Alkyl(C8, 72747-72752 [2012-29106]
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Federal Register / Vol. 77, No. 235 / Thursday, December 6, 2012 / Rules and Regulations
additional flexibility for transmix
processors who produce locomotive and
marine diesel fuel, and allowed solvent
yellow 124 marker to transition out of
the distribution system. We stated in the
direct final rule that if EPA received
timely adverse comment or a hearing
request on the rule or any specific
portion of the rule, we would publish a
withdrawal of the rule or a specific
portion of the rule in the Federal
Register informing the public that the
rule or portions of the rule with adverse
comment will not take effect. We
subsequently received adverse comment
on the RFS heating oil amendments and
the diesel transmix amendments. We
did not receive adverse comment on the
yellow marker amendments to 40 CFR
80.510, 80.598, 80.610, or the RFS
requirement for RIN generation, as
amended in 40 CFR 80.1426. Therefore,
EPA is withdrawing the direct final rule
with respect to the RFS heating oil
amendments and the diesel sulfur
transmix amendments, but leaving in
place the direct final rule with respect
to 40 CFR 80.510, 80.598, 80.610, and
80.1426. Those regulatory amendments
will take effect on December 10, 2012.
EPA intends to address all comments
received on the RFS heating oil and
diesel transmix amendments in
subsequent final actions, which will be
based on the parallel proposed rule also
published on October 9, 2012 (77 FR
61313). As stated in the direct final rule
and the parallel proposed rule, we will
not institute a second comment period
on this action.
Dated: November 30, 2012.
Lisa P. Jackson,
Administrator.
Accordingly, the regulatory
amendments to 40 CFR 80.511, 80.513,
80.572, 80.597, 80.1401, 80.1450,
80.1451, 80.1453, 80.1454, and 80.1460
published on October 9, 2012 (77 FR
61281) are withdrawn. The regulatory
amendments to 40 CFR 80.510, 80.598,
80.610, and 80.1426 will take effect on
December 10, 2012.
[FR Doc. 2012–29512 Filed 12–5–12; 8:45 am]
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ENVIRONMENTAL PROTECTION
AGENCY
72747
(703) 305–7990; email address:
cutchin.william@epa.gov.
SUPPLEMENTARY INFORMATION:
40 CFR Part 180
I. General Information
[EPA–HQ–OPP–2012–0106; FRL–9369–2]
A. Does this action apply to me?
Alkyl(C8-C18)
dimethylamidopropylamines;
Exemption From the Requirement of a
Tolerance
You may be potentially affected by
this action if you are an agricultural
producer, food manufacturer, or
pesticide manufacturer. The following
list of North American Industrial
Classification System (NAICS) codes is
not intended to be exhaustive, but rather
provides a guide to help readers
determine whether this document
applies to them. Potentially affected
entities may include:
• Crop production (NAICS code 111).
• Animal production (NAICS code
112).
• Food manufacturing (NAICS code
311).
• Pesticide manufacturing (NAICS
code 32532).
Environmental Protection
Agency (EPA).
ACTION: Final rule.
AGENCY:
This regulation establishes an
exemption from the requirement of a
tolerance for residues of the N-alkyl(C8C18) dimethylamidopropylamines where
the alkyl group is linear and may be
saturated and/or unsaturated when used
as an inert ingredient at levels not to
exceed 20% in herbicide formulations
applied to growing crops. Dow
AgroSciences, LLC, 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
establish a maximum permissible level
for residues of the N-alkyl(C8-C18)
dimethylamidopropylamines.
SUMMARY:
This regulation is effective
December 6, 2012. Objections and
requests for hearings must be received
on or before February 4, 2013, 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: The docket for this action,
identified by docket identification (ID)
number EPA–HQ–OPP–2012–0106, is
available at https://www.regulations.gov
or at the Office of Pesticide Programs
Regulatory Public Docket (OPP Docket)
in the Environmental Protection Agency
Docket Center (EPA/DC), EPA West
Bldg., Rm. 3334, 1301 Constitution Ave.
NW., Washington, DC 20460–0001. The
Public Reading Room is open from 8:30
a.m. to 4:30 p.m., Monday through
Friday, excluding legal holidays. The
telephone number for the Public
Reading Room is (202) 566–1744, and
the telephone number for the OPP
Docket is (703) 305–5805. Please review
the visitor instructions and additional
information about the docket available
at https://www.epa.gov/dockets.
FOR FURTHER INFORMATION CONTACT:
William Cutchin, Registration Division
(7505P), Office of Pesticide Programs,
Environmental Protection Agency, 1200
Pennsylvania Ave. NW., Washington,
DC 20460–0001; telephone number:
DATES:
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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 https://
ecfr.gpoaccess.gov/cgi/t/text/textidx?&c=ecfr&tpl=/ecfrbrowse/Title40/
40tab_02.tpl.
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–2012–0106 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 February 4, 2013. 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 (excluding
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 the nonCBI copy of your objection or hearing
request, identified by docket ID number
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mstockstill on DSK4VPTVN1PROD with
EPA–HQ–OPP–2012–0106, by one of
the following methods:
• Federal eRulemaking Portal: https://
www.regulations.gov. Follow the online
instructions for submitting comments.
Do not submit electronically any
information you consider to be
Confidential Business Information (CBI)
or other information whose disclosure is
restricted by statute.
• Mail: OPP Docket, Environmental
Protection Agency Docket Center (EPA/
DC), (28221T), 1200 Pennsylvania Ave.
NW., Washington, DC 20460–0001.
• Hand Delivery: To make special
arrangements for hand delivery or
delivery of boxed information, please
follow the instructions at https://
www.epa.gov/dockets/contacts.htm.
Additional instructions on commenting
or visiting the docket, along with more
information about dockets generally, is
available at https://www.epa.gov/
dockets.
II. Petition for Exemption
In the Federal Register of May 2, 2012
(77 FR 25957) (FRL–9346–1), EPA
issued a notice pursuant to FFDCA
section 408, 21 U.S.C. 346a, announcing
the filing of a pesticide petition (PP
1E7949) by Dow AgroSciences, LLC,
9330 Zionsville Rd., Indianapolis, IN
46268. The petition requested that 40
CFR 180.920 be amended by
establishing an exemption from the
requirement of a tolerance for residues
of the N-alkyl(C8-C18)
dimethylamidopropylamines where the
alkyl group is linear and may be
saturated and/or unsaturated (9octadecenamide, N-[3(dimethylamino)propyl]-,(9Z)-, CAS
Reg. No. 109–28–4; dodecanamide, N[3-(dimethylamino)propyl], CAS Reg.
No. 3179–80–4; octadecanamide, N-[3(dimethylamino)propyl], CAS Reg. No.
7651–02–7; octanamide, N-[3(dimethylamino)propyl], CAS Reg. No.
22890–10–4; decanamide, N-[3(dimethylamino)propyl], CAS Reg. No.
22890–11–5; hexadecanamide, N-[3(dimethylamino)propyl], CAS Reg. No.
39669–97–1; tetradecanamide, N-[3(dimethylamino)propyl], CAS Reg. No.
45267–19–4; amides, coco, N-[3(dimethylamino)propyl], CAS Reg. No.
68140–01–2; N-[3(dimethylamino)propyl]-C12-C18(even
numbered)-alkylamide, CAS Reg. No.
1147459–12–8; amides, C8-C18 and C18unsatd., N-[3-(dimethylamino)propyl],
CAS Reg. No. 146987–98–6) when used
as an inert ingredient at levels not to
exceed 20% in herbicide formulations
applied to growing crops. That notice
referenced a summary of the petition
prepared by Dow AgroSciences, LLC,
the petitioner, which is available in the
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docket, https://www.regulations.gov.
There were no comments received in
response to the notice of filing.
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(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
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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 FFDCA section
408(c)(2)(A), 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 the N-alkyl(C8C18) dimethylamidopropylamines
including exposure resulting from the
exemption established by this action.
EPA’s assessment of exposures and risks
associated with of the N-alkyl(C8-C18)
dimethylamidopropylamines 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 the N-alkyl(C8-C18)
dimethylamidopropylamines as well as
the no-observed-adverse-effect-level
(NOAEL) and the lowest-observedadverse-effect-level (LOAEL) from the
toxicity studies are discussed in this
unit.
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
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
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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 https://
www.epa.gov/pesticides/factsheets/
riskassess.htm.
The toxicity database for the Nalkyl(C8-C18)
dimethylamidopropylamines includes
acute toxicity studies, in vitro
genotoxicity assays and a repeat dose
developmental/reproductive screening
test (OECD 422) toxicity study on a
representative N-alkyl(C8-C18)
dimethylamidopropylamine member,
Amides, coco, N-[3-(dimethylamino)
propyl]; CAS Reg. No. 68140–01–2 (also
referred to as CADPMA). The database
is augmented by analogue information
in the public domain and EPA’s High
Production Volume (HPV) program.
CAPDMA is included in subcategory 3
of Category I amides within the 2004
HPV submission for Fatty Nitrogen
Derived Amides class. CAPDMA has
moderate acute oral toxicity with an
LD50 of 300 milligrams/kilogram/body
weight (mg/kg/bw) or greater and is
corrosive to the skin and eye,
respectively. CAPDMA and its broader
class of HPV analogues are negative for
genotoxicity across a series of in vitro
assays. A combined repeated dose
toxicity and reproduction and
developmental toxicity screening test
was conducted in rats with CAPDMA
via oral gavage under OECD 422
guidelines. No treatment-related effects
were observed in the reproductive or
developmental parameters examined.
No systemic toxicity was observed in
this study. The NOAEL for repeat dose
toxicity was 15 mg/kg/bw based on
localized gastric irritation due to the
irritation and corrosive nature of the
material, typical of surfactants seen at
the LOAEL of 45 mg/kg/day. The
NOAEL for reproductive and mg/kg/day
developmental toxicity was the highest
dose tested (HDT), 45 mg/kg/day.
CAPDMA was negative for mutagenicity
in the Ames assay and in vitro
mammalian chromosome aberration
assay. No chronic studies are available
for the N-alkyl(C8-C18)
72749
dimethylamidopropylamines but
negative findings for genotoxicity and
no preneoplastic lesions were observed
in the OECD 422 study on CAPDMA
that would suggest no potential for
carcinogenicity for the N-alkyl(C8-C18)
dimethylamidopropylamines. The
Agency used a qualitative structure
activity relationship (SAR) database,
DEREK Version 11, to determine if there
were structural alerts suggestive of
carcinogenicity. No structural alerts
were identified for the N-alkyl(C8-C18)
dimethylamidopropylamines Neither
IARC nor other authoritative bodies
have classified the N-alkyl(C8-C18)
dimethylamidopropylamines as
carcinogens based on the SAR analysis,
negative findings in both the
mutagenicity and clastogenicity studies
along with the lack of evidence of
specific target organ toxicity. The
Agency concluded that these inert
ingredients are unlikely to pose a cancer
risk to humans. No evidence of
immunotoxicity or neurotoxicity was
observed in the available database.
A summary of the toxicological
endpoints for the N-alkyl(C8-C18)
dimethylamidopropylamines used for
human risk assessment is shown in the
Table of this unit.
TABLE—SUMMARY OF TOXICOLOGICAL DOSES AND ENDPOINTS FOR THE N-ALKYL(C8-C18) DIMETHYLAMIDOPROPYLAMINES
FOR USE IN HUMAN RISK ASSESSMENT
Point of departure
and uncertainty/
safety factors
RfD, PAD, LOC for
risk assessment
Study and toxicological effect
No POD identified ...
None ........................
No endpoint of concern following a single exposure was identified in the data base.
Chronic RfD = 0.15
mg/kg/day.
cPAD = 0.15 mg/kg/
day.
MRID 48621602 Oral (Gavage) Combined Repeat Dose Toxicity Study with Reproduction/Developmental Toxicity Screening Test in the Rat, NOAEL 15 mg/kg/day based on localized
gastric irritation seen at the LOAEL of 45 mg/kg/day.
All Inhalation Exposure Scenarios.
NOAEL = 15 mg/kg/
day.
UFA = 10x
UFH = 10x
FQPA SF = 1x
NOAEL = 15 mg/kg/
day.
UFA = 10x
UFH = 10x
FQPA SF = 1x
100% inhalation absorption is assumed.
MOE = 100 ..............
MRID 48621602 Oral (Gavage) Combined Repeat Dose Toxicity Study with Reproduction/Developmental Toxicity Screening Test in the Rat, NOAEL.
15 mg/kg/day based on localized gastric irritation seen at the
LOAEL as of 45 mk/kg/day.
Cancer (Oral, dermal, inhalation).
There is no evidence for carcinogenic concern for the N-alkyl(C8-C18) dimethylamidopropylamines.
Exposure/scenario
Acute dietary (General population including infants and
children and Females 13–50
years of age).
Chronic dietary (All populations)
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UFA = extrapolation from animal to human (interspecies). UFH = potential variation in sensitivity among members of the human population
(intraspecies). FQPA SF = Food Quality Protection Act Safety Factor. PAD = population adjusted dose (a = acute, c = chronic). RfD = reference
dose. MOE = margin of exposure. LOC = level of concern.
C. Exposure Assessment
1. Dietary exposure from food and
feed uses. In evaluating dietary
exposure to the N-alkyl(C8-C18)
dimethylamidopropylamines, EPA
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considered exposure under the
proposed exemption from the
requirement of a tolerance. EPA
assessed dietary exposures from the Nalkyl(C8-C18)
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dimethylamidopropylamines in food as
using the I–Dietary Exposure Evaluation
Model (I–DEEM). I–DEEM is a highly
conservative model that is based on the
assumption that the residue level of the
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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 between the active and
inert ingredient (if any) 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.
Model estimates were calculated for oral
exposure from the use of the N-alkyl(C8C18) dimethylamidopropylamines at a
maximum concentration of 20% in
herbicidal formulations for all crops
(every food eaten by a person each day
has tolerance-level residues; D361707,
S. Piper, 2/25/09).
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 the Nalkyl(C8-C18)
dimethylamidopropylamines 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 nonoccupational, non-dietary exposure
(e.g., textiles (clothing and diapers),
carpets, swimming pools, and hard
surface disinfection on walls, floors,
tables).
The N-alkyl(C8-C18)
dimethylamidopropylamines are not
currently used, and are not proposed for
use as inert ingredients in residential
pesticide products. For the general
population some exposure to the Nalkyl(C8-C18)
dimethylamidopropylamines could
occur via cosmetic use (at very low
concentrations) including hair care dye
kits. There is also potential for exposure
to these chemicals through the use of
personal soaps and shampoos.
Incidential oral exposure to N-alkyl(C8C18) dimethylamidopropylamines
resulting from cosmetic uses is not
expected. Therefore, a quantitative oral
risk assessment was not conducted.
Since reliable data are not available, a
quantitative dermal/inhalation exposure
assessment was not conducted. The
current dietary risk assessment is highly
conservative and protective of any uses
potential exposure via consumer
products because the exposed
population, children 1–2 years old
utilize only 53% of the cPAD leaving
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about 47% of the cPAD for exposure via
consumer products.
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 the N-alkyl(C8-C18)
dimethylamidopropylamines to share a
common mechanism of toxicity with
any other substances, and the Nalkyl(C8-C18)
dimethylamidopropylamines do not
appear to produce a toxic metabolite
produced by other substances. For the
purposes of this tolerance action,
therefore, EPA has assumed that the Nalkyl(C8-C18)
dimethylamidopropylamines do 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 https://
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.
No evidence of developmental or
reproductive toxicity was observed at
doses up to 45 mg/kg/day in the
Reproduction/Developmental Toxicity
Screening Test in Rats (OECD 422
study). The corrosive nature of these
chemicals precluded testing at higher
doses.
3. Conclusion. EPA has determined
that reliable data show the safety of
infants and children would be
adequately protected if the FQPA SF
were reduced to 1X. That decision is
based on the following findings:
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i. The toxicity database for the Nalkyl(C8-C18)
dimethylamidopropylamines is
adequate for FQPA assessment. The
available data included acute toxicity
studies, mutagenicity and the
Reproduction/Developmental Toxicity
Screening Test in rats (OECD 422). The
available OECD 422 study evaluated
reproductive parameters and
developmental toxicity parameters in
rats. In addition, it also evaluated
hematology, clinical chemistry, organ
weights and histopathological
parameters. No effects on these
parameters were observed at the HDT.
ii. No effects on Functional
Observation Battery and motor activity
parameters were observed in the
Reproduction/Developmental Toxicity
Screening Test in rats (OECD 422).
Since there is no indication that the Nalkyl(C8-C18)
dimethylamidopropylamines are
neurotoxic chemical and there is no
need for a developmental neurotoxicity
study or additional uncertainty factor to
account for neurotoxicity.
iii. There is no evidence that the Nalkyl(C8-C18)
dimethylamidopropylamines result in
increased susceptibility of infants and
children based on the results of the
Reproduction/Developmental Toxicity
Screening Test in rats, in in utero rats
or rabbits in the prenatal developmental
studies.
iv. There is no evidence of
immunotoxicity in the available
database. Therefore, there is no need for
the immunotoxicity study or additional
uncertainty factor.
v. Although the duration of exposure
was short in the OECD 422 study, there
is no need for an additional uncertainty
factor because the effects observed were
related to local irritation due to
corrosive nature of these chemicals.
Based on the lack of progression of
severity of effects with time along with
the considerable similarities of effects
across the species tested and the
observation that the vast majority of the
effects observed were related to local
irritation and corrosive effects, EPA has
previously concluded that an additional
uncertainty factor for extrapolation from
subchronic toxicity study to a chronic
exposure scenario would not be needed
for highly irritating substances. As a
result, the typical 100-fold uncertainty
factor is sufficiently protective since it
is not expected that humans’ response
to local irritation/corrosiveness effects
would be markedly different based on
duration of exposure.
vi. There are no residual uncertainties
identified in the exposure databases.
The dietary food exposure assessments
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were performed using the highly
conservative I–DEEM model. EPA also
made conservative (protective)
assumptions in the ground and surface
water modeling used to assess exposure
to the N-alkyl(C8-C18)
dimethylamidopropylamines in
drinking water and with regard to
potential residential exposures. These
assessments will not underestimate the
exposure and risks posed by the Nalkyl(C8-C18)
dimethylamidopropylamines.
E. Aggregate Risks and Determination of
Safety
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, the N-alkyl(C8-C18)
dimethylamidopropylamines are 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 N-alkyl(C8-C18)
dimethylamidopropylamines from food
and water will utilize 16.5% of the
cPAD for the general population, and
53% of the cPAD for children 1–2 years
old, the population group receiving the
greatest exposure. Based on the
explanation in Unit IV.C.3., regarding
residential use patterns, chronic
residential exposure to N-alkyl(C8-C18)
could occur via cosmetic use. While the
lack of reliable exposure data precluded
the ability to perform a quantitative risk
assessment for these uses, the highly
conservative nature of the chronic
dietary risk assessment would be
protective of any uses potential chronic
exposure via consumer uses.
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). A short-term adverse
effect was identified; however, the Nalkyl(C8-C18)
dimethylamidopropylamines are not
currently used as an inert ingredient in
pesticide products that are registered for
any use patterns that would result in
short-term residential exposure. Based
on the explanation in Unit IV.C.3.,
regarding residential use patterns, shortterm residential exposure to N-alkyl(C8C18) could occur via cosmetic use. While
the lack of reliable exposure data
precluded the ability to perform a
quantitative risk assessment for these
uses, the highly conservative nature of
the chronic dietary risk assessment
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would be protective of any uses
potential short-term residential
exposure via consumer uses, and EPA
has determined that there are no
concerns for short-term aggregate risk
for the N-alkyl(C8-C18)
dimethylamidopropylamines.
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). An
intermediate-term adverse effect was
identified; however, the N-alkyl(C8-C18)
dimethylamidopropylamines are not
currently used as an inert ingredient in
pesticide products that are registered for
any use patterns that would result in
intermediate-term residential exposure.
Based on the explanation in Unit
IV.C.3., regarding residential use
patterns, intermediate-term residential
exposure to N-alkyl(C8-C18) could occur
via cosmetic use. While the lack of
reliable exposure data precluded the
ability to perform a quantitative risk
assessment for these uses, the highly
conservative nature of the chronic
dietary risk assessment would be
protective of any intermediate-term
residential exposure via consumer uses
and EPA has determined that there are
no concerns for intermediate-term
aggregate risk for the N-alkyl(C8-C18)
dimethylamidopropylamines.
5. Aggregate cancer risk for U.S.
population. Based on the SAR analysis,
negative findings in both the
mutagenicity and clastogenicity studies
along with the lack of evidence of
specific target organ toxicity, the
Agency concluded that the N-alkyl(C8C18) dimethylamidopropylamines are
unlikely to pose a cancer risk to
humans.
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 the Nalkyl(C8-C18)
dimethylamidopropylamines residues.
V. Other Considerations
A. Analytical Enforcement Methodology
An analytical method is not required
for enforcement purposes since the
Agency is not establishing a numerical
tolerance for residues of the N-alkyl(C8C18) dimethylamidopropylamines in or
on any food commodities. EPA is
establishing a limitation on the amount
of the N-alkyl(C8-C18)
dimethylamidopropylamines that may
be used in pesticide formulations. That
limitation will be enforced through the
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72751
pesticide registration process under the
Federal Insecticide, Fungicide, and
Rodenticide Act (FIFRA), 7 U.S.C. 136
et seq. EPA will not register any
pesticide for sale or distribution that
contains greater than 20% of the Nalkyl(C8-C18)
dimethylamidopropylamines 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
United Nation 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 the N-alkyl(C8-C18)
dimethylamidopropylamines.
VI. Conclusions
Therefore, an exemption from the
requirement of a tolerance is established
under 40 CFR 180.920 for the Nalkyl(C8-C18)
dimethylamidopropylamines when used
as an inert ingredient in herbicide
formulations applied to growing crops
at levels not to exceed 20% of the
formulation.
VII. Statutory and Executive Order
Reviews
This final rule establishes a tolerance
under FFDCA section 408(d) 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
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Federal Register / Vol. 77, No. 235 / Thursday, December 6, 2012 / Rules and Regulations
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 FFDCA section 408(d), 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 FFDCA section 408(n)(4). 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) (2 U.S.C. 1501 et seq.).
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) (15 U.S.C. 272 note).
VIII. Congressional Review Act
Pursuant to the Congressional Review
Act (5 U.S.C. 801 et seq.), EPA will
submit a report containing this rule and
other required information to the U.S.
Senate, the U.S. House of
Representatives, and the Comptroller
General of the United States prior to
publication of the rule in the Federal
Register. This action 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: November 21, 2012.
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. In § 180.920, alphabetically add the
following inert ingredients to the table
to read as follows:
■
§ 180.920 Inert ingredients used preharvest; exemptions from the requirement
of a tolerance.
*
*
*
*
Inert ingredients
Limits
*
*
*
*
N-alkyl(C8-C18) dimethylamidopropylamines where the alkyl group is linear and may
be saturated and/or unsaturated (CAS Reg. Nos. 109–28–4, 3179–80–4, 7651–
02–7, 22890–10–4, 22890–11–5, 39669–97–1, 45267–19–4, 68140–01–2,
1147459–12–8, 146987–98–6).
*
*
Not to exceed 20% by
weight in herbicide formulations.
*
*
*
BILLING CODE 6560–50–P
DEPARTMENT OF HEALTH AND
HUMAN SERVICES
42 CFR Part 8
RIN 0930–AA14
Opioid Drugs in Maintenance and
Detoxification Treatment of Opiate
Addiction; Proposed Modification of
Dispensing Restrictions for
Buprenorphine and Buprenorphine
Combination as Used in Approved
Opioid Treatment Medications
Substance Abuse and Mental
Health Services Administration
(SAMHSA), Department of Health and
Human Services (HHS).
ACTION: Final rule.
AGENCY:
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*
This final rule amends the
federal opioid treatment program
regulations by modifying the dispensing
requirements for buprenorphine and
buprenorphine combination products
approved by the Food and Drug
Administration (FDA) for opioid
dependence and used in federally
certified and registered opioid treatment
programs. In particular, this rule would
allow opioid treatment programs more
flexibility in dispensing take-home
supplies of buprenorphine—removing
restrictions on the time a patient needs
to be in treatment in order to receive
take-home supplies—after the
assessment and documentation of a
patient’s responsibility and stability to
receive opioid addiction treatment
medication. Opioid treatment programs
that use these products in the treatment
of opioid dependence will continue to
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Uses
*
SUMMARY:
[FR Doc. 2012–29106 Filed 12–5–12; 8:45 am]
mstockstill on DSK4VPTVN1PROD with
*
Sfmt 4700
*
Surfactants, related adjuvants of surfactants.
*
*
adhere to all other federal treatment
standards established for methadone.
DATES: This rule is effective January 7,
2013.
FOR FURTHER INFORMATION CONTACT:
Nicholas Reuter, Center for Substance
Abuse Treatment (CSAT), Division of
Pharmacologic Therapies, SAMHSA, 1
Choke Cherry Road, Room 2–1063,
Rockville, MD 20857, (240) 276–2716,
email:
Nicholas.Reuter@samhsa.hhs.gov.
SUPPLEMENTARY INFORMATION:
I. Executive Summary
A. Purpose of the Regulatory Action
This final rule will modify the way
that the narcotic treatment medication
buprenorphine will be dispensed by
treatment programs to individuals who
are dependent on heroin or on certain
prescription pain relievers by reducing
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Agencies
[Federal Register Volume 77, Number 235 (Thursday, December 6, 2012)]
[Rules and Regulations]
[Pages 72747-72752]
From the Federal Register Online via the Government Printing Office [www.gpo.gov]
[FR Doc No: 2012-29106]
-----------------------------------------------------------------------
ENVIRONMENTAL PROTECTION AGENCY
40 CFR Part 180
[EPA-HQ-OPP-2012-0106; FRL-9369-2]
Alkyl(C8-C18) dimethylamidopropylamines;
Exemption From the Requirement of a Tolerance
AGENCY: Environmental Protection Agency (EPA).
ACTION: Final rule.
-----------------------------------------------------------------------
SUMMARY: This regulation establishes an exemption from the requirement
of a tolerance for residues of the N-alkyl(C8-
C18) dimethylamidopropylamines where the alkyl group is
linear and may be saturated and/or unsaturated when used as an inert
ingredient at levels not to exceed 20% in herbicide formulations
applied to growing crops. Dow AgroSciences, LLC, 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 establish a maximum
permissible level for residues of the N-alkyl(C8-
C18) dimethylamidopropylamines.
DATES: This regulation is effective December 6, 2012. Objections and
requests for hearings must be received on or before February 4, 2013,
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: The docket for this action, identified by docket
identification (ID) number EPA-HQ-OPP-2012-0106, is available at https://www.regulations.gov or at the Office of Pesticide Programs Regulatory
Public Docket (OPP Docket) in the Environmental Protection Agency
Docket Center (EPA/DC), EPA West Bldg., Rm. 3334, 1301 Constitution
Ave. NW., Washington, DC 20460-0001. The Public Reading Room is open
from 8:30 a.m. to 4:30 p.m., Monday through Friday, excluding legal
holidays. The telephone number for the Public Reading Room is (202)
566-1744, and the telephone number for the OPP Docket is (703) 305-
5805. Please review the visitor instructions and additional information
about the docket available at https://www.epa.gov/dockets.
FOR FURTHER INFORMATION CONTACT: William Cutchin, Registration Division
(7505P), Office of Pesticide Programs, Environmental Protection Agency,
1200 Pennsylvania Ave. NW., Washington, DC 20460-0001; telephone
number: (703) 305-7990; email address: cutchin.william@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.
The following list of North American Industrial Classification System
(NAICS) codes is not intended to be exhaustive, but rather provides a
guide to help readers determine whether this document applies to them.
Potentially affected entities may include:
Crop production (NAICS code 111).
Animal production (NAICS code 112).
Food manufacturing (NAICS code 311).
Pesticide manufacturing (NAICS code 32532).
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 https://ecfr.gpoaccess.gov/cgi/t/text/text-idx?&c=ecfr&tpl=/ecfrbrowse/Title40/40tab_02.tpl.
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-2012-0106 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
February 4, 2013. 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 (excluding 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 the non-CBI copy
of your objection or hearing request, identified by docket ID number
[[Page 72748]]
EPA-HQ-OPP-2012-0106, by one of the following methods:
Federal eRulemaking Portal: https://www.regulations.gov.
Follow the online instructions for submitting comments. Do not submit
electronically any information you consider to be Confidential Business
Information (CBI) or other information whose disclosure is restricted
by statute.
Mail: OPP Docket, Environmental Protection Agency Docket
Center (EPA/DC), (28221T), 1200 Pennsylvania Ave. NW., Washington, DC
20460-0001.
Hand Delivery: To make special arrangements for hand
delivery or delivery of boxed information, please follow the
instructions at https://www.epa.gov/dockets/contacts.htm. Additional
instructions on commenting or visiting the docket, along with more
information about dockets generally, is available at https://www.epa.gov/dockets.
II. Petition for Exemption
In the Federal Register of May 2, 2012 (77 FR 25957) (FRL-9346-1),
EPA issued a notice pursuant to FFDCA section 408, 21 U.S.C. 346a,
announcing the filing of a pesticide petition (PP 1E7949) by Dow
AgroSciences, LLC, 9330 Zionsville Rd., Indianapolis, IN 46268. The
petition requested that 40 CFR 180.920 be amended by establishing an
exemption from the requirement of a tolerance for residues of the N-
alkyl(C8-C18) dimethylamidopropylamines where the
alkyl group is linear and may be saturated and/or unsaturated (9-
octadecenamide, N-[3-(dimethylamino)propyl]-,(9Z)-, CAS Reg. No. 109-
28-4; dodecanamide, N-[3-(dimethylamino)propyl], CAS Reg. No. 3179-80-
4; octadecanamide, N-[3-(dimethylamino)propyl], CAS Reg. No. 7651-02-7;
octanamide, N-[3-(dimethylamino)propyl], CAS Reg. No. 22890-10-4;
decanamide, N-[3-(dimethylamino)propyl], CAS Reg. No. 22890-11-5;
hexadecanamide, N-[3-(dimethylamino)propyl], CAS Reg. No. 39669-97-1;
tetradecanamide, N-[3-(dimethylamino)propyl], CAS Reg. No. 45267-19-4;
amides, coco, N-[3-(dimethylamino)propyl], CAS Reg. No. 68140-01-2; N-
[3-(dimethylamino)propyl]-C12-C18(even numbered)-
alkylamide, CAS Reg. No. 1147459-12-8; amides, C8-
C18 and C18-unsatd., N-[3-(dimethylamino)propyl],
CAS Reg. No. 146987-98-6) when used as an inert ingredient at levels
not to exceed 20% in herbicide formulations applied to growing crops.
That notice referenced a summary of the petition prepared by Dow
AgroSciences, LLC, the petitioner, which is available in the docket,
https://www.regulations.gov. There were no comments received in response
to the notice of filing.
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(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 FFDCA section 408(c)(2)(A), 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 the N-alkyl(C8-
C18) dimethylamidopropylamines including exposure resulting
from the exemption established by this action. EPA's assessment of
exposures and risks associated with of the N-alkyl(C8-
C18) dimethylamidopropylamines 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 the N-alkyl(C8-
C18) dimethylamidopropylamines 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.
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 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
[[Page 72749]]
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 https://www.epa.gov/pesticides/factsheets/riskassess.htm.
The toxicity database for the N-alkyl(C8-C18)
dimethylamidopropylamines includes acute toxicity studies, in vitro
genotoxicity assays and a repeat dose developmental/reproductive
screening test (OECD 422) toxicity study on a representative N-
alkyl(C8-C18) dimethylamidopropylamine member,
Amides, coco, N-[3-(dimethylamino) propyl]; CAS Reg. No. 68140-01-2
(also referred to as CADPMA). The database is augmented by analogue
information in the public domain and EPA's High Production Volume (HPV)
program. CAPDMA is included in subcategory 3 of Category I amides
within the 2004 HPV submission for Fatty Nitrogen Derived Amides class.
CAPDMA has moderate acute oral toxicity with an LD50 of 300
milligrams/kilogram/body weight (mg/kg/bw) or greater and is corrosive
to the skin and eye, respectively. CAPDMA and its broader class of HPV
analogues are negative for genotoxicity across a series of in vitro
assays. A combined repeated dose toxicity and reproduction and
developmental toxicity screening test was conducted in rats with CAPDMA
via oral gavage under OECD 422 guidelines. No treatment-related effects
were observed in the reproductive or developmental parameters examined.
No systemic toxicity was observed in this study. The NOAEL for repeat
dose toxicity was 15 mg/kg/bw based on localized gastric irritation due
to the irritation and corrosive nature of the material, typical of
surfactants seen at the LOAEL of 45 mg/kg/day. The NOAEL for
reproductive and mg/kg/day developmental toxicity was the highest dose
tested (HDT), 45 mg/kg/day. CAPDMA was negative for mutagenicity in the
Ames assay and in vitro mammalian chromosome aberration assay. No
chronic studies are available for the N-alkyl(C8-
C18) dimethylamidopropylamines but negative findings for
genotoxicity and no preneoplastic lesions were observed in the OECD 422
study on CAPDMA that would suggest no potential for carcinogenicity for
the N-alkyl(C8-C18) dimethylamidopropylamines.
The Agency used a qualitative structure activity relationship (SAR)
database, DEREK Version 11, to determine if there were structural
alerts suggestive of carcinogenicity. No structural alerts were
identified for the N-alkyl(C8-C18)
dimethylamidopropylamines Neither IARC nor other authoritative bodies
have classified the N-alkyl(C8-C18)
dimethylamidopropylamines as carcinogens based on the SAR analysis,
negative findings in both the mutagenicity and clastogenicity studies
along with the lack of evidence of specific target organ toxicity. The
Agency concluded that these inert ingredients are unlikely to pose a
cancer risk to humans. No evidence of immunotoxicity or neurotoxicity
was observed in the available database.
A summary of the toxicological endpoints for the N-
alkyl(C8-C18) dimethylamidopropylamines used for
human risk assessment is shown in the Table of this unit.
Table--Summary of Toxicological Doses and Endpoints for the N-alkyl(C8-C18) dimethylamidopropylamines for Use in
Human Risk Assessment
----------------------------------------------------------------------------------------------------------------
Point of departure
Exposure/scenario and uncertainty/ RfD, PAD, LOC for Study and toxicological effect
safety factors risk assessment
----------------------------------------------------------------------------------------------------------------
Acute dietary (General population No POD identified... None............... No endpoint of concern following a
including infants and children single exposure was identified in
and Females 13-50 years of age). the data base.
Chronic dietary (All populations) NOAEL = 15 mg/kg/day Chronic RfD = 0.15 MRID 48621602 Oral (Gavage)
UFA = 10x........... mg/kg/day. Combined Repeat Dose Toxicity
UFH = 10x........... cPAD = 0.15 mg/kg/ Study with Reproduction/
FQPA SF = 1x........ day.. Developmental Toxicity Screening
Test in the Rat, NOAEL 15 mg/kg/
day based on localized gastric
irritation seen at the LOAEL of
45 mg/kg/day.
All Inhalation Exposure Scenarios NOAEL = 15 mg/kg/day MOE = 100.......... MRID 48621602 Oral (Gavage)
UFA = 10x........... Combined Repeat Dose Toxicity
UFH = 10x........... Study with Reproduction/
FQPA SF = 1x........ Developmental Toxicity Screening
100% inhalation Test in the Rat, NOAEL.
absorption is 15 mg/kg/day based on localized
assumed.. gastric irritation seen at the
LOAEL as of 45 mk/kg/day.
----------------------------------------------------------------------------------------------------------------
Cancer (Oral, dermal, inhalation) There is no evidence for carcinogenic concern for the N-alkyl(C8-C18)
dimethylamidopropylamines.
----------------------------------------------------------------------------------------------------------------
UFA = extrapolation from animal to human (interspecies). UFH = potential variation in sensitivity among members
of the human population (intraspecies). FQPA SF = Food Quality Protection Act Safety Factor. PAD = population
adjusted dose (a = acute, c = chronic). RfD = reference dose. MOE = margin of exposure. LOC = level of
concern.
C. Exposure Assessment
1. Dietary exposure from food and feed uses. In evaluating dietary
exposure to the N-alkyl(C8-C18)
dimethylamidopropylamines, EPA considered exposure under the proposed
exemption from the requirement of a tolerance. EPA assessed dietary
exposures from the N-alkyl(C8-C18)
dimethylamidopropylamines in food as using the I-Dietary Exposure
Evaluation Model (I-DEEM). I-DEEM is a highly conservative model that
is based on the assumption that the residue level of the
[[Page 72750]]
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 between the active and inert ingredient
(if any) 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. Model estimates were
calculated for oral exposure from the use of the N-alkyl(C8-
C18) dimethylamidopropylamines at a maximum concentration of
20% in herbicidal formulations for all crops (every food eaten by a
person each day has tolerance-level residues; D361707, S. Piper, 2/25/
09).
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 the N-
alkyl(C8-C18) dimethylamidopropylamines 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).
The N-alkyl(C8-C18) dimethylamidopropylamines
are not currently used, and are not proposed for use as inert
ingredients in residential pesticide products. For the general
population some exposure to the N-alkyl(C8-C18)
dimethylamidopropylamines could occur via cosmetic use (at very low
concentrations) including hair care dye kits. There is also potential
for exposure to these chemicals through the use of personal soaps and
shampoos. Incidential oral exposure to N-alkyl(C8-
C18) dimethylamidopropylamines resulting from cosmetic uses
is not expected. Therefore, a quantitative oral risk assessment was not
conducted. Since reliable data are not available, a quantitative
dermal/inhalation exposure assessment was not conducted. The current
dietary risk assessment is highly conservative and protective of any
uses potential exposure via consumer products because the exposed
population, children 1-2 years old utilize only 53% of the cPAD leaving
about 47% of the cPAD for exposure via consumer products.
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 the N-alkyl(C8-C18)
dimethylamidopropylamines to share a common mechanism of toxicity with
any other substances, and the N-alkyl(C8-C18)
dimethylamidopropylamines do not appear to produce a toxic metabolite
produced by other substances. For the purposes of this tolerance
action, therefore, EPA has assumed that the N-alkyl(C8-
C18) dimethylamidopropylamines do 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 https://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. No evidence of developmental
or reproductive toxicity was observed at doses up to 45 mg/kg/day in
the Reproduction/Developmental Toxicity Screening Test in Rats (OECD
422 study). The corrosive nature of these chemicals precluded testing
at higher doses.
3. Conclusion. EPA has determined that reliable data show the
safety of infants and children would be adequately protected if the
FQPA SF were reduced to 1X. That decision is based on the following
findings:
i. The toxicity database for the N-alkyl(C8-
C18) dimethylamidopropylamines is adequate for FQPA
assessment. The available data included acute toxicity studies,
mutagenicity and the Reproduction/Developmental Toxicity Screening Test
in rats (OECD 422). The available OECD 422 study evaluated reproductive
parameters and developmental toxicity parameters in rats. In addition,
it also evaluated hematology, clinical chemistry, organ weights and
histopathological parameters. No effects on these parameters were
observed at the HDT.
ii. No effects on Functional Observation Battery and motor activity
parameters were observed in the Reproduction/Developmental Toxicity
Screening Test in rats (OECD 422). Since there is no indication that
the N-alkyl(C8-C18) dimethylamidopropylamines are
neurotoxic chemical and there is no need for a developmental
neurotoxicity study or additional uncertainty factor to account for
neurotoxicity.
iii. There is no evidence that the N-alkyl(C8-
C18) dimethylamidopropylamines result in increased
susceptibility of infants and children based on the results of the
Reproduction/Developmental Toxicity Screening Test in rats, in in utero
rats or rabbits in the prenatal developmental studies.
iv. There is no evidence of immunotoxicity in the available
database. Therefore, there is no need for the immunotoxicity study or
additional uncertainty factor.
v. Although the duration of exposure was short in the OECD 422
study, there is no need for an additional uncertainty factor because
the effects observed were related to local irritation due to corrosive
nature of these chemicals. Based on the lack of progression of severity
of effects with time along with the considerable similarities of
effects across the species tested and the observation that the vast
majority of the effects observed were related to local irritation and
corrosive effects, EPA has previously concluded that an additional
uncertainty factor for extrapolation from subchronic toxicity study to
a chronic exposure scenario would not be needed for highly irritating
substances. As a result, the typical 100-fold uncertainty factor is
sufficiently protective since it is not expected that humans' response
to local irritation/corrosiveness effects would be markedly different
based on duration of exposure.
vi. There are no residual uncertainties identified in the exposure
databases. The dietary food exposure assessments
[[Page 72751]]
were performed using the highly conservative I-DEEM model. EPA also
made conservative (protective) assumptions in the ground and surface
water modeling used to assess exposure to the N-alkyl(C8-
C18) dimethylamidopropylamines in drinking water and with
regard to potential residential exposures. These assessments will not
underestimate the exposure and risks posed by the N-
alkyl(C8-C18) dimethylamidopropylamines.
E. Aggregate Risks and Determination of Safety
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,
the N-alkyl(C8-C18) dimethylamidopropylamines are
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
N-alkyl(C8-C18) dimethylamidopropylamines from
food and water will utilize 16.5% of the cPAD for the general
population, and 53% of the cPAD for children 1-2 years old, the
population group receiving the greatest exposure. Based on the
explanation in Unit IV.C.3., regarding residential use patterns,
chronic residential exposure to N-alkyl(C8-C18)
could occur via cosmetic use. While the lack of reliable exposure data
precluded the ability to perform a quantitative risk assessment for
these uses, the highly conservative nature of the chronic dietary risk
assessment would be protective of any uses potential chronic exposure
via consumer uses.
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). A short-term
adverse effect was identified; however, the N-alkyl(C8-
C18) dimethylamidopropylamines are not currently used as an
inert ingredient in pesticide products that are registered for any use
patterns that would result in short-term residential exposure. Based on
the explanation in Unit IV.C.3., regarding residential use patterns,
short-term residential exposure to N-alkyl(C8-
C18) could occur via cosmetic use. While the lack of
reliable exposure data precluded the ability to perform a quantitative
risk assessment for these uses, the highly conservative nature of the
chronic dietary risk assessment would be protective of any uses
potential short-term residential exposure via consumer uses, and EPA
has determined that there are no concerns for short-term aggregate risk
for the N-alkyl(C8-C18)
dimethylamidopropylamines.
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). An intermediate-term adverse effect was identified; however,
the N-alkyl(C8-C18) dimethylamidopropylamines are
not currently used as an inert ingredient in pesticide products that
are registered for any use patterns that would result in intermediate-
term residential exposure. Based on the explanation in Unit IV.C.3.,
regarding residential use patterns, intermediate-term residential
exposure to N-alkyl(C8-C18) could occur via
cosmetic use. While the lack of reliable exposure data precluded the
ability to perform a quantitative risk assessment for these uses, the
highly conservative nature of the chronic dietary risk assessment would
be protective of any intermediate-term residential exposure via
consumer uses and EPA has determined that there are no concerns for
intermediate-term aggregate risk for the N-alkyl(C8-
C18) dimethylamidopropylamines.
5. Aggregate cancer risk for U.S. population. Based on the SAR
analysis, negative findings in both the mutagenicity and clastogenicity
studies along with the lack of evidence of specific target organ
toxicity, the Agency concluded that the N-alkyl(C8-
C18) dimethylamidopropylamines are unlikely to pose a cancer
risk to humans.
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 the N-alkyl(C8-C18)
dimethylamidopropylamines residues.
V. Other Considerations
A. Analytical Enforcement Methodology
An analytical method is not required for enforcement purposes since
the Agency is not establishing a numerical tolerance for residues of
the N-alkyl(C8-C18) dimethylamidopropylamines in
or on any food commodities. EPA is establishing a limitation on the
amount of the N-alkyl(C8-C18)
dimethylamidopropylamines that may be used in pesticide formulations.
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 pesticide for
sale or distribution that contains greater than 20% of the N-
alkyl(C8-C18) dimethylamidopropylamines 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 United Nation 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 the N-alkyl(C8-
C18) dimethylamidopropylamines.
VI. Conclusions
Therefore, an exemption from the requirement of a tolerance is
established under 40 CFR 180.920 for the N-alkyl(C8-
C18) dimethylamidopropylamines when used as an inert
ingredient in herbicide formulations applied to growing crops at levels
not to exceed 20% of the formulation.
VII. Statutory and Executive Order Reviews
This final rule establishes a tolerance under FFDCA section 408(d)
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
[[Page 72752]]
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 FFDCA section 408(d), 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 FFDCA section 408(n)(4). 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) (2 U.S.C. 1501 et seq.).
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) (15 U.S.C. 272 note).
VIII. Congressional Review Act
Pursuant to the Congressional Review Act (5 U.S.C. 801 et seq.),
EPA will submit a report containing this rule and other required
information to the U.S. Senate, the U.S. House of Representatives, and
the Comptroller General of the United States prior to publication of
the rule in the Federal Register. This action 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: November 21, 2012.
Lois Rossi,
Director, Registration Division, Office of Pesticide Programs.
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, alphabetically add the following inert ingredients
to the table to read as follows:
Sec. 180.920 Inert ingredients used pre-harvest; exemptions from the
requirement of a tolerance.
* * * * *
------------------------------------------------------------------------
Inert ingredients Limits Uses
------------------------------------------------------------------------
* * * * * * *
N-alkyl(C8-C18) Not to exceed 20% Surfactants,
dimethylamidopropylamines where by weight in related
the alkyl group is linear and herbicide adjuvants of
may be saturated and/or formulations. surfactants.
unsaturated (CAS Reg. Nos. 109-
28-4, 3179-80-4, 7651-02-7,
22890-10-4, 22890-11-5, 39669-97-
1, 45267-19-4, 68140-01-2,
1147459-12-8, 146987-98-6).
* * * * * * *
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[FR Doc. 2012-29106 Filed 12-5-12; 8:45 am]
BILLING CODE 6560-50-P