Document ID: EPA-HQ-OPP-2009-0130-0008
Agency: epa
Document Type: Rule
Title: Exemptions from Requirement of Tolerance: Tetrakis Ethylenediamine
Posted Date: 2010-11-24T05:00Z

[Federal Register: November 24, 2010 (Volume 75, Number 226)]
[Rules and Regulations]               
[Page 71550-71556]
From the Federal Register Online via GPO Access [wais.access.gpo.gov]
[DOCID:fr24no10-14]                         

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ENVIRONMENTAL PROTECTION AGENCY

40 CFR Part 180

[EPA-HQ-OPP-2009-0130; FRL-8851-8]

 
N,N,N',N'',-Tetrakis-(2-Hydroxypropyl) Ethylenediamine (NTHE); 
Exemption From the Requirement of a Tolerance

AGENCY: Environmental Protection Agency (EPA).

ACTION: Final rule.

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SUMMARY: This regulation establishes an exemption from the requirement 
of a tolerance for residues of N,N,N',N'',-Tetrakis-(2-Hydroxypropyl) 
Ethylenediamine (NTHE; CAS no. 102-60-3) when used as an inert 
ingredient stabilizer for formulation for pre- and post-harvest uses 
under 40 CFR 180.910 and application to animals under 40 CFR 180.930, 
at a maximum concentration of 20% by weight in pesticide formulations. 
The Joint Inerts Task Force (JITF), Cluster Support Team Number 15 (CST 
15) EPA Company No. 84947 submitted a petition to EPA under the Federal 
Food, Drug, and Cosmetic Act (FFDCA), requesting establishment of an 
exemption from the requirement of a tolerance. This regulation 
eliminates the need to

[[Page 71551]]

establish a maximum permissible level for residues of NTHE.

DATES: This regulation is effective November 24, 2010. Objections and 
requests for hearings must be received on or before January 24, 2011, 
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-2009-0130. All documents in the 
docket are listed in the docket index available at http://
www.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: Lisa Austin, Registration Division 
(7505P), Office of Pesticide Programs, Environmental Protection Agency, 
1200 Pennsylvania Ave., NW., Washington, DC 20460-0001; telephone 
number: (703) 305-7894; e-mail address: austin.lisa@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. 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 get electronic access to other related information?

    You may access a frequently updated electronic version of 40 CFR 
part 180 through the Government Printing Office's e-CFR site at http://
www.gpoaccess.gov/ecfr. To access the harmonized test guidelines 
referenced in this document electronically, please go to http://
www.epa.gov/ocspp and select ``Test Methods and Guidelines.''

C. How can I file an objection or hearing request?

    Under FFDCA section 408(g), 21 U.S.C. 346a, 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-2009-0130 in the subject line on the first 
page of your submission. All objections and requests for a hearing must 
be in writing, and must be received by the Hearing Clerk on or before 
January 24, 2011. Addresses for mail and hand delivery of objections 
and hearing requests are provided in 40 CFR 178.25(b).
    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. Information not marked confidential pursuant to 40 CFR part 2 
may be disclosed publicly by EPA without prior notice. Submit a copy of 
your non-CBI objection or hearing request, identified by docket ID 
number EPA-HQ-OPP-2009-0130, 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 Facility'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 Exemption

    In the Federal Register of March 24, 2010 (75 FR 14156) (FRL-8815-
6), EPA issued a notice pursuant to section 408 of FFDCA, 21 U.S.C. 
346a, announcing the filing of a pesticide petition (PP 
0E7683) by The Joint Inerts Task Force (JITF), Cluster Support 
Team Number 15 (CST 15) EPA Company No. 84947, c/o CropLife America, 
1156 15th St., Suite 400, Washington, DC 20005. The petition requested 
that 40 CFR 180.910 and 40 CFR 180.930 be amended by establishing an 
exemption from the requirement of a tolerance for residues of NTHE 
(102-60-3) when used as an inert ingredient stabilizer for formulation 
in pesticide formulations applied to pre- and post-harvest uses and 
application to animals at a maximum concentration of 20% by weight in 
pesticide formulations. That notice referenced a summary of the 
petition prepared by the Joint Inerts Task Force (JITF), Cluster 
Support Team Number 15 (CST 15) EPA Company No. 84947, the petitioner, 
which is available in the docket, http://www.regulations.gov. The 
Agency received one comment in response to the notice of filing. The 
comment was received from a private citizen who opposed the 
authorization to sell any pesticide that leaves a residue on food. The 
Agency understands the commenter's concerns and recognizes that some 
individuals believe that no residue of pesticides should be allowed. 
However, under the existing legal framework provided by section 408 of 
the Federal Food, Drug and Cosmetic Act (FFDCA) EPA is authorized to 
establish pesticide tolerances or exemptions where persons seeking such 
tolerances or exemptions have demonstrated that the pesticide meets the 
safety standard imposed by the statute.

III. Inert Ingredient Definition

    Inert ingredients are all ingredients that are not active 
ingredients as defined in 40 CFR 153.125 and include, but are not 
limited to, the following types of ingredients (except when they have a 
pesticidal efficacy of their own): Solvents such as alcohols and 
hydrocarbons; surfactants such as polyoxyethylene polymers and fatty

[[Page 71552]]

acids; carriers such as clay and diatomaceous earth; thickeners such as 
carrageenan and modified cellulose; wetting, spreading, and dispersing 
agents; propellants in aerosol dispensers; microencapsulating agents; 
and emulsifiers. The term ``inert'' is not intended to imply 
nontoxicity; the ingredient may or may not be chemically active. 
Generally, EPA has exempted inert ingredients from the requirement of a 
tolerance based on the low toxicity of the individual inert 
ingredients.

IV. Aggregate Risk Assessment and Determination of Safety

    Section 408(c)(2)(A)(i) of FFDCA allows EPA to establish an 
exemption from the requirement for 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 * * *.''
    EPA establishes exemptions from the requirement of a tolerance only 
in those cases where it can be clearly demonstrated that the risks from 
aggregate exposure to pesticide chemical residues under reasonably 
foreseeable circumstances will pose no appreciable risks to human 
health. In order to determine the risks from aggregate exposure to 
pesticide inert ingredients, the Agency considers the toxicity of the 
inert in conjunction with possible exposure to residues of the inert 
ingredient through food, drinking water, and through other exposures 
that occur as a result of pesticide use in residential settings. If EPA 
is able to determine that a finite tolerance is not necessary to ensure 
that there is a reasonable certainty that no harm will result from 
aggregate exposure to the inert ingredient, an exemption from the 
requirement of a tolerance may be established.
    Consistent with section 408(c)(2)(A) of FFDCA, and the factors 
specified in FFDCA section 408(c)(2)(B), 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 NTHE including exposure 
resulting from the exemption established by this action. EPA's 
assessment of exposures and risks associated with NTHE follows.

A. Toxicological Profile

    EPA has evaluated the available toxicity data and considered their 
validity, completeness, and reliability as well as the relationship of 
the results of the studies to human risk. EPA has also considered 
available information 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 NTHE as well as the no-observed-
adverse-effect-level (NOAEL) and the lowest-observed-adverse-effect-
level (LOAEL) from the toxicity studies are discussed in this unit.
    The existing toxicology database for NTHE consists of one OPPTS 
Harmonized Guideline 870.3650 (combined repeated dose toxicity study 
with the reproduction/developmental screening study in rats), a 90-day 
toxicity study in rats, and several studies in the scientific 
literature on acute oral toxicity and mutagenicity.
    The available toxicity data indicates that NTHE has low acute oral 
toxicity. NTHE was not mutagenic in an Ames test. In the OPPTS 
Harmonized Guideline 870.3650 rat reproductive/developmental toxicity 
screening study, there was no evidence of increased susceptibility. 
Parental toxicity manifested as microscopic brain lesions at 1000 mg/
kg/day (the highest dose tested). No developmental or reproductive 
effects were observed at doses of 100, 300, and 1000 mg/kg/day. There 
is no evidence of increased susceptibility to the offspring of rats 
following prenatal and post-natal exposure in the OPPTS Harmonized 
Guideline 870.3650 study. There were no offspring effects at any dose 
level up to the limit dose (1000 mg/kg/day).
    In addition, in a 90-day dietary study in rats (1956), where the 
NOAEL was set at 600-900 mg/kg/day (1% in diet), based on body-weight 
gain effects at 3% and 5% in the diet and a slightly greater incidence 
of borderline abnormalities of the liver of questionable significance, 
there are no other repeat dose toxicity data available. The NOAEL from 
the OPPTS Harmonized Guideline 870.3650 study (300 mg/kg/day) is 
protective of any potential liver toxicity.
    However, there is suggestive evidence of adverse neurotoxic effects 
in the adult animal in the OPPTS Harmonized Guideline 870.3650 study at 
the limit dose of 1000 mg/kg/day. These effects manifested as different 
sized vacuoles in the choroid plexus epithelial cells (some were 
signet-ring shaped) of the lateral ventricles of the brain in all high-
dose parental male and female rats. None of the low- or mid-dose or 
control animals showed a similar change.
    Pharmacokinetics in rats indicates that, following oral dosing, 
NTHE is poorly absorbed and rapidly excreted in the urine, mainly 
unchanged (92%-96%). None of the hypothetical metabolites, such as 
keto- or N-dealkylated derivatives, were observed. The calculated 
bioavailability factor (F = 0.018) revealed that less than 2% of the 
orally administered dose of NTHE is absorbed through the stomach and 
intestine. The half-life for elimination is 82 minutes (in non-diabetic 
rats) as a first order process.
    There are no chronic toxicity studies available for NTHE. The 
Agency used a qualitative structure activity relationship (SAR) 
database, DEREK 11, to determine if there were structural alerts 
suggestive of carcinogenicity. No structural alerts were identified. In 
addition, there was little concern about any of the postulated 
metabolites having greater toxicity than the parent compounds.
    Specific information on the studies received and the nature of the 
adverse effects caused by NTHE, as well as, the NOAEL and the lowest-
observed adverse-effect-level (LOAEL) from the toxicity studies can be 
found at http://www.regulations.gov in document ``N,N,N',N'',-Tetrakis-
(2-Hydroxypropyl) Ethylenediamine (NTHE--JITF CST 15 Inert Ingredient). 
Human Health Risk Assessment to Support Proposed Exemption from the 
Requirement of a Tolerance When Used as an Inert Ingredient in 
Pesticide Formulations'' at pp. 7-11 and 31-34 in docket ID number EPA-
HQ-OPP-2009-0130.

B. Toxicological Points of Departure/Levels of Concern

    Once a pesticide's toxicological profile is determined, EPA 
identifies toxicological points of departure (POD) and levels of 
concern to use in evaluating the risk posed by human exposure to the 
pesticide. For hazards that have a threshold below which there is no 
appreciable risk, the toxicological POD is used as the basis for 
derivation of reference values for risk assessment. PODs are developed 
based on a careful

[[Page 71553]]

analysis of the doses in each toxicological study to determine the dose 
at which no adverse effects are observed (the NOAEL) and the lowest 
dose at which adverse effects of concern are identified (the LOAEL). 
Uncertainty/safety factors are used in conjunction with the POD to 
calculate a safe exposure level--generally referred to as a population-
adjusted dose (PAD) or a reference dose (RfD)--and a safe margin of 
exposure (MOE). For non-threshold risks, the Agency assumes that any 
amount of exposure will lead to some degree of risk. Thus, the Agency 
estimates risk in terms of the probability of an occurrence of the 
adverse effect expected in a lifetime. 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/
pesticides/factsheets/riskassess.htm.
    A summary of the toxicological endpoints for NTHE used for human 
risk assessment is discussed in Unit IV.B. of the final rule published 
in the Federal Register of July 29, 2009 (74 FR 37568) (FRL-8429-3).

C. Exposure Assessment

    1. Dietary exposure from food and feed uses. In evaluating dietary 
exposure to NTHE, EPA considered exposure under the proposed exemption 
from the requirement of a tolerance. EPA assessed dietary exposures 
from NTHE in food as follows:
    i. Acute exposure. No adverse effects attributable to a single 
exposure of NTHE was seen in the toxicity databases; therefore, an 
acute exposure assessment for NTHE is not necessary.
    ii. Chronic exposure. In conducting the chronic dietary exposure 
assessment, EPA used food consumption information from the United 
States Department of Agriculture (USDA) 1994-1996 and 1998 Nationwide 
Continuing Surveys of Food Intake by Individuals (CSFII). As to residue 
levels in food, no residue data were submitted for NTHE. In the absence 
of specific residue data, EPA has developed an approach which uses 
surrogate information to derive upper bound exposure estimates for the 
subject inert ingredient. Upper bound exposure estimates are based on 
the highest tolerance for a given commodity from a list of high-use 
insecticides, herbicides, and fungicides. A complete description of the 
general approach taken to assess inert ingredient risks in the absence 
of residue data is contained in the memorandum entitled ``Alkyl Amines 
Polyalkoxylates (Cluster 4): Acute and Chronic Aggregate (Food and 
Drinking Water) Dietary Exposure and Risk Assessments for the Inerts'' 
(D361707, S. Piper, 2/25/09) and can be found at http://
www.regulations.gov in docket ID number EPA-HQ-OPP-2008-0738.
    In the dietary exposure assessment, the Agency assumed that the 
residue level of the inert ingredient would be no higher than the 
highest tolerance for a given commodity. Implicit in this assumption is 
that there would be similar rates of degradation (if any) between the 
active and inert ingredient and that the concentration of inert 
ingredient in the scenarios leading to these highest of tolerances 
would be no higher than the concentration of the active ingredient.
    The Agency believes the assumptions used to estimate dietary 
exposures lead to an extremely conservative assessment of dietary risk 
due to a series of compounded conservatisms. First, assuming that the 
level of residue for an inert ingredient is equal to the level of 
residue for the active ingredient will overstate exposure. The 
concentrations of active ingredient in agricultural products are 
generally at least 50% of the product and often can be much higher. 
Further, pesticide products rarely have a single inert ingredient; 
rather there is generally a combination of different inert ingredients 
used which additionally reduces the concentration of any single inert 
ingredient in the pesticide product in relation to that of the active 
ingredient. In the case of NTHE, EPA made a specific adjustment to the 
dietary exposure assessment to account for the use limitations of the 
amount of NTHE that may be in formulations (no more than 20% by weight 
in pesticide formulations) and assumed that NTHE is present at the 
maximum limitation rather than at equal quantities with the active 
ingredient. This remains a very conservative assumption because 
surfactants are generally used at levels far below this percentage.
    Second, the conservatism of this methodology is compounded by EPA's 
decision to assume that, for each commodity, the active ingredient 
which will serve as a guide to the potential level of inert ingredient 
residues is the active ingredient with the highest tolerance level. 
This assumption overstates residue values because it would be highly 
unlikely, given the high number of inert ingredients, that a single 
inert ingredient or class of ingredients would be present at the level 
of the active ingredient in the highest tolerance for every commodity. 
Finally, a third compounding conservatism is EPA's assumption that all 
foods contain the inert ingredient at the highest tolerance level. In 
other words, EPA assumed 100% of all foods are treated with the inert 
ingredient at the rate and manner necessary to produce the highest 
residue legally possible for an active ingredient. In summary, EPA 
chose a very conservative method for estimating what level of inert 
residue could be on food, then used this methodology to choose the 
highest possible residue that could be found on food and assumed that 
all food contained this residue. No consideration was given to 
potential degradation between harvest and consumption even though 
monitoring data shows that tolerance level residues are typically one 
to two orders of magnitude higher than actual residues in food when 
distributed in commerce.
    Accordingly, although sufficient information to quantify actual 
residue levels in food is not available, the compounding of these 
conservative assumptions will lead to a significant exaggeration of 
actual exposures. EPA does not believe that this approach 
underestimates exposure in the absence of residue data.
    iii. Cancer. The Agency used a qualitative SAR database, DEREK11, 
to determine if there were structural alerts suggestive of 
carcinogenicity. No structural alerts for carcinogenicity were 
identified. NTHE is not expected to be carcinogenic. Therefore a cancer 
dietary exposure assessment is not necessary to assess cancer risk.
    iv. Anticipated residue and percent crop treated (PCT) information. 
EPA did not use anticipated residue and/or PCT information in the 
dietary assessment for NTHE. Tolerance level residues and/or 100 PCT 
were assumed for all food commodities.
    2. Dietary exposure from drinking water. For the purpose of the 
screening level dietary risk assessment to support this request for an 
exemption from the requirement of a tolerance for NTHE, a conservative 
drinking water concentration value of 100 ppb based on screening level 
modeling was used to assess the contribution to drinking water for the 
chronic dietary risk assessments for parent compound. These values were 
directly entered into the dietary exposure model.
    3. From non-dietary exposure. The term ``residential exposure'' is 
used in this document to refer to non-occupational, non-dietary 
exposure (e.g., textiles (clothing and diapers), carpets, swimming 
pools, and hard surface disinfection on walls, floors, tables).
    A screening level residential exposure and risk assessment was 
completed for

[[Page 71554]]

products containing NTHE as an inert ingredient. In this assessment, 
representative scenarios, based on end-use product application methods 
and labeled application rates, were selected. The Agency did not 
identify any products intended for use on pets or home cleaning 
products that contain NTHE. For each of the use scenarios, the Agency 
assessed residential handler (applicator) inhalation exposure for 
outdoor scenarios with high exposure potential (i.e., exposure 
scenarios with high end unit exposure values) to serve as a screening 
assessment for all potential residential pesticides containing. 
Similarly, residential post application oral exposure assessments were 
also performed utilizing high end outdoor exposure scenarios. Further 
details of this residential exposure and risk analysis can be found at 
http://www.regulations.gov in the memorandum entitled ``JITF Inert 
Ingredients. Residential and Occupational Exposure Assessment 
Algorithms and Assumptions Appendix for the Human Health Risk 
Assessments to Support Proposed Exemption from the Requirement of a 
Tolerance When Used as Inert Ingredients in Pesticide Formulations'' 
(D364751, 5/7/09, Lloyd/LaMay) in docket ID number EPA-HQ-OPP-2008-
0710.
    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.''
    EPA has not found NTHE to share a common mechanism of toxicity with 
any other substances, and NTHE does not appear to produce a toxic 
metabolite produced by other substances. For the purposes of this 
tolerance action, therefore, EPA has assumed that NTHE does not have a 
common mechanism of toxicity with other substances. 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 EPA's Web site at http://www.epa.gov/pesticides/
cumulative.

D. Safety Factor for Infants and Children

    1. In general. Section 408(b)(2)(C) of FFDCA provides that EPA 
shall apply an additional tenfold (10X) 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 (SF). In applying this provision, EPA either retains the default 
value of 10X, or uses a different additional safety factor when 
reliable data available to EPA support the choice of a different 
factor.
    2. Prenatal and postnatal sensitivity. The existing toxicology 
database for NTHE consists of one OPPTS Harmonized Guideline 870.3650 
combined repeated dose toxicity study with the reproduction/
developmental screening study in rats, and several studies in the 
scientific literature on acute oral toxicity and mutagenicity.
    In the case of NTHE, there was no increased susceptibility to the 
offspring of rats following pre- and post-natal (PND 0-4) exposure in 
the OPPTS Harmonized Guideline 870.3650 study (gavage dosing of males 
for 28 days, females for 46 days). There were no offspring effects at 
any dose level up to the limit dose (1,000 mg/kg/day) where maternal/
paternal toxicity was manifested as microscopic lesions in the brain at 
1,000 mg/kg/day. Although the parental NOAEL selected as the point of 
departure for the chronic dietary, incidental oral, and inhalation risk 
assessments is protective of the adult animal, the particular findings 
in the parental animals lead to uncertainties for the offspring. There 
is a concern for neurodevelopment since this is not addressed in the 
OPPTS Harmonized Guideline 870.3650 screening study.
    3. Conclusion. Despite the fact that no quantitative or qualitative 
increased susceptibility to offspring was seen in the OPPTS Harmonized 
Guideline 870.3650 combined repeated dose toxicity study and the 
conservative exposure assessment, EPA has determined that the FQPA SF 
cannot be reduced because of the neurotoxic effects seen in the OPPTS 
Harmonized Guideline 870.3650 reproductive/developmental study and the 
absence of standard neurotoxicity and developmental studies. EPA 
considered the following factors in determining that a 10X FQPA SF 
should be retained:

    In the OPPTS Harmonized Guideline 870.3650 study in rats there 
is some evidence of neurotoxicity in the adult animals in the OPPTS 
Harmonized Guideline 870.3650 reproductive/developmental study, 
which occurred only at the highest dose tested of 1,000 mg/kg/day. 
The vacuoles in the choroid plexus epithelial cells of the lateral 
ventricles of the brain were of different size, and some of the 
epithelial cells were signet-ring shaped. None of the other dose 
groups (100 and 300 mg/kg/day) showed a similar change. These 
results indicate a potential concern for effects on neurodevelopment 
at high doses following repeat exposure. Given that neither 
neurotoxicity nor standard developmental toxicity studies are 
available on NTHE, retention of the FQPA Safety Factor is 
appropriate.

E. Aggregate Risks and Determination of Safety

    Determination of safety section. EPA determines whether acute and 
chronic dietary pesticide exposures are safe by comparing aggregate 
exposure estimates to the acute PAD (aPAD) and chronic PAD (cPAD). For 
linear cancer risks, EPA calculates the lifetime probability of 
acquiring cancer given the estimated aggregate exposure. Short-, 
intermediate-, and chronic-term risks are evaluated by comparing the 
estimated aggregate food, water, and residential exposure to the 
appropriate PODs to ensure that an adequate MOE exists.
    1. Acute risk. An acute aggregate risk assessment takes into 
account acute exposure estimates from dietary consumption of food and 
drinking water. No adverse effect resulting from a single oral exposure 
was identified and no acute dietary endpoint was selected. Therefore, 
NTHE is not expected to pose an acute risk.
    2. Chronic risk. Using the exposure assumptions described in this 
unit for chronic exposure, EPA has concluded that chronic exposure to 
NTHE from food and water will utilize 84% of the cPAD for children 1-2 
years old, the population group receiving the greatest exposure. Based 
on the explanation in this unit, regarding residential use patterns, 
chronic residential exposure to residues of NTHE is not expected.
    3. Short-term risk. Short-term aggregate exposure takes into 
account short-term residential exposure plus chronic exposure to food 
and water (considered to be a background exposure level).
    NTHE is currently used as an inert ingredient in pesticide products 
that are registered for uses that could result in short-term 
residential exposure, and the Agency has determined that it is 
appropriate to aggregate chronic exposure through food and water with 
short-term residential exposures to NTHE.
    Using the exposure assumptions described in this unit for short-
term exposures, EPA has concluded the combined short-term food, water, 
and residential exposures result in aggregate MOEs of 4,800 and 5,000 
for adult males and females, respectively. Adult

[[Page 71555]]

residential exposure includes high-end inhalation handler exposure from 
outdoor uses. EPA has concluded the combined short-term aggregated 
food, water, and residential exposures result in an aggregate MOE of 
1,100 for children. Children's residential exposure includes incidental 
oral exposure from treated turf. Because EPA's level of concern for 
NTHE is a MOE of 1,000 or below, these MOEs are not of concern.
    4. Intermediate-term risk. Intermediate-term aggregate exposure 
takes into account intermediate-term residential exposure plus chronic 
exposure to food and water (considered to be a background exposure 
level).
    NTHE is currently used as an inert ingredient in pesticide products 
that are registered for uses that could result in intermediate-term 
residential exposure, and the Agency has determined that it is 
appropriate to aggregate chronic exposure through food and water with 
intermediate-term residential exposures to NTHE.
    Using the exposure assumptions described in this unit for 
intermediate-term exposures, EPA has concluded that the combined 
intermediate-term food, water, and residential exposures result in 
aggregate MOEs of 4,800 and 5,100, for adult males and females, 
respectively. EPA has concluded the combined intermediate-term 
aggregated food, water, and residential exposures result in an 
aggregate MOE of 1,200 for children. Children's residential exposure 
includes incidental oral exposure from treated turf. Because EPA's 
level of concern for NTHE is a MOE of 1,000 or below, these MOEs are 
not of concern.
    5. Aggregate cancer risk for U.S. population. The Agency has not 
identified any concerns for carcinogenicity relating to NTHE.
    6. 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 NTHE residues.

V. Other Considerations

A. Analytical Enforcement Methodology

    EPA is establishing a limitation on the amount of NTHE that may be 
used in pesticide formulations applied to growing crops and raw 
agricultural commodities. That limitation will be enforced through the 
pesticide registration process under the Federal Insecticide, 
Fungicide, and Rodenticide Act (``FIFRA''), 7 U.S.C. 136 et seq. EPA 
will not register any such pesticide for sale or distribution that 
contains greater than 20% of NTHE by weight in the pesticide 
formulation.

B. International Residue Limits

    In making its tolerance decisions, EPA seeks to harmonize U.S. 
tolerances with international standards whenever possible, consistent 
with U.S. food safety standards and agricultural practices. EPA 
considers the international maximum residue limits (MRLs) established 
by the Codex Alimentarius Commission (Codex), as required by FFDCA 
section 408(b)(4). The Codex Alimentarius is a joint U.N. Food and 
Agriculture Organization/World Health Organization food standards 
program, and it is recognized as an international food safety 
standards-setting organization in trade agreements to which the United 
States is a party. EPA may establish a tolerance that is different from 
a Codex MRL; however, FFDCA section 408(b)(4) requires that EPA explain 
the reasons for departing from the Codex level.
    The Codex has not established a MRL for NTHE.

VI. Conclusions

    Therefore, an exemption from the requirement of a tolerance is 
established under 40 CFR 180.910 and 40 CFR 180.930 for NTHE (102-60-3) 
when used as an inert ingredient (stabilizer for formulation) in 
pesticide formulations applied to pre- and post-harvest uses and 
application to animals at a maximum concentration of 20% by weight in 
pesticide formulations.

VII. 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 final rule has been 
exempted from review under Executive Order 12866, this final rule is 
not subject to Executive Order 13211, entitled 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 9, 2000) do not apply to this final rule. In addition, 
this final 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) (Pub. L. 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).

VIII. 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).

[[Page 71556]]

List of Subjects in 40 CFR Part 180

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

    Dated: November 16, 2010.
Lois Rossi,
Director, Registration Division, Office of Pesticide Programs.

0
Therefore, 40 CFR chapter I is amended as follows:

PART 180--[AMENDED]

0
1. The authority citation for part 180 continues to read as follows:

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

0
2. In Sec.  180.910, the table is amended by adding alphabetically the 
following inert ingredients to read as follows:

Sec.  180.910  Inert ingredients used pre-and post-harvest; exemptions 
from the requirement of a tolerance.

* * * * *

------------------------------------------------------------------------
       Inert ingredients                Limits                Uses
------------------------------------------------------------------------

                              * * * * * * *
N,N,N',N'',-tetrakis-(2-        Concentration in        Stabilizer for
 hydroxypropyl)                  formulated end-use      formulation.
 ethylenediamine (102-60-3).     products not to
                                 exceed 20% by weight
                                 in pesticide
                                 formulations.

                              * * * * * * *
------------------------------------------------------------------------

0
3. In Sec.  180.930, the table is amended by adding alphabetically the 
following inert ingredients to read as follows:

Sec.  180.930  Inert ingredients applied to animals; exemptions from 
the requirement of a tolerance.

* * * * *

------------------------------------------------------------------------
       Inert ingredients                Limits                Uses
------------------------------------------------------------------------

                              * * * * * * *
N,N,N',N'',-tetrakis-(2-        Concentration in        Stabilizer for
 hydroxypropyl)                  formulated end-use      formulation.
 ethylenediamine (102-60-3).     products not to
                                 exceed 20% by weight
                                 in pesticide
                                 formulations.

                              * * * * * * *
------------------------------------------------------------------------

[FR Doc. 2010-29647 Filed 11-23-10; 8:45 am]
BILLING CODE 6560-50-P