were evaluated using an aquifer 

pH of 6.5, resulting in reduction factors 

of 0.54 and 0.16, respectively. At 

alkaline pH, the 50-foot setback is 

effective, but concentrations at these 

sites are already low due to hydrolytic 

degradation occurring during recharge. 

These results suggest that a 50–foot well 

setback is less effective in low pH 

environments due to the persistence of 

carbofuran under these conditions. 

In addition, the revised labels prohibit 

use throughout the Atlantic Coastal 

plain, and prohibit application to areas 

with soils greater than 90% sand and 

less than 1% organic matter, acidic soil 

and water conditions, and where 

shallow water tables predominate (e.g., 

where ground water is less than 30 feet). 

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, these criteria are not sufficient to 

prohibit use in all areas that could 

reasonably be expected to be vulnerable 

to ground water contamination from 

carbofuran use. Based on carbofuran’s 

characteristics, a diversity of soil 

conditions in the remaining proposed 

use area, and available monitoring data, 

there are valid scientific reasons to 

believe that additional soil and site 

characteristics could result in ground 

water contamination. For example, 

water table depth can vary with the time 

of the year, depending on such factors 

as the amount of rainfall that has 

occurred in the recent past, and how 

much irrigation has been applied to a 

field or removed from the aquifer. It is 

difficult to determine how the depth to 

the water table varies throughout fields, 

and the definition of a ‘‘shallow’’ water 

table on the September 2008 label is 

indeterminate (e.g., less than 30 ft.). 

Furthermore, the vulnerability 

associated with depth varies with 

location, for example, deeper aquifers 

may be vulnerable in areas with greater 

precipitation and rapid recharge. The 

September 2008 label restrictions in no 

way addressed these less sensitive, but 

still vulnerable, sites (Refs. 94 and 111). 

Accordingly, EPA continues to believe 

that its assessment of drinking water 

from ground water sources based on 

current labels is a reasonable 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 ground water, 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 ground water wells, drinking 

water from 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 

processes are less effective in removing 

carbofuran (Ref. 107). 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 

approximately 130% of the aPAD from 

water consumption alone. 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 

approximately 220% of the aPAD from 

water consumption alone. 

To further characterize carbofuran 

concentrations in surface water (e.g., 

Federal Register / Vol. 74, No. 93 / Friday, May 15, 2009 / Rules and Regulations 23081 

streams or rivers) that may drain into 

drinking water reservoirs, EPA analyzed 

the extensive source of national water 

monitoring data for pesticides, the 

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 

carbofuran was detected, these nontargeted 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-parts 

per billion range reported in additional 

watersheds (Ref. 107). The highest 

concentrations of carbofuran are 

reported from a sampling station on 

Zollner Creek, in Oregon. Zollner Creek, 

located in the Molalla-Pudding subbasin 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 and levels of approximately 1 to 

10 ppb measured in streams 

representative of those in watersheds 

that support drinking water systems 

(Ref. 107). 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 that the risks posed by 

carbofuran in surface drinking water are 

below thresholds of concern. Nor can 

the non-detections in the monitoring 

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. 

22 and 94) 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 CRA (Ref. 107). 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. For example, lime 

softening would likely reduce 

carbofuran concentrations. That process 

is used in 3 to 21% of drinking water 

treatment systems in the United States 

(Ref. 19). Activated carbon has been 

shown to also reduce carbofuran 

concentrations, but is used in 1 to 15% 

of drinking water treatment facilities 

(Ref. ibid.). 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 for many of the scenarios, 

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. 

Subsequently, for a refined 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. 17, 53, and 84). 

EPA 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 

23082 Federal Register / Vol. 74, No. 93 / Friday, May 15, 2009 / Rules and Regulations 

typical rather than maximum label rates, 

another set included simulation of 

different types of applications to corn 

(e.g., applications to control European 

corn borer, a rescue treatment for corn 

rootworm, and an in-furrow application 

at plant). 

For this final rule, EPA conducted 

additional refined modeling, based on 

the September 2008 label submitted by 

FMC. The modeling addressed all of the 

domestic uses that remain registered, 

and included certain refinements to 

better understand the impacts of varying 

pH. EPA also conducted modeling to 

assess the impact of the proposed spray 

drift buffer requirements and other 

spray drift measures included on the 

September label. 

EPA estimated carbofuran 

concentrations resulting from the use on 

pumpkins by adjusting the EDWCs from 

a previous run simulating melons in 

Missouri; adjustments accounted for 

differences in application rate and row 

spacing. Two EDWCs were calculated 

for pumpkins: One based on a 36–inch 

row spacing, representing pumpkins for 

consumption (77.6 μg/L); and a second 

based on a 60–inch row spacing, 

representing decorative pumpkins (46.6 

μg/L). 

EPA had previously evaluated the 

corn rootworm rescue treatment at 

seven representative sites, 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, peak 

concentrations for the corn rescue 

treatments simulated for Illinois, Iowa, 

Indiana, Kansas, Minnesota, Nebraska, 

and Texas ranged from 16.6 – 36.7 ppb 

(Ref. 61). Under the revised assessment 

to account for the new use restrictions, 

concentrations for corn, calculated 

including the proposed spray drift 

buffers in Kansas and Texas, decreased 

5.1% and 4.7%, respectively, from 

simulations with no buffer from the 

previous assessment (Ref. 61). In 

Kansas, the 1–in–10-year peak EDWCs 

decreased from 33.5 to 31.8 ppb when 

a 300–foot buffer was added, and in 

Texas, from 29.9 to 28.5 ppb with the 

addition of a 66–foot buffer. 

For the sunflower use, 12 simulations 

were performed for sunflowers, 9 in 

Kansas, and 3 in North Dakota. The 

North Dakota scenario was used to 

represent locations where sunflowers 

are grown that are vulnerable to 

pesticide movement to surface water 

while the Kansas scenario represents 

places that are not particularly 

vulnerable, based on the limited rainfall 

and generally well-drained soils 

(hydrologic group B soils) that are found 

in that area. Estimated 1–in–10–year 

concentrations ranged from 11.6 to 32.7 

μg/L. When simulating three 

applications, one at plant and two foliar 

with a 14–day interval between the two 

foliar applications and a 66–foot buffer, 

the 1–in–10-year peak EDWC for North 

Dakota was 22.4 μg/L. In contrast, the 

same three applications in Kansas with 

a 14–day interval between the foliar 

applications and a 300-foot buffer 

produced a 1–in–10-year peak EDWC of 

20.5 μg/L. The 1–in–10–year peak 

EDWCs assuming that carbofuran is 

applied only at plant were 14.0 and 16.0 

μg/L in Kansas and North Dakota 

respectively. EPA also evaluated the 

impact of pH on carbofuran 

concentrations for sunflowers, resulting 

in a 10% decrease in 1–in–10–year peak 

concentrations assuming high pH in the 

reservoir. Spray drift buffers of 66 and 

300 feet decreased concentrations 4.7 

and 5.1% for corn and 10.0% and 

16.0% for sunflowers, respectively, in 

comparison to previous labels that had 

no spray drift buffer requirements. 

Additional details on these assessments 

can be found at Reference 111. 

Consistent with the analysis 

summarized above these predicted 

carbofuran water concentrations are 

similar or lower than the peak 

concentrations reported in the USGSNAWQA 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. 17). 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. 74). 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 conduit to transport water and 

contaminants from the field to surface 

waters. 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 2 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 (modelderived) peak concentrations of 

carbofuran are similar to peak 

concentrations reported in stream 

monitoring studies. These 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 proposed September 

2008 label. Exposures from all modeled 

scenarios substantially exceeded EPA’s 

level of concern (Ref. 16). For example, 

a Kansas sunflower scenario, assuming 

two foliar applications at a typical 1-lb 

a.i. per acre use rate, applied at 14–day 

intervals, estimated a 1–in–10-year peak 

carbofuran water concentration of 11.6 

ppb. Exposures at the 99.9th percentile 

based on this modeled distribution 

ranged from 160% of the aPAD for 

youths 13 to 19 years, to greater than 

2,000% of the aPAD for infants. As 

previously noted, this scenario is 

intended to be representative of sites 

that are less vulnerable than most on 

which sunflowers could be grown. By 

contrast, exposure estimates from a 

comparable North Dakota sunflower 

scenario, intended to represent more 

vulnerable sites, estimated a 1–in–10- 

year peak concentration of 22.4 ppb. 

These concentrations would result in 

estimated exposures ranging between 

450% aPAD for youths 13 to 19 years, 

to 5,500% aPAD for infants. Similarly, 

exposures based on a Washington 

surface water potato scenario, and using 

a 3 lb a.i. acre rate, ranged from 230% 

of the aPAD for children 6 to 12 years 

to 890% of the aPAD for infants, with 

a 1–in–10-year peak carbofuran 

concentration of 7.2 ppb. Although 

other crop scenarios resulted in higher 

exposures, estimates for these two crops 

are presented here, as they are major 

Federal Register / Vol. 74, No. 93 / Friday, May 15, 2009 / Rules and Regulations 23083 

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 

References 16, 61, and 84. 

Restricting the sunflower application 

to a single at-plant application from 

three applications reduces the 1–in–10– 

year peak EDWCs from 32.7 to 16.0 μg/ 

L for the North Dakota scenario and 

from 20.5 to 14.0 μg/L in western 

Kansas. These concentrations would 

result in estimated exposures, based on 

the North Dakota scenario ranging 

between 350% aPAD for youths 13 to 19 

years, to 4,300% aPAD for infants. 

Based on the Kansas scenario, the 

estimated exposures would range 

between 250% aPAD for youths 13 to 19 

years, to 3,100% aPAD for infants. 

Table 4 below presents the results of 

one of EPA’s refined exposure analyses 

that 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 postplant, 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 HUC-8–sized basin in the United 

States. (The USGS has classified all 

watersheds in the United States 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 

References 16, 61, and 84. 

TABLE 4.—RESULTS OF ACUTE DIETARY (SURFACE WATER ONLY) EXPOSURE ANALYSIS INCORPORATING THE NEBRASKA

CORN ROOTWORM RESCUE SCENARIO

Population Subgroup aPAD (mg/ 

kg/day) 

95th Percentile 99th Percentile 99.9th Percentile 

Exposure 

(mg/kg/day) % aPAD Exposure (mg/kg/day) % aPAD Exposure (mg/kg/day) % aPAD 

All Infants (< 1 year old) 0.000075 0.000424 560 0.001201 1,600 0.002895 3,900 

Children 1–2 years old 0.000075 0.000182 240 0.0005047 670 0.001261 1,700 

Children 3–5 years old 0.000075 0.000169 230 0.000461 620 0.001137 1,500 

Children 6–12 years old 0.000075 0.000117 160 0.000320 430 0.000794 1,100 

Youth 13–19 years old 0.0002 0.000087 43 0.000248 120 0.000760 380 

Adults 20–49 years old 0.0002 0.000113 57 0.000305 150 0.000760 380 

Adults 50+ years old 0.0002 0.000120 60 0.000300 150 0.000672 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 

198% to 2,340% 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. 

As noted, EPA’s modeling indicates 

that while there is some mitigation 

value in the use of spray drift buffers, 

the loading to surface water is 

dominated by runoff even in semi-arid 

locations such as western Kansas, and 

the proposed mitigation measures do 

not substantially reduce exposure to 

carbofuran in surface water source 

drinking water systems. 

It is important to note that spray drift 

calculations have been conducted 

assuming that certain BMPs were used 

during the aerial spray application. 

Those practices are c swath 

displacement windward, a 10 foot 

release, wind speed no greater than 10 

mph, and a spray boom less than 75% 

of the aircraft’s wing (Ref. 106). There is 

advisory language on the revised labels 

regarding wind speed (‘‘Drift potential 

increases at wind speeds less the 3 mph 

(due to inversion potential) or more 

than 10 mph,’’ and boom height 

(‘‘setting the boom to the lowest height 

(if specified) which provides uniform 

coverage reduces the exposure of 

droplets to evaporation and wind.’’). 

The boom width is specifically 

restricted (‘‘the boom length should not 

exceed d the wing or rotor length.’’). 

There is no language on the label 

regarding swath displacement. While 

these ‘‘best management practices’’ are 

frequently used by aerial applicators, 

they are not used universally. To the 

extent these management practices are 

not used, EPA’s assessment would 

underestimate the additional loading 

expected to result from spray drift. 

Equally important is that EPA only 

assumed that the buffers would be 

effective in reducing spray drift from 

neighboring fields, rather than assuming 

that the buffers would be effective in 

preventing or mitigating field runoff. As 

explained in the proposed rule, EPA 

disagrees that these measures will be 

effective in reducing carbofuran’s 

movement to surface water. The 

proposed buffers were for fields where 

23084 Federal Register / Vol. 74, No. 93 / Friday, May 15, 2009 / Rules and Regulations 

soils were considered to be highly 

erodible. Buffer widths varied, 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. 98). 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, unvegetated buffers around water bodies, 

often referred to a ‘setback,’ are 

ineffective in reducing pesticide 

movement to surface water. 

As discussed in Unit VII.C.2., FMC 

has criticized EPA’s assessment for 

failing to account more fully for the 

percent of the crop likely to be treated 

in its modeling. 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 

factor 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. To be clear, this means that 

EPA assumed that 10% of the 46% of 

the watershed on which corn could be 

grown, would be treated with 

carbofuran, resulting in less than 5% of 

the watershed treated with carbofuran— 

an assumption that clearly 

underestimates exposures in many 

highly agricultural areas, such as 

Nebraska, and as discussed previously, 

requires several unrealistic 

assumptions. 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 

to 12 years 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 References 16, 17, and 84. 

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 even if EPA were to 

apply an extremely low PCT, aggregate 

exposures would still exceed 100% of 

the aPAD. 

In response to this sensitivity 

analysis, which had been presented in 

the proposed rule, FMC complained that 

EPA had failed to account in these 

analyses for the rapid nature of 

carbofuran’s recovery. Or in other 

words, the commenter wanted EPA to 

both apply a PCT figure and conduct an 

Eating Occasion Analysis, claiming that 

this analysis would show that 

carbofuran ‘‘passed.’’ 

EPA disagrees that conducting the 

analysis the commenter suggests would 

be appropriate, or would provide any 

information on which EPA could 

properly rely to support a determination 

of safety. As previously explained, the 

available information and methodology 

does not allow EPA to generate PCT 

estimates with any degree of confidence, 

and certainly not with the ‘‘reasonable 

certainty’’ demanded by the statute. 

EPA conducted its analysis purely in an 

attempt to understand the extent to 

which its assumption of PCT affected 

the risk assessment conclusions. It is not 

necessary to gain an understanding of 

the PCT impact, to compound the 

uncertainty by adding assumptions 

about the reversibility of carbofuran’s 

effects. 

The commenter provided the results 

of their dietary assessment, in which 

they appear to have conducted the 

analysis suggested above, and reported 

that the aPAD for infants from aggregate 

exposures (i.e., food + water) was 

107.06%. As previously discussed, the 

commenter did not provide any of the 

underlying support documentation for 

these reported results, and EPA was 

unable to replicate them. However, in 

its efforts to replicate the commenter’s 

analysis, the lowest aggregate exposure 

EPA was able to estimate for infants 

using the commenter’s PCT and half-life 

inputs was 126% of the aPAD, a figure 

that, for reasons discussed 

subsequently, is certainly an 

underestimate of exposure. Further 

discussion of the Eating Occasion 

Analyses EPA conducted for carbofuran 

is presented in Unit VIII.E.1.d. and in 

Reference 112. 

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 

within the range obtained from the 

monitoring and the model simulations 

are 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 

regarding locations in the country where 

the potential for carbofuran 

contamination to surface water and 

associated drinking water sources is 

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. 

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. As discussed in Unit V.B.3., 

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 

Federal Register / Vol. 74, No. 93 / Friday, May 15, 2009 / Rules and Regulations 23085 

time and location for a variety of 

reasons. Consequently, EPA conducted 

several estimates of aggregate dietary 

risks by combining exposures from food 

and drinking water. These estimates 

showed that, because drinking water 

exposures from any of the crops on the 

label exceed safe levels, aggregate 

exposures from food and water are 

unsafe. Although EPA’s assessments 

showed that, based on the Idaho potato 

scenarios, exposures from ground water 

from use on potatoes would be safe, 

surface water exposures from carbofuran 

use on potatoes far exceed the safety 

standard. 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 References 16 

and 17. 

Table 5 reflects the results of 

aggregate exposures from food and from 

drinking water derived from ground 

water in extremely vulnerable areas (i.e., 

from shallow wells associated with 

sandy soils and acidic aquifers, such as 

are found in Wisconsin). The estimates 

range between 780% of the aPAD for 

adults, to 9,400% of the aPAD for 

infants. 

TABLE 5.—RESULTS OF ACUTE DIETARY (FOOD AND WATER) EXPOSURE ANALYSIS INCORPORATING THE WISCONSIN

GROUND WATER SCENARIO PH 6.5 

Population Subgroup aPAD (mg/ 

kg/day) 

95th Percentile 99th Percentile 99.9th Percentile 

Exposure 

(mg/kg/day) % aPAD Exposure (mg/kg/day) % aPAD Exposure (mg/kg/day) % aPAD 

All Infants (< 1 year old) 0.000075 0.001602 2,100 0.003537 4,700 0.007053 9,400 

Children 1–2 years old 0.000075 0.000680 910 0.001490 2,000 0.003180 4,200 

Children 3–5 years old 0.000075 0.000626 840 0.001350 1,800 0.002845 3,800 

Children 6–12 years old 0.000075 0.000432 580 0.000935 1,200 0.002019 2,700 

Youth 13–19 years old 0.0002 0.000334 170 0.000751 380 0.001721 860 

Adults 20–49 years old 0.0002 0.000415 210 0.000896 450 0.001906 950 

Adults 50+ years old 0.0002 0.000415 210 0.000853 430 0.001552 780 

The peak concentration estimates in 

the Wisconsin ground water 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 34 

ppb while maximum values from a 

targeted ground water monitoring study 

in Maryland, with a higher application 

rate, was 65 ppb, with studies at other 

sites having similar or higher peak 

concentrations (Refs. 17 and 84). 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 

11 ppb. 

Table 6 presents the results of 

aggregate exposure from food and water 

derived from one of the least 

conservative surface water scenarios: 

Kansas sunflower, with two foliar 

applications. This table reflects the risks 

only for those people in watersheds 

with characteristics similar to that used 

in the scenario, and assuming that water 

treatment does not remove carbofuran. 

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 6.—RESULTS OF ACUTE DIETARY (FOOD AND WATER) EXPOSURE ANALYSIS USING THE DEEM-FCID(TM) AND

INCORPORATING THE KANSAS SURFACE WATER SUNFLOWER FOLIAR APPLICATION PH 7.8 SCENARIO

Population Subgroup aPAD (mg/ 

kg/day) 

95th Percentile 99th Percentile 99.9th Percentile 

Exposure 

(mg/kg/day) % aPAD Exposure (mg/kg/day) % aPAD Exposure (mg/kg/day) % aPAD 

All Infants (< 1 year old) 0.000075 0.000087 120 0.000425 570 0.001555 2100 

Children 1–2 years old 0.000075 0.000044 59 0.000185 250 0.000660 880 

Children 3–5 years old 0.000075 0.000039 53 0.000172 230 0.000610 800 

Children 6–12 years old 0.000075 0.000027 36 0.000117 160 0.000416 560 

Youth 13–19 years old 0.0002 0.000019 10 0.000089 45 0.000330 160 

Adults 20–49 years old 0.0002 0.000026 13 0.000114 57 0.000395 200 

Adults 50+ years old 0.0002 0.000028 14 0.000119 60 0.000373 190 

23086 Federal Register / Vol. 74, No. 93 / Friday, May 15, 2009 / Rules and Regulations 

More details on this assessment, as 

well as the assessments EPA conducted 

for other crop scenarios, can be found in 

References 16, 61, and 84. For example, 

in the proposed rule, EPA presented the 

results from aggregate exposures 

resulting from a Nebraska surface water 

scenario based on a Nebraska corn 

rootworm ‘‘rescue treatment.’’ Estimated 

exposures from that scenario ranged 

from 330% of the aPAD for youths 13 

to 19 years to 3,900% of the aPAD for 

infants. 

As noted previously, EPA’s food and 

water exposure assessments typically 

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 durations 

of exposure less than 24 hours. 

Accordingly, EPA has conducted an 

analysis using information about dietary 

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 to 

recovery information (herein called halflife information) to estimate the residual 

effects from carbofuran from previous 

exposures within the day. The 

carbofuran analyses are described in the 

2009 aggregate (dietary) memo (Ref. 71). 

EPA used the same approach for 

considering the impact of carbofuran’s 

rapid reversibility on exposure 

estimates in the food and drinking water 

risk assessments that had been 

previously used in the cumulative risk 

assessment of the NMC pesticides and/ 

or risk assessments for other NMC 

pesticides (e.g., methomyl and aldicarb) 

(Ref. 107). 

Using the two FMC time course 

studies in rat pups, EPA calculated halflives for recovery of 186 and 426 

minutes. The two values were derived 

from two different studies using rat 

pups of the same age (Refs. 30 and 31); 

the two values provide an indication 

that half-lives to recovery can vary 

among juvenile rats. By extension, 

children are expected to vary in their 

ability to recover from AChE inhibition 

where longer recoveries would be 

associated with a potentially higher 

‘‘persisting dose’’ (as described below). 

Incorporating Eating Occasion Analysis 

and the 186–minute or 426–minute 

recovery half-lives 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 from food alone. 

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 also 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, as shown in the 

above example. 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 Idaho potato surface 

water scenario, which estimated one of 

the lowest exposure distributions, 

aggregate exposures at the 99.9th 

percentile ranged from 328% of the 

aPAD under the scenario for which 

infants rapidly metabolize carbofuran 

(e.g., 186 minute half-life), to a high of 

473% of the aPAD under the scenario 

for which infants metabolize carbofuran 

more slowly, (e.g., scenarios in which a 

426 minute half life is assumed). 

Moreover, even accounting for the 

estimated decreased risk from 

accounting for carbofuran’s rapid 

reversibility, the Agency remains 

concerned about the risks from single 

eating or drinking events, as illustrated 

in the following example, based on an 

actual food consumption diary from the 

CSFII survey. A 4–month old male nonnursing infant weighing 10 kg is 

reported to have consumed a total of 

1,070 milliters (ml) of indirect water 

over eight different occasions during the 

day. The first eating occasion occurred 

at 6:30 a.m., when this 4 month old 

consumed 8 fluid ounces of formula 

prepared from powder. The FCID food 

recipes indicate that this particular food 

item consists of approximately 87.7% 

water, and therefore, 8 ounces of 

formula contains approximately 214 ml 

(or grams) of indirect water; with the 

powder (various nutrients, dairy, soy, 

oils, etc.) accounting for the remaining 

12.3%. This infant also reportedly 

consumed a full 8–ounce bottle of 

formula at 12 p.m., 4 p.m., and 8 p.m. 

that day. The food diary also indicates 

that the infant consumed about 1 

tablespoon of water (14.8 ml) added to 

prepare rice cereal at 10:00 a.m., about 

2 ounces of water (59.3 ml) added to 

pear juice at 11 a.m., another c tsp of 

water (2.5 ml) to prepare more rice 

cereal at 8:30 p.m.; and finally, he 

consumed another 4 ounces of formula 

(107 ml) at 9:30 p.m. 

The infant’s total daily water intake 

(1,070 ml, or approximately 107 ml/kg/ 

day) is not overly conservative, and 

represents substantially less than the 

90th percentile value from CSFII on a 

ml water/kg bodyweight (ml/kg/bw) 

basis. As noted, carbofuran has been 

detected in finished water at 

concentrations of 4 ppb. For this 10 kg 

body weight infant, an 8–ounce bottle of 

formula prepared from water containing 

carbofuran at 4 ppb leads to drinking 

water exposures of 0.0856 micrograms 

of active ingredient/kilogram of 

bodyweight (μg ai/kg bw), or 114% of 

the aPAD. Based on the total daily water 

intake of 1,070 ml/day (no reversibility), 

total daily exposures from water at 4 

ppb concentration would amount to 

0.4158 μg ai/kg bw, or 555% of the 

aPAD; this is the amount that would be 

used for this person-day in the Total 

Daily Approach. 

Peak inhibition occurs following each 

occasion on which the infant consumed 

8 fluid ounces of formula (6 a.m., 12 

p.m., 4 p.m. and 8 p.m.); however, the 

maximum persisting dose occurs 

following the 9:30 p.m. eating occasion, 

based on a 186–minute half-life 

parameter. This produces a maximum 

persisting dose of 0.1457 μg ai/kg bw, or 

about 30% of the total daily exposure of 

0.4158 μg ai/kg bw derived above, or 

expressed as a fraction of the level of 

concern, the maximum persisting dose 

amounts to about 194% of the aPAD (or 

30% of 554%). Note that with drinking 

water concentration at 4 ppb, an infant 

consuming one 8 oz bottle of formula - 

prepared from powder and tap water 

containing carbofuran at 4 ppb will 

obtain exposures of approximately 

114% of aPAD. Since many infants 

consume the equivalent of this amount 

on a single eating occasion, accounting 

for reversibility over multiple occasions 

is not essential to ascertain that infants 

quite likely have obtained drinking 

water exposures to carbofuran 

exceeding the level of concern based on 

drinking water concentrations found in 

public drinking water supplies. 

The approach discussed above is 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 from 

carbofuran is indeed not substantively 

overestimated using the current 

Federal Register / Vol. 74, No. 93 / Friday, May 15, 2009 / Rules and Regulations 23087 

exposure models and the 24–hour 

approach. 

In this regard, it is important to note 

EPA’s Eating Occasion Analyses 

underestimate exposures to the extent 

that they do not take into account carryover effects from previous days, and 

because drinking water concentrations 

are randomly picked from the entire 30– 

year distribution. As discussed 

previously, DEEM-FCID(TM) is a single 

day dietary exposure model, and the 

DEEM-based Eating Occasion Analysis 

accounts for reversibility within each 

simulated person-day. All of the 

empirical data regarding time and 

amounts consumed (and corresponding 

exposures based on the corresponding 

residues) from the CSFII survey are 

used, along with the half-life to assess 

an equivalent persisting dose that 

produced the peak inhibition expected 

over the course of that day. This is a 

reasonable assumption for food alone; 

since the time between exposure events 

across 2 days is relatively high 

(compared to the half-life)—most 

children (>9 months) tend to sleep 

through the night—and the time 

between dinner and breakfast the 

following morning is long enough it is 

reasonable to ‘‘ignore’’ persisting effects 

from the previous day. A single day 

exposure model will underestimate the 

persisting effects from drinking water 

exposures (formula) among infants, and 

newborns in particular (<3 months), 

since newborns tend to wake up every 

2 to 4 hours to feed. Any carry over 

effects may be important, especially if 

exposures from the previous day are 

relatively high, since the time between 

the last feeding (formula) of the day and 

the first feeding of the subsequent day 

is short. A single day model also does 

not account for the effect of seasonal 

variations in drinking water 

concentrations, which will make this 

effect more pronounced during the high 

use season (i.e., the time of year when 

drinking water concentrations are high). 

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 and water. 

The result of all of these analyses 

clearly demonstrates 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. 

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 ground water 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 drinking water from reservoirs 

located in small agricultural watersheds, 

prone to runoff, and predominated by 

crops that are treated with carbofuran, 

although there is more uncertainty 

associated with these exposure 

estimates. 

Although the recent cancellation of 

several registered uses has reduced the 

dietary risks to children, EPA’s analyses 

still show that estimated exposures 

significantly exceed EPA’s level of 

concern for children. 

While the registrant claims to have 

conducted an alternate analysis showing 

that aggregate carbofuran exposures to 

children will be safe, FMC failed to 

provide the data and details of that 

assessment to the Agency. They have 

also failed to provide several critical 

components that served to support key 

inputs into that assessment. And for 

several of these, EPA was unable to 

replicate the claimed results based on 

the information contained in the 

comments. In the absence of such 

critical components, the Agency cannot 

accept the validity or utility of the 

analyses, let alone rely on the results. 

But based on the summary 

descriptions provided in their 

comments, it is clear that the 

commenters’ analyses contain a critical 

flaw. The commenters’ determination of 

safety rests on the presumption that 

under real world conditions, events will 

always occur exactly as hypothesized by 

the multiple assumptions in their 

assessment. For example, they assume, 

despite all available evidence to the 

contrary, that children will not be 

appreciably more sensitive to 

carbofuran’s effects than adults. They 

assume that carbofuran’s effects will be 

highly reversible, and that children will 

be uniformly sensitive, such that the 

effects will be adequately accounted for 

by the assumption of a 150–minute halflife. They further assume that there will 

be no carry over effect from the 

preceding day’s exposures for infants. 

They assume that the cancellation of use 

on alfalfa will reduce carbofuran 

residues in milk by over 70%. They 

assume that residues will decrease 

between 19 and 23% as a result of the 

buffer requirements on the September 

2008 label, even though the label does 

not require the use of all of the 

recommended ‘‘best management 

practices’’ (e.g., no language regarding 

swath displacement), and applicators do 

not universally use such practices in the 

absence of any requirement. They 

assume that average ground water pH 

adequately characterizes the temporal 

and spatial heterogeneity common in 

most areas, despite the available 

evidence to the contrary. Finally, they 

assume that PCT in watersheds will 

never exceed 5% CT, despite varying 

pest pressures, consultant 

recommendations, and individual 

grower decisions. Leaving aside that 

EPA believes most, if not all of these 

assumptions are not supported by the 

available evidence, as described 

throughout this final rule, the 

probability of all these assumptions 

always simultaneously holding true 

under real world conditions is 

unreasonably low, and certainly does 

not approach the degree of certainty 

necessary for EPA to conclude that 

children’s exposures will be safe. 

Determining whether residues will be 

safe for U.S. children is not a theoretical 

paper exercise; it cannot suffice to 

hypothesize a unique set of 

circumstances that make residues ‘‘fit in 

the box.’’ There must be a reasonable 

certainty that under the variability that 

exists under real world conditions, 

exposures will be ‘‘safe.’’ EPA’s 

assessments incorporate a certain degree 

of conservatism precisely to account for 

the fact that assumptions must be made 

that may not prove accurate. This 

consideration is highly relevant for 

carbofuran, because as refined as EPA’s 

assessments are, areas of uncertainty 

remain with regard to carbofuran’s risk 

potential. For example, a recent 

epidemiological study reported that 

45% of maternal and cord blood 

samples in a cohort of New York City 

residents of Northern Manhattan and 

the South Bronx between 2000 and 

2004, contained low, but measurable 

residues of carbofuran (Ref. 118). The 

Agency is currently unable to account 

for the source of such sustained 

exposures at this frequency. 

A further consideration is that the 

risks of concern are acute risks to 

children. For acute risks, the higher 

values in a probabilistic risk assessment 

are often driven by relatively high 

values in a few exposures rather than 

relatively lower values in a greater 

number of exposures. 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 

consumption sources. Thus, to the 

extent that there is a high exposure it 

will be more likely due to a high residue 

value in a single consumption event. 

Additionally worrisome in this regard is 

that carbofuran is a highly potent (i.e., 

23088 Federal Register / Vol. 74, No. 93 / Friday, May 15, 2009 / Rules and Regulations 

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. 

In sum, these results strongly support 

EPA’s conclusion that aggregate 

exposures to carbofuran are not safe. 

IX. Procedural Matters 

A. When Do These Actions Become 

Effective? 

The revocations of the tolerances for 

all commodities will become effective 

December 31, 2009. EPA had proposed 

to establish an extended effective date 

for artichokes and sunflower seed; 

however, EPA ultimately agrees with 

those commenters who raised concern 

that continuance of use for an additional 

year on these crops would be 

inconsistent with the acute risks that 

carbofuran poses to children. 

Accordingly, the revocation for 

tolerances on these two crops will now 

be effective December 31, 2009. The 

Agency has set the effective date in 

December because this is the quickest 

time frame in which the decision could 

be practically implemented, given that 

some additional time will be necessary 

to allow the process applicable to stay 

requests to be completed. In addition, 

this time frame ensures that growers 

will have a reasonable amount of time 

to make reasoned decisions about their 

pest management strategies, and to 

exhaust any stocks of carbofuran 

currently in their possession. 

Any commodities listed in this rule 

treated with the pesticide subject to this 

rule, and in the channels of trade 

following the tolerance revocations, 

shall be subject to FFDCA section 

408(l)(5). 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. 

B. Request for Stay of Effective Date 

A person filing objections to this final 

rule may submit with the objections a 

petition to stay the effective date of this 

final rule. Such stay petitions must be 

received by the Hearing Clerk on or 

before July 14, 2009. A copy of the stay 

request filed with the Hearing Clerk 

shall be submitted to the Office of 

Pesticide Programs Docket Room. A stay 

may be requested for a specific time 

period or for an indefinite time period. 

The stay petition must include a citation 

to this final rule, the length of time for 

which the stay is requested, and a full 

statement of the factual and legal 

grounds upon which the petitioner 

relies for the stay. 

EPA received comments asserting that 

a hearing would definitely be requested, 

and requesting a stay pending resolution 

of that hearing. 

Until EPA has published its final rule, 

any request for a stay is purely 

speculative. EPA is only authorized to 

issue a stay of the regulation, ‘‘if after 

issuance of such regulation or order, 

objections are filed with respect to such 

regulation...’’ 21 U.S.C. 346a(g)(1). No 

objections have been filed, nor could 

they be until EPA publishes its final 

rule. Further, no demonstration has yet 

been made that any hearing is 

warranted, nor indeed, could the 

commenters have done so at this stage 

of the tolerance revocation process. See, 

40 CFR 178 Subpart B. EPA’s 

regulations require all parties who 

request a stay to justify the request with 

a statement of the factual and legal 

grounds upon which the petitioner 

relies. To the extent the commenters 

still wish to seek a stay of EPA’s final 

rule, they will have the opportunity to 

do so, as discussed above. 

In determining whether to grant a 

stay, EPA will consider the criteria set 

out in the Food and Drug 

Administration’s regulations regarding 

stays of administrative proceedings at 

21 CFR 10.35. Under those rules, a stay 

will be granted if it is determined that: 

(1) The petitioner will otherwise 

suffer irreparable injury; 

(2) The petitioner’s case is not 

frivolous and is being pursued in good 

faith; 

(3) The petitioner has demonstrated 

sound public policy grounds supporting 

the stay; 

(4) The delay resulting from the stay 

is not outweighed by public health or 

other public interests. 

Under FDA’s criteria, EPA may also 

grant a stay if EPA finds such action is 

in the public interest and in the interest 

of justice. 

Any person wishing to comment on 

any stay request may submit such 

comments and objections to a stay 

request to the Hearing Clerk, on or 

before July 29, 2009. Any subsequent 

decisions to stay the effect of this order, 

based on a stay request filed, will be 

published in the Federal Register, along 

with EPA’s response to comments on 

the stay request. 

X. Are The Agency’s Actions Consistent 

With International Obligations? 

The tolerance revocations in this final 

rule 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 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/. 

XI. Statutory and Executive Order 

Reviews 

In this final rule, EPA is revoking 

specific tolerances established under 

FFDCA section 408. The Office of 

Management and Budget (OMB) has 

exempted tolerance regulations from 

review under Executive Order 12866, 

entitled Regulatory Planning and 

Review (58 FR 51735, October 4, 1993). 

Because this final rule has been 

exempted from review under Executive 

Order 12866, this final rule is not 

subject to Executive Order 13211, 

Actions Concerning Regulations That 

Significantly Affect Energy Supply, 

Distribution, or Use (66 FR 28355, May 

22, 2001) or Executive Order 13045, 

entitled Protection of Children from 

Federal Register / Vol. 74, No. 93 / Friday, May 15, 2009 / Rules and Regulations 23089 

Environmental Health Risks and Safety 

Risks (62 FR 19885, April 23, 1997), 

which both apply to regulation actions 

reviewed under Executive Order 12866. 

This final rule does not contain any 

information collections subject to OMB 

approval under the Paperwork 

Reduction Act (PRA), 44 U.S.C. 3501 et 

seq., 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). 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). This final rule directly regulates 

growers, food processors, food handlers 

and food retailers, not States. This 

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 final 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). This final 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 final rule. 

The Regulatory Flexibility Act (RFA) 

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 final rule may 

have on potentially impacted small 

businesses. EPA prepared an analysis 

for the proposal and certified that its 

proposed rule would not have a 

significant economic impact on a 

substantial number of small entities. 

EPA received no comments on its 

analysis or certification. Based on its 

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 

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. Moreover, as the registrant 

has voluntarily cancelled the use of 

carbofuran on artichokes, any impact is 

more properly traced to the registrant’s 

decision to cancel the registration, than 

to the revocation of the tolerance. 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 Reference 85. 

XII. Congressional Review Act 

The Congressional Review Act, 5 

U.S.C. 801 et seq., generally provides 

that before a rule may take effect, the 

agency promulgating the rule must 

submit a rule report to each House of 

the Congress and the Comptroller 

General of the United States. EPA will 

submit a report containing this rule and 

other required information to the U.S. 

Senate, the U.S. House of 

Representatives, and the Comptroller 

General of the United States prior to 

publication of the rule in the Federal 

Register. This rule is not a ‘‘major rule’’ 

as defined by 5 U.S.C. 804(2). 

XIII. References 

The following is a list of the 

documents that are specifically 

referenced in this final rule and placed 

in the docket that was established under 

Docket ID number EPA-HQ-OPP-2005- 

0162. The public docket includes 

information considered by EPA in 

developing this final rule, such as the 

documents specifically referenced in 

this action that are listed in this unit, 

documents that are referenced in the 

documents that are in the docket, any 

public comments received, and other 

information related to this action. For 

information on accessing the docket, 

refer to the ADDRESSES unit at the 

beginning of this document. 

1. Abou-Donia, M.B., Khan, W.A., 

Dechkovskaia, A.M., Goldstein, L.B., 

Bullman, S.L., Abdel-Rahman, A., In 

utero exposure to nicotine and 

chlorpyrifos alone, and in combination 

produces persistent sensorimotor 

deficits and Purkinje neuron loss in the 

cerebellum of adult offspring rats. Arch 

Toxicol. 2006 Sep;80(9):620–31. Epub 

2006 Feb 16. 

2. Abramovitch, R., Tavor, E., JacobHirsch, J., Zeira, E., Amariglio, N., 

Pappo, O., Rechavi, G., Galun, E., 

Honigman, A., A pivotal role of cyclic 

AMP-responsive element binding 

protein in tumor progression. Cancer 

Research. 2004 Feb 15;64(4):1338–46. 

3. Acute oral (gavage) dose rangefinding 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. 

23090 Federal Register / Vol. 74, No. 93 / Friday, May 15, 2009 / Rules and Regulations 

4. 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. 

5. Acute Dose-Response Study of 

Carbofuran Technical Administered by 

Gavage to Adult and Postnatal Day 11 

Male and Female CD (Sprague-Dawley) 

Rats: Tyl and Myers. 2005. MRID. 

46688914. 

6. Aller, L., Bennet, T., Lehr, J.H., 

Petty, R.J., and Hackett, G. 1987. 

DRASTIC: A standardized system for 

evaluating groundwater pollution 

potential using hydrogeologic setting. 

EPA/600/2–87/035. Robert S. Kerr 

Environmental Research Laboratory, 

U.S. Environmental Protection Agency, 

622 pp. 

7. 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. 

8. 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. 

9. 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. 

10. Angier, Jonathan. 2005. Tier 2 

Drinking Water Assessment for Aldicarb 

and its Major Degradates Aldicarb 

Sulfoxide and Aldicarb Sulfone. (DP 

316754) Internal EPA Memorandum to 

Robert McNally dated May 10, 2005. 

11. 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. 

12. 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;. 

13. 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. 

14. Bretaud, S., Toutant, J.P., Saglio, 

P. 2000. Effects of carbofuran, diuron, 

and nicosulfuron on 

acetylcholinesterase activity in goldfish 

(Carassius auratus). Ecotoxicol Environ 

Saf. 2000 Oct; 47(2):117–24. 

15. California Department of Pesticide 

Regulation. Risk Characterization 

Document for Carbofuran. January 23, 

2006. 219 pgs. Available at: http:// 

www.cpdr.ca.gov/docs/risk/red/ 

carbofuran.pdf. 

16. Carbofuran Acute Aggregate 

Dietary (Food and Drinking Water) 

Exposure and Risk Assessments for the 

Reregistration Eligibility Decision (T. 

Morton, 7/22/08, D351371). EPA-HQOPP–2005–0162–0508. 

17. Carbofuran Environmental Risk 

Assessment and Human Drinking Water 

Exposure Assessment for IRED. March 

2006. EPA–HQ–OPP–2005–0162–0080. 

18. Carringer, 2000. Carbamate Market 

Basket Survey. Reviewed by S. Piper, 

D267539, 8/8/02. (MRID 45164701 S. 

Carringer, 5/12/00). 

19. Carbofuran. HED Revised Risk 

Assessment for the Reregistration 

Eligibility Decision (RED) Document 

(Phase 6). (PC 090601) D 330541, July 

26, 2006. EPA–HQ–OPP–2005–0162– 

0307. 

20. Carbofuran. HED Revised Risk 

Assessment for the Notice of Intent to 

Cancel . (PC 090601) D 347038, January 

2007. EPA–HQ–OPP–2007–1088–0034. 

21. 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. 

22. 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. 

23. Crumpton T.L., Seidler, F.J., 

Slotkin, T.A. Developmental 

neurotoxicity of chlorpyrifos in vivo and 

in vitro: Effects on nuclear transcription 

factors involved in cell replication and 

differentiation. Brain Research. 2000 

Feb 28;857(1–2):87–98. 

24. Data Evaluation Record for Acute 

dose-response study of carbofuran 

technical administered by gavage to 

adult and postnatal day 11 male and 

female CD®(Sprague-Dawley) rats. 

MRID 46688914. EPA-HQ-OPP–2007– 

1088–0045. 

25. Data Evaluation Record for 

Cholinesterase depression in juvenile 

(day 11) and adult rats following acute 

oral (gavage) dose of carbofuran 

technical. MRIDs 47143703, 47143704 

and 47143705. EPA-HQ-OPP–2005– 

0162–0468. 

26. Davison, A.N. and Dobbing, J. 

1966. Myelination as a vulnerable 

period in brain development. British 

Medical Bulletin. 22:40–44. 

27. Dobbing, J. and Smart, J.L. (1974) 

Vulnerability of developing brain and 

behaviour. British Medical Bulletin. 

30:164–168. 

28. Dose-time response modeling of 

rat brain AChE activity: carbofuran 

gavage dosing 10/5/07 (CarbofuranRatBrainDR.pdf) EPA–HQ–OPP–2007– 

1088–0053. 

29. Dose-time response modeling of 

rat RBC-AChE activity: carbofuran 

gavage dosing 10/23/07 

(RatRBC_DR.pdf). EPA–HQ–OPP–2007– 

1088–0029. 

30. Dose-Time Response Modeling of 

Rat Brain AChE Activity: Carbofuran 

Gavage Dosing: BMD50s for PND11 

animals, January 14, 2009. 

31. Dose-Time Response Modeling of 

Rat RBC AChE Activity: Carbofuran 

Gavage Dosing: BMD50s for PND11 

Animals, January 14, 2009. 

32. Dumaz, N., Hayward, R., Martin, 

J., Ogilvie, L., Hedley, D., Curtin, J.A., 

Bastian, B.C., Springer, C., Marais, R. In 

Melanoma, RAS Mutations Are 

Accompanied by Switching Signaling 

from BRAF to CRAF and Disrupted 

Cyclic AMP Signaling. Cancer Resarch. 

2006 Oct 1;66(19):9483–91. 

33. Bernard, Engel, Fawcett, Richard 

S. and Williams, W. Martin. 2008. 

Comments to the FIFRA Scientific 

Advisory Panel – Volume V: The Water 

Risk Assessment for Carbofuran. From 

Carbofuran Scientific Advisory Panel 

Meeting, Feb. 5–8, 2008, Docket ID 

Number: EPA–HQ–OPP–2007–1088 

FMC Corporation, Agricultural Products 

Group Written Comments. 

34. 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). 

35. Estimated Drinking Water 

Concentrations (email communication 

D. Young to D. Drew, March 8, 2006). 

36. Fawcett, R., Engel, B., Williams, 

W. 2007. An Investigation into the 

Potential for Carbofuran Leaching to 

Ground Water Based on Historical and 

Current Product Uses. (MRID 47221602) 

Federal Register / Vol. 74, No. 93 / Friday, May 15, 2009 / Rules and Regulations 23091 

Project Number PC/0363. 32 p. EPA– 

HQ–OPP–2005–0162–0454.1. 

37. 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. 

38. 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. 

39. SAP. 2001a. REPORT: FIFRA 

Scientific Advisory PanelMeeting, 

September 29, 2000, held at the 

Sheraton Crystal City Hotel, Arlington, 

Virginia. Session VI - A Set of Scientific 

Issues Being Considered by the 

Environmental Protection Agency 

Regarding: Progress Report on 

Estimating Pesticide Concentrations in 

Drinking Water and Assessing Water 

Treatment Effects on Pesticide Removal 

and Transformation: A Consultation. 

SAP Report No 2002–2. 

40. FIFRA SAP. 2002a. ‘‘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. 

41. FIFRA SAP. 2002b. 

‘‘Determination of the Appropriate 

FQPA Safety Factor(s) in the 

Organophosphorous Pesticide 

Cumulative Risk Assessment: 

Susceptibility and Sensitivity to the 

Common Mechanism, 

Acetylcholinesterase Inhibition Meeting 

Minutes from the FIFRA Scientific 

Advisory Panel Meeting of June 26–27, 

2002 (Minutes dated July 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. 

42. 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 February15- 

18, 2005. (report dated April 15, 2005) 

Available at: http://www.epa.gov/ 

scipoly/sap/2005/february/minutes.pdf. 

43. 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 August 23- 

26, 2005. Available at: http:// 

www.epa.gov/scipoly/sap/2005/august/ 

minutes.pdf. 

44. 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. Available at: http:// 

www.epa.gov/scipoly/sap/meetings/ 

2008/february/carbofuransapfinal.pdf. 

45. Final report on cholinesterase 

inhibition study of carbofuran: PND17 

rats. MRID 47167801 (ORD study). EPA– 

HQ–OPP–2007–1088–0064. 

46. Final Report on cholinesterase 

depression in juvenile (day 11) and 

adult rats following acute oral (gavage) 

dose of carbofuran technical. Study by 

Charles River Laboratories for FMC. 

May 31, 2007. EPA-HQ-OPP–2005– 

0162–0080. 

47. Fite, Edward, Randall, Donna, 

Young, Dirk, Odenkirchen, Edward and 

Salice, Christopher. 2006. Reregistration 

Eligibility Science Chapter for 

Carbofuran. (DP 322206+) Office of 

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2006. 

48. Fort, Felecia, Taylor, Linda and 

Dawson, Jeff. 2007. Aldicarb (List A 

Case 0140, Chemical ID No. 098301). 

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49. Hetrick, James, Parker, Ronald, 

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Nelson. 2000. Progress Report on 

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and Transformation: A Consultation. 

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50. Hunter, D.L., Marshall, R.S. and 

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51. Hunter, D.L., Lassiter, T.L., and 

Padilla, S. 1999. Gestational exposure to 

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dam. Toxicology and Applied 

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52. Interim Reregistration Eligibility 

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2006. Regulations.gov document 

number: EPA–HQ–OPP–2005–0162– 

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53. IPCS World Health Organization. 

2005. Chemical Specific Adjustment 

factors for Interspecies Differences and 

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for use of Data in Dose/ConcentrationResponse Assessment. Available at: 

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54. Issue Paper for the FIFRA SAP 

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Risk Assessment Reregistration 

Eligibility Science Chapter for 

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Effects Chapter. March 2006. EPA–HQ– 

OPP–2007–1088–0031. 

55. Johnson, C.D. and Russell, R.L. 

(1975) A rapid, simple radiometric assay 

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determinations. Analytical 

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56. Jones, R. David, Abel, Sidney, 

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57. Jones, R. David. 2007a. EFED 

Revised Drinking Water Assessment in 

support of the reregistration of 

carbofuran. (DP 342405) Internal EPA 

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58. Jones, R. David. 2007b. Additional 

chemographs for potatoes and cucurbits 

for drinking water exposure assessment 

in support of the reregistration of 

carbofuran. Internal EPA Memorandum 

to Jude Andreasen and Danette Drew 

dated October 23, 2007. EPA–HQ–OPP– 

2005–0162–0486. 

59. Jones, R. David. 2007c. Summary 

Evaluation of Recently Submitted FMC 

Water Exposure Studies. (DP 347901) 

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Andreasen dated December 26, 2007. 

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60. Jones, R. David 2008a. (5/1/2008). 

Additional refinements for estimations 

of drinking water exposure from 

carbofuran use on corn. (DP 351653). 

61. Jones, R. David. 2008b. Additional 

Refinements of the Drinking Water 

Exposure Assessment for the Use of 

Carbofuran on corn and Melons. (DP 

353714) Internal EPA Memorandum to 

Jude Andreasen and Thurston Morton, 

dated June 23, 2008. EPA–HQ–OPP– 

2005–0162–0510. 

62. Jones, R. David. (2008c) Updated 

Refinements of the Drinking Water 

Exposure Assessment for the Use of 

Carbofuran on corn and Melons, 8/18/ 

2008. (DP 355584) Internal EPA 

Memorandum to Jude Andreasen and 

Thurston Morton, dated August 18, 

2008. 

63. Jones, R. David (8/20/2008). 

Transmittal of updated refinements of 

the drinking water exposure assessment 

for the use of carbofuran on cron and 

melons. (DP 355584). EPA–HQ–OPP– 

2005–0162–0516. 

64. Lauzon, John D., O’Halloran, Ivan 

P., Fallow, David J., von Bertoldi, Peter 

A. and Aspinall, Doug. 2005. Spatial 

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plasma, erythrocyte, heart and brain 

cholinesterase and analytical 

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68. McDaniel, K.L. and Moser, V.C. 

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to fenamiphos or profenofos. 

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69. 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. 

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70. Morton, T. (7/22/08), D351371 & 

353544. Carbofuran Acute Aggregate 

Dietary (Food and Drinking Water) 

Exposure and Risk Assessments for the 

Reregistration Eligibility Decision. EPA– 

HQ–OPP–2005–0162–0508. 

71. Morton, T., 4/29/09, D358037, 

Carbofuran Acute Aggregate Dietary 

(Food and Drinking Water) Exposure 

and Risk Assessments for the 

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72. Moser V.C. (1995) Comparisons of 

the acute effects of cholinesterase 

inhibitors using a neurobehavioral 

screening battery in rats. 

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73. National Assessment of the 

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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. 

74. National Resources Inventory 

1992, cited in USGS 2002, ‘‘Herbicide 

Concentrations in the Mississippi River 

Basin—the importance of 

chloracetanilide degradates.’’ R.A. 

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90. Slotkin T.A., Cousins, M.M., Tate, 

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vivo: Transcriptional responses of 

Federal Register / Vol. 74, No. 93 / Friday, May 15, 2009 / Rules and Regulations 23093 

pathways for brain cell development, 

cell signaling, cytotoxicity and 

neurotransmitter systems. Brain 

Research Bulletin. May 30;72(4–6):232– 

74. Epub 2007 Jan 25. 

92. Slotkin, T.A., Tate, C.A., Ryde, 

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95. Thelin, Gail P., and Leonard P. 

Gianessi. 2000. U.S. Method for 

Estimating Pesticide Use for County 

Areas of the Conterminous United 

States Geological Survey Open-File 

Report 00–250. Sacramento, California, 

2000. 

96. Trask, Jennifer R., and Amos, 

Joshua. 2005.. Prepared by Waterborne 

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0162–0061. 

97. Transmittal of Meeting Minutes of 

the FIFRA Scientific Advisory Panel 

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Released on July 19, 2002, 26. EPA–HQ– 

OPP–2007–1088–0146. 

98. USDA NRCS. Conservation Buffer 

to Reduce Pesticide Losses. Natural 

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Worth, TX, 21 pp. 

99. USEPA. 2000a. 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. 

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report. Risk Assessment Forum, Office 

of Research and Development, U.S. 

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101. USEPA. 2000c. Choosing a 

Percentile of Acute Dietary Exposure as 

a Threshold of Regulatory Concern. 

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trac2b054.pdf. 

102. USEPA. 2000d. The Use of Data 

on Cholinesterase Inhibition for Risk 

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Carbamate Pesticides. August 18, 2000. 

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pesticides/trac/science/cholin.pdf. 

103. USEPA. 2001a. 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. 

104. USEPA. 2001b. Pesticide 

Registration (PR) Notice 2001–X Draft: 

Spray and Dust Drift Label Statements 

for Pesticide Products. http:// 

www.epa.gov/PR_Notices/prdraftspraydrift801.htm. 

105. 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. 

106. USEPA. 2005. Preliminary NMethyl Carbamate Cumulative Risk 

Assessment. Available at: http:// 

www.epa.gov/oscpmont/sap/2005/ 

index.htm#august. 

107. 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. 

108. USEPA 2007c. Carbaryl. HED 

Chapter of the Reregistration Eligibility 

Decision Document (RED). PC Code: 

056801, DP Barcode: D334770. 28 June 

2007. 

109. U.S. Environmental Protection 

Agency. 2008a. EPA response to the 

transmittal of meeting minutes of the 

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Agency’s proposed action under FIFRA 

6(b) Notice of Intent to Cancel 

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110. U.S. Environmental Protection 

Agency. 2008b. Memorandum 

(November 18, 2008) from Linda L. 

Taylor. ‘‘Aldicarb: Determination of 

Whether Cited Study Fulfills Data 

Requirements for Comparative 

Cholinesterase Assay.’’ D299880. 

111. USEPA. 2009a. Jones, R. David, 

Reuben Baris, and Marietta Echeverria. 

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proposed tolerance revocations for 

carbofuran specifically related to 

drinking water exposure assessment. 

Internal EPA memorandum to Jude 

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D362182. 

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Comments in Opposition To Proposed 

Tolerance Revocations For Carbofuran 

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submitted by the National Potato 

Council, National Corn Growers 

Association, National Cotton Council, 

National Sunflower Association, And 

FMC Corporation (September 29, 2008). 

April 29, 2009. D364288. 

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Comments from the Children’s 

Environmental Health Network and the 

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(Dated September 28. 2008) & the 

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summaries of pesticide compounds in 

stream water. http://water.usgs.gov/ 

nawqa/pnsp/pubs/circ1291/appendix7/ 

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updated December , 2008. http:// 

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received Dec 5, 1978 under 275–2712; 

prepared by WARF Institute, Inc., 

submitted by FMC Corp., Philadelphia, 

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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. 

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1088–0021. 

118. Whyatt, R., Barr, D., Camann, D., 

Kinney, P., Barr, J., Andrews, H., et al. 

2003. Contemporary-use pesticides in 

personal air samples during pregnancy 

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methods for measurement of erythrocyte 

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Dasgupta, S., and Hoogeweg, C.G. 

2007a. An In-Depth Investigation to 

Estimate Surface Water Concentrations 

of Carbofuran within Indiana 

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47221603) Performed by Waterborne 

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Environmental, Inc., , Leesburg, VA, 

Engel Consulting, and Fawcett 

Consulting. Submitted by FMC. 

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528.01, FMC Report No. PC-0378. EPA– 

HQ–OPP–2005–0162–0453. 

121. Williams, W.M., Engel, B., 

Dasgupta, S. and Hoogeweg, C.G. 2007b. 

An In-Depth Investigation to Estimate 

Surface Water Concentrations of 

Carbofuran within Indiana Community 

Water Supplies. Performed by 

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47272301) Leesburg, VA, Engel 

Consulting, and Fawcett Consulting. 

Submitted by FMC. Corporation, 

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122. Wyatt, T.J. (10/30/08). Percent 

crop treated estimates for dietary risk 

analysis, carbofuran on domestic 

potatoes and imported bananas (DP 

357726). 

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Fowler, K.S. 1966. Substrate and 

dilution effects on the inhibition of 

acetylcholinesterase by carbamates. 

Biochemistry Journal. 101:127–134. 

124 USEPA. 2007d. Memorandum 

(June 29, 2007) from E Reaves. Carbaryl: 

Updated Endpoint Selection for Single 

Chemical Risk Assessment. D337054 

125. USEPA. Memorandum 

(December 12, 2008) Setzer. W., PND17 

BMDs and BMDLs and Recovery HalfLives for the Effect of Carbofuran on 

Brain and Blood AChE. 

126. Vecchia, A.V. and C. G. 

Crawford, 2006. Simulation Of Daily 

Pesticide Concentrations From 

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60 pgs. 

List of Subjects in 40 CFR Part 180 

Environmental protection, 

Administrative practice and procedure, 

Agricultural commodities, Pesticides 

and pests, Reporting and recordkeeping 

requirements. 

Dated: May 11, 2009. 

Debra Edwards, 

Director, Office of Pesticide Programs. 

■ Therefore, 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 tables in paragraphs (a) and 

(c) to read as follows: 

§ 180.254 Carbofuran; tolerances for 

residues. 

(a) * * * 

Commodity 

Parts per 

million 

(ppm) 

Expiration/ 

Revocation 

date 

Alfalfa, forage (of which no more than 5 ppm are carbamates) ......................................................................................... 10 12/31/09 

Alfalfa, hay (of which no more than 20 ppm are carbamates) ........................................................................................... 40 12/31/09 

Banana ................................................................................................................................................................................. 0.1 12/31/09 

Barley, grain (of which not more than 0.1 ppm is carbamates) .......................................................................................... 0.2 12/31/09 

Barley, straw (of which no more than 1.0 ppm is carbamates) .......................................................................................... 5.0 12/31/09 

Beet, sugar, roots ................................................................................................................................................................ 0.1 12/31/09 

Beet, sugar, tops (of which no more than 1 ppm is carbamates) ...................................................................................... 2 12/31/09 

Coffee, bean, green ............................................................................................................................................................. 0.1 12/31/09 

Corn, forage (of which no more than 5 ppm are carbamates) ........................................................................................... 25 12/31/09 

Corn, grain (including popcorn) (of which no more than 0.1 ppm is carbamates) ............................................................. 0.2 12/31/09 

Corn, stover (of which no more than 5 ppm are carbamates) ............................................................................................ 25 12/31/09 

Corn, sweet, kernel plus cob with husks removed (of which no more than 0.2 ppm is carbamates) ............................... 1.0 12/31/09 

Cotton, undelinted seed (of which no more than 0.2 ppm is carbamates) ......................................................................... 1.0 12/31/09 

Cranberry (of which no more than 0.3 ppm is carbamates) ............................................................................................... 0.5 12/31/09 

Cucumber (of which not more than 0.2 ppm is carbamates) ............................................................................................. 0.4 12/31/09 

Grape (of which no more than 0.2 ppm is carbamates) ..................................................................................................... 0.4 12/31/09 

Grape, raisin (of which no more than 1.0 ppm is carbamate ............................................................................................. 2.0 12/31/09 

Grape, raisin, waste (of which no more than 3.0 ppm is carbamates ................................................................................ 6.0 12/31/09 

Melon (of which not more than 0.2 ppm is carbamates) .................................................................................................... 0.4 12/31/09 

Milk (of which no more than 0.02 ppm is carbamates) ....................................................................................................... 0.1 12/31/09 

Oat, grain (of which not more than 0.1 ppm is carbamates) .............................................................................................. 0.2 12/31/09 

Oat, straw (of which not more than 1.0 ppm is carbamates) ............................................................................................. 5.0 12/31/09 

Pepper (of which no more than 0.2 ppm is carbamates) ................................................................................................... 1 12/31/09 

Potato (of which no more than 1 ppm is carbamates) ........................................................................................................ 2 12/31/09 

Pumpkin (of which not more than 0.6 ppm is carbamates) ................................................................................................ 0.8 12/31/09 

Rice, grain ............................................................................................................................................................................ 0.2 12/31/09 

Rice, straw (of which no more than 0.2 ppm is carbamates) ............................................................................................. 1 12/31/09 

Sorghum, forage (of which no more than 0.5 ppm is carbamates) .................................................................................... 3 12/31/09 

Sorghum, grain, grain .......................................................................................................................................................... 0.1 12/31/09 

Sorghum, grain, stover (of which no more than 0.5 ppm is carbamates) .......................................................................... 3 12/31/09 

Strawberry (of which no more than 0.2 ppm is carbamates) .............................................................................................. 0.5 12/31/09 

Soybean (of which not more than 0.2 ppm is carbamates) ................................................................................................ 1.0 12/31/09 

Soybean, forage (of which not more than 20.0 ppm are carbamates) ............................................................................... 35.0 12/31/09 

Soybean, hay (of which not more than 20.0 ppm are carbamates) ................................................................................... 35.0 12/31/09 

Squash (of which not more than 0.6 ppm is carbamates) .................................................................................................. 0.8 12/31/09 

Sugarcane, cane .................................................................................................................................................................. 0.1 12/31/09 

Sunflower, seed (of which not more than 0.5 ppm is carbamates) .................................................................................... 1.0 12/31/09 

Wheat, grain (of which not more than 0.1 ppm is carbamates) ......................................................................................... 0.2 12/31/09 

Wheat, straw (of which not more than 1.0 ppm is carbamates) ......................................................................................... 5.0 12/31/09 

* * * * * (c) * * * 

Federal Register / Vol. 74, No. 93 / Friday, May 15, 2009 / Rules and Regulations 23095 

Commodity 

Parts per 

million 

(ppm) 

Expiration/ 

Revocation 

date 

Artichoke, globe (of which not more than 0.2 ppm is carbamates) .................................................................................... 0.4 12/31/09 

* * * * * 

[FR Doc. E9–11396 Filed 5–12–09; 4:15 pm] 

BILLING CODE 6560–50–S