Document ID: EPA-HQ-OPP-2009-0130-0004
Agency: epa
Document Type: Rule
Title: N,N,N,N,-Tetrakis-(2-Hydroxypropyl) Ethylenediamine; Exemption from the Requirement of a Tolerance
Posted Date: 2009-07-29T04:00Z

[Federal Register: July 29, 2009 (Volume 74, Number 144)]
[Rules and Regulations]               
[Page 37564-37571]
From the Federal Register Online via GPO Access [wais.access.gpo.gov]
[DOCID:fr29jy09-12]                         

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ENVIRONMENTAL PROTECTION AGENCY

40 CFR Part 180

[EPA-HQ-OPP-2009-0130; FRL-8429-3]

 
N,N,N',N'',-Tetrakis-(2-Hydroxypropyl) Ethylenediamine; 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) when used as an inert ingredient for pre-harvest 
uses under 40 CFR 180.920 at a maximum of 20% by weight in pesticide 
formulations. The Joint Inerts Task Force (JITF), Cluster Support Team 
Number 15 (CST 15), submitted a petition to EPA under the Federal Food, 
Drug, and Cosmetic Act (FFDCA), requesting an exemption from the 
requirement of a tolerance. This regulation eliminates the need to 
establish a maximum permissible level for residues of NTHE.

DATES: This regulation is effective July 29, 2009. Objections and 
requests for hearings must be received on or before September 28, 2009, 
and must be filed in accordance with the instructions provided in 40 
CFR part 178 (see also Unit I.C. of the SUPPLEMENTARY INFORMATION).

ADDRESSES: 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: Kerry Leifer, Registration Division 
(7505P), Office of Pesticide Programs, Environmental Protection Agency, 
1200 Pennsylvania Ave., NW., Washington, DC 20460-0001; telephone 
number: (703) 308-8811; e-mail address: leifer.kerry@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).
     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 to 
provide a guide for readers regarding entities likely to be

[[Page 37565]]

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 electronically available documents 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 e-CFR cite 
at http://www.gpoaccess.gov/ecfr. To access the OPPTS Harmonized 
Guidelines referenced in this document, go directly to the guidelines 
at http://www.epa.gov/opptsfrs/home/guidelin.htm.

C. Can I File an Objection or Hearing Request?

    Under section 408(g) of FFDCA, 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 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 September 28, 2009.
    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-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. Background

    In the Federal Register of April 15, 2009 (74 FR 17487) (FRL-8409-
7), 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 
9E7531) by JITF, CST 15, c/o CropLife America, 1156 15\th\ St., NW., 
Suite 400, Washington, DC 20005. The petition requested that 40 CFR 
180.920 be amended by establishing exemptions from the requirement of a 
tolerance for residues of the inert ingredient NTHE. That notice 
referenced a summary of the petition prepared by JITF, CST 15, the 
petitioner, which is available to the public in the docket, http://
www.regulations.gov.
    The Agency received only one comment in response to the notice of 
filing. One 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 FFDCA section 
408, 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 that statute.
    Based upon review of the data supporting the petition, EPA has 
modified the exemption requested by limiting NTHE to a maximum of 20% 
by weight in pesticide formulations. This limitation is based on the 
Agency's risk assessment which 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 in 
docket ID number EPA-HQ-OPP-2009-0130.
    This petition was submitted in response to a final rule published 
in the Federal Register issue of August 9, 2006, (71 FR 45415) (FRL-
8084-1) in which the Agency revoked, under FFDCA section 408(e)(1), the 
existing exemptions from the requirement of a tolerance for residues of 
certain inert ingredients because of insufficient data to make the 
determination of safety required by FFDCA section 408(b)(2). The 
expiration date for the tolerance exemptions subject to revocation was 
August 9, 2008, which was later extended to August 9, 2009 by a final 
rule published in the Federal Register of August 4, 2008 (73 FR 45312) 
(FRL-8372-7) to allow for data to be submitted to support the 
establishment of tolerance exemptions for these inert ingredients prior 
to the effective date of the tolerance exemption revocation.

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 
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(b)(2)(A)(i) of FFDCA allows EPA to establish an 
exemption from the requirement of 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

[[Page 37566]]

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 performs a number of analyses to determine the risks from 
aggregate exposure to pesticide residues. First, EPA determines the 
toxicity of pesticides. Second, EPA examines exposure to the pesticide 
through food, drinking water, and through other exposures that occur as 
a result of pesticide use in residential settings.
    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 exemption 
from the requirement of a tolerance for residues of NTHE provided that 
the concentration of NTHE inerts is limited to no more than 20% by 
weight in pesticide formulations. EPA's assessment of exposures and 
risks associated with establishing tolerances 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 concerning the variability of the sensitivities 
of major identifiable subgroups of consumers, including infants and 
children.
     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 1,000 
milligrams/kilograms/day (mg/kg/day) (the highest dose tested). No 
developmental or reproductive effects were observed at doses of 100, 
300, and 1,000 mg/kg/day. There is no evidence of increased 
susceptibility to the offspring of rats following prenatal and 
postnatal exposure in the OPPTS Harmonized Guideline 870.3650 study. 
There were no offspring effects at any dose level up to the limit dose 
(1,000 mg/kg/day). In addition, in a 90-day dietary study in rats 
(1956), where the no-observed-adverse-effect-level (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 1,000 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 indicate 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 Endpoints

    For hazards that have a threshold below which there is no 
appreciable risk, a toxicological point of departure (POD) is 
identified as the basis for derivation of reference values for risk 
assessment. The POD may be defined as the highest dose at which no 
adverse effects are observed (the NOAEL) in the toxicology study 
identified as appropriate for use in risk assessment. However, if a 
NOAEL cannot be determined, the lowest dose at which adverse effects of 
concern are identified (the LOAEL) or a benchmark dose (BMD) approach 
is sometimes used for risk assessment. Uncertainty/safety factors (UFs) 
are used in conjunction with the POD 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 
dietary risks by comparing aggregate food and water 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 POD by all applicable UFs. Aggregate short-, intermediate-
, and chronic-term risks are evaluated by comparing food, water, and 
residential exposure to the POD to ensure that the margin of exposure 
(MOE) called for by the product of all applicable UFs is not exceeded. 
This latter value is referred to as the level of concern (LOC).
    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 
greater than that 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 
health risk assessment is shown in Table 1 of this unit.

[[Page 37567]]

         Table 1.--Summary of Toxicological Doses and Endpoints for Use in Human Health Risk Assessment
----------------------------------------------------------------------------------------------------------------
                                         POD and Uncertainty/    RfD, PAD, LOC for Risk  Study and Toxicological
          Exposure/Scenario                 Safety Factors             Assessment                Effects
----------------------------------------------------------------------------------------------------------------
Acute dietary                           No appropriate endpoint was identified for acute dietary assessment. The
(all populations)....................    brain lesions observed following repeat dosing at the limit dose would
                                                  not be expected to occur following a single exposure.
----------------------------------------------------------------------------------------------------------------
Chronic dietary                        NOAEL= 300 mg/kg/day     Chronic RfD = 3 mg/kg/   OPPTS Harmonized
(all populations)....................  UFA = 10X..............   day                      Guideline 870.3650
                                       UFH = 10X..............  cPAD = 3 mg/kg/day.....   reproduction/
                                       FQPA SF = 10X..........                            developmental screen
                                                                                          in rats
                                                                                         LOAEL = 1,000 mg/kg/
                                                                                          day, based on
                                                                                          microscopic lesions
                                                                                          (vacuoles in choroid
                                                                                          plexus epithelial
                                                                                          cells of the lateral
                                                                                          ventricles) of the
                                                                                          brain in all high-dose
                                                                                          animals (both sexes).
----------------------------------------------------------------------------------------------------------------
Short-Term (1-30 days) Incidental      NOAEL= 300 mg/kg/day     Residential LOC for MOE  OPPTS Harmonized
 Oral and Inhalation                   UFA = 10X..............   = 1,000                  Guideline 870.3650
                                       UFH = 10X..............                            reproduction/
                                       FQPA SF = 10X..........                            developmental screen
                                       Inhalation hazard                                  in rats
                                        assumed to be                                    LOAEL = 1,000 mg/kg/
                                        equivalent to oral                                day, based on
                                        hazard.                                           microscopic lesions
                                                                                          (vacuoles in choroid
                                                                                          plexus epithelial
                                                                                          cells of the lateral
                                                                                          ventricles) of the
                                                                                          brain in all high-dose
                                                                                          animals (both sexes).
----------------------------------------------------------------------------------------------------------------
Intermediate- and Long-Term (1-6       Oral NOAEL = 300 mg/kg/  Residential LOC for MOE  OPPTS Harmonized
 months and >6 months) Incidental       day                      = 1,000                  Guideline 870.3650
 Oral and Inhalation                   UFA = 10X..............                            reproduction/
                                       UFH = 10X..............                            developmental screen
                                       FQPA SF = 10X..........                            in rats
                                       Inhalation hazard                                 LOAEL = 1,000 mg/kg/
                                        assumed to be                                     day, based on
                                        equivalent to oral                                microscopic lesions
                                        hazard.                                           (vacuoles in choroid
                                                                                          plexus epithelial
                                                                                          cells of the lateral
                                                                                          ventricles) of the
                                                                                          brain in all high-dose
                                                                                          animals (both sexes).
--------------------------------------
                                                                                         (oral, dermal,
                                                                                          inhalation)

----------------------------------------------------------------------------------------------------------------
Point of departure (POD) = A data point or an estimated point that is derived from observed dose-response data
  and used to mark the beginning of extrapolation to determine risk associated with lower environmentally
  relevant human exposures. NOAEL = no-observed-adverse-effect-level. LOAEL = lowest-observed-adverse-effect-
  level. UF = uncertainty factor. UFA = extrapolation from animal to human (interspecies). UFH = potential
  variation in sensitivity among members of the human population (intraspecies). PAD = population adjusted dose
  (a=acute, c=chronic). FQPA SF = Food Quality Protection Act of 1996 Safety Factor. RfD = reference dose. MOE =
  margin of exposure. LOC = level of concern. SAR = structure activity relationship.

C. Exposure Assessment

    Limited information is available on the metabolism and 
environmental degradation of this compound. The Agency has considered 
the chemical structure, the submitted physicochemical data, as well as 
SAR information, to determine the residues of concern for this inert 
ingredient.
    A rat metabolism study showed little absorption, with most of the 
parent compound excreted unchanged in the urine. Although data on plant 
metabolism and environmental degradation are not available, any 
postulated metabolites as a result of de-alkylation are likely to be 
highly water soluble (like the parent) and are not likely to be more 
toxic than the parent compound. Therefore, a risk assessment based on 
the toxicity data for the parent compound is not likely to 
underestimate risk.
     Available data indicate that oral absorption of NTHE is low, and 
dermal absorption is expected to be very low. Low dermal absorption is 
expected based on its physicochemical properties. Therefore, it is 
concluded that quantification of dermal risk is not necessary for NTHE.
    1. Dietary exposure from food and feed uses. In evaluating dietary 
exposure to NTHE, EPA considered exposure under the petitioned-for 
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

[[Page 37568]]

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 is 
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. The Agency used screening 
level water exposure models in the dietary exposure analysis and risk 
assessment for NTHE in drinking water. These simulation models take 
into account data on the physical, chemical, and fate/transport 
characteristics of NTHE. Further information regarding EPA drinking 
water models used in the pesticide exposure assessment can be found at 
http://www.epa.gov/oppefed1/models/water/index.htm.
    A screening level drinking water analysis, based on the Pesticide 
Root Zone Model /Exposure Analysis Modeling System (PRZM/EXAMS) was 
performed to calculate the estimated drinking water concentrations 
(EDWCs) of NTHE. Modeling runs on four surrogate inert ingredients 
using a range of physical chemical properties that would bracket those 
of NTHE were conducted. Modeled acute drinking water values ranged from 
0.001 part per billion (ppb) to 41 ppb. Modeled chronic drinking water 
values ranged from 0.0002 ppb to 19 ppb. Further details of this 
drinking water analysis can be found at http://www.regulations.gov in 
the 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. 11-12 and 
36-38 in docket ID number EPA-HQ-OPP-2009-0130.
    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., for lawn and garden pest control, indoor pest control, 
termiticides, and flea and tick control on pets). NTHE may be used as 
inert ingredients in pesticide products that are registered for 
specific uses that may result in outdoor residential exposures.
    A screening level residential exposure and risk assessment was 
completed for 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

[[Page 37569]]

cumulative effects of a particular pesticide's residues and ``other 
substances that have a common mechanism of toxicity.''
    EPA has not found 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 website 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 SF. In 
applying this provision, EPA either retains the default value of 10X, 
or uses a different additional SF 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 postnatal (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 POD 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 reproduction/developmental 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. A 10X FQPA SF is retained for the following reason:
    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 SF is appropriate.

E. Aggregate Risks and Determination of Safety

    EPA determines whether acute and chronic pesticide exposures are 
safe by comparing aggregate exposure estimates to the aPAD and cPAD. 
The aPAD and cPAD represent the highest-safe exposures, taking into 
account all appropriate SFs. EPA calculates the aPAD and cPAD by 
dividing the POD by all applicable UFs. For linear cancer risks, EPA 
calculates the probability of additional cancer cases 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 POD to ensure that the MOE called for 
by the product of all applicable UFs is not exceeded.
    1. Acute risk.There was no hazard attributable to a single exposure 
seen in the toxicity database for NTHE. Therefore, NTHE is not expected 
to pose an acute risk.
    2. Chronic risk. A chronic aggregate risk assessment takes into 
account exposure estimates from chronic dietary consumption of food and 
drinking water. Using the exposure assumptions discussed in this unit 
for chronic exposure and the use limitations of not more than 20% by 
weight in pesticide formulations, the chronic dietary exposure from 
food and water to NTHE is 26% of the cPAD for the U.S. population and 
84% of the cPAD for children 1-2 years old, the most highly exposed 
population subgroup.
    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 used as an inert ingredient in pesticide products that are 
currently 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, EPA has concluded that the combined 
short-term aggregated food, water, and residential exposures result in 
aggregate MOEs of 4,800 and 5,000 for adult males and females, 
respectively. Adult 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. As the LOC is for 
MOEs that are lower than 1,000, 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 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, EPA has concluded that the 
combined intermediate-term aggregated 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. As the LOC is for MOEs that are lower than 
1,000, 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.

[[Page 37570]]

    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 residues of NTHE.

V. Other Considerations

A. Analytical Enforcement Methodology

     An analytical method is not required for enforcement purposes 
since the Agency is establishing an exemption from the requirement of a 
tolerance without any numerical limitation.

B. International Residue Limits

     The Agency is not aware of any country requiring a tolerance for 
NTHE nor have any CODEX Maximum Residue Levels been established for any 
food crops at this time.

VI. Conclusion

    Therefore, an exemption from the requirement of a tolerance is 
established for residues.of N,N,N',N'',-tetrakis-(2-hydroxypropyl) 
ethylenediamine when used as an inert ingredient for pre-harvest uses 
under 40 CFR 180.920 at a maximum of 20% by weight in pesticide 
formulations.

VII. Statutory and Executive Order Reviews

    This final rule establishes tolerances 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) (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).

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).

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 21, 2009.
G. Jeffrey Herndon,
Acting 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. 180.920, the table is amended by adding alphabetically the 
following inert ingredient to read as follows:

Sec.  180.920  Inert ingredients used pre-harvest; exemptions from the 
requirement of a tolerance.

* * * * *

------------------------------------------------------------------------
        Inert Ingredients               Limits               Uses
------------------------------------------------------------------------
                                * * * * *
N,N,N',N'',-tetrakis-(2-          Concentration in    Stabilizer for
 hydroxypropyl) ethylenediamine    formulated end-     formulation
 (CAS Reg. No. 102-60-3).          use products not
                                   to exceed 20% by
                                   weight in
                                   pesticide
                                   formulations.
                                * * * * *
------------------------------------------------------------------------

[[Page 37571]]

[FR Doc. E9-17945 Filed 7-28-09; 8:45 am]

BILLING CODE 6560-50-S