Federal Register / Vol. 73, No. 25 / Wednesday, February 6, 2008 / Rules and Regulations 6851 

that this regulation will not have a 

significant economic impact on a 

substantial number of small business 

entities. This rule imposes no new costs 

or burden on small entities. Rather, this 

rule adds Spain to the list of nontraditional countries permitted to export 

NRM to the United States, helping to 

ensure that United States importers and 

manufacturers will have access to, and 

be able to procure, supplies of NRM to 

meet legitimate United States medical, 

scientific, research, and industrial 

needs, to ensure maintenance of 

adequate reserve stocks, and to meet 

lawful export requirements. 

Additionally, this rule provides DEA 

registered importers with another source 

from which to purchase NRM which are 

utilized for the production of controlled 

substances used in the United States for 

medical purposes. 

Executive Order 12866 

The Deputy Assistant Administrator, 

Office of Diversion Control, further 

certifies that this rulemaking has been 

drafted in accordance with the 

principles in Executive Order 12866 

Section 1(b). It has been determined that 

this is a significant regulatory action. 

Therefore, this action has been reviewed 

by the Office of Management and 

Budget. 

Executive Order 12988 

This rule meets the applicable 

standards set forth in Sections 3(a) and 

3(b)(2) of Executive Order 12988. 

Executive Order 13132 

This rule does not preempt or modify 

any provision of State law; nor does it 

impose enforcement responsibilities on 

any State; nor does it diminish the 

power of any State to enforce its own 

laws. Accordingly, this rulemaking does 

not have federalism implications 

warranting the application of Executive 

Order 13132. 

Unfunded Mandates Reform Act of 1995 

This rule will not result in the 

expenditure by State, local, and tribal 

governments, in the aggregate, or by the 

private sector, of $120,000,000 or more 

(adjusted for inflation) in any one year, 

and will not significantly or uniquely 

affect small governments. Therefore, no 

actions were deemed necessary under 

the provisions of the Unfunded 

Mandates Reform Act of 1995. 

Congressional Review Act 

This rule is not a major rule as 

defined by Section 804 of the Small 

Business Regulatory Enforcement 

Fairness Act of 1996 (Congressional 

Review Act). This rule will not result in 

an annual effect on the economy of 

$100,000,000 or more; a major increase 

in costs or prices; or significant adverse 

effects on competition, employment, 

investment, productivity, innovation, or 

on the ability of United States-based 

companies to compete with foreignbased companies in domestic and 

export markets. 

List of Subjects in 21 CFR Part 1312 

Administrative practice and 

procedure, Drug traffic control, Exports, 

Imports, Reporting and recordkeeping 

requirements. 

■ For the reasons set out above, 21 CFR 

part 1312 is amended as follows: 

PART 1312—IMPORTATION AND 

EXPORTATION OF CONTROLLED 

SUBSTANCES 

■ 1. The authority citation for part 1312 

continues to read as follows: 

Authority: 21 U.S.C. 952, 953, 954, 957, 

958. 

■ 2. Section 1312.13 is amended by 

revising paragraphs (f) and (g) to read as 

follows: 

§ 1312.13 Issuance of import permit. 

* * * * * 

(f) Notwithstanding paragraphs (a)(1) 

and (a)(2) of this section, the 

Administrator shall permit, pursuant to 

section 1002(a)(1) or 1002(a)(2)(A) of the 

Act (21 U.S.C. 952(a)(1) or (a)(2)(A)), the 

importation of approved narcotic raw 

material (opium, poppy straw and 

concentrate of poppy straw) having as 

its source: 

(1) Turkey, 

(2) India, 

(3) Spain, 

(4) France, 

(5) Poland, 

(6) Hungary, and 

(7) Australia. 

(g) At least eighty (80) percent of the 

narcotic raw material imported into the 

United States shall have as its original 

source Turkey and India. Except under 

conditions of insufficient supplies of 

narcotic raw materials, not more than 

twenty (20) percent of the narcotic raw 

material imported into the United States 

annually shall have as its source Spain, 

France, Poland, Hungary and Australia. 

Dated: January 30, 2008. 

Joseph T. Rannazzisi, 

Deputy Assistant Administrator, Office of 

Diversion Control. 

[FR Doc. E8–2142 Filed 2–5–08; 8:45 am] 

BILLING CODE 4410–09–P 

ENVIRONMENTAL PROTECTION 

AGENCY 

40 CFR Part 180 

[EPA–HQ–OPP–2007–0280; FRL–8346–9] 

Clothianidin; Pesticide Tolerance 

AGENCY: Environmental Protection 

Agency (EPA). 

ACTION: Final rule. 

SUMMARY: This regulation establishes a 

tolerance for residues of clothianidin in 

or on sugar beet roots, tops and 

molasses. Bayer CropScience requested 

this tolerance under the Federal Food, 

Drug, and Cosmetic Act (FFDCA). 

DATES: This regulation is effective 

February 6, 2008. Objections and 

requests for hearings must be received 

on or before April 7, 2008, and must be 

filed in accordance with the instructions 

provided in 40 CFR part 178 (see also 

Unit I.C. of the SUPPLEMENTARY

INFORMATION). 

ADDRESSES: EPA has established a 

docket for this action under docket 

identification (ID) number EPA–HQ–

OPP–2007–0280. To access the 

electronic docket, go to http:// 

www.regulations.gov, select ‘‘Advanced 

Search,’’ then ‘‘Docket Search.’’ Insert 

the docket ID number where indicated 

and select the ‘‘Submit’’ button. Follow 

the instructions on the regulations.gov 

website to view the docket index or 

access available documents. All 

documents in the docket are listed in 

the docket index available in 

regulations.gov. Although listed in the 

index, some information is not publicly 

available, e.g., Confidential Business 

Information (CBI) or other information 

whose disclosure is restricted by statute. 

Certain other material, such as 

copyrighted material, is not placed on 

the Internet and will be publicly 

available only in hard copy form. 

Publicly available docket materials are 

available in the electronic docket at 

http://www.regulations.gov, or, if only 

available in hard copy, at the OPP 

Regulatory Public Docket in Rm. S–

4400, One Potomac Yard (South Bldg.), 

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

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

to 4 p.m., Monday through Friday, 

excluding legal holidays. The Docket 

Facility telephone number is (703) 305–

5805. 

FOR FURTHER INFORMATION CONTACT: 

Kable Bo Davis, Registration Division 

(7505P), Office of Pesticide Programs, 

Environmental Protection Agency, 1200 

Pennsylvania Ave., NW., Washington, 

DC 20460–0001; telephone number: 


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(703) 306–0415; e-mail address: 

davis.kable@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 those engaged in the 

following activities: 

• Crop production (NAICS code 111), 

e.g., agricultural workers; greenhouse, 

nursery, and floriculture workers; 

farmers. 

• Animal production (NAICS code 

112), e.g., cattle ranchers and farmers, 

dairy cattle farmers, livestock farmers. 

• Food manufacturing (NAICS code 

311), e.g., agricultural workers; farmers; 

greenhouse, nursery, and floriculture 

workers; ranchers; pesticide applicators. 

• Pesticide manufacturing (NAICS 

code 32532), e.g., agricultural workers; 

commercial applicators; farmers; 

greenhouse, nursery, and floriculture 

workers; residential users. 

This listing is not intended to be 

exhaustive, but rather to provide a guide 

for readers regarding entities likely to be 

affected by this action. Other types of 

entities not listed in this unit could also 

be affected. The North American 

Industrial Classification System 

(NAICS) codes have been provided to 

assist you and others in determining 

whether this action might apply to 

certain entities. If you have any 

questions regarding the applicability of 

this action to a particular entity, consult 

the person listed under FOR FURTHER

INFORMATION CONTACT. 

B. How Can I Access Electronic Copies 

of this Document? 

In addition to accessing an electronic 

copy of this Federal Register document 

through the electronic docket at http:// 

www.regulations.gov, you may access 

this Federal Register document 

electronically through the EPA Internet 

under the ‘‘Federal Register’’ listings at 

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

also access a frequently updated 

electronic version of EPA’s tolerance 

regulations at 40 CFR part 180 through 

the Government Printing Office’s pilot 

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

ecfr. 

C. Can I File an Objection or Hearing 

Request? 

Under section 408(g) of FFDCA, any 

person may file an objection to any 

aspect of this regulation and may also 

request a hearing on those objections. 

You must file your objection or request 

a hearing on this regulation in 

accordance with the instructions 

provided in 40 CFR part 178. To ensure 

proper receipt by EPA, you must 

identify docket ID number EPA–HQ–

OPP–2007–0280 in the subject line on 

the first page of your submission. All 

requests must be in writing, and must be 

mailed or delivered to the Hearing Clerk 

as required by 40 CFR part 178 on or 

before April 7, 2008. 

In addition to filing an objection or 

hearing request with the Hearing Clerk 

as described in 40 CFR part 178, please 

submit a copy of the filing that does not 

contain any CBI for inclusion in the 

public docket that is described in 

ADDRESSES. Information not marked 

confidential pursuant to 40 CFR part 2 

may be disclosed publicly by EPA 

without prior notice. Submit this copy, 

identified by docket ID number EPA–

HQ–OPP–2007–0280, by one of the 

following methods: 

• Federal eRulemaking Portal: http:// 

www.regulations.gov. Follow the on-line 

instructions for submitting comments. 

• Mail: Office of Pesticide Programs 

(OPP) Regulatory Public Docket (7502P), 

Environmental Protection Agency, 1200 

Pennsylvania Ave., NW., Washington, 

DC 20460–0001. 

• Delivery: OPP Regulatory Public 

Docket (7502P), Environmental 

Protection Agency, Rm. S–4400, One 

Potomac Yard (South Bldg.), 2777 S. 

Crystal Dr., Arlington, VA. Deliveries 

are only accepted during the Docket’s 

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

4 p.m., Monday through Friday, 

excluding legal holidays). Special 

arrangements should be made for 

deliveries of boxed information. The 

Docket Facility telephone number is 

(703) 305–5805. 

II. Petition for Tolerance 

In the Federal Register of April 30, 

2007 (72 FR 21263) (FRL–8124–5), EPA 

issued a notice pursuant to section 

408(d)(3) of FFDCA, 21 U.S.C. 

346a(d)(3), announcing the filing of a 

pesticide petition (PP 6F7159) by Bayer 

CropScience, 2 T.W. Alexander Drive, 

Research Triangle Park, NC 27709. The 

petition requested that 40 CFR 180.586 

be amended by establishing a tolerance 

for residues of the insecticide 

clothianidin, (E)-1-(2-chloro-1,3-thiazol5-ylmethyl)-3-methyl-2-nitroguanidine, 

in or on beet, sugar, root at 0.02 parts 

per million (ppm); beet, sugar, tops at 

0.04 ppm; and beet, sugar, molasses at 

0.06 ppm. That notice referenced a 

summary of the petition prepared by 

Bayer CropScience, the registrant, 

which is available to the public in the 

docket, http://www.regulations.gov. 

There were no comments received in 

response to the notice of filing. 

Upon completing review of the 

current clothianidin database, the 

Agency concluded that the appropriate 

tolerance levels for clothianidin 

residues in or on pending crops should 

be established as follows: Beet, sugar, 

roots at 0.02 ppm, beet, sugar, molasses 

at 0.05 ppm and beet, sugar, dried pulp 

at 0.03 ppm. The Agency no longer 

considers sugar beet tops to be a 

significant livestock feedstuff; therefore, 

a separate tolerance for tops is not 

required. 

III. Aggregate Risk Assessment and 

Determination of Safety 

Section 408(b)(2)(A)(i) of FFDCA 

allows EPA to establish a tolerance (the 

legal limit for a pesticide chemical 

residue in or on a food) only if EPA 

determines that the tolerance is ‘‘safe.’’

Section 408(b)(2)(A)(ii) of 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. Section 

408(b)(2)(C) of FFDCA requires EPA to 

give special consideration to exposure 

of infants and children to the pesticide 

chemical residue in establishing a 

tolerance and to ‘‘ensure that there is a 

reasonable certainty that no harm will 

result to infants and children from 

aggregate exposure to the pesticide 

chemical residue....’’ These provisions 

were added to FFDCA by the Food 

Quality Protection Act (FQPA) of 1996. 

Consistent with FFDCA section 

408(b)(2)(D), and the factors specified in 

FFDCA section 408(b)(2)(D), EPA has 

reviewed the available scientific data 

and other relevant information in 

support of this action. EPA has 

sufficient data to assess the hazards of 

and to make a determination on 

aggregate exposure for the petitioned-for 

tolerance for residues of clothianidin on 

beet, sugar, roots at 0.02 ppm, beet, 

sugar, molasses at 0.05 ppm and beet, 

sugar, dried pulp at 0.03. EPA’s 

assessment of exposures and risks 

associated with establishing the 

tolerance follows. 

A. Toxicological Profile 

EPA has evaluated the available 

toxicity data and considered its validity, 

completeness, and reliability as well as 

the relationship of the results of the 

studies to human risk. EPA has also 

considered available information 


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concerning the variability of the 

sensitivities of major identifiable 

subgroups of consumers, including 

infants and children. Specific 

information on the studies received and 

the nature of the adverse effects caused 

by clothianidin as well as the noobserved-adverse-effect-level (NOAEL) 

and the lowest-observed-adverse-effectlevel (LOAEL) from the toxicity studies 

can be found at http:// 

www.regulations.gov. The risk 

assessment is available in the docket 

established by this action, which is 

described under ADDRESSES, and is 

identified as EPA–HQ–OPP–2007–0280 

in that docket. 

Clothianidin does not appear to 

exhibit toxicity towards a consistent 

specific target organ. Decreases in body 

weight and body weight gain were 

observed in rats, dogs, and mice. In 

single-dose studies, mice (acute toxicity 

category II) appear more sensitive than 

rats (category IV). Clinical signs of 

neurotoxicity were exhibited in both 

mice (decreased motor activity, tremors, 

and deep respirations at 50 milligram/ 

kilogram (mg/kg)) and rats (transient 

signs of decreased arousal, motor 

activity, and locomotor activity at 100 

mg/kg) in acute neurotoxicity studies 

following exposure by gavage; however, 

no indications of neurotoxicity were 

observed following dietary exposure in 

the subchronic neurotoxicity study in 

rats. In a developmental neurotoxicity 

study in rats, decreased body weights, 

body weight gains, motor activity, and 

acoustic startle response amplitude 

(females) were seen in offspring at doses 

lower than those resulting in maternal 

toxicity. Although the NOAELs were 

similar for the subchronic and chronic 

feeding studies in the rat, a greater 

spectrum of effects was observed in the 

chronic study (decreased body weight, 

body weight gain, and food 

consumption plus additional 

observations in the liver, ovary, and 

kidney) versus the subchronic study 

(effects only on body weight and food 

consumption). In the rat, administration 

via the oral route appears to be more 

toxic than via the dermal route. In 

longer term studies, dogs exhibited 

clinical signs of anemia. The only 

observed effects in mice following 

chronic dietary administration were 

increases in vocalization and decreases 

in body weight and body weight gain. 

Clothianidin has been classified as not 

likely to be carcinogenic to humans. 

There was no evidence of increased 

quantitative or qualitative susceptibility 

of rat or rabbit offspring in 

developmental studies; however, 

increased quantitative susceptibility of 

rat pups was seen in both the 

reproduction and developmental 

neurotoxicity studies. The degree of 

concern for both of these studies is low 

because the observed effects are well 

characterized, and there are clear 

NOAELs and LOAELs. The NOAEL for 

the effects of concern identified in the 

reproduction study (decreased mean 

body weight gain and absolute thymus 

weights in pups, delayed sexual 

maturation, and an increase in still 

births) is the basis for the endpoint 

selected for the chronic dietary and 

short-term, intermediate-term and longterm non-dietary risk assessments. 

In adult rats, a guideline 

immunotoxicity study shows no 

clothianidin-mediated immunotoxicity 

at doses lower than those resulting in 

generalized signs of toxicity (e.g., 

decreases in body weight); however, it 

cannot be concluded that a similar lack 

of effects will occur in offspring. Based 

on evidence of decreased absolute and 

adjusted organ weights of the thymus 

and spleen in multiple studies in the 

clothianidin data base and on evidence 

of increased quantitative susceptibility 

of juvenile rats, compared to adults, in 

the 2–generation reproduction study to 

these effects, a developmental 

immunotoxicity (DIT) study has been 

required. 

B. Toxicological Endpoints 

For hazards that have a threshold 

below which there is no appreciable 

risk, the toxicological level of concern 

(LOC) is derived from the highest dose 

at which the NOAEL in the toxicology 

study identified as appropriate for use 

in risk assessment. However, if a 

NOAEL cannot be determined, the 

LOAEL is sometimes used for risk 

assessment. Uncertainty/safety factors 

(UFs) are used in conjunction with the 

LOC to take into account uncertainties 

inherent in the extrapolation from 

laboratory animal data to humans and in 

the variations in sensitivity among 

members of the human population as 

well as other unknowns. Safety is 

assessed for acute and chronic risks by 

comparing aggregate exposure to the 

pesticide to the acute population 

adjusted dose (aPAD) and chronic 

population adjusted dose (cPAD). The 

aPAD and cPAD are calculated by 

dividing the LOC by all applicable UFs. 

Short-term, intermediate-term, and longterm risks are evaluated by comparing 

aggregate exposure to the LOC to ensure 

that the margin of exposure (MOE) 

called for by the product of all 

applicable UFs is not exceeded. 

For non-threshold risks, the Agency 

assumes that any amount of exposure 

will lead to some degree of risk and 

estimates risk in terms of the probability 

of occurrence of additional adverse 

cases. Generally, cancer risks are 

considered non-threshold. For more 

information on the general principles 

EPA uses in risk characterization and a 

complete description of the risk 

assessment process, see http:// 

www.epa.gov/fedrgstr/EPA-PEST/1997/ 

November/Day–26/p30948.htm. 

A summary of the toxicological 

endpoints for clothianidin used for 

human risk assessment can be found at 

http://www.regulations.gov in document 

‘‘Clothianidin: Human Health Risk 

Assessment for Proposed Use on Sugar 

Beet’’ at pages 18–20 in docket ID 

number EPA–HQ–OPP–2007–0280. 

C. Exposure Assessment 

1. Dietary exposure from food and 

feed uses. In evaluating dietary 

exposure to clothianidin, EPA 

considered exposure under the 

petitioned-for tolerances as well as all 

existing clothianidin tolerances in (40 

CFR 180.586). EPA assessed dietary 

exposures from clothianidin in food as 

follows: 

i. Acute exposure. Quantitative acute 

dietary exposure and risk assessments 

are performed for a food-use pesticide, 

if a toxicological study has indicated the 

possibility of an effect of concern 

occurring as a result of a 1–day or single 

exposure. 

In estimating acute dietary exposure, 

EPA used food consumption 

information from the U.S. Department of 

Agriculture (USDA) 1994–1996 and 

1998 Nationwide Continuing Surveys of 

Food Intake by Individuals (CSFII). The 

acute assessment is based on maximum 

residues of clothianidin observed in 

clothianidin and thiamethoxam field 

trials and assumes 100 percent crop 

treated (%CT). 

ii. Chronic exposure. In conducting 

the chronic dietary exposure assessment 

EPA used the food consumption data 

from the USDA 1994–1996 and 1998 

CSFII. The chronic assessment is based 

on average residues from clothianidin 

and thiamethoxam field trials and 

assumes 100% CT. 

iii. Cancer. Because clothianidin is 

not expected to pose a cancer risk, a 

quantitative dietary exposure 

assessment for the purposes of assessing 

cancer risk was not conducted. 

iv. Anticipated residue and percent 

crop treated (PCT) information. Section 

408(b)(2)(E) of FFDCA authorizes EPA 

to use available data and information on 

the anticipated residue levels of 

pesticide residues in food and the actual 

levels of pesticide residues that have 

been measured in food. If EPA relies on 

such information, EPA must pursuant to 

FFDCA section 408(f)(1) require that 


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data be provided 5 years after the 

tolerance is established, modified, or 

left in effect, demonstrating that the 

levels in food are not above the levels 

anticipated. For the present action, EPA 

will issue such data call-ins as are 

required by FFDCA section 408(b)(2)(E) 

and authorized under FFDCA section 

408(f)(1). Data will be required to be 

submitted no later than 5 years from the 

date of issuance of this tolerance. 

The Agency used PCT information as 

follows: 

The acute assessment is based on 

maximum residues of clothianidin 

observed in clothianidin field trials and 

assumes 100% crop treated. The chronic 

assessment is based on average residues 

from clothianidin field trials and also 

assumes 100% CT. 

The Agency believes that the three 

conditions listed in Unit III. have been 

met. With respect to Condition 1, PCT 

estimates are derived from Federal and 

private market survey data, which are 

reliable and have a valid basis. The 

Agency is reasonably certain that the 

percentage of the food treated is not 

likely to be an underestimation. As to 

Conditions 2 and 3, regional 

consumption information and 

consumption information for significant 

subpopulations is taken into account 

through EPA’s computer-based model 

for evaluating the exposure of 

significant subpopulations including 

several regional groups. Use of this 

consumption information in EPA’s risk 

assessment process ensures that EPA’s 

exposure estimate does not understate 

exposure for any significant 

subpopulation group and allows the 

Agency to be reasonably certain that no 

regional population is exposed to 

residue levels higher than those 

estimated by the Agency. Other than the 

data available through national food 

consumption surveys, EPA does not 

have available information on the 

regional consumption of food to which 

clothianidin may be applied in a 

particular area. 

2. Dietary exposure from drinking 

water. The Agency lacks sufficient 

monitoring data to complete a 

comprehensive dietary exposure 

analysis and risk assessment for 

clothianidin in drinking water. Because 

the Agency does not have 

comprehensive monitoring data, 

drinking water concentration estimates 

are made by reliance on simulation or 

modeling taking into account data on 

the environmental fate characteristics of 

clothianidin. Further information 

regarding EPA drinking water models 

used in pesticide exposure assessment 

can be found at http://www.epa.gov/ 

oppefed1/models/water/index.htm. 

Based on the First Index Reservoir 

Screening Tool (FIRST) and Screening 

Concentration in Ground Water (SCIGROW) models, the estimated 

environmental concentrations (EECs) of 

clothianidin for acute exposures are 

estimated to be 7.29 parts per billion 

(ppb) for surface water and 5.84 ppb for 

ground water. The EECs for chronic 

exposures are estimated to be 1.35 ppb 

for surface water and 5.84 ppb for 

ground water. 

Modeled estimates of drinking water 

concentrations were directly entered 

into the dietary exposure model. For 

acute dietary risk assessment, the water 

concentration value of 7.29 ppb was 

used to access the contribution to 

drinking water. For chronic dietary risk 

assessment, the water concentration of 

value 5.84 ppb was used to access the 

contribution to drinking water. 

3. From non-dietary exposure. The 

term ‘‘residential exposure’’ is used in 

this document to refer to nonoccupational, non-dietary exposure 

(e.g., for lawn and garden pest control, 

indoor pest control, termiticides, and 

flea and tick control on pets). 

Clothianidin is currently registered 

for the following residential non-dietary 

sites: Turfgrass. EPA assessed 

residential exposure using the following 

assumptions: The following exposure 

scenarios were assessed for residential 

post-application risks: Toddlers playing 

on treated turf, adults performing yard 

work on treated turf, and adults and 

youths playing golf on treated turf. 

Additional information on residential 

exposure assumptions can be found at 

www.regulations.gov (Docket ID EPA–

HQ–OPP–2007–0280, pages 26 through 

27). 

4. Cumulative effects from substances 

with a common mechanism of toxicity. 

Section 408(b)(2)(D)(v) of FFDCA 

requires that, when considering whether 

to establish, modify, or revoke a 

tolerance, the Agency consider 

‘‘available information’’ concerning the 

cumulative effects of a particular 

pesticide’s residues and ‘‘other 

substances that have a common 

mechanism of toxicity.’’

Clothianidin is a member of the 

neonicotinoid class of pesticides and is 

a metabolite of another neonicotinoid, 

thiamethoxam. Structural similarities or 

common effects do not constitute a 

common mechanism of toxicity. 

Evidence is needed to establish that the 

chemicals operate by the same, or 

essentially the same sequence of major 

biochemical events (EPA, 2002). 

Although clothianidin and 

thiamethoxam bind selectively to insect 

nicotinic acetylcholine receptors 

(nAChR), the specific binding site(s)/ 

receptor(s) for clothianidin, 

thiamethoxam, and the other 

neonicotinoids are unknown at this 

time. Additionally, the commonality of 

the binding activity itself is uncertain, 

as preliminary evidence suggests that 

clothianidin operates by direct 

competitive inhibition, while 

thiamethoxam is a non-competitive 

inhibitor. Furthermore, even if future 

research shows that neonicotinoids 

share a common binding activity to a 

specific site on insect nicotinic 

acetylcholine receptors, there is not 

necessarily a relationship between this 

pesticidal action and a mechanism of 

toxicity in mammals. Structural 

variations between the insect and 

mammalian nAChRs produce 

quantitative differences in the binding 

affinity of the neonicotinoids towards 

these receptors, which, in turn, confers 

the notably greater selective toxicity of 

this class towards insects, including 

aphids and leafhoppers, compared to 

mammals. While the insecticidal action 

of the neonicotinoids is neurotoxic, the 

most sensitive regulatory endpoint for 

clothianidin is based on unrelated 

effects in mammals, including changes 

in body and thymus weights, delays in 

sexual maturation, and still births. 

Additionally, the most sensitive 

toxicological effect in mammals differs 

across the neonicotinoids (e.g., 

testicular tubular atrophy with 

thiamethoxam; mineralized particles in 

thyroid colloid with imidaclopid). Thus, 

there is currently no evidence to 

indicate that neonicotinoids share 

common mechanisms of toxicity, and 

EPA is not following a cumulative risk 

approach based on a common 

mechanism of toxicity for the 

neonicotinoids. For information 

regarding EPA’s efforts to determine 

which chemicals have a common 

mechanism of toxicity and to evaluate 

the cumulative effects of such 

chemicals, see the policy statements 

concerning common mechanism 

determinations and procedures for 

cumulating effects from substances 

found to have a common mechanism 

released by EPA’s Office of Pesticide 

Programs on EPA’s website at http:// 

www.epa.gov/pesticides/cumulative/. 

Note that because clothianidin is a 

major metabolite of thiamethoxam, EPA 

has combined exposure to clothianidin 

resulting both from thiamethoxam use 

and from use of clothianidin as an 

active ingredient and has compared this 

aggregate exposure estimate to relevant 

endpoints for clothianidin. EPA has 

taken the further conservative step of 

assuming that, in instances where both 

thiamethoxam and clothianidin are 


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registered for use on a crop, both 

pesticides will, in fact, be used on that 

crop. 

D. Safety Factor for Infants and 

Children 

1. In general. Section 408 of FFDCA 

provides that EPA shall apply an 

additional (‘‘10X’’) 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 database on toxicity 

and exposure unless EPA determines 

based on reliable data that a different 

margin of safety will be safe for infants 

and children. This additional margin of 

safety is commonly referred to as the 

FQPA safety factor. In applying this 

provision, EPA either retains the default 

value of 10X when reliable data do not 

support the choice of a different factor, 

or, if reliable data are available, EPA 

uses a different additional FQPA safety 

factor value based on the use of 

traditional UFs and/or special FQPA 

safety factors, as appropriate. 

2. Prenatal and postnatal sensitivity. 

In the developmental neurotoxicity 

study, toxicity in the offspring was 

observed at a lower dose level than the 

dose that caused toxicity in the maternal 

animals. Maternal effects included 

decreased body weights, body weight 

gains, and food consumption. Effects 

seen in the offspring included decreased 

body weights, body weight gains, motor 

activity, and acoustic startle response in 

the females. However, EPA determined 

that the degree of concern for the 

developmental neurotoxicity study is 

low and there are no residual 

uncertainties for prenatal and/or 

postnatal toxicity due to the results of 

the developmental neurotoxicity study 

because the observed effects are well 

characterized and there are clear 

NOAELs/LOAELs. 

In the 2–generation reproduction 

study, offspring toxicity (decreased 

body weight gains, delayed sexual 

maturation in males, decreased absolute 

thymus weights in F1 pups of both 

sexes, and an increase in stillbirths in 

both generations) was seen at a lower 

dose than the dose that caused parental 

toxicity. Based on evidence of decreased 

absolute and adjusted organ weights of 

the thymus and spleen in multiple 

studies in the clothianidin data base and 

on evidence of increased quantitative 

susceptibility of juvenile rats, compared 

to adults, in the 2–generation 

reproduction study to these effects. EPA 

has required that testing be conducted 

to assess immune system function in 

adults and in young animals following 

exposure during the period of 

organogenesis. No quantitative or 

qualitative susceptibility was observed 

in either of the developmental rat or 

rabbit studies. In the rat, no 

developmental toxicity was observed at 

the highest dose tested, although this 

dose level induced decreases in body 

weight gain and food consumption in 

the dams. In the rabbit, premature 

deliveries, decreased gravid uterine 

weights, an increase in litter incidence 

of a missing lobe of the lung, and a 

decrease in the litter average for ossified 

sternal centra per fetus were noted at a 

dose level in which maternal death, a 

decrease in food consumption, and 

clinical signs (scant feces and orange 

urine) were observed. Since the 

developmental effects observed in the 

rabbit study were seen in the presence 

of maternal toxicity, they are not 

considered to be qualitatively more 

severe than the maternal effects. 

3. Conclusion. The exposure data for 

clothianidin are complete or are 

estimated based on data that reasonably 

accounts for potential exposures. The 

acute dietary exposure assessment is 

based on maximum residues of 

clothianidin observed in clothianidin 

and thiamethoxam field trials and 

assumes 100% CT. The chronic 

assessment is based on average residues 

from clothianidin and thiamethoxam 

field trials and also assumes 100% CT. 

For water, the highest acute estimate 

from conservative models was used for 

both the acute and the chronic dietary 

exposure analyses. By using these 

conservative assessments, acute and 

chronic exposures/risks will not be 

underestimated. The residential 

exposure assessment utilizes residential 

standard operation procedures (SOPs) to 

assess post-application exposure to 

children as well as incidental oral 

ingestion by toddlers. The residential 

SOPs are based on reasonable worstcase assumptions and will not likely 

underestimate exposure/risk. These 

assessments are unlikely to 

underestimate the potential exposure to 

74,800 infants and children resulting 

from the use of clothianidin. 

The toxicology data base for 

clothianidin, however, is not complete 

for FQPA purposes. A complete 

complement of acceptable 

developmental, reproduction, 

developmental neurotoxicity, 

mammalian neurotoxicity and special 

neurotoxicity studies are available; 

however, due to evidence of decreased 

absolute and adjusted organ weights of 

the thymus and spleen in multiple 

studies in the clothianidin database, and 

because juvenile rats in the two–

generation reproduction study appear to 

be more susceptible to these effects, 

EPA has determined that testing should 

be conducted to assess immune system 

function in adults and in young animals 

following developmental exposures. 

Given the levels at which this testing 

should be conducted it could result in 

selection of a more protective (i.e., 

lower) regulatory endpoint. 

Due to the uncertainty with regard to 

potential effects on immune system 

function in young animals, EPA cannot 

conclude that there are reliable data 

supporting selection of a children’s 

safety factor different from the 

presumptive 10X factor. Therefore, the 

10X FQPA children’s safety factor will 

be retained. This safety factor will be in 

the form of a database uncertainty factor 

to account for the lack of the testing 

with regard to immune system function 

with clothianidin. 

E. Aggregate Risks and Determination of 

Safety 

Safety is assessed for acute and 

chronic risks by comparing aggregate 

exposure to the pesticide to the aPAD 

and cPAD. The aPAD and cPAD are 

calculated by dividing the LOC by all 

applicable UFs. For linear cancer risks, 

EPA calculates the probability of 

additional cancer cases given aggregate 

exposure. Short-term, intermediateterm, and long-term risks are evaluated 

by comparing aggregate exposure to the 

LOC to ensure that the MOE called for 

by the product of all applicable UFs is 

not exceeded. 

1. Acute risk. Using the exposure 

assumptions discussed in this unit for 

acute exposure, the acute dietary 

exposure from food and water to 

clothianidin will occupy 45% of the 

aPAD for the population group (children 

1–2 years old) receiving the greatest 

exposure. 

2. Chronic risk. Using the exposure 

assumptions described in this unit for 

chronic exposure, EPA has concluded 

that exposure to clothianidin from food 

and water will utilize 16% of the cPAD 

for the population group (children 1–2 

years old). Based on the use pattern, 

chronic residential exposure to residues 

of clothianidin is not expected. 

3. Short-term / Intermediate-term risk. 

Short-term aggregate and intermediateterm aggregate exposures take into 

account residential exposure plus 

chronic exposure to food and water 

(considered to be a background 

exposure level). 

Clothianidin is currently registered 

for use(s) that could result in short-term 

residential exposure and the Agency has 

determined that it is appropriate to 

aggregate chronic food and water and 

short-term exposures for clothianidin. 

EPA has determined that, for 

clothianidin, the toxicological effects 


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6856 Federal Register / Vol. 73, No. 25 / Wednesday, February 6, 2008 / Rules and Regulations 

are the same across oral, dermal, and 

inhalation routes of exposure and has 

selected the same endpoint and dose for 

short-term and intermediate-term 

exposure scenarios. Therefore, the 

exposures are simply summed 

(combined/aggregated) for use in risk 

calculations. Short- and intermediate 

aggregate risk estimates range from an 

MOE of 1,100 for toddlers (food + water 

+ treated turf + treated soil + dermal) to 

22,000 for youth golfers (food + water + 

post-application treated turf). The shortterm and intermediate-term aggregate 

risks associated with the registered and 

proposed uses of clothianidin do not 

exceed the Agency’s LOC for the general 

U.S. population or any population 

subgroup. 

4. Aggregate cancer risk for U.S. 

population. Clothianidin has been 

classified as a ‘‘not likely human 

carcinogen.’’ It is not expected to pose 

a cancer risk. 

5. Determination of safety. Based on 

these risk assessments, EPA concludes 

that there is a reasonable certainty that 

no harm will result to the general 

population, or to infants and children 

from aggregate exposure to clothianidin 

residues. 

IV. Other Considerations 

A. Analytical Enforcement Methodology 

Adequate liquid chromotography/ 

mass spectrometry/mass spectrometry 

(LC/MS/MS) methods are available for 

both collecting data and enforcing 

tolerances for clothianidin residues in 

plant (Bayer Methods 00552 and 

109240–1) and animal (Bayer Method 

00624) commodities. The validated 

limit of quantitation (LOQ) for 

clothianidin in plant commodities is 

0.010 ppm, except for wheat straw 

(0.020 ppm), and the validated LOQs are 

0.010 ppm in milk and 0.020 ppm in 

animal tissues. All three of these 

methods have been reviewed by EPA’s 

Analytical Chemistry Laboratory (ACL), 

approved for tolerance enforcement, and 

forwarded to FDA for inclusion in PAM 

Volume II. 

B. International Residue Limits 

There are no established or proposed 

Canadian, Mexican, or Codex maximum 

residue limits (MRLs) for clothianidin 

residues on sugar beet commodities. 

V. Conclusion 

Therefore, the tolerance is established 

for residues of (E)-1-(2-chloro-1,3- 

thiazol-5-ylmethyl)-3-methyl-2- 

nitroguanidine, in or on beet, sugar, 

roots at 0.02 ppm, beet, sugar, molasses 

at 0.05 ppm and beet, sugar, dried pulp 

at 0.03. 

VI. Statutory and Executive Order 

Reviews 

This final rule establishes a tolerance 

under section 408(d) of FFDCA in 

response to a petition submitted to the 

Agency. The Office of Management and 

Budget (OMB) has exempted these types 

of actions from review under Executive 

Order 12866, entitled Regulatory 

Planning and Review (58 FR 51735, 

October 4, 1993). Because this rule has 

been exempted from review under 

Executive Order 12866, this rule is not 

subject to Executive Order 13211, 

Actions Concerning Regulations That 

Significantly Affect Energy Supply, 

Distribution, or Use (66 FR 28355, May 

22, 2001) or Executive Order 13045, 

entitled Protection of Children from 

Environmental Health Risks and Safety 

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

This final rule does not contain any 

information collections subject to OMB 

approval under the Paperwork 

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

seq., nor does it require any special 

considerations under Executive Order 

12898, entitled Federal Actions to 

Address Environmental Justice in 

Minority Populations and Low-Income 

Populations (59 FR 7629, February 16, 

1994). 

Since tolerances and exemptions that 

are established on the basis of a petition 

under section 408(d) of FFDCA, such as 

the tolerance in this final rule, do not 

require the issuance of a proposed rule, 

the requirements of the Regulatory 

Flexibility Act (RFA) (5 U.S.C. 601 et 

seq.) do not apply. 

This final rule directly regulates 

growers, food processors, food handlers, 

and food retailers, not States or tribes, 

nor does this action alter the 

relationships or distribution of power 

and responsibilities established by 

Congress in the preemption provisions 

of section 408(n)(4) of FFDCA. As such, 

the Agency has determined that this 

action will not have a substantial direct 

effect on States or tribal governments, 

on the relationship between the national 

government and the States or tribal 

governments, or on the distribution of 

power and responsibilities among the 

various levels of government or between 

the Federal Government and Indian 

tribes. Thus, the Agency has determined 

that Executive Order 13132, entitled 

Federalism (64 FR 43255, August 10, 

1999) and Executive Order 13175, 

entitled Consultation and Coordination 

with Indian Tribal Governments (65 FR 

67249, November 6, 2000) do not apply 

to this rule. In addition, This rule does 

not 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). 

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). 

VII. Congressional Review Act 

The Congressional Review Act, 5 

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

that before a rule may take effect, the 

agency promulgating the rule must 

submit a rule report to each House of 

the Congress and to the Comptroller 

General of the United States. EPA will 

submit a report containing this rule and 

other required information to the U.S. 

Senate, the U.S. House of 

Representatives, and the Comptroller 

General of the United States prior to 

publication of this final rule in the 

Federal Register. This final rule is not 

a ‘‘major rule’’ as defined by 5 U.S.C. 

804(2). 

List of Subjects in 40 CFR Part 180 

Environmental protection, 

Administrative practice and procedure, 

Agricultural commodities, Pesticides 

and pests, Reporting and recordkeeping 

requirements. 

Dated: January 22, 2008. 

Lois Rossi, 

Director, Registration Division, Office of 

Pesticide Programs. 

■ Therefore, 40 CFR chapter I is 

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 180.586 is amended by 

alphabetically adding the following 

commodities to the table in paragraph 

(a) to read as follows: 

§ 180.586 Clothianidin; tolerances for 

residues. 

(a) * * * 

Commodity Parts per million 

Beet, sugar, dried pulp ... 0.03 

Beet, sugar, molasses .... 0.05 

Beet, sugar, roots ........... 0.02 

*****

* * * * * 

[FR Doc. E8–1784 Filed 2–5–08; 8:45 am] 

BILLING CODE 6560–50–S 


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