44864 Federal Register / Vol. 73, No. 148 / Thursday, July 31, 2008 / Proposed Rules 

ENVIRONMENTAL PROTECTION 

AGENCY 

40 CFR Part 180 

[EPA–HQ–OPP–2005–0162; FRL–8373–8] 

Carbofuran; Proposed Tolerance 

Revocations 

AGENCY: Environmental Protection 

Agency (EPA). 

ACTION: Proposed rule. 

SUMMARY: EPA is proposing to revoke all 

tolerances for carbofuran. The Agency 

has determined that the risk from 

aggregate exposure from the use of 

carbofuran does not meet the safety 

standard of section 408(b)(2) of the 

Federal Food, Drug, and Cosmetic Act 

(FFDCA). EPA is specifically soliciting 

comment on whether there is an interest 

in retaining any individual tolerance, or 

group of tolerances, and whether 

information exists to demonstrate that 

such tolerance(s) meet(s) the FFDCA 

section 408(b)(2) safety standard. EPA 

encourages interested parties to 

comment on the tolerance revocations 

proposed in this document and on the 

proposed time frame for tolerance 

revocation. Issues not raised during the 

comment period may not be raised as 

objections to the final rule, or in any 

other challenge to the final rule. 

DATES: Comments must be received on 

or before September 29, 2008. 

ADDRESSES: Submit your comments, 

identified by docket identification (ID) 

number EPA–HQ–OPP–2005–0162, by 

one of the following methods: 

• Federal eRulemaking Portal: http:// 

www.regulations.gov. Follow the on-line 

instructions for submitting comments. 

• Mail: Office of Pesticide Programs 

(OPP) Regulatory Public Docket (7502P), 

Environmental Protection Agency, 1200 

Pennsylvania Ave., NW., Washington, 

DC 20460–0001. 

• Delivery: OPP Regulatory Public 

Docket (7502P), Environmental 

Protection Agency, Rm. S–4400, One 

Potomac Yard (South Building), 2777 S. 

Crystal Drive, Arlington, VA. Deliveries 

are only accepted during the Docket’s 

normal hours of operation (8:30 a.m. to 

4 p.m., Monday through Friday, 

excluding legal holidays). Special 

arrangements should be made for 

deliveries of boxed information. The 

Docket telephone number is (703) 305– 

5805. 

Instructions: Direct your comments to 

docket ID number EPA–HQ–OPP–2005– 

0162. EPA’s policy is that all comments 

received will be included in the docket 

without change and may be made 

available on-line at http:// 

www.regulations.gov, including any 

personal information provided, unless 

the comment includes information 

claimed to be Confidential Business 

Information (CBI) or other information 

whose disclosure is restricted by statute. 

Do not submit information that you 

consider to be CBI or otherwise 

protected through regulations.gov or email. The Federal regulations.gov 

website is an ‘‘anonymous access’’ 

system, which means EPA will not 

know your identity or contact 

information unless you provide it in the 

body of your comment. If you send an 

e-mail comment directly to EPA without 

going through regulations.gov, your email address will be automatically 

captured and included as part of the 

comment that is placed in the docket 

and made available on the Internet. If 

you submit an electronic comment, EPA 

recommends that you include your 

name and other contact information in 

the body of your comment and with any 

disk or CD-ROM you submit. If EPA 

cannot read your comment due to 

technical difficulties and cannot contact 

you for clarification, EPA may not be 

able to consider your comment. 

Electronic files should avoid the use of 

special characters, any form of 

encryption, and be free of any defects or 

viruses. 

Docket: All documents in the docket 

are listed in the docket index. Although 

listed in the index, some information is 

not publicly available, e.g., CBI or other 

information whose disclosure is 

restricted by statute. Certain other 

material, such as copyrighted material, 

is not placed on the Internet and will be 

publicly available only in hard copy 

form. Publicly available docket 

materials are available either in the 

electronic docket at http:// 

www.regulations.gov, or, if only 

available in hard copy, at the OPP 

Regulatory Public Docket in Rm. S– 

4400, One Potomac Yard (South 

Building), 2777 S. Crystal Drive, 

Arlington, VA. The hours of operation 

of this Docket Facility are from 8:30 a.m. 

to 4 p.m., Monday through Friday, 

excluding legal holidays. The Docket 

telephone number is (703) 305–5805. 

FOR FURTHER INFORMATION CONTACT: Jude 

Andreasen Special Review and 

Reregistration Division (7508C), Office 

of Pesticide Programs, Environmental 

Protection Agency, 1200 Pennsylvania 

Ave, NW., Washington, DC 20460-0001; 

telephone number: (703) 305–0076; 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. What Should I Consider as I Prepare 

My Comments for EPA? 

1. Submitting CBI. Do not submit this 

information to EPA through 

regulations.gov or e-mail. Clearly mark 

the part or all of the information that 

you claim to be CBI. For CBI 

information in a disk or CD ROM that 

you mail to EPA, mark the outside of the 

disk or CD ROM as CBI and then 

identify electronically within the disk or 

CD ROM the specific information that is 

claimed as CBI. In addition to one 

complete version of the comment that 

includes information claimed as CBI, a 

copy of the comment that does not 

contain the information claimed as CBI 

must be submitted for inclusion in the 

public docket. Information so marked 

will not be disclosed except in 

accordance with procedures set forth in 

40 CFR part 2. 

2. Tips for preparing your comments. 

When submitting comments, remember 

to: 

i. Identify the document by docket ID 

number and other identifying 

information (subject heading, Federal 

Register date and page number). 

ii. Follow directions. The Agency may 

ask you to respond to specific questions 

or organize comments by referencing a 


jlentini on PROD1PC65 with PROPOSALS3
Federal Register / Vol. 73, No. 148 / Thursday, July 31, 2008 / Proposed Rules 44865 

Code of Federal Regulations (CFR) part 

or section number. 

iii. Explain why you agree or disagree; 

suggest alternatives and substitute 

language for your requested changes. 

iv. Describe any assumptions and 

provide any technical information and/ 

or data that you used. 

v. If you estimate potential costs or 

burdens, explain how you arrived at 

your estimate in sufficient detail to 

allow for it to be reproduced. 

vi. Provide specific examples to 

illustrate your concerns and suggest 

alternatives. 

vii. Explain your views as clearly as 

possible, avoiding the use of profanity 

or personal threats. 

viii. Make sure to submit your 

comments by the comment period 

deadline identified. 

C. What Can I Do if I Wish the Agency 

to Maintain a Tolerance that the Agency 

Proposes to Revoke? 

This proposed rule provides a 

comment period of 60 days for any 

interested person to submit comments 

on the Agency’s proposal. EPA issues a 

final rule after considering comments 

that are submitted in response to this 

proposed rule. Comments should be 

limited only to the pesticide and 

tolerances subject to this proposed 

notice. 

EPA’s finding that aggregate exposure 

from all existing uses of carbofuran is 

not safe does not necessarily mean that 

no individual tolerance or group of 

tolerances could meet the FFDCA 

408(b)(2) safety standard and be 

maintained. For example, in its Interim 

Reregistration Eligibility Decision 

(IRED), EPA concluded that the Agency 

could maintain import tolerances for 

bananas, coffee, rice, and sugarcane, 

because dietary risks from the food 

residues from the import tolerances are 

below the Agency’s level of concern 

when considered together with the food 

residues from the phase-out crops, but 

with no other domestic uses (Ref. 35). 

However, as discussed in more detail 

below, EPA can only maintain 

tolerances that it can determine will be 

‘‘safe’’ within the meaning of section 

408(b)(2)(A)(ii). Accordingly, 

commenters interested in retaining any 

tolerance or group of tolerances should 

consider submitting information to 

demonstrate that the tolerance(s) meet 

the statutory standard, rather than 

merely indicating an interest in 

retaining the tolerance. Commenters 

should also be aware that even if EPA 

determines that any carbofuran 

tolerance(s) meet the safety standard, 

those tolerances can only be maintained 

if EPA can also determine that the 

cumulative effects from those 

tolerances, when considered with the 

exposures from other N-methyl 

carbamate pesticide chemicals, will 

meet the FFDCA 408(b)(2) safety 

standard. EPA will not respond to any 

comments on subjects that do not relate 

to the evaluation or safety of the 

pesticide tolerances subject to this 

proposed notice. 

After consideration of comments, EPA 

will issue a final regulation determining 

whether revocation of the tolerances is 

appropriate and making a final finding 

on whether these tolerances are ‘‘safe’’

within the meaning of section 

408(b)(2)(A)(ii). Such regulation will be 

subject to objections pursuant to section 

408(g) (21 U.S.C. 346a(g)). 

In addition to submitting comments 

in response to this proposal, you may 

also submit an objection at the time of 

the final rule. If you anticipate that you 

may wish to file objections to the final 

rule, you must raise those issues in your 

comments on this proposal. EPA will 

treat as waived, any issue not originally 

raised in comments on this proposal. 

Similarly, if you fail to file an objection 

to the final rule within the time period 

specified, you will have waived the 

right to raise any issues resolved in the 

final rule. After the specified time, 

issues resolved in the final rule cannot 

be raised again in any subsequent 

proceedings on this rule. 

II. Introduction 

A. What Action is the Agency Taking? 

EPA is proposing to revoke all of the 

existing tolerances for residues of 

carbofuran. Currently, tolerances have 

been established on the following crops: 

alfalfa, fresh; alfalfa, hay; artichoke, 

globe; banana; barley, grain; barley, 

straw, sugar beet; sugar beet, tops; coffee 

bean; corn, forage; corn, fresh (including 

sweet corn); corn, grain (including 

popcorn); corn, stover; cotton, 

undelinted seed; cranberry; cucumber; 

grape; grape (raisin); melon; milk; oat, 

grain; oat, straw; pepper; potato; 

pumpkin; raisins, waste; rice, grain; 

rice, straw; sorghum, fodder; sorghum, 

forage; sorghum, grain; strawberry; 

soybean; soybean, forage; soybean, hay; 

squash; sugarcane, cane; sunflower, 

seed; wheat, grain; wheat, straw. The 

Agency is proposing to revoke 

tolerances for these crops because 

aggregate dietary exposure to residues of 

carbofuran, including all anticipated 

dietary exposures and all other 

exposures for which there is reliable 

information, is not safe. 

EPA has determined that aggregate 

exposure to carbofuran greater than 

0.000075 mg/kg/day (i.e., greater than 

the acute Population Adjusted Dose 

(aPAD)) does not meet the safety 

standard of section 408(b)(2) of the 

FFDCA. Based on the contribution from 

food alone, the more sensitive children’s 

subpopulations receive unsafe 

exposures to carbofuran. At the 99.9th 

percentile of exposure, aggregate 

carbofuran dietary exposure from food 

alone was estimated to range between 

0.000121 mg/kg/day for children 6–12 

(160% of the aPAD) and 0.000156 mg/ 

kg/day (210% of the aPAD) for children 

3–5 years old, the population subgroup 

with the highest estimated dietary 

exposure. In addition, EPA’s analyses 

show that those individuals–both adults 

and children—who receive their 

drinking water from vulnerable sources 

are also exposed to levels that exceed 

EPA’s level of concern—in some cases 

by orders of magnitude. This primarily 

includes those populations consuming 

drinking water from groundwater from 

shallow wells in acidic aquifers overlaid 

with sandy soils that have had crops 

treated with carbofuran. Aggregate 

exposures from food and from drinking 

water derived from ground water in 

vulnerable areas (i.e., from shallow 

wells associated with sandy soils and 

acidic aquifers, such as are found in the 

Delmarva Peninsula of Delaware, 

Maryland, and Virginia) result in even 

higher estimated exceedances. The 

aggregate estimates for food and ground 

water exposure range between 1100% of 

the aPAD for adults over 50 years, to 

over 10,000% of the aPAD for infants. 

Similarly, EPA analyses show 

substantial exceedances for those 

populations that obtain their drinking 

water from reservoirs (i.e., surface 

water) located in small agricultural 

watersheds, prone to runoff, and 

predominated by crops that are treated 

with carbofuran, even though there is 

more uncertainty associated with these 

exposure estimates. For example, 

estimated aggregate exposures from food 

and drinking water derived from surface 

water, based on the corn use in 

Nebraska, range between 340% of the 

aPAD for youths 13–19, and 3900% of 

the aPAD for infants. 

Every sensitivity analysis EPA has 

performed has shown that estimated 

exposures (both for food alone as well 

as for food and water) significantly 

exceed EPA’s level of concern for 

children. Although the magnitude of the 

exceedance varies depending the level 

of conservatism in the assessment, the 

fact that in each case aggregate 

exposures from carbofuran fail to meet 

the FFDCA section 408(b)(2) safety 

standard, including where EPA relied 

on highly refined estimates of risk, 


jlentini on PROD1PC65 with PROPOSALS3
44866 Federal Register / Vol. 73, No. 148 / Thursday, July 31, 2008 / Proposed Rules 

1USDA’s Pesticide Data Program monitors for 

pesticides in certain foods at the distribution points 

just before release to supermarkets and grocery 

stores. 

using all relevant data and methods, 

strongly corroborates EPA’s conclusion 

that aggregate exposures from 

carbofuran are not safe. 

B. What is the Agency’s authority for 

Taking this Action? 

EPA is taking this action, pursuant to 

the authority in FFDCA sections 

408(b)(1)(b), 408(b)(2)(A), and 

408(e)(1)(A). 21 U.S.C. 346a(b)(1)(b), 

(b)(2)(A), (e)(1)(A). 

III. Statutory and Regulatory 

Background 

A ‘‘tolerance’’ represents the 

maximum level for residues of pesticide 

chemicals legally allowed in or on raw 

agricultural commodities (including 

animal feed) and processed foods. 

Section 408 of the FFDCA, 21 U.S.C. 

346a, as amended by the Food Quality 

Protection Act (FQPA) of 1996, Public 

Law 104–170, authorizes the 

establishment of tolerances, exemptions 

from tolerance requirements, 

modifications in tolerances, and 

revocation of tolerances for residues of 

pesticide chemicals in or on raw 

agricultural commodities and processed 

foods. Without a tolerance or 

exemption, food containing pesticide 

residues is considered to be unsafe and 

therefore ‘‘adulterated’’ under section 

402(a) of the FFDCA, 21 U.S.C. 342(a). 

Such food may not be distributed in 

interstate commerce (21 U.S.C. 331(a)). 

For a food-use pesticide to be sold and 

distributed, the pesticide must not only 

have appropriate tolerances under the 

FFDCA, but also must be registered 

under the Federal Insecticide Fungicide 

and Rodenticide Act (FIFRA) (7 U.S.C. 

136 et seq.). Food-use pesticides not 

registered in the United States must 

have tolerances in order for 

commodities treated with those 

pesticides to be imported into the 

United States. 

Section 408(e) of the FFDCA, 21 

U.S.C. 346a(e), authorizes EPA to 

modify or revoke tolerances on its own 

initiative. EPA is proposing to revoke 

these tolerances to implement the 

Agency’s findings made during the 

reregistration and tolerance 

reassessment processes. As part of these 

processes, EPA is required to determine 

whether each of the existing tolerances 

meets the safety standard of section 

408(b)(2) (21 U.S.C. 346a(b)(2)). Section 

408(b)(2)(A)(i) of the FFDCA requires 

EPA to modify or revoke a tolerance if 

EPA determines that the tolerance is not 

‘‘safe.’’ (21 U.S.C. 346a(b)(2)(A)(i)). 

Section 408(b)(2)(A)(ii) of the FFDCA 

defines ‘‘safe’’ to mean that ‘‘there is a 

reasonable certainty that no harm will 

result from aggregate exposure to the 

pesticide chemical residue, including 

all anticipated dietary exposures and all 

other exposures for which there is 

reliable information.’’ This includes 

exposure through drinking water and in 

residential settings, but does not include 

occupational exposure. 

Risks to infants and children are given 

special consideration. Specifically, 

section 408(b)(2)(C) states that EPA: 

shall assess the risk of the pesticide 

chemical based on— ... 

(II) available information concerning the 

special susceptibility of infants and children 

to the pesticide chemical residues, including 

neurological differences between infants and 

children and adults, and effects of in utero 

exposure to pesticide chemicals; and 

(III) available information concerning the 

cumulative effects on infants and children of 

such residues and other substances that have 

a common mechanism of toxicity. ... 

(21 U.S.C. 346a(b)(2)(C)(i)(II) and (III)). 

This provision further directs that 

‘‘[i]n the case of threshold effects, ... an 

additional tenfold margin of safety for 

the pesticide chemical residue and other 

sources of exposure shall be applied for 

infants and children to take into account 

potential pre- and post-natal toxicity 

and completeness of the data with 

respect to exposure and toxicity to 

infants and children.’’ (21 U.S.C. 

346a(b)(2)(C)). EPA is permitted to ‘‘use 

a different margin of safety for the 

pesticide chemical residue only if, on 

the basis of reliable data, such margin 

will be safe for infants and children.’’

(Id.). The additional safety margin for 

infants and children is referred to 

throughout this proposal as the 

‘‘children’s safety factor.’’

IV. Carbofuran Background and 

Regulatory History 

In July 2006, EPA completed a refined 

acute probabilistic dietary risk 

assessment for carbofuran as part of the 

reassessment program under section 

408(q) of the FFDCA. The assessment 

was conducted using Dietary Exposure 

Evaluation Model-Food Commodity 

Intake Database (DEEM-FCID(TM)

, 

Version 200–2.02), which incorporates 

consumption data from the United 

States Department of Agriculture’s 

(USDA’s) Nationwide Continuing 

Surveys of Food Intake by Individuals 

(CSFII), 1994–1996 and 1998, as well as 

carbofuran monitoring data from 

USDA’s Pesticide Data Program1 (PDP), 

estimated percent crop treated 

information, and processing/cooking 

factors, where applicable. The 

assessment was conducted applying an 

additional 500–fold safety factor that 

included a 5X children’s safety factor, 

pursuant to section 408(b)(2)(C). That 

refined assessment showed acute 

dietary risks from carbofuran residues in 

food above EPA’s level of concern (Ref 

15). Since 2006, EPA has evaluated 

additional data submitted by the 

registrant, FMC Corporation, and has 

further refined its original assessment 

by incorporating more recent 2005/2006 

PDP data, and by conducting additional 

analyses. In January 2008, EPA 

published a draft Notice of Intent to 

Cancel (NOIC) all carbofuran 

registrations, based in part on 

carbofuran’s dietary risks. As mandated 

by FIFRA, EPA solicited comments from 

the Scientific Advisory Panel (SAP) on 

its draft NOIC. Having considered the 

comments from the SAP, EPA is 

initiating the process to revoke all 

carbofuran tolerances. As noted above, 

aggregate exposures from food and 

water to the US population at the upper 

percentiles of exposure substantially 

exceed the safe daily levels and thus are 

‘‘unsafe’’ within the meaning of FFDCA 

section 408(b)(2) (Ref 12). It is 

particularly significant that under every 

analysis EPA has conducted, the levels 

of carbofuran exceed the safe daily dose 

for children, even when EPA used the 

most refined data and models available. 

Based on these findings, EPA has 

decided to move as expeditiously as 

possible to address the unacceptable 

dietary risks to children. EPA still 

expects to issue the NOIC subsequent to 

undertaking the activities required to 

revoke the carbofuran tolerances. 

In May 2008, FMC Corporation, the 

sole U.S. registrant, submitted a 

conditional request to cancel use of 

carbofuran on certain crops and to add 

use restrictions intended to mitigate 

ground and surface water contamination 

from use on other crops (Ref. 32). The 

tolerances that would have been 

affected by that proposal are: alfalfa, 

fresh; alfalfa, hay; artichoke, globe; 

barley, grain; barley, straw; sugar beet, 

tops; cranberry; cucumber; grape; grape 

(raisin); oat, grain; oat, straw; pepper; 

sorghum, fodder; sorghum, forage; 

sorghum, grain; strawberry; soybean; 

soybean, forage; soybean, hay; squash; 

wheat, grain; wheat, straw. FMC, 

however, conditioned the request on 

receiving assurance from EPA that the 

Agency would permit the retention of 

several uses that do not meet the FFDCA 

408(b)(2) safety standard or the FIFRA 

registration standard (Id.). EPA, 

therefore, could not accept the request, 

and FMC has withdrawn it (Id.). The 

tolerances that FMC would have sought 

to retain under that proposal were: 


jlentini on PROD1PC65 with PROPOSALS3
Federal Register / Vol. 73, No. 148 / Thursday, July 31, 2008 / Proposed Rules 44867 

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. 

58). In capsule, a probabilistic pesticide exposure 

analysis constructs a distribution of potential 

exposures based on data on consumption patterns 

and residue levels and provides a ranking of the 

probability that each potential exposure will occur. 

People consume differing amounts of the same 

foods, including none at all, and a food will contain 

differing amounts of a pesticide residue, including 

none at all. 

banana, coffee bean; corn, forage; corn, 

fresh; corn, grain (including popcorn); 

corn, stover; cotton, undelinted seed; 

melon; milk; potato; rice, grain; rice, 

straw; sugarcane, cane; and sunflower, 

seed. Based on the contribution from 

these foods alone, dietary exposures to 

carbofuran would still be unsafe for the 

more sensitive children’s 

subpopulations. At the 99.9th 

percentile, carbofuran dietary exposure 

from food alone was estimated at 

0.000082 mg/kg/day (110% of the 

aPAD) for children 3–5 years old, the 

population subgroup with the highest 

estimated dietary exposure (Ref. 12). In 

addition, as discussed in more detail in 

Refs 18 and 54, although FMC’s 

proposed groundwater restrictions 

would have protected against further 

contamination in the most vulnerable 

locations, the Agency could not 

conclude that the restrictions would be 

protective of all vulnerable 

groundwater. EPA also has substantial 

questions about the efficacy of FMC’s 

proposed surface water restrictions to 

reduce drinking water exposure in 

vulnerable reservoirs (Refs. 18 and 54). 

Accordingly, it has not been shown that 

drinking water residues of carbofuran 

would no longer contribute significantly 

to unsafe aggregate exposures, nor that 

such exposures would meet the FFDCA 

safety standard. 

V. EPA’s Approach to Dietary Risk 

Assessment 

EPA performs a number of analyses to 

determine the risks from aggregate 

exposure to pesticide residues. A short 

summary is provided below to aid the 

reader. For further discussion of the 

regulatory requirements of section 408 

of the FFDCA and a complete 

description of the risk assessment 

process, see http://www.epa.gov/ 

fedrgstr/EPA–PEST/1999/January/Day–

04/p34736.htm. 

To assess the risk of a pesticide 

tolerance, EPA combines information on 

pesticide toxicity with information 

regarding the route, magnitude, and 

duration of exposure to the pesticide. 

The risk assessment process involves 

four distinct steps: (1) identification of 

the toxicological hazards posed by a 

pesticide; (2) determination of the 

exposure ‘‘level of concern’’ for humans; 

(3) estimation of human exposure; and 

(4) characterization of human risk based 

on comparison of human exposure to 

the level of concern. 

A. Hazard Identification and Selection 

of Toxicological Endpoint 

Any risk assessment begins with an 

evaluation of a chemical’s inherent 

properties, and whether those properties 

have the potential to cause adverse 

effects (i.e., a hazard identification). 

EPA then evaluates the hazards to 

determine the most sensitive and 

appropriate adverse effect of concern, 

based on factors such as the effect’s 

relevance to humans and the likely 

routes of exposure. 

Once a pesticide’s potential hazards 

are identified, EPA determines a 

toxicological level of concern for 

evaluating the risk posed by human 

exposure to the pesticide. In this step of 

the risk assessment process, EPA 

essentially evaluates the levels of 

exposure to the pesticide at which 

effects might occur. An important aspect 

of this determination is assessing the 

relationship between exposure (dose) 

and response (often referred to as the 

dose-response analysis). In evaluating a 

chemical’s dietary risks EPA uses a 

reference dose (RfD) approach, which 

involves a number of considerations 

including: 

• 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); and 

•The need for an additional safety 

factor to protect infants and children, as 

specified in FFDCA section 408(b)(2)(C). 

EPA uses the chosen PoD to calculate 

a safe dose or RfD. The RfD is calculated 

by dividing the chosen PoD by all 

applicable safety or uncertainty factors. 

Typically in EPA risk assessments, a 

combination of safety or uncertainty 

factors providing at least a hundredfold 

(100X) margin of safety is used: 10X to 

account for interspecies extrapolation 

and 10X to account for intraspecies 

extrapolation. Further, in evaluating the 

dietary risks for pesticide chemicals, an 

additional safety factor of 10X is 

presumptively applied to protect infants 

and children, unless reliable data 

support selection of a different factor. In 

implementing FFDCA section 408, EPA 

also calculates a variant of the RfD 

referred to as a PAD. A PAD is the RfD 

divided by any portion of the children’s 

safety factor that does not correspond to 

one of the traditional additional 

uncertainty/safety factors used in 

general Agency risk assessment. The 

reason for calculating PADs is so that 

other parts of the Agency, which are not 

governed by FFDCA section 408, can, 

when evaluating the same or similar 

substances, easily identify which 

aspects of a pesticide risk assessment 

are a function of the particular statutory 

commands in FFDCA section 408. For 

acute assessments, the risk is expressed 

as a percentage of a maximum 

acceptable dose or the acute PAD (i.e., 

the acute dose which EPA has 

concluded will be ‘‘safe’’). As discussed 

below in Unit V.C., dietary exposures 

greater than 100 percent of the acute 

PAD are generally cause for concern and 

would be considered ‘‘unsafe’’ within 

the meaning of FFDCA section 

408(b)(2)(B). Throughout this document 

general references to EPA’s calculated 

safe dose are denoted as an acute PAD, 

or aPAD, because the relevant point of 

departure for carbofuran is based on an 

acute risk endpoint. 

B. Estimating Human Dietary Exposure 

Levels 

Pursuant to section 408(b) of the 

FFDCA, EPA has evaluated carbofuran’s 

dietary risks based on ‘‘aggregate 

exposure’’ to carbofuran. By ‘‘aggregate 

exposure,’’ EPA is referring to exposure 

to carbofuran alone by multiple 

pathways of exposure. EPA uses 

available data, together with 

assumptions designed to be protective 

of public health and standard analytical 

methods, to produce separate estimates 

of exposure for a highly exposed 

subgroup of the general population, for 

each potential pathway and route of 

exposure. For acute risks, EPA then 

calculates potential aggregate exposure 

and risk by using probabilistic2

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 


jlentini on PROD1PC65 with PROPOSALS3
44868 Federal Register / Vol. 73, No. 148 / Thursday, July 31, 2008 / Proposed Rules 

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 the data comes 

from federally-conducted surveys, 

including the PDP conducted by the 

USDA. Further, market basket studies, 

which are typically performed by 

registrants, can provide additional 

residue data. These data generally 

provide a characterization of pesticide 

residues in or on foods consumed by the 

U.S. population that closely 

approximates real world exposures 

because they are sampled closer to the 

point of consumption in the chain of 

commerce than field trial data, which 

are generated to establish the maximum 

level of legal residues that could result 

from maximum permissible use of the 

pesticide. In certain circumstances, EPA 

will rely on field trial data, as it can 

provide more accurate exposure 

estimates (see below in Unit VI.E.1). 

EPA uses a computer program known 

as the DEEM-FCID to estimate exposure 

by combining data on human 

consumption amounts with residue 

values in food commodities. DEEMFCID also compares exposure estimates 

to appropriate RfD or PAD values to 

estimate risk. EPA uses DEEM-FCID to 

estimate exposure for the general U.S. 

population as well as for 32 subgroups 

based on age, sex, ethnicity, and region. 

DEEM-FCID allows EPA to process 

extensive volumes of data on human 

consumption amounts and residue 

levels in making risk estimates. 

Matching consumption and residue 

data, as well as managing the thousands 

of repeated analyses of the consumption 

database conducted under probabilistic 

risk assessment techniques, requires the 

use of a computer. 

DEEM-FCID contains consumption 

and demographic information on the 

individuals who participated in the 

USDA’s CSFII in 1994–1996 and 1998. 

The 1998 survey was a special survey 

required by the FQPA to supplement the 

number of children survey participants. 

DEEM-FCID also contains ‘‘recipes’’ that 

convert foods as consumed (e.g., pizza) 

back into their component raw 

agricultural commodities (e.g., wheat 

from flour, or tomatoes from sauce, etc.). 

This is necessary because residue data 

are generally gathered on raw 

agricultural commodities rather than on 

finished ready-to-eat food. Data on 

residue values for a particular pesticide 

and the RfD or PADs for that pesticide 

are inputs to the DEEM-FCID program to 

estimate exposure and risk. 

For carbofuran’s assessment, EPA 

used DEEM-FCID to calculate risk 

estimates based on a probabilistic 

distribution. DEEM-FCID combines the 

full range of residue values for each 

food with the full range of data on 

individual consumption amounts to 

create a distribution of exposure and 

risk levels. More specifically, DEEMFCID creates this distribution by 

calculating an exposure value for each 

reported day of consumption per person 

(‘‘person/day’’) in CSFII, assuming that 

all foods potentially bearing the 

pesticide residue contain such residue 

at the chosen value. The exposure 

amounts for the thousands of person/ 

days in the CSFII are then collected in 

a frequency distribution. EPA also uses 

DEEM-FCID to compute a distribution 

taking into account both the full range 

of data on consumption levels and the 

full range of data on potential residue 

levels in food. Combining consumption 

and residue levels into a distribution of 

potential exposures and risk requires 

use of probabilistic techniques. 

The probabilistic technique that 

DEEM-FCID uses to combine differing 

levels of consumption and residues 

involves the following steps: 

(1) Identification of any food(s) that 

could bear the residue in question for 

each person/day in the CSFII; 

(2) Calculation of an exposure level 

for each of the thousands of person/days 

in the CSFII database, based on the 

foods identified in Step #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; 

and 

(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)). These models calculate 

estimated water concentrations of 

pesticides using laboratory data that 

describe how fast the pesticide breaks 

down to other chemicals and how it 

moves in the environment at these 

vulnerable locations. The modeling 

provides an estimate of pesticide 

concentrations in ground and surface 

water. Depending on the modeling 

algorithm (e.g., surface water modeling 

scenarios), daily concentrations can be 

estimated continuously over long 

periods of time, and for places that are 

of most interest for any particular 

pesticide. 

EPA relies on models it has developed 

for estimating pesticide concentrations 

in both surface water and ground water. 

Typically EPA uses a two-tiered 

approach to modeling pesticide 

concentrations in surface and ground 

water. If the first tier model suggests 

that pesticide levels in water may be 

unacceptably high, a more refined 

model is used as a second tier 

assessment. The second tier model is 

actually a combination of two models: 

the Pesticide Root Zone Model (PRZM) 

and the Exposure Analysis Model 

System (EXAMS). 

A detailed description of the models 

routinely used for exposure assessment 

is available from the EPA OPP Water 

Models web site: http://www.epa.gov/ 

oppefed1/models/water/index.htm. 

These models provide a means for EPA 

to estimate daily pesticide 

concentrations in surface water sources 

of drinking water (a reservoir) using 

local soil, site, hydrology, and weather 


jlentini on PROD1PC65 with PROPOSALS3
Federal Register / Vol. 73, No. 148 / Thursday, July 31, 2008 / Proposed Rules 44869 

characteristics along with pesticide 

application and agricultural 

management practices, and pesticide 

environmental fate and transport 

properties. Consistent with the 

recommendations of the FIFRA SAP, 

EPA also considers regional percent 

cropped area factors (PCA) which takes 

into account the potential extent of 

cropped areas that could be treated with 

pesticides in a particular area. The 

PRZM and EXAMS models used by EPA 

were developed by EPA’s Office of 

Research and Development (ORD), and 

are used by many international 

pesticide regulatory agencies to estimate 

pesticide exposure in surface water. 

EPA’s use of the percent cropped area 

factors and the Index Reservoir scenario 

was reviewed by the FIFRA SAP in 1999 

and 1998, respectively (Refs. 25 and 26). 

In modeling potential surface water 

concentrations, EPA attempts to model 

areas of the country that are highly 

vulnerable to surface water 

contamination rather than simply model 

‘‘typical’’ concentrations occurring 

across the nation. Consequently, EPA 

models exposures occurring in small 

highly agricultural watersheds in 

different growing areas throughout the 

country, over a 30 year period. The 

scenarios are designed to capture 

residue levels in drinking water from 

reservoirs with small watersheds with a 

large percentage of land use in 

agricultural production. EPA believes 

these assessments are likely reflective of 

a small subset of the watersheds across 

the country that maintain drinking 

water reservoirs, representing a drinking 

water source generally considered to be 

more vulnerable to frequent high 

concentrations of pesticides than most 

locations that could be used for crop 

production. 

EPA uses the output of daily 

concentration values from tier two 

modeling as an input to DEEM-FCID, 

which combines water concentrations 

with drinking water consumption 

information in the daily diet to generate 

a distribution of exposures from 

consumption of drinking water 

contaminated with pesticides. These 

results are then used to calculate a 

probabilistic assessment of the aggregate 

human exposure and risk from residues 

in food and drinking water. 

C. Selection of Acute Dietary Exposure 

Level of Concern 

Because probabilistic assessments 

generally present a realistic range of 

residue values to which the population 

may be exposed, EPA’s starting point for 

estimating exposure and risk for such 

aggregate assessments is the 99.9th 

percentile of the population under 

evaluation. When using a probabilistic 

method of estimating acute dietary 

exposure, EPA typically assumes that, 

when the 99.9th percentile of acute 

exposure is equal to or less than the 

aPAD, the level of concern for acute risk 

has not been exceeded. By contrast, 

where the analysis indicates that 

estimated exposure at the 99.9th 

percentile exceeds the aPAD, EPA 

would generally conduct one or more 

sensitivity analyses to determine the 

extent to which the estimated exposures 

at the high-end percentiles may be 

affected by unusually high food 

consumption or residue values. To the 

extent that one or a few values seem to 

‘‘drive’’ the exposure estimates at the 

high end of exposure, EPA would 

consider whether these values are 

reasonable and should be used as the 

primary basis for regulatory decision 

making (Ref 58). 

VI. Aggregate Risk Assessment and 

Conclusions Regarding Safety 

Consistent with section 408(b)(2)(D) 

of FFDCA, EPA has reviewed the 

available scientific data and other 

relevant information in support of this 

action. EPA’s assessment of exposures 

and risks associated with carbofuran use 

follows: 

A. Toxicological Profile 

Carbofuran is an N-methyl carbamate 

(NMC) pesticide. Like other pesticides 

in this class, the primary toxic effect 

seen following carbofuran exposure is 

neurotoxicity resulting from inhibition 

of the enzyme acetylcholinesterase 

(AChE). AChE breaks down 

acetylcholine (ACh), a compound that 

assists in transmitting signals through 

the nervous system. Carbofuran inhibits 

the AChE activity in the body. When 

AChE is inhibited at nerve endings, the 

inhibition prevents the ACh from being 

degraded and results in prolonged 

stimulation of nerves and muscles. 

Physical signs and symptoms of 

carbofuran poisoning include headache, 

nausea, dizziness, blurred vision, 

excessive perspiration, salivation, 

lacrimation (tearing), vomiting, 

diarrhea, aching muscles, and a general 

feeling of severe malaise. Uncontrollable 

muscle twitching and bradycardia 

(abnormally slow heart rate) can occur. 

Severe poisoning can lead to 

convulsions, coma, pulmonary edema, 

muscle paralysis, and death by 

asphyxiation. Carbofuran poisoning also 

may cause various psychological, 

neurological and cognitive effects, 

including confusion, anxiety, 

depression, irritability, mood swings, 

difficulty concentrating, short-term 

memory loss, persistent fatigue, and 

blurred vision (Refs. 15 and 16). 

The most sensitive and appropriate 

effect associated with the use of 

carbofuran is its toxicity following acute 

exposure. Acute exposure is defined as 

an exposure of short duration, usually 

characterized as lasting no longer than 

a day. EPA classifies carbofuran as 

Toxicity Category I, the most toxic 

category, based on its potency by the 

oral and inhalation exposure routes. The 

lethal potencies of chemicals are usually 

described in terms of the ‘‘dose’’ given 

orally or the ‘‘concentration’’ in air that 

is estimated to cause the death of 50 

percent of the animals exposed 

(abbreviated as 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. 12, 16 and 48). The lethal 

dose and lethal concentration levels for 

the oral and inhalation routes fall well 

below the limits for the Toxicity 

Category I, < 50 mg/kg and < 0.2 mg/l, 

respectively (40 CFR 156.62). 

Carbofuran has a steep dose-response 

curve. In other words, a marginal 

increase in administered doses of 

carbofuran can result in a significant 

change in the toxic effect. For example, 

carbofuran data in juvenile rats 

(postnatal day 11 and 17) demonstrate 

that small differences in carbofuran 

doses (0.1 mg/kg to 0.3 mg/kg) can 

change the measured effect from 

significant brain and red blood cell 

(RBC) AChE inhibition without clinical 

signs (0.1 mg/kg) to significant AChE 

inhibition, and resultant tremors, and 

decreased motor activity (0.3 mg/kg) 

(Refs. 31 and 46). In other words there 

is a slight difference in exposure levels 

that produce no noticeable outward 

effects and the level that causes adverse 

effects. This means that small 

differences in human exposure levels 

can have significant adverse 

consequences for large numbers of 

individuals. For example, as discussed 

in greater detail in Unit VI.E.1.b below, 

the difference between the amount of 

food with carbofuran residues that can 

be safely consumed without adverse 

effect, and the amount that provides a 

dose that exceeds safe levels is minimal. 

Children who consume typical amounts 

of watermelon (i.e., 8 grams) containing 

carbofuran residues of 0.009 ppm–a 

residue level detected in PDP data—

receive a safe daily dose, but those 

consuming the same amount of 

watermelon with a PDP residue level of 

0.013 receive an exposure of 130% of 

the safe daily dose. 


jlentini on PROD1PC65 with PROPOSALS3
44870 Federal Register / Vol. 73, No. 148 / Thursday, July 31, 2008 / Proposed Rules 

B. Deriving Carbofuran’s point of 

departure 

EPA uses a weight of evidence 

approach to determine the toxic effect 

that will serve as the appropriate PoD 

for a risk assessment for AChE 

inhibiting pesticides, such as carbofuran 

(Ref. 61). The neurotoxicity that 

carbofuran causes can occur in both the 

central (brain) and peripheral nervous 

systems (PNS). In its weight of the 

evidence analysis, EPA reviews data, 

such as AChE inhibition data from the 

brain, peripheral tissues and blood (e.g., 

RBC or plasma), in addition to data on 

clinical signs and other functional 

effects related to AChE inhibition. Based 

on these data, EPA selects the most 

appropriate effect on which to regulate; 

such effects can include clinical signs of 

AChE inhibition, central or peripheral 

nervous tissue measurements of AChE 

inhibition or RBC AChE measures (Id.). 

Although RBC AChE inhibition is not 

adverse in itself, it is a surrogate for 

inhibition in peripheral tissues when 

peripheral data are not available. As 

such, RBC AChE inhibition provides an 

indirect indication of adverse effects on 

the nervous system (Id.). Due to 

technical difficulties regarding 

dissection of peripheral nerves and the 

rapid nature of carbofuran toxicity, 

measures of AChE inhibition in the PNS 

are very rare for NMC pesticides. For 

these reasons, other state and national 

agencies such as California, 

Washington, Canada, the European 

Union, as well as the World Health 

Organization (WHO), all use blood 

measures in human health risk 

assessment and/or worker safety 

monitoring programs. 

AChE inhibition in brain and the PNS 

is the initial adverse biological event 

which results from exposure to 

carbofuran, and with sufficient levels of 

inhibition leads to other effects such as 

tremors, dizziness, as well as 

gastrointestinal and cardiovascular 

effects, including bradycardia (Ref. 16). 

Thus, AChE inhibition provides the 

most appropriate effect to use in risk 

extrapolation for derivation of RfDs and 

PADs. Protecting against AChE 

inhibition ensures that the other adverse 

effects mentioned above do not occur. 

EPA has relied on a benchmark dose 

approach for deriving the PoD from the 

available rat toxicity studies. A 

benchmark dose, or BMD, is a point 

estimate along a dose-response curve 

that corresponds to a specific response 

level. For example, a BMD10 represents 

a 10% change from the background or 

typical value for the response of 

concern. Generically, the direction of 

change from background can be an 

increase or a decrease depending on the 

biological parameter and the chemical 

of interest. In the case of carbofuran, 

inhibition of AChE is the toxic effect of 

concern. Following exposure to 

carbofuran, the normal biological 

activity of the AChE enzyme is 

decreased (i.e., the enzyme is inhibited). 

Thus, when evaluating BMDs for 

carbofuran, the Agency is interested in 

a decrease in AChE activity compared to 

normal activity levels, which are also 

termed ‘‘background’’ levels. 

Measurements of ‘‘background’’ AChE 

activity levels are usually obtained from 

animals in experimental studies that are 

not treated with the pesticide of interest 

(i.e., ‘‘negative control’’ animals). 

In addition to the BMD, a ‘‘confidence 

limit’’ was also calculated. Confidence 

limits express the uncertainty in a BMD 

that may be due to sampling and/or 

experimental error. The lower 

confidence limit on the dose used as the 

BMD is termed the BMDL, which the 

Agency uses as the PoD. Use of the 

BMDL for deriving the PoD rewards 

better experimental design and 

procedures that provide more precise 

estimates of the BMD, resulting in 

tighter confidence intervals. Use of the 

BMDL also helps ensure with high 

confidence (e.g., 95% confidence) that 

the selected percentage of AChE 

inhibition is not exceeded. From the 

PoD, EPA calculates the RfD and aPAD. 

Numerous scientific peer review 

panels over the last decade have 

supported the Agency’s application of 

the BMD approach as a scientifically 

supportable method for deriving PoDs 

in human health risk assessment, and as 

an improvement over the historically 

applied approach of using no-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. 27, 28, 29 and 

57). Specific to carbofuran and other 

NMCs, the FIFRA SAP has reviewed 

and supported the statistical methods 

used by the Agency to derive BMDs and 

BMDLs on two occasions, February 

2005 and August 2005 (Refs. 28 and 29). 

Recently, in reviewing EPA’s draft 

NOIC, the SAP again unanimously 

concluded that the Agency’s approach 

in using a benchmark dose to derive the 

PoD from carbofuran brain AChE data in 

juvenile rats is ‘‘state of the art science 

and the Panel strongly encouraged the 

Agency to follow this approach for all 

studies where possible’’ (Ref. 30). 

There are laboratory data on 

carbofuran for cholinesterase activity in 

plasma, RBC, and brain. EPA evaluated 

the quality of the AChE data in all the 

available studies. In this review, 

particular attention was paid to the 

methods used to assay AChE inhibition 

in the laboratory conducting the study. 

Because of the nature of carbofuran 

inhibition of AChE, care must be taken 

in the laboratory such that experimental 

conditions do not promote enzyme 

reactivation (i.e., recovery) while 

samples of blood and brain are being 

processed and analyzed. If this 

reactivation occurs during the assay, the 

results of the experiment will 

underestimate the toxic potential of 

carbofuran (Refs. 33, 37, 43, 66 and 67). 

Through its review of available studies, 

the Agency identified problems and 

irregularities with the RBC AChE data 

from both FMC supported studies. 

These problems are described in detail 

in the Agency’s study review (Refs. 19 

and 20). As such, the Agency 

determined that the RBC AChE 

inhibition data from both FMC studies 

were unreliable and not useable in 

extrapolating human health risk. In 

addition, RBC data from a study 

performed at EPA ORD did not provide 

doses low enough to adequately 

characterize the full dose-response in 

postnatal day 11 (PND11) rats. In the 

recent SAP review of the draft 

carbofuran NOIC, the Panel 

unanimously agreed with the Agency’s 

conclusion, remarking that ‘‘[t]he 

Agency is well-justified in taking the 

position that the data on AChE 

inhibition in rat RBC, particularly with 

regard to the PND11 pups, are not 

acceptable for the purpose of predicting 

health risk from carbofuran’’ (Ref. 30). 

By contrast, the brain AChE data from 

the FMC and EPA-ORD studies are 

acceptable and have been used in the 

Agency’s BMD analysis. 

In EPA’s BMD dose analysis to derive 

PoDs for carbofuran, the Agency used a 

response level of 10% brain AChE 

inhibition and thus calculated 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 organophosphate 

pesticides and NMCs including 

carbofuran. For a variety of toxicological 

and statistical reasons, EPA chose 10% 


jlentini on PROD1PC65 with PROPOSALS3
Federal Register / Vol. 73, No. 148 / Thursday, July 31, 2008 / Proposed Rules 44871 

brain AChE inhibition as the response 

level for use in BMD and BMDL 

calculations. EPA analyses have 

demonstrated that 10% is a level that 

can be reliably measured in the majority 

of rat toxicity studies; is generally at or 

near the limit of sensitivity for 

discerning a statistically significant 

decrease in AChE activity across the 

brain compartment; and is a response 

level close to the background AChE 

level (Refs. 28 and 29) 

The Agency used a meta-analysis to 

calculate the 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. 

28 and 29). The meta-analysis approach 

offers the advantage over using single 

studies by combining information across 

multiple studies and thus provides a 

robust PoD. 

There are three studies available 

which compare the effects of carbofuran 

on PND11 rats with those in young 

adult rats (herein called ‘comparative 

AChE studies’) (Refs. 1, 2 and 46). Two 

of these studies were submitted by FMC, 

the registrant, and one was performed 

by EPA-ORD. An additional study 

conducted by EPA-ORD involved 

PND17 rats (Ref. 45). Although it is not 

possible to directly correlate ages of 

juvenile rats to humans, PND11 rats are 

believed to be close in development to 

newborn humans. PND17 rats are 

believed to be closer developmentally to 

human toddlers (Ref. 9). Other studies 

in adult rats used in the Agency’s 

analysis included additional data from 

EPA-ORD (Refs 44 and 46). 

Using quality brain AChE data from 

the three studies (2 FMC, 1 EPA–ORD) 

conducted with PND11 rats, in 

combination, provides data to describe 

both low and high doses. By combining 

the three studies in PND11 animals 

together in a meta-analysis, the entire 

dose-response range is covered (see 

Figure 1 in Unit VI.C. below). The 

Agency believes the BMD analysis for 

the PND11 brain AChE data is the most 

robust analysis for purposes of PoD 

selection. 

The studies in juvenile rats show a 

consistent pattern that juvenile rats are 

more sensitive than adult rats to the 

effects of carbofuran. These effects 

include inhibition in AChE in addition 

to incidence of clinical signs of 

neurotoxicity such as tremors. This 

pattern has also been observed for other 

NMC pesticides, which exhibit the same 

mechanism of toxicity as carbofuran 

(Ref. 63). It is not unusual for juvenile 

rats, or indeed, for infants or young 

children, to be more sensitive to 

chemical exposures as metabolic 

detoxification processes in the young 

are still developing. Because juvenile 

rats, called ‘pups’ herein, are more 

sensitive than adult rats, data from pups 

provide the most relevant information 

for evaluating risk to infants and young 

children and are thus used to derive the 

PoD. In addition, typically (and is the 

case for carbofuran) young children 

(ages 0–5) tend to be the most exposed 

age groups because they tend to eat 

larger amounts of food per their body 

weight than do teenagers or adults. As 

such, the focus of EPA’s analysis of 

carbofuran’s dietary risk from residues 

in food and water is on young children 

(ages 0–5). Since these age groups 

experience the highest levels of dietary 

risk, protecting these groups against the 

effects of carbofuran will, in turn, also 

protect other age groups. 

Using data from PND11 pup brain 

AChE levels, the estimated oral dose 

that will result in 10% brain AChE 

inhibition (BMD10) is 0.04 mg/kg. The 

lower 95% confidence limit on the 

BMD10 (BMDL10) is 0.03 mg/kg—this 

BMDL10 of 0.03 mg/kg provides the PoD. 

As noted, although EPA does not 

consider RBC AChE inhibition as an 

adverse effect in its own right, in the 

absence of data from peripheral tissues, 

RBC AChE inhibition data are a critical 

component to determining that a 

selected PoD will be sufficiently 

protective of PNS effects. Because of the 

problems discussed previously with the 

available RBC AChE inhibition data, 

there remains uncertainty surrounding 

the dose-response relationship for RBC 

AChE inhibition in pups, which the 

EPA-ORD data clearly show to be a 

more sensitive endpoint than brain 

AChE. Consequently, EPA cannot 

reliably estimate the BMD10 and 

BMDL10 for RBC AChE data in pups. 

Furthermore, given that the EPA-ORD 

data clearly show RBC AChE to be more 

sensitive than brain AChE, EPA cannot 

conclude that reliance on the pup brain 

data as the PoD would be sufficiently 

protective of PNS effects in pups. This 

uncertainty provides the scientific basis, 

in part, for retention of the children’s 

safety factor as described below. 

C. Safety Factor for Infants and Children 

1. In general. Section 408 of the 

FFDCA provides that EPA shall apply 

an additional tenfold margin of safety 

for infants and children in the case of 

threshold effects to account for prenatal 

and postnatal toxicity and the 

completeness of the data base on 

toxicity and exposure unless EPA 

determines that a different margin of 

safety will be safe for infants and 

children. Margins of safety are 

incorporated into EPA assessments 

either directly through use of a margin 

of exposure analysis or through using 

uncertainty (safety) factors in 

calculating a dose level that poses 

acceptable risk to humans. 

In applying the children’s safety 

factor provision, EPA has interpreted 

the statutory language as imposing a 

presumption in favor of applying an 

additional 10X safety factor (Ref. 60). 

Thus, EPA generally refers to the 

additional 10X factor as a presumptive 

or default 10X factor. EPA has also 

made clear, however, that the 

presumption can be overcome if reliable 

data demonstrate that a different factor 

is safe for children (Id.). In determining 

whether a different factor is safe for 

children, EPA focuses on the three 

factors listed in section 408(b)(2)(C) - 

the completeness of the toxicity 

database, the completeness of the 

exposure database, and potential 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.). 

2. Prenatal and postnatal sensitivity. 

As noted in the previous section, there 

are several studies in juvenile rats that 

show they are more sensitive than adult 

rats to the effects of carbofuran. These 

effects include inhibition of brain AChE 

in addition to the incidence of clinical 

signs of neurotoxicity (such as tremors) 

at lower doses in the young rats. The 

SAP concurred with EPA that the data 

clearly indicate that the juvenile rat is 

more sensitive than the adult rat with 

regard to brain AChE (Ref. 30). 

However, the Agency does not have 

AChE data for cabofuran in the 

peripheral tissue of adult or juvenile 

animals; nor does the Agency have 

adequate RBC AChE inhibition data at 

low doses relevant to risk assessment to 

serve as a surrogate in pups. As 

previously noted the RBC AChE data 

from both FMC supported studies are 

not reliable and thus are not appropriate 

for use in risk assessment. Although the 

EPA studies did provide reliable RBC 

data, they did not include data at the 

low end of the dose-response curve, 

which is the area on the dose-response 

curve most relevant for risk assessment 

(see Figure 1). 

BILLING CODE 6560–50–S 


jlentini on PROD1PC65 with PROPOSALS3
44872 Federal Register / Vol. 73, No. 148 / Thursday, July 31, 2008 / Proposed Rules 

BILLING CODE 6560–50–C 


jlentini on PROD1PC65 with PROPOSALS3EP31JY08.018
Federal Register / Vol. 73, No. 148 / Thursday, July 31, 2008 / Proposed Rules 44873 

3EPA made a mathematical error when it 

originally calculated the children’s safety factor, 

which resulted in a factor of 5X (Ref. 50). Correcting 

the mathematical error results in a 4X actor. 

There is indication in a toxicity study 

where pregnant rats were exposed to 

carbofuran that effects on the PNS are of 

concern; specifically, chewing motions 

or mouth smacking was observed in a 

clear dose-response pattern immediately 

following dosing each day (Ref. 64). 

Based on this study, the California 

Department of Pesticide Regulation 

calculated a BMD05 and BMDL05 of 0.02 

and 0.01 mg/kg/day, and established the 

acute PoD (Refs. 11 and 30). These BMD 

estimates are notable as they are close 

to the values EPA has calculated for 

brain AChE inhibition and being used as 

the PoD for extrapolating risk to 

children. It is important to note that 

these clinical signs have been reported 

for at least one other cholinesterase 

inhibiting pesticide at doses producing 

only blood, not brain, AChE inhibition 

(Ref. 38). Thus, although RBC AChE 

inhibition is not an adverse effect, per 

se, blood measures are used as 

surrogates in the absence of peripheral 

tissue data. Assessment of potential for 

neurotoxicity in peripheral tissues is a 

critical element of hazard 

characterization for NMCs, like 

carbofuran. The lack of an appropriate 

surrogate to assess the potential for RBC 

AChE inhibition is a key uncertainty in 

the carbofuran toxicity database. Thus, 

EPA cannot conclude that reliance on 

the pup brain data solely as the PoD will 

be protective of PNS effects in pups. 

To account for the lack of RBC data 

in pups at the low end of the response 

curve, and for the fact that RBC AChE 

inhibition appears to be a more sensitive 

point of departure compared to brain 

AChE inhibition (and is considered an 

appropriate surrogate for the peripheral 

nervous system), EPA is retaining a 

portion of the children’s safety factor. 

On the other hand, there are data 

available, albeit incomplete, which 

characterize the toxicity of carbofuran in 

juvenile animals, and the Agency 

believes the weight of the evidence 

supports reducing the statutory factor of 

10X to a value lower than 10X. This 

results in a children’s safety factor that 

is less than 10 but more than 1. 

This modified safety factor should 

take into account the greater sensitivity 

of the RBC AChE. The preferred 

approach to comparing the relative 

sensitivity of brain and RBC AChE 

inhibition would be to compare the 

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 

(Figure 1). 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 recommended the 

application of a children’s safety factor 

of 4X, based on a weight-of-evidence 

approach. This safety factor is 

calculated using the difference in RBC 

and brain AChE inhibition, using the 

data on administered dose for the 

animals from the EPA-ORD studies and 

the FMC studies combined. In other 

words, EPA estimated the BMD50 for 

PND11 animals from each quality study 

and used the ratio from the combined 

analysis, resulting in a BMD50 ratio of 

4.1X3. 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, 

resulting in a BMD50 of 3.3 X. 

Conceptually, the RBC to brain potency 

ratio could be estimated using two 

different approaches: 1) EPA’s data for 

RBC (the only reliable RBC data in 

PND11 animals for carbofuran) and all 

available data in PND11 animals for 

brain; or 2) using only EPA’s data in 

PND11 animals for both RBC and brain. 

The former procedure, the approach 

used by EPA, yields a ratio of about 

fourfold, while the latter gives a twofold 

ratio for carbofuran. EPA has elected to 

use the 4X factor as the more health 

protective choice. This selection was 

made based on: 1) uncertainty regarding 

lack of an appropriate measure of 

peripheral toxicity (i.e., lack of RBC 

AChE inhibition data at the low end of 

the dose response curve), and 2) the 

RBC to brain AChE ratio at the BMD50

for PND17 animals of 3.3X which 

suggests that a factor of 2X would not 

be protective of PND11 pups. 

BILLING CODE 6560–50–S 


jlentini on PROD1PC65 with PROPOSALS3
44874 Federal Register / Vol. 73, No. 148 / Thursday, July 31, 2008 / Proposed Rules 

BILLING CODE 6560–50–C 


jlentini on PROD1PC65 with PROPOSALS3EP31JY08.019
Federal Register / Vol. 73, No. 148 / Thursday, July 31, 2008 / Proposed Rules 44875 

EPA recently presented its dietary risk 

assessment of carbofuran to the FIFRA 

SAP, and requested comment on the 

Agency’s approach to selecting the point 

of departure and the children’s safety 

factor. Overall, the Agency believes that 

the Panel’s responses support the 

Agency’s approach with regard to 

carbofuran’s hazard identification and 

hazard characterization. For example, 

the Agency notes that the Panel 

‘‘unanimously’’ agreed with the Agency 

with regard to the conclusion that the 

second FMC comparative cholinesterase 

(ChE) study provides reliable brain, but 

not RBC, AChE data. The Panel further 

remarked that, ‘‘EPA is well-justified in 

taking the position that the data on 

AChE inhibition in rat RBC, particularly 

with PND11 pups, are not acceptable for 

the purpose of predicting health risk 

from carbofuran’’ (Ref. 30). The Panel 

went on to concur with the Agency that 

the brain AChE inhibition data from the 

FMC and EPA-ORD studies show ‘‘good 

concordance.’’ With regard to the use of 

a benchmark dose approach to derive a 

PoD from brain AChE data in pups, the 

Panel stated that the Agency’s approach 

is ‘‘state-of-the-art science and the Panel 

strongly encouraged the Agency to 

follow this approach for all studies 

where possible’’ (Id.). 

The Panel provided five ‘scenarios’ or 

options for applying the children’s 

safety factor and/or PoD. Four of the five 

scenarios included the application of a 

children’s safety factor. Because the 

Panel report stated that the Panel was 

‘‘not in agreement regarding the 

magnitude of a [children’s] safety 

factor,’’ it is reasonable to conclude that 

a majority did not support any one of 

the five scenarios, including the one 

advocating removal of the children’s 

safety factor (Ref. 30). It follows that a 

majority of the Panel agreed with the 

Agency that at least a portion of the 

safety factor should be retained; 

however, recommendations for the 

appropriate factor ranged between a 2X 

and 10X. Two of the scenarios were 

consistent with the Agency’s approach 

in which the magnitude of the safety 

factor is derived based on the 

differences in RBC and brain AChE 

responses, quantified by the 

administered dose. The remaining two 

scenarios were based on retention of the 

10X safety factor. Those Panel members 

supporting retention of the 10X safety 

factor did so on the basis that the 

statutory requirement that EPA may use 

a different factor ‘‘‘only if, on the basis 

of reliable data, such margin will be safe 

for infants and children.’ Given the 

uncertainty in the data and in its 

interpretation for risk assessment by the 

entire Panel, these Panel members 

believes that this standard for change 

had not been met’’ (Id.). EPA believes 

that, on balance, the application of a 4X 

children’s safety factor is consistent 

with the SAP’s advice. Additional detail 

on the SAP’s advice and EPA’s 

responses can be found at Ref. 23. 

In sum, EPA has concluded that there 

is reliable data to support the 

application of a 4X safety factor and has 

therefore applied this safety factor in its 

dietary risk estimates. However, in light 

of the disagreement among the SAP 

panelists on the appropriate factor to 

apply, the Agency solicits comment on 

this issue. 

D. Hazard Characterization and Point of 

Departure Conclusions 

The doses and toxicological endpoints 

selected and Margins of Exposures for 

various exposure scenarios are 

summarized in Table 1 below. 

TABLE 1—TOXICOLOGY ENDPOINT SELECTION

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

for Risk Assessment Study and Toxicological Effects 

Acute Dietary Infants 

and Children 

BMDL 10 = 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 

Children’s SF = 1X 

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 

E. Dietary Exposure and Risk 

Assessment 

1. Dietary exposure to carbofuran 

(food)—a. EPA methodology and 

background. EPA conducted a refined 

(Tier 3) acute probabilistic dietary risk 

assessment for carbofuran residues in 

food. Carbofuran is registered for use on 

the following crops: alfalfa, artichokes, 

banana, barley, corn, cranberry, 

cucumber, grapes, melons, milk, oats, 

peppers, potatoes, pumpkin, rice, 

sorghum, soybean, spinach, squash, 

strawberry, sugar beets, sugar cane, 

sunflower seed, and wheat. To conduct 

the assessment, EPA relied on DEEMFCID, Version 2.00–2.02, which uses 

food consumption data from the USDA’s 

CSFII from 1994–1996 and 1998. 

Using data on the percent of the crop 

actually treated with carbofuran and 

data on the level of residues that may be 

present on the treated crop, EPA 

developed estimates of combined 

anticipated residues of carbofuran and 

3-hydroxycarbofuran on food. 3- 

Hydroxycarbofuran is a degradate of 

carbofuran and is assumed to have toxic 

potency equivalent to carbofuran (Refs. 

12, 16 and 48). Anticipated residues of 

carbofuran for most foods were derived 

using USDA PDP monitoring data from 

recent years (through 2006 for all 

available commodities). In some cases, 

where PDP data were not available for 

a particular crop, EPA translated PDP 

monitoring data from surrogate crops 

based on the characteristics of the crops 

and the use patterns. For example, PDP 

data for cantaloupes were used to derive 

anticipated residues for casaba and 

honeydew. 

USDA PDP provides the most 

comprehensive sampling design, and 

the most extensive and intensive 

sampling procedures for pesticide 

residues of the various data sources 

available to EPA. Additionally, the 

intent of PDP’s sampling design is to 

provide statistically representative 

samples of food commodities eaten by 

the U.S. population specifically for the 

purpose of performing dietary risk 

assessments for pesticides. The program 

focuses on high-consumption foods for 


jlentini on PROD1PC65 with PROPOSALS3
44876 Federal Register / Vol. 73, No. 148 / Thursday, July 31, 2008 / Proposed Rules 

children and reflects foods typically 

available throughout the year. A 

complete description of the PDP 

program (including all data through 

2006) is available online. 

The PDP analyzed for parent 

carbofuran and its metabolite of 

concern, 3-hydroxycarbofuran. Most of 

the samples analyzed by the PDP were 

measured using a high Level of 

Detection (LOD) and contained no 

detectable residues of carbofuran or 3- 

hydroxycarbofuran. Consequently, the 

acute assessment for food assumed a 

concentration equal to c of the LOD for 

PDP monitoring samples with no 

detectable residues, and 0.00 ppm 

carbofuran to account for the percent of 

the crop not treated with carbofuran. 

An additional source of data on 

carbofuran residues was provided by a 

market basket survey of NMC pesticides 

in single-serving samples of fresh fruits 

and vegetables collected in 1999–2000 

(Ref. 14), which was sponsored by the 

Carbamate Market Basket Survey Task 

Force. EPA relied on these data to 

construct the residue distribution files 

for 2 crops (bananas and grapes) because 

the use of these data resulted in more 

refined exposure estimates. The 

combined Limits of Quantitation (LOQs) 

for carbofuran and its metabolite in the 

Market Basket Survey (MBS) were 

between tenfold and twentyfold lower 

than the combined LODs in the PDP 

monitoring data. 

For certain crops where PDP data 

were not available (sugar beets, 

sugarcane, and sunflower seed), 

anticipated residues were based on field 

trial data. EPA also relied on field trial 

data for particular food commodities 

that are blended during marketing 

(barley, field corn, popcorn, oats, rice, 

soybeans and wheat), as use of PDP data 

can result in significant overestimates of 

exposure when evaluating blended 

foods. Field trial data are typically 

considered to overestimate the residues 

that are likely to occur in food as 

actually consumed because they reflect 

the maximum application rate and 

shortest preharvest interval allowed by 

the label. However, for crops that are 

blended during marketing, such as corn 

or wheat, use of field trial data can 

provide a more refined estimate than 

PDP data, by allowing EPA to better 

account for the percent of the crop 

actually treated with carbofuran. 

EPA used average and maximum 

percent crop treated (PCT) estimates for 

most crops, following the guidance 

provided in HED SOP 99.6 

(Classification of Food Forms with 

Respect to level of Blending; 8/20/99), 

and available processing and/or cooking 

factors. The maximum PCT estimates 

were used to refine the acute dietary 

exposure estimates. Maximum PCT 

ranged from <1 to 35%. The estimated 

percent of the crop imported was 

applied to crops with tolerances 

currently maintained solely for import 

purposes (cranberry, rice, strawberry). 

b. Acute dietary exposure (food alone) 

results and conclusions. The estimated 

acute dietary exposure from carbofuran 

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

additional carbofuran exposure from 

drinking water), exceeds EPA’s level of 

concern for all but one of the children’s 

population subgroups at the 99.9th 

percentile of exposure. Carbofuran 

dietary exposure at the 99.9th percentile 

was estimated at 0.000156 mg/kg/day 

(210% of the aPAD) for children 3–5 

years old, the population subgroup with 

the highest estimated dietary exposure. 

Estimated dietary exposure to 

carbofuran also exceeds EPA’s level of 

concern for children 1–2 years old and 

6–12 years at the 99.9th percentile of 

exposure. (See results Table 2 below). 

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

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 0.000025 33 0.000070 93 

Children 1–2 years old 0.000075 0.000045 60 0.000152 200 

Children 3–5 years old 0.000075 0.000036 48 0.000156 210 

Children 6–12 years old 0.000075 0.000024 32 0.000121 160 

Exposure estimates for all of the major 

food contributors were based on PDP 

monitoring data adjusted to account for 

the percent of the crop treated with 

carbofuran and, therefore, may be 

considered highly refined. 

As noted previously, because most of 

the PDP samples contained no 

detectable residues of carbofuran or its 

3-hydroxy metabolite, the acute 

assessment for food assumed a 

concentration equal to c of the LOD for 

PDP monitoring samples with no 

detectable residues, with 0.00 ppm 

carbofuran incorporated to account for 

the percent of the crop not treated with 

carbofuran. In accordance with OPP 

policy for analyzing commodities with 

non-detectable residues, EPA performed 

additional analyses to determine the 

impact of using c the LOD to estimate 

exposure (Ref. 56). 

In the first analysis (Sensitivity 

Analysis #1), those commodities that 

had no detectable residues at all in 

either the monitoring data or field trials 

were eliminated from the assessment. 

The commodities that were eliminated 

included barley, coffee, corn, cranberry, 

oats, potato, raisin, rice, soybean, 

spinach, strawberry, sugar beet, 

sunflower, winter squash, and wheat. 

For the remaining commodities, on 

which carbofuran was detected, EPA 

continued to substitute the c LOD values 

for the percent of the crop treated with 

carbofuran, with 0.00 ppm carbofuran 

incorporated to account for the 

remaining untreated percent of the crop. 

This analysis resulted in estimated 

exposures that were still above EPA’s 

level of concern for children 1–2 at the 

99.9th percentile (115% of the aPAD; 

see Table 3 below). 

To further understand the extent to 

which the c LODs from the PDP 

monitoring data were affecting the risk 

assessment, EPA conducted an 

additional sensitivity analysis, 

(Sensitivity Analysis #2) that excluded 

the crops for which PDP and MBS data 

were not available and assigned 0.00 

ppm carbofuran for all non-detected 

residues in commodities sampled in the 

PDP or MBS. In other words, an analysis 

using only detectable residues from 

residue monitoring programs was 

conducted. In this analysis, estimated 

dietary exposures at the 99.9th 

percentile of exposure remained above 

EPA’s level of concern for children 1–

2 yrs. old (114% of the aPAD). The 


jlentini on PROD1PC65 with PROPOSALS3
Federal Register / Vol. 73, No. 148 / Thursday, July 31, 2008 / Proposed Rules 44877 

results of these sensitivity analyses at 

the 99.9th percentile of exposure are 

compared to the results using c LOD for 

non-detectable residues in Table 3 

below. 

TABLE 3—IMPACT OF USING W LOD FOR NON-DETECTABLE RESIDUES ON ESTIMATED EXPOSURE FROM FOOD1

Population Subgroup aPAD (mg/ 

kg/day) 

Analysis Assuming W 

LOD for Non-Detectable 

Residues 

Sensitivity Analysis #12 Sensitivity Analysis #23

Exposure 

(mg/kg/day) % aPAD 

Exposure 

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

All Infants (< 1 year old) 0.000075 0.000070 93 0.000044 58 0.000043 57 

Children 1–2 years old 0.000075 0.000152 200 0.000086 115 0.000086 114 

Children 3–5 years old 0.000075 0.000156 210 0.000066 88 0.000065 87 

Children 6–12 years old 0.000075 0.000121 160 0.000039 52 0.000038 51 

1 At the 99.9th Percentile of Exposure. 2 Non-detectable PDP residues assumed to be zero only for commodities having no detectable residues at all in the PDP monitoring data and 

field trials (i.e., these commodities were eliminated from the analysis). Crops without PDP data and detectable residues in field trials were included, based on the distribution of residues from field trial studies. 3 Non-detectable residues assumed to be zero for all commodities. Commodities without PDP or Market Basket data were excluded from the 

analysis. 

The major contributors in Sensitivity 

Analysis #2, to the estimated dietary 

exposure of children are listed in Table 

4 below. 

TABLE 4—MAJOR CONTRIBUTORS TO CARBOFURAN ACUTE EXPOSURE AT THE 99.9TH PERCENTILE IN SENSITIVITY

ANALYSIS #2 (EXPRESSED AS AN APPROXIMATE PERCENT OF TOTAL EXPOSURE) 

Food Infants, <1 

year old 

Children, 1–

2 Years Old 

Children, 3–

5 Years Old 

Cantaloupe 9 18 20 

Squash 10 2 1 

Grape 15 10 5 

Cucumbers 2 20 29 

Milk 32 <1 1 

Watermelon 29 39 41 

EPA’s evaluation of these two 

sensitivity analyses and other 

information on carbofuran residue 

levels yields three conclusions. First, 

the results of the sensitivity analyses 

indicate that the dietary risk assessment 

for carbofuran is sensitive to the 

assumed concentrations (i.e., c LOD) for 

non-detectable residues in the PDP 

monitoring data. This sensitivity 

appears to be more of a factor for 

commodities with no detections because 

the main difference between the 

Sensitivity Analyses #1 and #2 was 

substituting 0.00 ppm for c LODs for 

commodities with detects in the second 

analysis yet that analysis yielded similar 

results to the first sensitivity analysis. 

On the other hand, both sensitivity 

analyses were approximately 2X lower 

than the analysis that used c LOD for all 

treated commodities. The finding that 

the use of a c LOD assumption had a 

noticeable impact on the risk estimate is 

contrary to EPA’s experience in 

conducting pesticide risk assessments. 

Generally, risk estimates do not show 

noticeable differences whether nondetects are treated as true zeros or c 

LODs. In all likelihood, this is a factor 

of the relatively insensitive level of the 

carbofuran method’s LOD. 

Second, given that there are data 

showing that carbofuran is found at 

levels below the LOD when a more 

sensitive method was used, EPA finds 

that use of either of the approaches in 

the sensitivity analyses will understate 

carbofuran risk. The available 

information demonstrates that 

carbofuran residues are present; when a 

lower level of detection was utilized, 

both in the most recent PDP milk 

analyses and in the Carbamate MBS 

data; residues of carbofuran and 3- 

hydroxycarbofuran were detected in 

commodities that previously had no 

detections. Moreover, detected residues 

ranged between levels below and above 

c LOD. Thus, unlike the circumstance 

where a relatively sensitive method of 

detection is used and there is some 

uncertainty as to whether a non-detect 

may mask an actual exposure, with 

cabofuran there is no question – treating 

all non-detects as zero clearly would 

mask actual exposures to carbofuran. 

Thus, these sensitivity analyses do not 

provide a basis for concluding that EPA 

has overestimated risk. 

Third, and most important, EPA 

would call attention to the fact that 

these sensitivity analyses, although 

clearly underestimating actual 

carbofuran exposure and risk, still 

indicate that one group of children will 

have exposures exceeding the safe level. 

Because it appears that carbofuran’s 

dietary risks to children are driven by 


jlentini on PROD1PC65 with PROPOSALS3
44878 Federal Register / Vol. 73, No. 148 / Thursday, July 31, 2008 / Proposed Rules 

relatively low residues in a small 

percentage of commodities, and to try to 

gain further insight into the potential 

impact of using c LOD in this case, EPA 

conducted a third sensitivity analysis to 

evaluate whether its estimates that food 

only and aggregate carbofuran exposure 

results in risks of concern were 

overstated. EPA combined actual 

residue values measured in the food 

supply (from PDP and MBS data) with 

the typical (50th percentile) and highend (90th percentile) amounts of a 

single commodity that a child would be 

expected to consume, and compared 

that to the aPAD, without considering 

the likelihood that a child would be 

exposed to that residue value. The 

results one of these analyses are 

summarized in Table 5 below. 

TABLE 5—RISK TO CHILDREN CONSUMING TYPICAL OR HIGH-END AMOUNTS OF FRESH (UNCOOKED) CUCUMBERS

CONTAINING CARBOFURAN RESIDUES

Food 

Population 

Subgroup 

Typical: 50th Percentile of Consumption High-End: 90th Percentile of Consumption 

Consumption 

(g/kg bw) 

PDP Residue1 (ppm) 

Exposure 

(mg/kg 

bw) 

% aPAD Consumption 

(g/kg bw) 

PDP Residue1 (ppm) 

Exposure 

(mg/kg 

bw) 

% aPAD 

Cucumbers 

(Uncooked) 

DEEM food 

form 110 

Children 

1–2 

1.0 0.005 0.000005 7 4.3 0.005 0.000022 29 

0.029 0.000029 39 0.029 0.000125 170 

0.063 0.000063 84 0.063 0.000271 360 

0.117 0.000117 160 0.117 0.000503 670 

0.137 0.000137 180 0.137 0.000589 790 

0.147 0.000147 200 0.147 0.000632 840 

0.437 0.000437 580 0.437 0.001879 2,500 

0.537 0.000537 720 0.537 0.002309 3,100 

Children 

3–5 

0.8 0.005 0.000004 5 5.1 0.005 0.000026 34 

0.029 0.000023 31 0.029 0.000148 200 

0.063 0.000050 67 0.063 0.000321 430 

0.117 0.000094 120 0.117 0.000597 800 

0.137 0.000110 150 0.137 0.000699 930 

0.147 0.000118 160 0.147 0.000750 1,000 

0.437 0.000350 470 0.437 0.002229 3,000 

0.537 0.000430 570 0.537 0.002739 3,700 

1The PDP detected residues of carbofuran in 11 of 1479 cucumber samples at levels ranging from 0.005 ppm to 0.537 ppm. 

Detectable residues of carbofuran and/ 

or 3-hydroxycarbofuran were found in 

only a few samples of cucumber in 

monitoring data (11 out of 1479 or less 

than one percent). However, if young 

children aged 1 to 5 consume moderate 

amounts of cucumber (i.e., the median 

or 50th percentile of consumption, 

corresponding to approximately 1 gram 

per kg of body weight of cucumber) that 

contain actual levels of carbofuran 

measured in the food supply, the 

percent of the aPAD that would be 

utilized ranges from about 7% of the 

safe daily dose for the lower observed 

residue values to 720% of the safe daily 

dose for the higher observed values. For 

children who consume larger amounts 

of cucumber (i.e., the 90th percentile of 

consumption, corresponding to 5 grams 

per kg of body weight of cucumber or 

roughly c cup), exposure increases 

approximately tenfold (29% to over 

3700% of the aPAD). Many of these 

values significantly exceed the Agency’s 

level of concern based on the 

consumption of a single daily serving of 

one commodity. 

Additional analyses are summarized 

in Table 6 below, and analyses on 

additional foods can be found in Ref. 12. 

EPA focused on children in making 

these calculations, because children 

have the highest estimated dietary 

exposure to carbofuran; however, it is 

reasonable to assume that adult 

exposures from a single treated food 

item could also exceed EPA’s level of 

concern, particularly at the high end of 

consumption. 


jlentini on PROD1PC65 with PROPOSALS3
Federal Register / Vol. 73, No. 148 / Thursday, July 31, 2008 / Proposed Rules 44879 

TABLE 6—RISK TO CHILDREN CONSUMING TYPICAL OR HIGH-END AMOUNTS OF CANTALOUPE OR WATERMELON

CONTAINING CARBOFURAN RESIDUES

Population 

Subgroup 

Typical: 50th Percentile of Consumption High-End: 90th Percentile of Consumption 

Consumption (g/ 

kg bw) 

PDP Residue (ppm) Exposure 

(mg/kg bw) % aPAD Consumption (g/ kg bw) 

PDP Residue 

(ppm) 

Exposure 

(mg/kg bw) % aPAD 

Cantaloupe 

Children 

1–2 

Approx. 

6g 

0.009 0.0000531 71 Approx. 12 g 0.009 0.0001035 140 

0.01 0.000059 79 0.01 0.000115 150 

0.02 0.000118 160 0.02 0.00023 310 

0.06 0.000354 470 0.06 0.00069 920 

0.085 0.0005015 670 0.085 0.0009775 1,300 

0.357 0.0021063 2,800 0.357 0.0041055 5,500 

Children 

3–5 

approx. 

5g 

0.009 0.0000441 59 approx. 15g or W 

cup 

0.009 0.0001368 180 

0.01 0.000049 65 0.01 0.000152 200 

0.02 0.000098 130 0.02 0.000304 400 

0.06 0.000294 390 0.06 0.000912 1,200 

0.085 0.0004165 560 0.085 0.001292 1,700 

0.357 0.0017493 2,300 0.357 0.0054264 7,200 

Watermelon 

Children 

1–2 

approx. 

8g 

0.0057 0.00004332 58 less than 30g 0.0057 0.00014706 200 

0.009 0.0000684 91 0.009 0.0002322 310 

0.0132 0.00010032 130 0.0132 0.00034056 450 

0.014 0.0001064 140 0.014 0.0003612 480 

0.062 0.0004712 630 0.062 0.0015996 2,100 

0.081 0.0006156 820 0.081 0.0020898 2,800 

0.205 0.001558 2,100 0.205 0.005289 7,100 

Children 

3–5 

approx. 

12g 

0.0057 0.00007125 95 approx. 35g 0.0057 0.00019893 270 

0.009 0.0001125 150 0.009 0.0003141 420 

0.0132 0.000165 220 0.0132 0.00046068 610 

0.014 0.000175 230 0.014 0.0004886 650 

0.062 0.000775 1,000 0.062 0.0021638 2,900 

0.081 0.0010125 1,400 0.081 0.0028269 3,800 

0.205 0.0025625 3,400 0.205 0.0071545 9,500 


jlentini on PROD1PC65 with PROPOSALS3
44880 Federal Register / Vol. 73, No. 148 / Thursday, July 31, 2008 / Proposed Rules 

The analyses in Tables 5 and 6 

demonstrate three significant points. 

First, the fact that individual children, 

consuming typical amounts of a single 

food item receive unsafe levels of 

carbofuran, based on actual residue 

levels measured in the food supply, 

strongly supports EPA’s findings that 

aggregate exposures to carbofuran are 

unsafe. It is true that the results 

described in Tables 5 and 6, as well as 

the additional analyses in Ref. 12, do 

not describe the probability that an 

individual child will receive those 

residues on the foods they consume. By 

contrast, EPA’s analyses in Tables 2 and 

3 account for the probability that a 

particular level of residues will be 

present on a food item, as well as the 

likelihood that an individual will 

consume a particular food. It is EPA’s 

typical approach, as was done with 

carbofuran, to conduct its estimates of 

exposure across the entire population, 

generally assuming that as long as the 

99.9th percentile of the estimated daily 

exposure is equal to or less than the 

aPAD, there is a reasonable certainty of 

no harm to the general population, 

including all significant subpopulations 

(Ref. 58). In practice, this can mean that 

if only a small portion of the population 

reported eating the commodity, or if the 

residues are infrequently detected, 

individual high-end risks may fall above 

EPA’s usual benchmark of the 99.9th 

percentile, or in other words, fall in the 

‘‘tail end’’ of the distribution curve. 

Admittedly, some of the results 

described in Tables 5 and 6 would be 

expected to fall within this tail end, 

given the relatively infrequent 

detections of carbofuran in sampled 

commodities. However, taking into 

account the analysis of the risk drivers 

in Table 4 above, it is clear that some 

of these values do fall within the 99.9th 

percentile. 

In any event, given all of the facts, it 

is just as appropriate for EPA to evaluate 

whether the eating occasions that drive 

a conclusion that risks at the 99.9th 

percentile yield unacceptable risks are 

realistic, as it is for EPA to examine 

whether eating occasions in the tail of 

a distribution curve are examples of 

consumption events the Agency should 

be concerned about. In this regard, it is 

notable that even the high-end 

consumption values described in Tables 

5 and 6 are extremely likely to be valid 

reported consumption events—or in 

other words, consumption of the 

amounts at the 90th percentile are quite 

realistic. For example, a child between 

3–5 years, who consumes a c cup of 

cantaloupe would receive a dose 

ranging between 180% and 7,200% of 

the aPAD. Accordingly, this analysis by 

itself supports a conclusion that the 

carbofuran tolerances are not safe and 

certainly buttresses EPA’s conclusions 

that exposures from carbofuran in food 

or water alone or from carbofuran 

residues in food and water aggregated 

when assessed at the 99.9th percentile 

are not safe. 

Additionally, because of the 

uncertainty surrounding carbofuran’s 

exposure potential, investigation of 

individual children’s risks, even if in 

the ‘‘tail end,’’ is particularly relevant. 

There are a number of reasons that 

significant uncertainty remains with 

respect to carbofuran’s exposure 

potential. One primary consideration 

stems from the high LOD for carbofuran 

and consequent large numbers of nondetects in the PDP data. The LOD for 

most commodities is tenfold to 

twentyfold higher than the more precise 

methods used for the CMS and some of 

the more recent PDP data. Generally, 

EPA would consider use of c LOD as a 

conservative way of addressing nondetects but that may not be the case 

where the LOD is relatively insensitive 

and the risk of concern is an acute 

exposure. For acute risks, the higher 

values in a probabilistic risk assessment 

are often driven by relatively high 

values in a few commodities rather than 

relatively lower values in a greater 

number of commodities. This is due to 

the fact that an acute assessment looks 

at a narrow window of exposure where 

there are unlikely to be a great variety 

of foods consumed. Thus, to the extent 

that there is a high exposure it will be 

more likely due to a high residue value 

in a single commodity. However, 

assuming c LOD for non-detects does 

not reflect that the non-detects actually 

will bear a range of values from close to 

or near zero to close to or near the LOD. 

Importantly, those commodities bearing 

residues only slightly below the LOD 

may result in an exceedance of the 

aPAD where assuming c LOD would not. 

In this way, the c LOD analysis may 

actually understate risk. In these 

circumstances, reliance on c LOD can 

skew the distribution of residues, which 

in turn masks the true ‘‘tail end’’ of 

exposures. In other words, to the extent 

that the c LOD underestimates 

exposures for some individual 

commodities, it effectively decreases the 

probability of receiving higher residues, 

thereby shifting those values with 

greater risks to the tail end of the 

distribution curve, above the 99.9th 

percentile. 

The second important point from 

these tables is that the exceedances from 

both the 50th and 90th percentile 

consumer are quite large—sometimes 

orders of magnitude above safe doses. 

The size of these exceedances gives rise 

to concerns that the exceedances are 

more likely to result in actual harm to 

exposed individuals, particularly if they 

are also consuming carbofurancontaminated drinking water. 

Additionally worrisome in this regard is 

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

has a very steep dose-response curve), 

acute toxicant, and therefore any aPAD 

exceedances are more likely to have 

greater significance in terms of the 

potential likelihood of actual harm. 

Finally, that Tables 5 and 6 show 

large exceedances across several crops 

for which relatively more residue data 

are available suggests these results are 

not unique to the specific crops for 

which precise residues have been 

detected in PDP and MBS. In other 

words, crops for which such residue 

data are not available may be posing 

similar risks. 

In sum, these results strongly support 

EPA’s conclusion that its dietary 

exposure assessment for carbofuran has 

not overstated exposure and risk. 

Further, serious questions remain as to 

the extent to which similar exceedances 

exist for all crops, but which remain 

undetected, because, as result of the 

high LOD, EPA lacks precise residue 

levels for the majority of crops. 

2. Drinking water exposures. EPA’s 

drinking water assessment uses both 

monitoring data for carbofuran and 

modeling methods, and takes into 

account contributions from both surface 

water and groundwater sources (Refs. 3, 

4, 13, 36 and 47). Concentrations of 

carbofuran in drinking water, as with 

any pesticide, are in large part 

determined by the amount, method, 

timing and location of pesticide 

application, the chemical properties of 

the pesticide, the physical 

characteristics of the watersheds and/or 

aquifers in which the community water 

supplies or private wells are located, 

and other environmental factors, such as 

rainfall, which can cause the pesticide 

to move from the location where it was 

applied. While there is a considerable 

body of monitoring data that has 

measured carbofuran residues in surface 

and groundwater sources, the locations 

of sampling and the sampling 

frequencies generally are not sufficient 

to capture peak concentrations of the 

pesticide in a watershed or aquifer 

where carbofuran is used. Capturing 

these peak concentrations is particularly 

important for assessing risks from 

carbofuran because the toxicity endpoint of concern results from single-day 

exposure (acute effects). Because 

pesticide loads in surface water tend to 

move in relatively quick pulses in 


jlentini on PROD1PC65 with PROPOSALS3
Federal Register / Vol. 73, No. 148 / Thursday, July 31, 2008 / Proposed Rules 44881 

flowing water, frequent targeted 

sampling is necessary to reliably capture 

peak concentrations for surface water 

sources of drinking water. Pesticide 

concentrations in ground water, 

however, are generally the result of 

longer-term processes and less frequent 

sampling can better characterize peak 

ground water concentrations. However, 

such data must be targeted at vulnerable 

aquifers in locations where carbofuran 

applications are documented in order to 

capture peak concentrations. As a 

consequence, monitoring data for both 

surface and groundwater tends to 

underestimate exposure for acute 

endpoints. Simulation modeling 

complements monitoring by making 

estimations at vulnerable sites and can 

be used to represent daily concentration 

profiles, based on a distribution of 

weather conditions. Thus, modeling can 

account for the cases when a pesticide 

is used in drinking water watersheds at 

any rate and is applied to a substantial 

proportion of the crop. It can also 

account for stochastic processes, such as 

rainfall represented by 30 years of 

existing weather data maintained by the 

National Oceanic and Atmospheric 

Administration. 

a. Exposure to carbofuran from 

drinking water derived from ground 

water sources. Drinking water taken 

from shallow wells is particularly 

vulnerable to contamination in areas 

where carbofuran is used around sandy, 

highly acidic soil. Some areas with 

these characteristics include Long 

Island, parts of Florida, and the Atlantic 

coastal plain, in addition to other areas 

of the country. Exposure estimates for 

this assessment are drawn primarily 

from (1) the results of a prospective 

groundwater (PGW) study developed by 

the registrant in the early 1980s; and (2) 

additional groundwater modeling 

conducted as part of the NMC 

cumulative assessment in 2007. The 

results of the PGW study are consistent 

with a number of other targeted 

groundwater studies conducted in the 

1980s showing that high concentrations 

of carbofuran can occur in vulnerable 

areas; the results of these studies as well 

as the PGW study are summarized in 

(Refs. 13 and 47). For example, a study 

in Manitoba, Canada assessed the 

movement of carbofuran into tile drains 

and groundwater from the application of 

liquid carbofuran to potato and corn 

fields. The application rates ranged 

between 0.44–0.58 pounds a.i./acre, and 

the soils at the site included fine sand, 

loamy fine sand, and silt loam, with pH 

ranging between 6.5–8.3. Concentrations 

of carbofuran in groundwater samples 

ranged between 0 (non-detect) and 158 

ppb, with a mean of 40 ppb (Refs. 13 

and 47). 

While there have been additional 

groundwater monitoring studies that 

included carbofuran as an analyte since 

that time, there has been no additional 

monitoring targeted to carbofuran use in 

areas where aquifers are vulnerable. 

Accordingly, EPA believes the PGW 

study continues to be the most relevant 

monitoring data for assessing drinking 

water exposures from private wells at 

vulnerable sites. Because this study was 

conducted over only one growing 

season, however, and was conducted at 

use rates that now exceed current label 

maximum rates for the use being 

studied (3 lb ai/acre vs. the current 2 lb 

ai/acre for corn), EPA has scaled the 

results to represent impacts from 

carbofuran use over a long-term period 

(25 years) at current label rates. 

Temporal scaling was necessary because 

the PGW study represents water quality 

impacts from a single application rather 

than repeated years of use. Based on 

EPA’s assessment, the maximum 90–day 

average carbofuran concentrations in 

vulnerable groundwater for various 

application rates were estimated to 

range from a low of 11 parts per billion 

(ppb) based on a 1 pound per acre 

application rate, to a high of 34 ppb, 

based on a 3 pound per acre application 

rate. The peak concentration measured 

in the PGW study was 65 ppb. Because 

the degradate 3-hydroxycarbofuran, 

which is assumed to be of equal potency 

with the parent compound, was not 

measured in this study, exposure was 

not estimated. Although the failure to 

include the degradate is expected to 

underestimate exposure to some degree, 

the extent to which it would contribute 

to exposure is unclear. 

EPA conducted additional 

groundwater modeling for the NMC 

cumulative risk assessment, and 

developed a time series of exposures at 

locations selected based on potential for 

exposure to a combination of carbamate 

insecticides relevant for cumulative 

exposure assessment for use in 

probabilistic dietary assessments using 

DEEM. EPA estimated carbofuran 

groundwater concentrations associated 

with two possible use scenarios: 

potatoes in northeastern Florida and 

cucurbits on the Delmarva Peninsula in 

the Mid-Atlantic region. While the 

modeled potato use scenario in Florida 

did not show concentrations of 

carbofuran of concern, estimated 

carbofuran concentrations associated 

with the cucurbit use in the Delmarva 

Peninsula – a region with shallow, 

acidic groundwater and acidic, sandy 

soils – are consistent with EPA’s 

assessment of the PGW study discussed 

above. Specifically, the assessment 

indicated that at an application rate of 

1.25 pounds a.i. per acre, on cucurbits, 

maximum concentrations were 38.5 ppb 

(Ref. 63). EPA does not believe the 

results of this assessment are 

particularly conservative, since the 

application rate used in this assessment 

was less than the maximum rate of 1.94 

lb/acre that growers can use. Also, 

concentrations of the degradate, 3- 

hydroxycarbofuran were not included in 

modeling simulations, which would 

tend to underestimate exposure to some 

degree. 

Based on these estimates, EPA 

compiled a distribution of estimated 

carbofuran concentrations in water that 

could be used to generate probabilistic 

assessments of the potential exposures 

from drinking water derived from 

vulnerable ground water sources. The 

results of EPA’s probabilistic 

assessments are represented below in 

Table 7. As discussed in the previous 

section, it is important to remember that 

the aPAD for carbofuran is quite low, 

hence, relatively low concentrations of 

carbofuran monitored or estimated in 

vulnerable groundwater can have a 

significant impact on the aPAD utilized. 

TABLE 7—RESULTS OF ACUTE DIETARY (GROUND WATER ONLY) EXPOSURE ANALYSIS USING DEEM FCID AND

INCORPORATING THE DELMARVA GROUND WATER SCENARIO (REPRESENTING PRIVATE WELLS) 

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 0.003800 5,100 0.006006 8,000 0.010030 >10,000 

Children 1–2 years old 0.000075 0.001612 2,100 0.002732 3,600 0.004628 6,200 


jlentini on PROD1PC65 with PROPOSALS3
44882 Federal Register / Vol. 73, No. 148 / Thursday, July 31, 2008 / Proposed Rules 

TABLE 7—RESULTS OF ACUTE DIETARY (GROUND WATER ONLY) EXPOSURE ANALYSIS USING DEEM FCID AND

INCORPORATING THE DELMARVA GROUND WATER SCENARIO (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 3–5 years old 0.000075 0.001459 1,900 0.002405 3,200 0.004613 5,600 

Children 6–12 years old 0.000075 0.001018 1,360 0.001710 2,300 0.002792 3,700 

Youth 13–19 years old 0.0002 0.000809 400 0.001441 720 0.002919 1,500 

Adults 20–49 years old 0.0002 0.000955 480 0.001632 820 0.003073 1,500 

Adults 50+ years old 0.0002 0.000884 440 0.001345 670 0.002271 1,100 

While the registrant has attempted to 

address drinking water exposure from 

ground water sources by including on 

current carbofuran product labeling an 

advisory statement warning growers 

against application in vulnerable areas, 

this language does not prohibit use in 

such areas. In addition, EPA does not 

believe that the available information 

demonstrates that even the additional 

restrictions that FMC included on its 

labels submitted in May, 2008 would 

adequately mitigate the risk of 

contaminating all vulnerable ground 

water (Refs. 18 and 54). For example, 

those restrictions were based on the use 

of a particular methodology to evaluate 

the characteristics in the site used in the 

PGW study in the Delmarva Penninsula. 

Using that as a surrogate to identify sites 

with vulnerability to ground water 

contamination, FMC identified counties 

that had higher vulnerability scores than 

the site used for the PGW study in the 

Delmarva Penninsula, and proposed 

label restrictions to preclude use in such 

areas. While EPA agrees in principle 

that precluding use in sites vulnerable 

to leaching can mitigate the risks, and 

even presuming that the methodology 

used by FMC adequately identifies those 

sites, sites less vulnerable than the PGW 

site would still be vulnerable to 

contamination, and the proposed 

restrictions in no way addressed the less 

sensitive, but still vulnerable, sites 

(Refs. 18 and 54). Accordingly, EPA 

continues to believe that its assessment 

of drinking water from groundwater 

sources based on current labels is a 

realistic assessment of potential 

exposures to those portions of the 

population consuming drinking water 

from shallow wells in highly vulnerable 

areas. 

b. Exposure from drinking water 

derived from surface water sources. 

EPA’s evaluation of environmental 

drinking water concentrations of 

carbofuran from surface water, as with 

its evaluation of groundwater, takes into 

account the results of both surface water 

monitoring and modeling. 

Data compiled in 2002 by EPA’s 

Office of Water show that carbofuran 

was detected in treated drinking water 

at a few locations. Based on samples 

collected from 12, 531 ground water and 

1,394 surface water source drinking 

water supplies in 16 states, carbofuran 

was found at no public drinking water 

supply systems at concentrations 

exceeding 40 ppb (the MCL). Carbofuran 

was found at one public ground water 

system at a concentration of greater than 

7 ppb and in two ground water systems 

and one surface water public water 

system at concentrations greater than 4 

ppb (measurements below this limit 

were not reported). Sampling is costly 

and is conducted typically four times a 

year or less at any single drinking water 

facility. The overall likelihood of 

collecting samples that capture peak 

exposure events is, therefore, low. For 

chemicals with acute risks of concern, 

such as carbofuran, higher 

concentrations and resulting risk is 

primarily associated with these peak 

events, which are not likely to be 

captured in monitoring unless the 

sampling rate is very high. 

Unlike drinking water derived from 

private groundwater wells, public water 

supplies (surface water or ground water 

source) will generally be treated before 

it is distributed to consumers. An 

evaluation of laboratory and field 

monitoring data indicate that carbofuran 

may be effectively removed (60 – 100%) 

from drinking water by lime softening 

and activated carbon; other treatment 

process are less effective in removing 

carbofuran (Ref. 63). The detections 

between 4 and 7 ppb, reported above, 

represent concentrations in samples 

collected post-treatment. As such, these 

levels are of particular concern to the 

Agency. An infant who consumes a 

single 8 ounce serving of water with a 

concentration of 4 ppb, as detected in 

the monitoring, would receive 121% of 

the aPAD. An infant who consumes a 

single 8 ounce serving of water with the 

higher detected concentration of 7 ppb, 

as detected in the monitoring, would 

receive 210% of the aPAD. 

To further characterize carbofuran 

concentrations in surface water (e.g., 

streams or rivers) that may drain into 

drinking water reservoirs, EPA analyzed 

the extensive source of national water 

monitoring data for pesticides, the 

United States Geological Survey 

National Water Quality Assessment 

(USGS NAWQA) program. The NAWQA 

program focuses on ambient water 

rather than on drinking water sources, is 

not specifically targeted to the high use 

area of any specific pesticide, and is 

sampled at a frequency (generally 

weekly or bi-weekly during the use 

season) insufficient to provide reliable 

estimates of peak pesticide 

concentrations in surface water. For 

example, significant fractions of the data 

may not be relevant to assessing 

exposure from carbofuran use, as there 

may be no use in the basin above the 

monitoring site. Unless ancillary usage 

data are available to determine the 

amount and timing of the pesticide 

applied, it is difficult to determine 

whether non-detections of carbofuran 

were due to a low tendency to move to 

water or from a lack of use in the basin. 

The program, rather, provides a good 

understanding on a national level of the 

occurrence of pesticides in flowing 

water bodies that can be useful for 

screening assessments of potential 

drinking water sources. A detailed 

description of the pesticide monitoring 

component of the NAWQA program is 

available on the NAWQA Pesticide 

National Synthesis Project (PNSP) web 

site (http://ca.water.usgs.gov/pnsp/). 

A summary of the first cycle of 

NAWQA monitoring from 1991 to 2001 

indicates that carbofuran was the most 

frequently detected carbamate pesticide 

in streams and ground water in 

agricultural areas. Overall, where 


jlentini on PROD1PC65 with PROPOSALS3
Federal Register / Vol. 73, No. 148 / Thursday, July 31, 2008 / Proposed Rules 44883 

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-ppb 

range reported in additional watersheds 

(Ref. 63). The highest concentrations of 

carbofuran are reported from at a 

sampling station on Zollner Creek, in 

Oregon. Zollner Creek, located in the 

Molalla-Pudding sub-basin of the 

Willamette River, is not directly used as 

a drinking water source. This creek is a 

low-order stream and its watershed is 

small (approximately 40 km2) and 

intensively farmed, with a diversity of 

crops grown, including plant nurseries. 

USGS monitoring at that location from 

1993 to 2006 detected carbofuran 

annually in 40–100 % of samples. 

Although the majority of concentrations 

detected there are also in the sub-part 

per billion range, concentrations have 

exceeded 1 ppb in 8 of the 14 years of 

sampling. The maximum measured 

concentration was 32.2 ppb, observed in 

the spring of 2002. The frequency of 

detections generally over a 14–year 

period suggests that standard use 

practices rather than aberrational 

misuse incidents in the region are 

responsible for high concentration 

levels at this location. 

While available monitoring from other 

portions of the country suggests that the 

circumstances giving rise to high 

concentrations of carbofuran may be 

rare, overall, the national monitoring 

data indicate that EPA cannot dismiss 

the possibility of detectable carbofuran 

concentrations in some surface waters 

under specific use and environmental 

conditions. Even given the limited 

utility of the available monitoring data, 

there have been relatively recent 

measured concentrations of carbofuran 

in surface water systems at levels above 

4 ppb (concentrations of 4–7 ppb would 

result in exposures of 121–210% of the 

aPAD for an infant consuming 8 oz of 

water) and levels of approximately 1 to 

30 ppb measured in streams 

representative of those in watersheds 

that support drinking water systems 

(Ref. 63). Based on this analysis, and 

since monitoring programs have not 

been sampling at a frequency sufficient 

to detect daily-peak concentrations that 

are needed to assess carbofuran’s acute 

risk, the available monitoring data, in 

and of themselves, are not sufficient to 

establish the risks posed by carbofuran 

in surface drinking water are below 

thresholds of concern. Nor can this data 

be reasonably used to establish a lower 

bound of potential carbofuran risk 

through this route of exposure. 

To further characterize carbofuran 

risk through drinking water derived 

from surface water sources, EPA 

modeled estimated daily drinking water 

concentrations of carbofuran using 

PRZM to simulate field runoff processes 

and EXAMS to simulate receiving water 

body processes. These models were 

summarized in Unit V.B.2. 

There are sources of uncertainty 

associated with estimating exposure of 

carbofuran in surface water source 

drinking water. Several of the most 

significant of these are the effect of 

treatment in removing carbofuran from 

finished drinking water before it is 

delivered to the consumer supply 

system, the impact of percent crop 

treated assumptions, and the variation 

in pH across the landscape. The effect 

of the percent crop treated assumption 

in the case of carbofuran is discussed in 

detail in EPA’s assessment of additional 

data submitted by the registrant (Refs. 

18 and 54) and summarized below. 

Available data on the degree to which 

carbofuran may be removed from 

treatment systems was summarized 

previously and is discussed in more 

detail in Appendix E-3 of the Revised 

NMC Cumulative Assessment (Ref. 63). 

Although EPA is aware of the mitigating 

effects of specific treatment processes, 

the processes employed at public water 

supply utilities across the country vary 

significantly both from location to 

location and throughout the year, and 

therefore are difficult to incorporate 

quantitatively in drinking water 

exposure estimates. Therefore, EPA 

assumes that there is no reduction in 

carbofuran concentrations in surface 

water source drinking water due to 

treatment, which is a source of 

conservatism in surface water exposure 

estimates used for human health risk 

assessment. While it is well established 

that carbofuran will degrade at higher 

rates when the pH is above 7, and lower 

rates when below pH 7, due to the high 

variation of pH across the country a 

neutral pH (pH 7) default value was 

used to estimate water concentrations. 

Finally, available environmental fate 

studies do not show formation of 3- 

hydroxycarbofuran through most 

environmental processes except soil 

photolysis, where in one study it was 

detected in very low amounts. Although 

3-hydroxycarbofuran was not explicitly 

considered as a separate entity in the 

drinking water exposure assessment, it 

is unclear whether it would 

significantly add to exposure estimates. 

EPA compiled a distribution of 

estimated carbofuran concentrations in 

surface water in order to conduct 

probabilistic assessments of the 

potential exposures from drinking 

water. For the IRED, EPA modeled crops 

representing 80 percent of total 

carbofuran use at locations that would 

be considered among the more 

vulnerable where the crops are grown. 

Modeling was conducted at a range of 

application rates and included 

adjustments to reflect different regional 

levels for agricultural intensity, 

resulting in estimated 1-in-10-year 

(peak) concentrations of 0.11–75 ppb 

(Refs. 5 and 36). For corn, carbofuran 

concentration estimates assuming 

different rates and regional percent 

cropped area (PCA) factors reflective of 

corn intensity nationally resulted in a 

range of peak concentrations of 4 – 26 

ppb. For the dietary risk assessment, 

EPA generated distributions for 13 

different scenarios representing all 

labeled uses of carbofuran treated at 

maximum label rates and adjusted with 

PCA factors (Refs. 3, 13 and 47). Peak 

concentrations for these distributions 

ranged from 3.2 to 168 ppb (excluding 

use on bananas), with the corn use at 26 

ppb (Refs. 3 and 47). 

EPA has subsequently conducted 

several rounds of modeling to refine 

estimates for specific uses and 

agricultural practices. One set of 

refinements addressed use of carbofuran 

on corn at typical rather than maximum 

label rates and application practices that 

assume the only use of carbofuran in a 

watershed is on corn. Simulations 

included those specific to control 

European corn borer, a rescue treatment 

for corn rootworm, and an in-furrow 

application at plant. The assessment 

also included estimates resulting from 

treatment at the maximum label rate, for 

comparative purposes. The peak 

concentrations estimated ranged from 

3.9 to 16.6 ppb for the refined analyses, 

compared to 32.9 ppb at the maximum 

application rate (Ref. 4). The range of 

3.9 to 16.6 ppb is approximately 1 to 4 

times the values of the 4 ppb detected 

in finished water from a surface water 

drinking plant, as summarized 

previously, and approximately twofold 

to tenfold lower than the maximum 

peak concentration of 32.2 ppb reported 

in the USGS-NAWQA data set. 

Additional refined modeling 

assessments were based on a proposed 

label submitted by FMC in May 2008. 

The refinements focused on two uses 

currently allowed on the existing label 

that would have remained under the 

withdrawn label: a corn rootworm 

rescue treatment, evaluated at 7 

representative sites, and an at-plant 


jlentini on PROD1PC65 with PROPOSALS3
44884 Federal Register / Vol. 73, No. 148 / Thursday, July 31, 2008 / Proposed Rules 

treatment for melons evaluated at 4 

additional sites. EPA developed 5 

additional corn scenarios representing 

use in states with extensive carbofuran 

usage at locations more vulnerable than 

most in each state in areas corn is 

grown. Using measured rainfall values, 

and assuming typical rather than 

maximum use rates, these assessments 

focused on the corn rescue treatment 

(Ref. 4). Peak concentrations for the corn 

rescue treatments simulated for Illinois, 

Iowa, Indiana, Kansas, Minnesota, 

Nebraska, and Texas ranged from 16.6 –

36.7 ppb. For refinement of estimates for 

the other use, melons, EPA developed 3 

additional melon scenarios representing 

states with extensive carbofuran usage 

at locations more vulnerable than most 

in each state in areas melons are grown. 

EPA used measured rainfall values and 

a wide row spacing to simulate an 

application rate less than half of what is 

allowed as the maximum rate for 

melons (0.65 versus 1.94 lb/A). Peak 

concentrations resulting from a single 

ground application of carbofuran at 

plant in Florida, Michigan, Missouri, 

and New Jersey resulted in peak 

concentrations from 4.2 – 24.4 ppb (Id.). 

Additional details on these assessments 

can be found at Ref. 4. Consistent with 

the analysis summarized above these 

predicted carbofuran water 

concentrations are similar to or lower 

than the peak concentrations reported in 

the USGS-NAWQA monitoring data and 

similar to or not more than tenfold 

higher than the 4 ppb reported in 

finished water from a surface water 

drinking plant. 

There are few surface water field-scale 

studies targeted to carbofuran use that 

could be compared with modeling 

results. Most of these studies were 

conducted in fields that contain tile 

drains, which is a common practice 

throughout midwestern states to 

increase drainage in agricultural fields 

(Ref. 13). Drains are common in the 

upper Mississippi river basin (Illinois, 

Iowa, and the southern part of 

Minnesota), and the northern part of the 

Ohio River Basin (Indiana, Ohio, and 

Michigan) (Ref. 42). Although it is not 

possible to directly correlate the 

concentrations found in most of the 

studies with drinking water 

concentrations, these studies confirm 

that carbofuran use under such 

circumstances can contaminate surface 

water, as tile drains have been identified 

as a pathway for contamination of 

surface water. For example, one study 

conducted in the United Kingdom in 

1991 and 1992 looked at concentrations 

in tile drains and surface water treated 

at a rate of 2.7 lbs a.i. per acre (granular 

formulation). Resulting concentrations 

in surface water downstream of the field 

ranged from 49.4 ppb almost two 

months after treatment to 0.02 ppb 6 

months later, and were slightly lower 

than concentrations measured in the tile 

drains, which were a transport pathway. 

Even with the factors that limit the 

study’s relevance to the majority of 

current carbofuran use—the high use 

rate and granular formulation—the 

study clearly confirms that tile drains 

can serve as a source of significant 

surface water contamination. Although 

EPA’s models do not account for tile 

drain pathways, and acknowledging the 

uncertainties in comparing carbofuran 

monitoring data to the concentrations 

predicted from the exposure models, as 

noted previously, estimated (modelderived) peak concentrations of 

carbofuran are similar to peak 

concentrations reported in stream 

monitoring studies and are no more 

than tenfold higher than a value 

reported from a drinking water plant 

where it is unlikely the sample design 

would have ensured that water was 

sampled on the day of the peak 

concentration. 

EPA conducted dietary exposure 

analyses based on the modeling 

scenarios for the current label as well as 

scenarios comparable to the uses on 

FMC’s proposed label of May 2008. 

Exposures from all modeled scenarios 

substantially exceeded EPA’s level of 

concern (Ref. 12). For example, an 

Illinois corn scenario, assuming 2 foliar 

applications at a typical 1–lb a.i. per 

acre use rate, estimated a 1-in-10-year 

peak carbofuran water concentration of 

26 ppb. Exposures at the 99.9th 

percentile based on this modeled 

distribution ranged from 860% of the 

aPAD for youths 13–19 to greater than 

10,000% of the aPAD for infants. This 

scenario is intended to be representative 

of highly vulnerable sites on which corn 

could be grown on a national basis, and 

is used as a screen for corn on a national 

basis. Similarly, exposures based on an 

Idaho potato scenario, and using a 3 lb 

a.i. acre rate, ranged from 230% of the 

aPAD for children 6–12 to 890% of the 

aPAD for infants, with a1-in-10-year 

peak carbofuran concentration of 10 

ppb. Although other crop scenarios 

resulted in higher exposures, estimates 

for these two crops are presented here, 

as they are major crops on which a large 

percentage of carbofuran use occurs. 

More details on these assessments, as 

well as the assessments EPA conducted 

for other crop scenarios, can be found in 

Refs. 4, 12 and 47. 

Table 8 below presents the results of 

one of EPA’s refined exposure analyses 

that addresses a use comparable to one 

in FMC’s proposed May 2008 label. This 

example is based on a Nebraska corn 

rootworm ‘‘rescue treatment’’ scenario, 

and assumes a single aerial application 

at a typical rate of 1 pound a.i. per acre. 

To simulate an application made 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 Hydrologic Unit Code 8-sized basin in 

the United States. (The U.S. Geological 

Survey has classified all watersheds in 

the US into basins of various sizes, 

according to hydrologic unit codes, in 

which the number of digits indicates the 

size of the basin). The full distribution 

of daily concentrations over a 30–year 

period was used in the probabilistic 

dietary risk assessment. The 1-in-10- 

year peak concentration of the 

distribution of values for the Nebraska 

corn rescue treatment was 22.3 ppb. 

More details on these assessments, as 

well as the assessments EPA conducted 

for other crop scenarios, can be found in 

Refs. 4, 12 and 47. 

TABLE 8—RESULTS OF ACUTE DIETARY (SURFACE WATER ONLY) EXPOSURE ANALYSIS INCORPORATING THE NEBRASKA

CORN ROOTWORM RESCUE SCENARIO

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 0.000444 590 0.001236 1,650 0.002912 3,900 

Children 1–2 years old 0.000075 0.000190 250 0.000517 690 0.001267 1,700 

Children 3–5 years old 0.000075 0.000177 240 0.000473 630 0.001144 1,500 


jlentini on PROD1PC65 with PROPOSALS3
Federal Register / Vol. 73, No. 148 / Thursday, July 31, 2008 / Proposed Rules 44885 

TABLE 8—RESULTS OF ACUTE DIETARY (SURFACE WATER ONLY) EXPOSURE ANALYSIS INCORPORATING THE NEBRASKA

CORN ROOTWORM RESCUE SCENARIO—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 0.000122 160 0.000329 440 0.000801 1,100 

Youth 13–19 years old 0.0002 0.000091 45 0.000255 130 0.000671 340 

Adults 20–49 years old 0.0002 0.000118 60 0.000313 160 0.000766 380 

Adults 50+ years old 0.0002 0.000125 60 0.000307 150 0.000671 340 

The populations described in the 

‘‘Nebraska corn’’ assessments are those 

people who consume water from a 

reservoir located in a small watershed 

predominated by corn production (with 

the assumption that treatment does not 

reduce carbofuran concentrations). The 

only crop treated by carbofuran in the 

watershed is corn, and all of that crop 

is assumed treated with carbofuran at 

the rate of 1 lb per acre. To the extent 

a drinking water plant drawing water 

from the reservoir normally treats the 

raw intake water with lime softening or 

activated carbon processes the finished 

water concentrations could be reduced 

from 60 to 100% with the resultant 

aPADs ranging from approximately 460 

to 102% of the aPAD to 0% of the aPAD, 

respectively, at the 99.9th percentile of 

exposure. 

As discussed in the previous sections, 

it is important to remember that 

carbofuran’s aPAD is quite low, hence 

relatively low concentrations of 

carbofuran monitored or estimated in 

surface water can have a significant 

impact on the percent of the aPAD 

utilized. Thus, while the refined 

carbofuran water concentrations for the 

corn ‘‘rescue’’ treatment in the range of 

approximately 16.6 to 36.7 ppb are 

comparable to maximum peak 

concentrations reported in the 

monitoring studies, these concentrations 

can result in very significant 

exceedences of the aPAD for various age 

groups, primarily because carbofuran is 

inherently very toxic. 

FMC has criticized EPA’s assessment 

for failing to account more fully for the 

percent of the crop treated (PCT) in its 

modeling. Uncertainty associated with 

PCT assumptions can be a major factor 

in EPA’s drinking water exposure 

assessment for surface-water sources. 

Estimates of the percent of major crops 

(for example, corn) that are treated with 

pesticides are available at the state level, 

but are generally not available on a 

smaller scale suitable for estimating 

drinking water exposure in a watershed. 

In addition, the PCT should be assessed 

at a watershed-scale, aggregating all 

crops treated with the pesticide in a 

watershed. If state-scale estimates are 

used to account for PCT it will 

underestimate the risk for some of the 

drinking water facilities in the state as 

the state-wide estimate represents an 

average: values for individual facilities 

will be both lower and higher than the 

state-wide estimate. In some cases, the 

underestimate can be substantial if the 

application pattern tends to form cluster 

or pockets of high usage. Insecticides 

like carbofuran are particularly prone to 

this use pattern, as insect outbreaks 

often tend to be locally intense, rather 

than widespread. In addition, marginal 

use practice changes in a given 

watershed can substantially affect the 

percentage of the crop treated, and such 

changes are effectively impossible to 

track. Without data collected at a finer 

spatial scale, it is not possible to know 

whether pesticide usage is evenly 

dispersed through the state or is locally 

clustered. This results in large 

uncertainty in the drinking water 

exposure assessments when percent 

crop treated is moderate or low. 

Consequently, EPA does not typically 

include such information in its surfacewater exposure assessments. 

However, in response to FMC’s 

concerns, EPA performed a sensitivity 

analysis of an exposure assessment 

using a PCT in the watershed to 

determine the extent to which some 

consideration of this factor could 

meaningfully affect the outcome of the 

risk assessment. The registrant has at 

different times, suggested the 

application of a 5 or 10% crop treated 

based on county sales data. While 

substantial questions remain as to the 

support for these percentages for a given 

basin where carbofuran may be used, 

EPA used the upper figure for the 

purpose of conducting a sensitivity 

analysis. The results suggest that, even 

at levels below 10% crop treated, 

exposures from drinking water derived 

from surface waters can contribute 

significantly to the aggregate dietary 

risks, particularly for infants and 

children. For example, applying a 10% 

crop treated figure to the Nebraska corn 

scenario described above, in addition to 

the corn-PCA of 0.46 incorporated into 

that scenario, results in estimated 

exposures from water alone, ranging 

from 110% of the aPAD for children 6–

12 to 390% of the aPAD for infants, 

assuming water treatment processes do 

not affect concentrations in drinking 

water consumed. Details on the 

assessments EPA conducted for other 

crop scenarios, which showed higher 

contributions from drinking water, can 

be found in Refs. 12, 13 and 47. 

Accordingly, these assessments suggest 

that EPA’s use of PCA alone, rather than 

in conjunction with PCT, will not 

meaningfully affect the carbofuran risk 

assessment, as aggregate exposures 

would still exceed 100% of the aPAD. 

In conclusion, the large difference 

between concentrations seen in the 

monitoring data on the low side, and the 

simulation modeling on the high side, is 

an indication of the uncertainty in the 

assessment for surface-water source 

drinking water exposure. The majority 

of drinking water concentrations 

resulting from use of carbofuran are 

likely to be occurring at higher 

concentrations than those measured in 

most monitoring studies, but below 

those estimated with simulation 

modeling; however the exact values are 

highly uncertain. However, the 

monitoring data show a consistent 

pattern of low concentrations, with the 

occasional, infrequent spike of high 

concentrations. Those infrequent high 

concentrations are consistent with 

EPA’s modeling, which is intended to 

capture the exposure peaks. For a 

chemical with an acute risk, like 

carbofuran, the spikes or peaks in 

exposures, even though infrequent, are 

the most relevant for assessing the risks. 

And, as previously noted, the available 

monitoring has its own limitations for 

estimating exposure for risk assessment. 

Further, the results of the modeling 

analyses provide critical insights 


jlentini on PROD1PC65 with PROPOSALS3
44886 Federal Register / Vol. 73, No. 148 / Thursday, July 31, 2008 / Proposed Rules 

regarding locations in the country where 

the potential for carbofuran 

contamination to surface water and 

associated drinking water sources are 

more likely. These locations include 

areas with soils prone to runoff (such as 

those high in clay or containing 

restrictive layers), in regions with 

intensive agriculture with crops on 

which carbofuran is used (e.g. corn), 

which have high rainfall amounts and/ 

or are subject to intense storm events in 

the spring around the times applications 

are being made. Drinking water facilities 

with small basins tend to be more 

vulnerable, as it is more likely that a 

large proportion of the crop acreage will 

be treated in small basins. 

Apparently FMC also has determined 

that some drinking water facilities 

associated with surface source waters 

are vulnerable to carbofuran exposure. 

In the now withdrawn labels FMC 

proposed to require buffer zones around 

surface waters in certain locations of the 

country, presumably to protect surface 

water. The proposed buffers were for 

fields where soils were considered to be 

highly erodible. Buffers were to be 66 

feet wide and were to be vegetated with 

‘‘crop, seeded with grass, or other 

suitable crop’’. In 2000, EPA 

participated in the development of a 

guidance document on how to reduce 

pesticide runoff using conservation 

buffers (Ref. 55). Results of this effort 

found that properly designed buffers 

can reduce runoff of weakly absorbed 

pesticides like carbofuran by increasing 

filtration so that the pesticide can be 

trapped and degraded in the buffer. 

However, it is of critical importance that 

sheet flow be maintained across the 

buffer in order for this to occur. To 

ensure sheet flow, buffers need to be 

specifically designed for that purpose 

and they must be well-maintained, as 

over time sediment trapped in the buffer 

causes flow to become more 

channelized and the buffer then 

becomes ineffective. The guidance 

concludes that un-maintained, unvegetated buffers around water bodies, 

often referred to a ‘setback,’ are 

ineffective in reducing pesticide 

movement to surface water. 

3. Aggregate dietary exposures (food 

and drinking water). EPA conducted a 

number of probabilistic analyses to 

combine the national food exposures 

with the exposures from the individual 

region and crop-specific drinking water 

scenarios. Although food is distributed 

nationally, and residue values are 

therefore not expected to vary 

substantially throughout the country, 

drinking water is locally derived and 

concentrations of pesticides in source 

water fluctuate over time and location 

for a variety of reasons. Pesticide 

residues in water fluctuate daily, 

seasonally, and yearly as a result of the 

timing of the pesticide application, the 

vulnerability of the water supply to 

pesticide loading through runoff, spray 

drift and/or leaching, and changes in the 

weather. Concentrations are also 

affected by the method of application, 

the location and characteristics of the 

sites where a pesticide is used, the 

climate, and the type and degree of pest 

pressure. Consequently, EPA conducted 

several estimates of aggregate dietary 

risks by combining exposures from food 

and drinking water. All of these 

estimates showed that aggregate 

exposures to carbofuran residues are 

unsafe. More details on the individual 

aggregate assessments presented below, 

as well as the assessments EPA 

conducted for other regional and crop 

scenarios, can be found in Refs. 12 and 

13. 

Table 9 below reflects the results of 

aggregate exposures from food and from 

drinking water derived from ground 

water in vulnerable areas (i.e., from 

shallow wells associated with sandy 

soils and acidic aquifers, such as are 

found in the Delmarva Peninsula). The 

estimates range between 1,100% of the 

aPAD for adults, to over 10,000% of the 

aPAD for infants. 

TABLE 9—RESULTS OF ACUTE DIETARY (FOOD AND WATER) EXPOSURE ANALYSIS INCORPORATING THE DELMARVA

GROUND WATER SCENARIO

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 0.003799 5,100 0.006026 8,000 0.010011 >10,000 

Children 1–2 years old 0.000075 0.001622 2,200 0.002740 3,700 0.004644 6,200 

Children 3–5 years old 0.000075 0.001465 2,000 0.002414 3,200 0.004273 5,700 

Children 6–12 years old 0.000075 0.001026 1,400 0.001715 2,300 0.002825 3,800 

Youth 13–19 years old 0.0002 0.000813 410 0.001442 720 0.002921 1,500 

Adults 20–49 years old 0.0002 0.000958 480 0.001638 820 0.003091 1,500 

Adults 50+ years old 0.0002 0.000888 440 0.001351 680 0.002278 1,100 

The peak concentration estimates in 

the Delmarva groundwater scenario time 

series are consistent with monitoring 

data from wells in vulnerable areas 

where carbofuran was used. For 

example, the maximum water 

concentration from the time series is 

38.5 ppb while maximum values from a 

targeted ground water monitoring study 

at the same site was 65 ppb, with 

studies at other sites having similar or 

higher peak concentrations (Refs. 13 and 

47). For studies with multiple 

measurements at each well, central 

tendency estimates were also in the 

same range as the time series. For 

example, the mean carbofuran 

concentration from wells under no-till 

agriculture in Queenstown, MD was 7 

ppb, while the median for the modeling 

was 15.5 ppb. The 90–day average 

concentration, based on the registrant’s 

PGW study conducted on corn in the 

Delmarva (adjusted for current 

maximum application rates) is 22 ppb. 

Table 10 below presents the results of 

aggregate exposure from food and 

derived from surface water using the 

Nebraska corn surface water scenario. 

This table reflects the risks only for 

those people in drinking watersheds 

with characteristics similar to that used 

in the scenario, and assuming that water 

treatment does not remove carbofuran. 


jlentini on PROD1PC65 with PROPOSALS3
Federal Register / Vol. 73, No. 148 / Thursday, July 31, 2008 / Proposed Rules 44887 

As discussed previously, the estimated 

water concentrations are comparable to 

the maximum peak concentrations 

reported in monitoring studies that were 

not designed to detect peak, daily 

concentrations of carbofuran in 

vulnerable locations. 

TABLE 10—RESULTS OF ACUTE DIETARY (FOOD AND WATER) EXPOSURE ANALYSIS USING THE NEBRASKA CORN

SURFACE WATER SCENARIO

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 0.000448 600 0.001240 1,700 0.002899 3,900 

Children 1–2 years old 0.000075 0.000200 270 0.000533 710 0.001326 1,800 

Children 3–5 years old 0.000075 0.000187 250 0.000486 650 0.001190 1,600 

Children 6–12 years old 0.000075 0.000128 170 0.000336 450 0.000824 1,100 

Youth 13–19 years old 0.0002 0.000095 48 0.000264 130 0.000685 340 

Adults 20–49 years old 0.0002 0.000122 61 0.000318 160 0.000785 390 

Adults 50+ years old 0.0002 0.000129 65 0.000312 160 0.000689 340 

Typically, EPA’s food and water 

exposure assessments sum exposures 

over a 24–hour period, and EPA used 

this 24–hour total in developing its 

acute dietary risk assessment for 

carbofuran. Because of the rapid nature 

of carbofuran toxicity and recovery, EPA 

considered that it might be appropriate 

to consider durations of exposure less 

than 24 hours. EPA has developed an 

analysis using information about 

external exposure, timing of exposure 

within a day, and half-life of AChE 

inhibition from rats to estimate risk to 

carbofuran at durations less than 24 

hours. Specifically, EPA has evaluated 

individual eating and drinking 

occasions and used the AChE half-life 

information to estimate the residual 

effects from carbofuran from previous 

exposures within the day. The 

carbofuran analyses are described in the 

July 2008 aggregate (dietary) memo (Ref. 

12). 

EPA has used two approaches for 

considering the impact of rapid 

reversibility on exposure estimates in 

the food and drinking water risk 

assessments. EPA previously used these 

approaches in the cumulative risk 

assessment of the NMC pesticides and/ 

or risk assessments for other NMC 

pesticides (e.g., methomyl and aldicarb) 

(Ref. 63). 

Incorporating eating occasion analysis 

and either the 150 minute or 300 minute 

recovery half life for carbofuran into the 

food only analysis does not significantly 

change the risk estimates when 

compared to baseline levels (for which 

a total daily consumption basis – and 

not eating occasion - was used). From 

this, it is apparent that modifying the 

analysis such that information on eating 

(i.e. food) occasions and carbofuran half 

life is incorporated results in only minor 

reductions in estimated risk. 

The food analysis showed that over 

70% of exposures at the top 0.2 

percentile for children ages 1–2 and 3–

5 are from a single eating event of 

carbofuran indicating that carbofuran’s 

food risk is not substantively overstated. 

Moreover, when incorporating half-life 

to recovery information, risks from 

summing exposures over 24 hours are 

similar to those when incorporating 

half-life to recovery of 150 or 300 

minutes. Regarding drinking water 

exposure, accounting for drinking water 

consumption throughout the day and 

using the half-life to recovery 

information, risk is reduced by 

approximately 2–3X. 

Consequently, risk estimates for 

which food and drinking water are 

jointly considered and incorporated (i.e, 

Food + Drinking Water) are reduced 

considerably—by a factor of two or more 

in some cases—compared to baseline. 

This is not unexpected, as infants 

receive much of their exposures from 

indirect drinking water in the form of 

water used to prepare infant formula. 

But even though the risk estimates from 

aggregate exposure are reduced, they 

nonetheless still substantially exceed 

EPA’s level of concern for infants and 

children. Using drinking water derived 

from the surface water from the New 

Jersey melon scenario, which estimated 

one of the lower exposure distributions, 

aggregate exposures ranged from a low 

of 280% of the aPAD for infants, based 

on a 150–minute half-life, to a high of 

370% of the aPAD for infants, based on 

a 300–minute half-life. 

The two approaches discussed above 

are used to evaluate the extent to which 

the Agency’s 24–hour approach to 

dietary risk assessment overestimates 

risk from carbofuran exposure. The 

results of both approaches indicate that 

the risk to carbofuran is indeed not 

substantively overestimated using the 

current exposure models and the 24–

hour approach. This is due to the fact 

that exposure to carbofuran occurs 

predominantly through single eating 

events and not from multiple events that 

occur throughout the day. Based on 

these analyses, the Agency concludes 

that the current exposure assessment 

methods used in the carbofuran dietary 

assessment provide realistic and high 

confidence estimates of risk to 

carbofuran exposure through food. 

The result of all of these analyses 

clearly demonstrate that aggregate 

exposure from all uses of carbofuran fail 

to meet the FFDCA section 408 safety 

standard, and revocation of the 

associated tolerances is warranted. 

Based on the contribution from food 

alone, dietary exposures to carbofuran 

exceed EPA’s level of concern for all of 

the more sensitive subpopulations of 

infants and children. In addition, EPA’s 

analyses show that those individuals–

both adults as well as children—who 

receive their drinking water from 

vulnerable sources are also exposed to 

levels that exceed EPA’s level of 

concern—in some cases by orders of 

magnitude. This primarily includes 

those populations consuming drinking 

water from groundwater from shallow 

wells in acidic aquifers overlaid with 

sandy soils that have had crops treated 

with carbofuran. It could also include 

those populations that obtain their 


jlentini on PROD1PC65 with PROPOSALS3
44888 Federal Register / Vol. 73, No. 148 / Thursday, July 31, 2008 / Proposed Rules 

drinking water from reservoirs located 

in small agricultural watersheds, prone 

to runoff, and predominated by crops 

that are treated with carbofuran, 

although there is substantially more 

uncertainty associated with these 

exposure estimates. Every sensitivity 

analysis EPA has performed has shown 

that estimated exposures significantly 

exceed EPA’s level of concern for 

children. Although the magnitude of the 

exceedance varies depending the level 

of conservatism in the assessment, the 

fact that in each case, aggregate 

exposures from dietary exposures of 

carbofuran fail to meet the FFDCA 

section 408 safety standard strongly 

corroborates EPA’s conclusion that 

aggregate exposures from all uses of 

carbofuran are not safe. 

VII. When Do These Actions Become 

Effective? 

The Agency is proposing that the 

revocations of the tolerances for all 

commodities except artichoke and 

sunflower seed become effective 60 days 

after a final rule is published. EPA is 

also proposing to establish an extended 

effective date for artichokes and 

sunflower seed, to allow growers of 

these crops additional time to transition 

to alternative compounds. The 

revocation for these two tolerances will 

become effective two years after a final 

rule or order is published. The Agency 

believes that these revocation dates will 

allow users to exhaust stocks of 

carbofuran currently in their possession. 

However, if EPA is presented with 

information during the comment period 

on this proposal that end-users may 

need additional time to utilize 

carbofuran stocks currently in their 

possession, and that information is 

verified, the Agency will consider 

extending the expiration date of the 

tolerance. If you have comments 

regarding the effective date, or if you 

have comments on how long it would 

take you to utilize the carbofuran stocks 

currently in your possession, please 

submit comments as described under 

SUPPLEMENTARY INFORMATION. 

Any commodities listed in this 

proposal treated with the pesticide 

subject to this proposal, and in the 

channels of trade following the 

tolerance revocations, shall be subject to 

FFDCA section 408(1)(5), as established 

by FQPA. Under this section, any 

residues of these pesticides in or on 

such food shall not render the food 

adulterated so long as it is shown to the 

satisfaction of the Food and Drug 

Administration that: 

1. The residue is present as the result 

of an application or use of the pesticide 

at a time and in a manner that was 

lawful under FIFRA, and 

2. The residue does not exceed the 

level that was authorized at the time of 

the application or use to be present on 

the food under a tolerance or exemption 

from tolerance. Evidence to show that 

food was lawfully treated may include 

records that verify the dates when the 

pesticide was applied to such food. 

VIII. Are the Proposed Actions 

Consistent with International 

Obligations? 

The tolerance revocations in this 

proposal are not discriminatory and are 

designed to ensure that both 

domestically-produced and imported 

foods meet the food safety standard 

established by the FFDCA. The same 

food safety standards apply to 

domestically produced and imported 

foods. 

EPA is working to ensure that the U.S. 

tolerance reassessment program under 

FQPA does not disrupt international 

trade. EPA considers Codex Maximum 

Residue Limits (MRLs) in setting U.S. 

tolerances and in reassessing them. 

MRLs are established by the Codex 

Committee on Pesticide Residues, a 

committee within the Codex 

Alimentarius Commission, an 

international organization formed to 

promote the coordination of 

international food standards. It is EPA’s 

policy to harmonize U.S. tolerances 

with Codex MRLs to the extent possible, 

provided that the MRLs achieve the 

level of protection required under 

FFDCA. EPA’s effort to harmonize with 

Codex MRLs is summarized in the 

tolerance reassessment section of 

individual Reregistration Eligibility 

Decision documents. EPA has 

developed guidance concerning 

submissions for import tolerance 

support (65 FR 35069, June 1, 2000) 

(FRL–6559–3). This guidance will be 

made available to interested persons. 

Electronic copies are available on the 

internet at http://www.epa.gov/. On the 

Home Page select ‘‘Laws, Regulations, 

and Dockets,’’ then select Regulations 

and Proposed Rules and then look up 

the entry for this document under 

‘‘Federal Register—Environmental 

Documents.’’ You can also go directly to 

the ‘‘Federal Register’’ listings at http:// 

www.epa.gov/fedrgstr/. 

IX. Statutory and Executive Order 

Reviews 

In this proposed rule, EPA is 

proposing to revoke specific tolerances 

established under FFDCA section 408. 

The Office of Management and Budget 

(OMB) has exempted this type of action 

(e.g., tolerance revocation for which 

extraordinary circumstances do not 

exist) from review under Executive 

Order 12866, entitled Regulatory 

Planning and Review (58 FR 51735, 

October 4, 1993). Because this proposed 

rule has been exempted from review 

under Executive Order 12866 due to its 

lack of significance, this proposed rule 

is not subject to Executive Order 13211, 

Actions Concerning Regulations That 

Significantly Affect Energy Supply, 

Distribution, or Use (66 FR 28355, May 

22, 2001). This proposed rule does not 

contain any information collections 

subject to OMB approval under the 

Paperwork Reduction Act (PRA), 44 

U.S.C. 3501 et seq., or impose any 

enforceable duty or contain any 

unfunded mandate as described under 

Title II of the Unfunded Mandates 

Reform Act of 1995 (UMRA) (Public 

Law 104–4). Nor does it require any 

special considerations as required by 

Executive Order 12898, entitled Federal 

Actions to Address Environmental 

Justice in Minority Populations and 

Low-Income Populations (59 FR 7629, 

February 16, 1994); or OMB review or 

any other Agency action under 

Executive Order 13045, entitled 

Protection of Children from 

Environmental Health Risks and Safety 

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

This action does not involve any 

technical standards that would require 

Agency consideration of voluntary 

consensus standards pursuant to section 

12(d) of the National Technology 

Transfer and Advancement Act of 1995 

(NTTAA), Public Law 104–113, section 

12(d) (15 U.S.C. 272 note). In addition, 

the Agency has determined that this 

action will not have a substantial direct 

effect on States, on the relationship 

between the national government and 

the States, or on the distribution of 

power and responsibilities among the 

various levels of government, as 

specified in Executive Order 13132, 

entitled Federalism (64 FR 43255, 

August 10, 1999). Executive Order 

13132 requires EPA to develop an 

accountable process to ensure 

‘‘meaningful and timely input by State 

and local officials in the development of 

regulatory policies that have federalism 

implications.’’ ‘‘Policies that have 

federalism implications’’ is defined in 

the Executive order to include 

regulations that have ‘‘substantial direct 

effects on the States, on the relationship 

between the national government and 

the States, or on the distribution of 

power and responsibilities among the 

various levels of government.’’ This 

proposed rule directly regulates 

growers, food processors, food handlers 

and food retailers, not States. This 


jlentini on PROD1PC65 with PROPOSALS3
Federal Register / Vol. 73, No. 148 / Thursday, July 31, 2008 / Proposed Rules 44889 

action does not alter the relationships or 

distribution of power and 

responsibilities established by Congress 

in the preemption provisions of section 

408(n)(4) of the FFDCA. For these same 

reasons, the Agency has determined that 

this proposed rule does not have any 

‘‘tribal implications’’ as described in 

Executive Order 13175, entitled 

Consultation and Coordination with 

Indian Tribal Governments (65 FR 

67249, November 6, 2000). Executive 

Order 13175, requires EPA to develop 

an accountable process to ensure 

‘‘meaningful and timely input by tribal 

officials in the development of 

regulatory policies that have tribal 

implications.’’ ‘‘Policies that have tribal 

implications’’ is defined in the 

Executive order to include regulations 

that have ‘‘substantial direct effects on 

one or more Indian tribes, on the 

relationship between the Federal 

Government and the Indian tribes, or on 

the distribution of power and 

responsibilities between the Federal 

Government and Indian tribes.’’ This 

proposed rule will not have substantial 

direct effects on tribal governments, on 

the relationship between the Federal 

Government and Indian tribes, or on the 

distribution of power and 

responsibilities between the Federal 

Government and Indian tribes, as 

specified in Executive Order 13175. 

Thus, Executive Order 13175 does not 

apply to this proposed rule. 

The Regulatory Flexibility Act (RFA) 

of 1980, as amended by the Small 

Business Regulatory Enforcement 

Fairness Act of 1996 (SBREFA), 5 USC 

601 et.seq, generally requires an agency 

to prepare a regulatory flexibility 

analysis of any rule subject to notice 

and comment rulemaking requirements 

under the Administrative Procedures 

Act or any other statute. This is required 

unless the agency certifies that the rule 

will not have a significant economic 

impact on a substantial number of small 

entities. Small entities include small 

businesses, small organizations, and 

small governmental jurisdictions. The 

Agency has determined that no small 

organizations or small governmental 

jurisdictions are impacted by today’s 

rulemaking. 

For purposes of assessing the impacts 

of today’s determination on businesses, 

a small business is defined either by the 

number of employees or by the annual 

dollar amount of sales/revenues. The 

level at which an entity is considered 

small is determined for each North 

American Industry Classification 

System (NAICS) code by the Small 

Business Administration (SBA). Farms 

are classified under NAICS code 111, 

Crop Production, and the SBA defines 

small entities as farms with total annual 

sales of $750,000 or less. 

The Agency has examined the 

potential effects today’s proposed rule 

may have on potentially impacted small 

businesses. Based on this analysis, EPA 

concludes that the Agency can certify 

that revoking the food tolerances for 

carbofuran will not have a significant 

economic impact on a substantial 

number of small entities (No SISNOSE) 

for alfalfa, artichoke, banana, chili 

pepper, coffee, cotton, cucurbits 

(cucumber, melons, pumpkin, and 

squash), grape, grains (barley, flax, oats, 

and wheat), field corn, potato, soybean, 

sorghum, sugarbeet, sugarcane, 

sunflower, and sweet corn. Even in a 

worst-case scenario, in which a grower 

obtains income only from a single crop 

and his/her entire acreage is affected, 

the impact generally amounts to less 

than 2% of gross income and would be 

felt by fewer than 3% of affected small 

producers. Estimates of impacts to corn 

growers were refined to account for the 

sporadic nature of need for carbofuran 

while still maintaining some 

assumptions that would bias the 

estimates upward. Refined estimates 

were also made for artichoke and 

sunflower, which consider the diversity 

in growers’ revenue. The largest impact 

may be felt by artichoke growers, with 

impacts as high as 5% of gross revenue, 

but fewer than five growers are likely to 

be affected. EPA could not quantify the 

impacts to banana, sugarcane, and sweet 

corn producers, but the number of 

impacted farms is less than 2% of the 

farms subject to the action. Additional 

detail on the analyses EPA conducted in 

support of this certification can be 

found in Ref. 49. 

X. References 

EPA has established an official record 

for this rulemaking. The official record 

includes all information considered by 

EPA in developing this proposed rule 

including documents specifically 

referenced in this action and listed 

below, any public comments received 

during an applicable comment period, 

and any other information related to this 

action, including any information 

claimed as CBI. This official record 

includes all information physically 

CAlocated in docket ID number EPA–

HQ–OPP–2005–0162, as well as any 

documents that are referenced in the 

documents listed below or in the 

docket. The public version of the official 

record does not include any information 

claimed as CBI. 

1. Acute oral (gavage) dose 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. 

2. Acute oral (gavage) time course 

study of cholinesterase depression from 

carbofuran technical in adult and 

juvenile (day 11 postpartum) rats. 

Hoberman, 2007. MRID 47143704 

(unpublished FMC study) EPA–HQ–

OPP–2007–1088–0063. 

3. Additional chemographs for 

potatoes and cucurbits for drinking 

water exposure assessment in support of 

the reregistration of carbofuran (PC 

Code 090601) (R. David Jones, 10/23/07 

D345729). EPA–HQ–OPP–2005–0162–

0486. 

4. Additional refinements of the 

drinking water exposure assessment for 

the use of carbofuran on corn and 

melons (PC code 090601)(R. David 

Jones, 06/2008 D353714). 

5. An In-Depth Investigation to 

Estimate Surface Water Concentrations 

of Carbofuran within Indiana 

Community Water Supplies. Performed 

by Waterborne Environmental, Inc., 

Leesburg, VA, Engel Consulting, and 

Fawcett Consulting. Submitted by FMC. 

Corporation, Philadelphia, PA. WEI No 

528.01, FMC Report No. PC–0378. MRID 

47221603. EPA–HQ–OPP–2007–1088–

0023. 

6. An Investigation into the Potential 

for Carbofuran Leaching to Ground 

Water Based on Historical and Current 

Use Practices. Submitted by FMC. 

Corporation, Philadelphia, PA. Report 

No. PC–0363. MRID 47221602. EPA–

HQ–OPP–2007–1088–0022. 

7. An Investigation into the Potential 

for Carbofuran Leaching to Ground 

Water Based on Historical and Current 

Use Practices: Supplemental Report on 

Twenty-one Additional States. 

Submitted by FMC Corporation, 

Philadelphia, PA. Report No. PC–0383. 

MRID 47244901. EPA–HQ–OPP–2007–

1088-0025. 

8. Benchmark dose analysis of 

cholinesterase inhibition data in 

neonatal and adult rats (MRID no. 

46688914) following exposure to 

carbofuran (A.Lowit, 1/19/06, D325342, 

TXR no. 0054034). EPA–HQ–OPP–

2007–1088–0045. 

9. Benjamins, J.A. and McKhann, 

G.M. (1981) Development, regeneration, 

and aging of the brain. In: Basic 

Neurochemistry, 3rd edition. Edited by 

Siegel, G.J., Albers, R.W., Agranoff, 

B.W., and Katzman, R. Little, Brown and 

Co., Boston. pp 445–469; Dobbing, J. 

and Smart, J.L. (1974) Vulnerability of 

developing brain and behaviour. British 

Medical Bulletin. 30:164–168; Davison, 

A.N. and Dobbing, J. (1966) Myelination 

as a vulnerable period in brain 

development. British Medical Bulletin. 

22:40–44. 


jlentini on PROD1PC65 with PROPOSALS3
44890 Federal Register / Vol. 73, No. 148 / Thursday, July 31, 2008 / Proposed Rules 

10. Best Management Practices to 

Reduce Carbofuran Losses to Ground 

And Surface Water. Submitted by FMC. 

Corporation, Philadelphia, PA. Report 

No. PC–0362. MRID 47279201. EPA–

HQ–OPP–2005–0162–0464. 

11. California Department of Pesticide 

Regulation. Risk Characterization 

Document for Carbofuran. January 23, 

2006. 219 pgs. 

12. Carbofuran Acute Aggregate 

Dietary (Food and Drinking Water) 

Exposure and Risk Assessments for the 

Reregistration Eligibility Decision (T. 

Morton, 7/22/08, D351371). 

13. Carbofuran Environmental Risk 

Assessment and Human Drinking Water 

Exposure Assessment for IRED. March 

2006. EPA–HQ–OPP–2005–0162–0080. 

14. Carringer, 2000. Carbamate Market 

Basket Survey. Reviewed by S. Piper, 

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

Carringer, 5/12/00). 

15. 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. 

16. Carbofuran. HED Revised Risk 

Assessment for the Notice of Intent to 

Cancel. (PC 090601) D 347038, January 

2007. EPA–HQ–OPP–2007–1088–0034. 

17. Cholinesterase depression in 

juvenile (day 11) and adult rats 

following acute oral (gavage) dose of 

carbofuran technical. Hoberman, 2007. 

MRID 47143705 (unpublished FMC 

study). EPA–HQ–OPP–2007–1088–

0066. 

18. Context Document for Carbofuran 

Risk Assessment Issues not Specifically 

Addressed in the FIFRA SAP Charge 

Questions (M. Panger, C. Salice, R. 

David Jones, E. Odenkirchen, I. 

Sunzenauer, 1/08 D348292). EPA–HQ–

OPP–2007–1088–0071. 

19. Data Evaluation Record for Acute 

dose-response study of carbofuran 

technical administered by gavage to 

adult and postnatal day 11 male and 

female CD(Sprague-Dawley) rats. 

MRID 46688914. EPA–HQ–OPP–2007–

1088–0045. 

20. Data Evaluation Record for 

Cholinesterase depression in juvenile 

(day 11) and adult rats following acute 

oral (gavage) dose of carbofuran 

technical. MRID 47143705. 

21. Dose-time response modeling of 

rat brain AChE activity: carbofuran 

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

1088–0053. 

22. Dose-time response modeling of 

rat RBC-AChE activity: carbofuran 

gavage dosing 10/23/07 

(RatRBC_DR.pdf). EPA–HQ–OPP–2007–

1088–0029. 

23. EPA Response to the Transmittal 

of Meeting Minutes of the FIFRA 

Scientific Advisory Panel Meeting Held 

February 5–8 2008 on the Agency’s 

Proposed Action under FIFRA 6(b) 

Notice of Intent to Cancel Carbofuran 

(E.Reaves, A. Lowit, J. Liccione 7/2008 

D352315). 

24. Estimated Drinking Water 

Concentrations (email communication 

D.Young to D.Drew, 3/8/06). 

25. FIFRA SAP (1998) ‘‘A set of 

Scientific Issues Being Considered by 

the Agency in Connection with 

Proposed Methods for Basin-scale 

Estimation of Pesticide Concentrations 

in Flowing Water and Reservoirs for 

Tolerance Reassessment.’’ Final Report 

from the FIFRA Scientific Advisory 

Panel Meeting of July 29–30, 1998 

(Report dated September 2, 1998). 

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

scipoly/sap/meetings/1998/july/ 

final1.pdf. 

26. FIFRA SAP (1999) ‘‘Sets of 

Scientific Issues Being Considered by 

the Environmental Protection Agency 

Regarding Use of Watershed-derived 

Percent Crop Areas as a Refinement 

Tool in FQPA Drinking Water Exposure 

Assessments for Tolerance 

Reassessment.’’ Final Report from the 

FIFRA Scientific Advisory Panel 

Meeting of February 5–7, 2002 (Report 

dated May 25, 1999). SAP Report 99–

03C. Available at: http://www.epa.gov/ 

scipoly/sap/meetings/1999/may/ 

final.pdf. 

27. FIFRA SAP. (2002). ‘‘Methods 

Used to Conduct a Preliminary 

Cumulative Risk Assessment for 

Organophosphate Pesticides.’’ Final 

Report from the FIFRA Scientific 

Advisory Panel Meeting of February 5–

7, 2002 (Report dated March 19, 2002). 

FIFRA Scientific Advisory Panel, Office 

of Science Coordination and Policy, 

Office of Prevention, Pesticides and 

Toxic Substances, U.S. Environmental 

Protection Agency. Washington, DC. 

SAP Report 2002–01. 

28. FIFRA Science Advisory Panel 

(SAP). 2005a. ‘‘Final report on N-Methyl 

Carbamate Cumulative Risk Assessment: 

Pilot Cumulative Analysis.’’ Final 

Report from the FIFRA Scientific 

Advisory Panel Meeting of February , 

2005 (Report dated September 2, 1998). 

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

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

29. FIFRA Science Advisory Panel 

(SAP). 2005b. ‘‘Final report on 

Preliminary N-Methyl Carbamate 

Cumulative Risk Assessment.’’ Final 

Report from the FIFRA Scientific 

Advisory Panel Meeting of July 29–30, 

1998 (Report dated September 2, 1998). 

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

scipoly/sap/2005/august/minutes.pdf. 

30. FIFRA Science Advisory Panel 

(SAP). 2008. ‘‘Final report on the 

Agency’s Proposed Action under FIFRA 

6(b) Notice of Intent to Cancel 

Carbofuran.’’ Report from the FIFRA 

Scientific Advisory Panel Meeting of 

February , 5–8 2008 (Report dated 

September 2, 1998). Available at: http:// 

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

2008/february/carbofuransapfinal.pdf. 

31. Final report on cholinesterase 

inhibition study of carbofuran: PND17 

rats. MRID 47167801 (ORD study). EPA–

HQ–OPP–2007–1088–0064. 

32. FMC Letter Requesting Proposed 

Label Amendments and Voluntary 

Cancellations. Dated May 9, 2008. EPA–

HQ–OPP–2005–0162–0496 and –0497. 

Email Communication from John 

Cummings to Steven Bradbury, dated 

June 10, 2008. EPA–HQ–OPP–2005–

0162–0499. 

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

Padilla, S. (1997). Automated 

instrument analysis of cholinesterase 

activity in tissues from carbamatetreated animals: A cautionary note. 

Toxicology Mechanisms and Methods, 

7:43–53. 

34. Interim Reregistration Eligibility 

Decision for Carbofuran. D. Edwards. 

2006. Regulations.gov document 

number: EPA–HQ–OPP–2005–0162–

0304. 

35. IPCS World Health Organization. 

2005. Chemical Specific Adjustment 

factors for Interspecies Differences and 

Human Variability: Guidance Document 

for use of Data in Dose/ConcentrationResponse Assessment. 

36. Issue Paper for the FIFRA SAP 

Meeting on Carbofuran: Human Health 

Risk Assessment Reregistration 

Eligibility Science Chapter for 

Carbofuran, Environmental Fate and 

Effects Chapter. March 2006. EPA–HQ–

OPP–2007–1088–0031. 

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

(1975) A rapid, simple radiometric assay 

for cholinesterase, suitable for multiple 

determinations. Analytical 

Biochemistry. 64:229–238. 

38. McDaniel K.L. and Moser V.C. 

(2004) Differential profiles of 

cholinesterase inhibition and 

neurobehavioral effects in rats exposed 

to fenamiphos or profenofos. 

Neurotoxicology and Teratology. 

26:407–415. 

39. McDaniel K.L., Padilla S., 

Marshall R.S., Phillips P.M., Podhorniak 

L., Qian Y., Moser V.C. (2007) 

Comparison of acute neurobehavioral 

and cholinesterase inhibitory effects of 

N-methyl carbamates in rats. Toxicology 

Sciences. 98, 552–560. 

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

the acute effects of cholinesterase 

inhibitors using a neurobehavioral 


jlentini on PROD1PC65 with PROPOSALS3
Federal Register / Vol. 73, No. 148 / Thursday, July 31, 2008 / Proposed Rules 44891 

screening battery in rats. Neurotoxical 

and Teratology 17: 617–625. 

41. National Assessment of the 

Relative Vulnerability of Community 

Water Supply Reservoirs in Carbofuran 

Use Areas. Performed by Waterborne 

Environmental Inc., Leesburg, VA and 

Engel Consulting, West Lafayette, IN. 

Submitted by FMC Corporation, 

Philadelphia, PA. WEI Report No. 

528.01–B, FMC Report No. PC–0387. 

MRID 47272301. EPA–HQ–OPP–2007–

1088–0024. 

42. National Resources Inventory 

1992, cited in USGS 2002, ‘‘Herbicide 

Concentrations in the Mississippi River 

Basin—the importance of 

chloracetanilide degradates.’’ R.A. 

Rebich, R.H. Coupe, E.M.Thurman. 

43. Nostrandt, A.C., Duncan, J.A., and 

Padilla, S. (1993). A modified 

spectrophotometric method appropriate 

for measuring cholinesterase activity in 

tissues from carbaryl-treated animals. 

Fundamentals of Applied Toxicology. 

21:196–203. 

44. Padilla S., Marshall R.S., Hunter 

D.L., and Lowit A. 2007. Time course of 

cholinesterase inhibition in adult rats 

treated acutely with carbaryl, 

carbofuran, formetanate, methomyl, 

methiocarb, oxamyl, or propoxur. 

Toxicology and Applied Pharmacology, 

219; 202–209. 

45. PND17 BMDs and BMDLs and 

recovery half-lives for the effects of 

carbofuran on brain and blood AChE 

(PND17_DR.pdf). EPA–HQ–OPP–2007–

1088–0047. 

46. Report on cholinesterase 

sensitivity study of carbofuran: Adult 

and PND11 MRID 47289001 (ORD 

study). EPA–HQ–OPP–2007–1088–

0065. 

47. Revised Drinking Water 

Assessment in Support of the 

Reregistration of Carbofuran (PC Code 

090601) (R. David Jones, 9/5/07 

D3424057). EPA–HQ–OPP–2005–0162–

0485. 

48. Revised HED Product Chemistry 

and Residue Chemistry Chapter of the 

RED (D. Drew, 1/13/05, D306796). EPA–

HQ–OPP–2005–0162–0028. 

49. Screening Level analysis of the 

small business impacts of revoking 

carbofuran tolerances. (Wyatt, T.J. July 

2008) 28 pgs. 

50. Setzer W. 2008 Carbofuran: 

Updated Statistical Analysis of the 

FQPA Factor Based on the BMD50 ratio 

of Adult/Pup RBC Data. 7 pgs. 

51. Setzer W. October 23, 2007. Dosetime response modeling of rat RBC 

AChE activity: Carbofuran gavage 

dosing. 47 pgs. EPA–HQ–OPP–2007–

1088–0029. 

52. Setzer W. October 25, 2007. 

PND17 BMDs and BMDLs and recovery 

half-lives for the effect of Carbofuran on 

brain and blood AChE. 12 pgs. EPA–

HQ–OPP–2007–1088–0047. 

53. Setzer W. October 5, 2007. Dosetime response modeling of rat brain 

AChE activity: Carbofuran gavage 

dosing. 64 pgs. EPA–HQ–OPP–2007–

1088–0053. 

54. Summary Evaluation of Recently 

Submitted FMC Water Exposure 

Studies. (PC Code 090601) (R. David 

Jones, 12/26/07 D347901), 12 pgs. EPA–

HQ–OPP–2007–1088–0016. 

55. USDA NRCS. Conservation Buffer 

to Reduce Pesticide Losses. Natural 

Resources Conservation Service, Fort 

Worth, TX, 21 pp. 

56. USEPA (2000) ‘‘Assigning Values 

to Nondetected/Nonquantified Pesticide 

Residues in Human Health Dietary 

Exposure Assessments.’’ March 23, 

2000. Available at: http://www.epa.gov/ 

pesticides/trac/science/trac3b012.pdf. 

57. USEPA. (2000b). ‘‘Benchmark 

Dose Technical Guidance Document.’’

Draft report. Risk Assessment Forum, 

Office of Research and Development, 

U.S. Environmental Protection Agency. 

Washington, DC. EPA/630/R–00/001. 

58. USEPA. (2000) ‘‘Choosing a 

Percentile of Acute Dietary Exposure as 

a Threshold of Regulatory Concern.’’

March 16, 2000. Available at: http:// 

www.epa.gov/pesticides/trac/science/ 

trac2b054.pdf . 

59. USEPA. (2001). Memorandum 

from Marcia Mulkey to Lois Rossi. 

‘‘Implementation of the Determinations 

of a Common Mechanism of Toxicity for 

N-Methyl Carbamate Pesticides and for 

Certain Chloroacetanilide Pesticides.’’

July 12, 2001. Available at: http:// 

www.epa.gov/oppfead1/cb/csb_page/ 

updates/carbamate.pdf. 

60. USEPA. (2002). ‘‘Office of 

Pesticide Programs’ Policy on the 

Determination of the Appropriate FQPA 

Safety Factor(s) For Use in Tolerance 

Assessment.’’ Available at: http:// 

www.epa.gov/oppfead1/trac/science/ 

determ.pdf. 

61. USEPA. (2000). ‘‘The Use of Data 

on Cholinesterase Inhibition for Risk 

Assessments of Organophosphorous and 

Carbamate Pesticides.’’ August 18, 2000. 

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

pesticides/trac/science/cholin.pdf. 

62. USEPA. (2005). ‘‘Preliminary NMethyl Carbamate Cumulative Risk 

Assessment.’’ Available at: http:// 

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

index.htm#august. 

63. USEPA (2007). ‘‘Revised N-Methyl 

Carbamate Cumulative Risk Assessment 

U.S. Environmental Protection Agency, 

Office of Pesticide Programs,’’

September 24, 2007. Available at: http:// 

www.epa.gov/oppsrrd1/REDs/ 

nmc_revised_cra.pdf. 

64. WARF, 1978. Rao, G.N.; Davis, 

G.J.; Giesler, P.; et al. (1978) 

Teratogenicity of Carbofuran in Rats: 

ACT 184.33. (Unpublished study 

received Dec 5, 1978 under 275–2712; 

prepared by WARF Institute, Inc., 

submitted by FMC Corp., Philadelphia, 

Pa.; CDL:236593–A). 

65. Watershed Regressions for 

Pesticides (WARP) Model Estimates for 

Carbofuran in Illinois Watershed. 

Performed by Waterborne 

Environmental, Inc., Leesburg, VA. WEI 

362.07. Submitted by FMC Corporation, 

Philadelphia, PA. Report No. P-3786. 

MRID 46688915. EPA–HQ–OPP–2007–

1088–0021. 

66. Williams, C.H. and Casterline, J.L., 

Jr. (1969). A comparison of two methods 

for measurement of erythrocyte 

cholinesterase inhibition after 

carbamate administration to rats. Food 

and Cosmetics Toxicology. 7:149–151. 

67. Winteringham, F.P.W. and Fowler, 

K.S. (1966) Substrate and dilution 

effects on the inhibition of 

acetylcholinesterase by carbamates. 

Biochemical Journal. 101:127–134. 

List of Subjects in 40 CFR Part 180 

Environmental protection, 

Administrative practice and procedure, 

Agricultural commodities, Pesticides 

and pests, Reporting and recordkeeping 

requirements. 

Dated: July 23, 2008. 

Debra Edwards, 

Director, Office of Pesticide Programs. 

Therefore, it is proposed that 40 CFR 

chapter I be amended as follows: 

PART 180—[AMENDED] 

1. The authority citation for part 180 

continues to read as follows: 

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

2. Section 180.254 is amended by 

revising the table in paragraph (a) and 

the table in paragraph (c), and by 

removing paragraph (d) to read as 

follows. 

§ 180.254 Carbofuran; tolerances for 

residues. 

(a) * * * 

Commodity Parts per 

million 

Expiration/ 

Revocation 

Date 

Sunflower, seed 

(of which no 

more than 0.2 

ppm is carbamate) 1.0 10/31/10 

* * * * * 

(c) * * * 


jlentini on PROD1PC65 with PROPOSALS3
44892 Federal Register / Vol. 73, No. 148 / Thursday, July 31, 2008 / Proposed Rules 

Commodity Parts per 

million 

Expiration/ 

Revocation 

Date 

Artichoke, globe 

(of which no 

more than 0.2 

ppm is carbamate) 0.4 10/31/10 

[FR Doc. E8–17660 Filed 7–29–08; 1:15 pm] 

BILLING CODE 6560–50–S 


jlentini on PROD1PC65 with PROPOSALS3