Alkyl (C12-C16) Dimethyl Ammonio Acetate; Exemption From the Requirement of a Tolerance, 19261-19268 [2010-8298]
Download as PDF
Federal Register / Vol. 75, No. 71 / Wednesday, April 14, 2010 / Rules and Regulations
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:
Elizabeth Fertich, Registration Division
(7505P), Office of Pesticide Programs,
Environmental Protection Agency, 1200
Pennsylvania Ave., NW., Washington,
DC 20460–0001; telephone number:
(703) 347–8560; e-mail address:
fertich.elizabeth@epa.gov.
SUPPLEMENTARY INFORMATION:
[FR Doc. 2010–8526 Filed 4–13–10; 8:45 am]
BILLING CODE 6560–50–P
ENVIRONMENTAL PROTECTION
AGENCY
40 CFR Part 180
[EPA–HQ–OPP–2009–0479; FRL–8816–5]
Alkyl (C12-C16) Dimethyl Ammonio
Acetate; Exemption From the
Requirement of a Tolerance
AGENCY: Environmental Protection
Agency (EPA).
ACTION: Final rule.
I. General Information
This regulation establishes an
exemption from the requirement of a
tolerance for residues of Alkyl (C12-C16)
dimethyl ammonio acetate, herein
referred to in this document as ADAA,
when used as an inert ingredient
(surfactant) in pesticide formulations for
pre-harvest uses under 40 CFR 180.920
or applied to animals under 40 CFR
180.930 at a maxiumum concentration
of 20% in pesticide product
formulations. Technology Sciences
Group, Inc., on behalf of Rhodia, Inc.,
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 ADAA.
DATES: This regulation is effective April
14, 2010. Objections and requests for
hearings must be received on or before
June 14, 2010, and must be filed in
accordance with the instructions
provided in 40 CFR part 178 (see also
Unit I.C. of the SUPPLEMENTARY
INFORMATION).
SUMMARY:
EPA has established a
docket for this action under docket
identification (ID) number EPA–HQ–
OPP–2009–0479. All documents in the
docket are listed in the docket index
available at https://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
https://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
jlentini on DSKJ8SOYB1PROD with RULES
ADDRESSES:
VerDate Nov<24>2008
16:13 Apr 13, 2010
Jkt 220001
A. Does This Action Apply to Me?
You may be potentially affected by
this action if you are an agricultural
producer, food manufacturer, or
pesticide manufacturer. Potentially
affected entities may include, but are
not limited to:
• Crop production (NAICS code 111).
• Animal production (NAICS code
112).
• Food manufacturing (NAICS code
311).
• Pesticide manufacturing (NAICS
code 32532).
This listing is not intended to be
exhaustive, but rather provides a guide
for readers regarding entities likely to be
affected by this action. Other types of
entities not listed in this unit could also
be affected. The North American
Industrial Classification System
(NAICS) codes have been provided to
assist you and others in determining
whether this action might apply to
certain entities. If you have any
questions regarding the applicability of
this action to a particular entity, consult
the person listed under FOR FURTHER
INFORMATION CONTACT.
B. How Can I Get Electronic Access to
Other Related Information?
You may access a frequently updated
electronic version of 40 CFR part 180
through the Government Printing
Office’s e-CFR cite at https://
www.gpoaccess.gov/ecfr. To access the
OPPTS harmonized test quidelines
referenced in this document
electronically, please go to https://
www.epa.gov/oppts and select ‘‘Test
Methods and Guidelines.’’
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. The EPA procedural
regulations which govern the
submission of objections and requests
PO 00000
Frm 00077
Fmt 4700
Sfmt 4700
19261
for hearings appear in 40 CFR part 178.
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–2009–0479 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
on or before June 14, 2010.
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 your
copies, identified by docket ID number
EPA–HQ–OPP–2009–0479, by one of
the following methods:
• Federal eRulemaking Portal: https://
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 and Statutory Findings
In the Federal Register of August 19,
2009 (74 FR 41895) (FRL–8429–9), EPA
issued a notice pursuant to section 408
of FFDCA, 21 U.S.C. 346a, announcing
the filing of a pesticide petition (PP
9E7557) by Rhodia, Inc., 5171
Glenwood Avenue, Suite 402, Raleigh,
NC 27612. The petition requested that
40 CFR 180.920 and 40 CFR 180.930 be
amended by establishing an exemption
from the requirement of a tolerance for
residues of Alkyl (C12-C16) dimethyl
ammonio acetate, herein referred to in
this document as ADAA. That notice
included a summary of the petition
prepared by the petitioner. There were
no comments received in response to
the notice of filing.
E:\FR\FM\14APR1.SGM
14APR1
19262
Federal Register / Vol. 75, No. 71 / Wednesday, April 14, 2010 / Rules and Regulations
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.
jlentini on DSKJ8SOYB1PROD with RULES
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
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 section 408(b)(2)(D)
of FFDCA, and the factors specified in
section 408(b)(2)(D) of FFDCA, EPA has
reviewed the available scientific data
and other relevant information in
support of this action. EPA has
VerDate Nov<24>2008
16:13 Apr 13, 2010
Jkt 220001
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 ADAA when
used as inert ingredients in pesticide
formulations for pre-harvest uses and on
animals at a maximum of 20% by
weight in pesticide formulations. EPA’s
assessment of exposures and risks
associated with establishing tolerances
follows.
A. Toxicological Profile
Consistent with section 408(b)(2)(D)
of FFDCA, EPA has reviewed the
available scientific data and other
relevant information in support of this
action and considered its validity,
completeness and reliability and the
relationship of this information 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
nature of the toxic effects caused by
ADAA are discussed in this unit.
Acute oral toxicity studies were
performed using C12-ADAA and C16ADAA. ADAA has moderate to low
acute toxicity via the oral and dermal
routes of exposure. Low acute toxicity is
generally associated with C16-ADAA
while moderate acute toxicity is
associated with C12-ADAA. In acute
dermal and eye irritation studies, C12ADAA was severely irritating to the skin
and eyes. A mixture of C12-C16 ADAA
was used in a local lymph node assay
(LLNA) to evaluate the potential to
cause skin sensitization, C12-C16 ADAA
was found to be a sensitizer; however,
it gave a negative response for skin
sensitization in in vivo guinea pigs as
determined by Magnusson-Kligman test.
Two developmental studies were
available; an oral toxicity study in the
rat and a screening level developmental
dermal toxicity study in the rabbit. In
the developmental toxicity study in the
rat, maternal toxicity was manifested as
reduced body weight gain, stained and
matted haircoats, and respiratory rates
at 50 milligrams/kilograms/day (mg/kg/
day) and above. Offspring toxicity was
manifested as reduced or absent
ossification of the skull, sternebrae #5
and/or #6, and other sternebrae at 250
mg/kg/day. The NOAEL for
developmental toxicity in rats was 150
mg/kg/day. In the screening level
developmental dermal toxicity study in
rabbits, maternal toxicity manifested as
skin irritation, inhibition of body weight
gain, decreased food consumption and
resorptions at doses of 100 mg/kg/day
and above while offspring toxicity was
manifested as increased incidence of
PO 00000
Frm 00078
Fmt 4700
Sfmt 4700
resorptions and decreased average litter
size at ≥ 100 mg/kg/day. The NOAEL for
systemic and developmental toxicity in
rabbits via dermal route was 40 mg/kg/
day.
A dose range-finding and a main
study of Combined Repeated Dose
Toxicity Study with the Reproduction/
Developmental Toxicity Screening Test
according to the OPPTS Harmonized
Test Guideline 870.3650 study were
available in the rat. In the range-finding
study, at ≥ 100 mg/kg/day, a reduction
was observed in mean food
consumption, body weight, and body
weight gain during the pre-pairing
period in all animals. Also, animals
pushed their heads through the bedding
throughout the treatment period at
doses ≥ 100 mg/kg/day. At 1,000 mg/kg/
day, mortality was observed in all
animals within 24 hours. In the main
OPPTS Harmonized Test Guideline
870.3650 study, parental toxicity was
manifested as microscopic lesions
(squamous hyperplasia, hyperkeratosis,
submucosal inflammation and edema)
in the forestomach at the lowest dose
tested (50 mg/kg/day). Reproductive and
developmental toxicity was manifested
as increased implantation losses,
decreased birth and viability indices,
and decreased pup weight at 300 mg/kg/
day (highest dose tested). The NOAEL
for reproductive/developmental toxicity
was 150 mg/kg/day.
Several mutagenicity studies (two
Ames assays and chromosome
aberration assay) were available for
review. The results for these studies
were negative. No animal
carcinogenicity studies are available in
the database. Based on Structure
Activity Relationship (SAR) analysis, no
structural alerts for carcinogenicity were
identified.
Two in vitro dermal absorption
studies were available in hairless mice.
The dermal absorption factor of C12ADAA and C16-ADAA was estimated to
be <1%.
The Agency notes the surfactants are
surface-active materials that can damage
the structural integrity of cellular
membranes at high dose levels. Thus,
surfactants are often corrosive and
irritating in concentrated solutions. The
observed toxicity seen in the repeated
dose studies, such as microscopic
stomach lesions or decreased body
weight gain, are attributed to the
corrosive and irritating nature of these
surfactants.
There are no published or
unpublished ADAA metabolism studies.
However, ADAA are expected to
metabolized via three potential
metabolic pathways:
E:\FR\FM\14APR1.SGM
14APR1
Federal Register / Vol. 75, No. 71 / Wednesday, April 14, 2010 / Rules and Regulations
1. Omega oxidation followed by beta
oxidation of the carbon chain,
2. Conjugation of ADAA at the
carboxylic acid portion of the molecule
by any of a number of amino acids, or
3. Glucuronidation at the same site on
ADAA, followed by elimination.
Specific information on the studies
received and the nature of the adverse
effects caused by ADAA, as well as, the
no-observed-adverse-effect-level
(NOAEL) and the lowest-observedadverse-effect-level (LOAEL) from the
toxicity studies can be found at https://
www.regulations.gov in document
‘‘Decision Document for Alkyl (C12-C16)
dimethyl ammonio acetate (CAS Reg.
Nos. 683–10–3, 2601–33–4 and 693–33–
4),’’ pages 8-16 in docket ID number
EPA–HQ–OPP–2009–0479.
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 https://www.epa.gov/
pesticides/factsheets/riskassess.htm.
For the purpose of this risk
assessment, a protective overall NOAEL
of 40 mg/kg/day was selected for all
exposure scenarios based on weight-ofevidence from three studies in which
systemic toxicity was observed at doses
of 100 mg/kg/day or above. The
different NOAELs observed in these
studies are due to the dose selection
19263
process. For example, a NOAEL of 33
mg/kg/day and LOAEL of 100 mg/kg/
day (based on pushing head through
bedding, decreased food consumption
and weight gain) were established in a
range finding study for a combined
reproduction/ developmental toxicity
screening test. In the main study,
Organization for Economic Cooperation
and Development (OECD) combined
repeated dose toxicity study with the
reproduction/developmental toxicity
screening test, the LOAEL was
established at 50 mg/kg/day (lowest
dose tested). However, the LOAEL was
based on irritation in the forestomach of
rats due to the physical/chemical
properties of ADAA, which was not
considered relevant for human risk
assessments. Also the NOAEL of 40 mg/
kg/day is considered to be protective of
marginal decreases in body weights seen
at the LOAEL of 50 mg/kg/day in the
oral development toxicity study in rats
because body weight effects were not
observed in the OECD 422 study (main
study) at a dose level of 150 mg/kg/day.
Additionally, this NOAEL is supported
by the developmental dermal toxicity
study in the rabbit. In this study, a
NOAEL of 40 was established based on
the effects (uncoordinated movement,
partial paralysis and increased
incidence of resorptions) observed at
100 mg/kg/day in the presence of severe
skin irritation.
A summary of the toxicological
endpoints for ADAA used for human
risk assessment is shown in the Table of
this unit.
TABLE.—SUMMARY OF TOXICOLOGICAL DOSES AND ENDPOINTS FOR ADAA FOR USE IN HUMAN HEALTH RISK
ASSESSMENT
Point of Departure and Uncertainty/Safety Factors
Exposure/Scenario
RfD, PAD, LOC for Risk
Assessment
Study and Toxicological Effects
The Agency notes the surfactants are surface-active materials that can damage the structural integrity of cellular membranes at high dose levels. Moderate acute toxicity is associated with C12ADAA. However, these effects are considered local irritations rather than systemic toxicity. Therefore this endpoint is not appropriate for risk assessment. In addition, no endpoint of concern attributed to a single dose was identified in the database.
Chronic dietary
(all populations)
jlentini on DSKJ8SOYB1PROD with RULES
Acute dietary
(all populations)
NOAEL = 40 mg/kg/day
UFA = 10x
UFH = 10x
FQPA SF = 1x
Chronic RfD = 0.40 mg/kg/day
cPAD = 0.40 mg/kg/day
Overall NOAEL based on three
studies
OECD 422 range finding and
main study
Developmental toxicity study in
rabbits via dermal route,
Oral developmental toxicity
study in rats
Incidental Oral, dermal and inhalation
(Short- and Intermediate-Term)
NOAEL= 40 mg/kg/day
UFA = 10x
UFH = 10x
FQPA SF = 1x
LOC for MOE = 100
Overall NOAEL based on three
studies
OECD 422 range finding and
main study
Developmental toxicity study in
rabbits via dermal route,
Oral developmental toxicity
study in rats
VerDate Nov<24>2008
16:13 Apr 13, 2010
Jkt 220001
PO 00000
Frm 00079
Fmt 4700
Sfmt 4700
E:\FR\FM\14APR1.SGM
14APR1
19264
Federal Register / Vol. 75, No. 71 / Wednesday, April 14, 2010 / Rules and Regulations
TABLE.—SUMMARY OF TOXICOLOGICAL DOSES AND ENDPOINTS FOR ADAA FOR USE IN HUMAN HEALTH RISK
ASSESSMENT—Continued
Point of Departure and Uncertainty/Safety Factors
Exposure/Scenario
RfD, PAD, LOC for Risk
Assessment
Study and Toxicological Effects
Dermal short- and intermediate term (1
to 30 days) (1 to 6 months)
NOAEL= 40 mg/kg/day
UFA = 10x
UFH = 10x
FQPA SF = 1x
10% dermal absorption factor
LOC for MOE = 100
Overall NOAEL based on three
studies
OECD 422 range finding and
main study
Developmental toxicity study in
rabbits via dermal route,
Oral developmental toxicity
study in rats
Inhalation short- and intermediate term
(1 to 30 days) (1 to 6 months)
100% inhalation absorption
LOC for MOE = 100
Overall NOAEL based on three
studies
OECD 422 range finding and
main study
Developmental toxicity study in
rabbits via dermal route,
Oral developmental toxicity
study in rats
Cancer (oral, dermal, inhalation)
Not necessary. No cancer concerns were identified.
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 = FQPA Safety Factor. RfD = reference dose. MOE = margin of exposure. LOC = level of concern. N/A = not applicable.
V. Aggregate Exposures
jlentini on DSKJ8SOYB1PROD with RULES
A. Dietary Exposure
1. Dietary exposure from food and
feed uses. In evaluating dietary
exposure to the ADAA, EPA considered
exposure under the petitioned-for
exemptions from the requirement of a
tolerance. EPA assessed dietary
exposures from ADAA in food as
follows:
i. Acute exposure. The Agency notes
the surfactants are surface-active
materials that can damage the structural
integrity of cellular membranes at high
dose levels. Moderate acute toxicity is
associated with C12-ADAA. However,
these effects are considered local
irritations rather than systemic toxicity.
Therefore this endpoint is not
appropriate for risk assessment. In
addition, no endpoint of concern
attributed to a single dose was identified
in the database.
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 ADAA. 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
VerDate Nov<24>2008
16:13 Apr 13, 2010
Jkt 220001
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 https://www.regulations.gov in
docket ID number EPA–HQ–OPP–2008–
0738.
In the dietary exposure assessment,
the Agency assumed that the residue
level of the inert ingredient would be no
higher than the highest tolerance for a
given commodity. Implicit in this
assumption is that there would be
similar rates of degradation (if any)
between the active and inert ingredient
and that the concentration of inert
ingredient in the scenarios leading to
these highest levels 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
PO 00000
Frm 00080
Fmt 4700
Sfmt 4700
products are generally at least 50
percent 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 ADAA, EPA
made a specific adjustment to the
dietary exposure assessment to account
for the use limitations of the amount of
ADAA that may be in formulations (to
no more than 20% by weight in
pesticide products) and assumed that
the ADAA are 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
E:\FR\FM\14APR1.SGM
14APR1
jlentini on DSKJ8SOYB1PROD with RULES
Federal Register / Vol. 75, No. 71 / Wednesday, April 14, 2010 / Rules and Regulations
conservatism is EPA’s assumption that
all foods contain the inert ingredient at
the highest tolerance level. In other
words, EPA assumed 100 percent 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. ADAA is not expected to
be carcinogenic since there was no
evidence of carcinogenicity in the
available studies. Since the Agency has
not identified any concerns for
carcinogenicity relating to ADAA, a
cancer dietary exposure assessment was
not conducted.
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 ADAA, a
conservative drinking water
concentration value of 100 ppb based on
screening level modeling was used to
assess the contribution to drinking
water for chronic dietary risk
assessments for ADAA. 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., for lawn and garden pest control,
indoor pest control, termiticides, and
flea and tick control on pets). ADAA
may be used as inert ingredients in
pesticide products that are registered for
specific uses that may result in both
indoor and outdoor residential
exposures. A screening level residential
exposure and risk assessment was
completed for products containing
ADAA as inert ingredients. The ADAA
inerts are used in pesticide formulations
that may be used around the home in
VerDate Nov<24>2008
16:13 Apr 13, 2010
Jkt 220001
pesticide formulations used on lawn,
turf, or gardens. In addition, these inerts
may be present in personal care
products. The Agency selected
representative scenarios and conducted
an assessment to represent worst-case
residential exposure by assessing ADAA
in pesticide formulations (outdoor
scenarios) and ADAA in disinfectanttype uses (indoor scenarios). Based on
information contained in the petition,
ADAA can be present in personal care
products (maximum concentration 5%).
Therefore, the Agency assessed the
personal care products containing
ADAA using exposure scenarios used by
OPP’s Antimicrobials Division to
represent worst-case residential handler
exposure. The Agency conducted an
assessment to represent worst-case
residential exposure by assessing post
application exposures and risks from
ADAA in pesticide formulations
(Outdoor Scenarios) and ADAA in
disinfectant-type uses (Indoor
Scenarios). Further details of this
residential exposure and risk analysis
can be found at https://
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.
VI. Cumulative Effects
Section 408(b)(2)(D)(v) of FFFDCA
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.’’
Unlike other pesticide ingredients for
which EPA has followed as cumulative
risk approach based on a common
mechanism of toxicity, EPA has not
made a common mechanism of toxicity
finding as to ADAA acetate and any
other substances and, ADAA does not
appear to produce a toxic metabolite
produced by other substances. For the
purposes of this tolerance action,
therefore, EPA has not assumed that
ADAA has 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 the policy statements
PO 00000
Frm 00081
Fmt 4700
Sfmt 4700
19265
released by EPA’s Office of Pesticide
Programs concerning common
mechanism determinations and
procedures for cumulating effects from
substances found to have a common
mechanism on EPA’s website at https://
www.epa.gov/pesticides/cumulative/.
VII. Additional Safety Factor for the
Protection of 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
Food Quality Protection Act (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 is available to EPA support the
choice of a different factor. EPA
concluded that the FQPA safety factor
should be reduced to 1X for ADAA.
2. Prenatal and postnatal sensitivity.
There was no evidence of increased
susceptibility of infants and children in
the available developmental toxicity
studies via dermal and oral routes of
exposure. In these studies
developmental toxicity was observed in
the presence of maternal toxicity and/or
at one dose level higher. There was no
evidence of increased susceptibility of
infants and children in the OPPTS
870.3650 study (OECD 422) study. In
this study, the maternal toxicity was
manifested as body weight changes and
microscopic changes, while the fetal
toxicity was manifested as increased
implantation losses and decreased pup
weight. The maternal and
developmental NOAEL was 150 mg/kg/
day.
3. Conclusion. EPA has determined
that reliable data show that 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 database is considered adequate
for FQPA assessment. The following
acceptable studies are available:
Developmental toxicity study in rats
(1)
Developmental dermal toxicity study
in rabbits
Combined development/reproduction
repeated dose toxicity study (1)
ii. Fetal susceptibility was not
observed in the oral developmental
toxicity study in the rat, the
E:\FR\FM\14APR1.SGM
14APR1
jlentini on DSKJ8SOYB1PROD with RULES
19266
Federal Register / Vol. 75, No. 71 / Wednesday, April 14, 2010 / Rules and Regulations
developmental dermal toxicity study in
the rabbit or in the OPPTS Harmonized
Test Guideline 870.3650 study. In these
studies fetal toxicity was observed at
doses that were higher than the dose
that caused maternal toxicity. Therefore,
there are low concerns and no residual
uncertainties concerning prenatal and
postnatal toxicity.
iii. Clinical signs of neurotoxicity
(uncoordinated movement, partial
paralysis) were observed in the
developmental dermal study in the
rabbit. However, no effects on
Functional Observation Battery (FOB)
parameters were observed at doses up to
and including 300 mg/kg/day in the
OPPTS 870.3650 study (OECD 422
study). Therefore, EPA concluded that
the developmental neurotoxicity study
is not required.
iv. No evidence of immunotoxicity
was observed in the database.
v. No chronic toxicity or
carcinogenicity studies are available in
the database, however the Agency notes
that surfactants are surface-active
materials that can damage the structural
integrity of cellular membranes at high
dose levels. Thus, surfactants are often
corrosive and irritating in concentrated
solutions. The observed toxicity seen in
the repeated dose studies, such as
microscopic lesions or decreased body
weight gain, are attributed to the
corrosive and irritating nature of these
surfactants. The Agency has
considerable toxicity information on
surfactants which indicates that the
effects do not progressively increase in
severity over time. In addition, use of
the full 10X interspecies factor will
actually provide an additional margin of
safety because it is not expected that
humans’ response to local irritation/
corrosiveness effects would be markedly
different from animals. The database on
ADAA indicates that the target organ
toxicity is occurring at relatively high
doses. Based on the consideration in
this unit, the Agency concluded that an
additional FQPA safety factor for the
lack of a chronic study is not necessary.
vi. The dietary food exposure
assessment utilizes highly conservative
default assumptions and would not
underestimate the dietary risk to all
populations. For the purpose of the
screening level dietary risk assessment
to support this request for an exemption
from the requirement of a tolerance for
ADAA, a value of 100 ppb based on
screening level modeling was used for
the chronic dietary risk assessment. The
value of 100 ppb is considered to be a
high end, conservative assumption that
is not likely to underestimate drinking
water risks.
VerDate Nov<24>2008
16:13 Apr 13, 2010
Jkt 220001
Taking into consideration the
available information, EPA concludes
the additional 10X FQPA safety factor
can be reduced to 1X.
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. The Agency notes the
surfactants are surface-active materials
that can damage the structural integrity
of cellular membranes at high dose
levels. Moderate acute toxicity is
associated with C12-ADAA. However,
these effects are considered local
irritations rather than systemic toxicity.
Therefore this endpoint is not
appropriate for risk assessment. In
addition, no endpoint of concern
attributed to a single dose was identified
in the database.
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 limitation of not
more than 20% by weight in pesticide
formulations, the chronic dietary
exposure from food and water to ADAA
is 19.5% of the cPAD for the U.S.
population and 62.9% 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).
ADAA are used as inert ingredients 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
ADAA. Using the exposure assumptions
described in this unit, EPA has
PO 00000
Frm 00082
Fmt 4700
Sfmt 4700
concluded that the combined short-term
aggregated food, water, and residential
exposures result in aggregate MOEs of
110 for adult males and adult females.
Adult residential exposure combines
high end dermal and inhalation handler
exposure from indoor hard surface
wiping with a high end post application
dermal exposure from contact with
treated lawns. EPA has concluded the
combined short-term aggregated food,
water, and residential exposures result
in an aggregate MOE of 130 for children.
Children’s residential exposure includes
total exposures associated with contact
with treated lawns (dermal and hand-tomouth exposures). As the level of
concern is for MOEs that are lower than
100, 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).
ADAA are currently registered for
uses that could result in intermediateterm 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 ADAA. Using the exposure
assumptions described in this unit, EPA
has concluded that the combined
intermediate-term aggregated food,
water, and residential exposures result
in aggregate MOEs of 450 for adult
males and adult females. Adult
residential exposure includes high end
post application dermal exposure from
contact with treated lawns. EPA has
concluded the combined intermediateterm aggregated food, water, and
residential exposures result in an
aggregate MOE of 150 for children.
Children’s residential exposure includes
total exposures associated with contact
with treated lawns (dermal and hand-tomouth exposures). As the level of
concern is for MOEs that are lower than
100, this MOE is not of concern.
5. Aggregate cancer risk for U.S.
population. The Agency has not
identified any concerns for
carcinogenicity relating to ADAA.
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
ADAA when used as inert ingredients in
pesticide formulations for pre-harvest
uses and on animals at a maximum of
20% by weight in pesticide
formulations.
E:\FR\FM\14APR1.SGM
14APR1
Federal Register / Vol. 75, No. 71 / Wednesday, April 14, 2010 / Rules and Regulations
20% by weight in formulation) from the
requirement of a tolerance will be safe.
VIII. Other Considerations
A. Endocrine Disruptors
EPA is required under the Federal
Food, Drug and Cosmetic Act (FFDCA),
as amended by FQPA, to develop a
screening program to determine whether
certain substances (including all
pesticide active and other ingredients)
‘‘may have an effect in humans that is
similar to an effect produced by a
naturally occurring estrogen, or other
such endocrine effects as the
Administrator may designate.’’
Following recommendations of its
Endocrine Disruptor and Testing
Advisory Committee (EDSTAC), EPA
determined that there was a scientific
basis for including, as part of the
program, the androgen and thyroid
hormone systems, in addition to the
estrogen hormone system. EPA also
adopted EDSTAC’s recommendation
that the Program include evaluations of
potential effects in wildlife. For
pesticide chemicals, EPA will use
FIFRA and, to the extent that effects in
wildlife may help determine whether a
substance may have an effect in
humans, FFDCA authority to require the
wildlife evaluations. As the science
develops and resources allow, screening
of additional hormone systems may be
added to the Endocrine Disruptor
Screening Program (EDSP).
When additional appropriate
screening and/or testing protocols being
considered under the Agency’s EDSP
have been developed, ADAA may be
subjected to further screening and/or
testing to better characterize effects
related to endocrine disruption.
B. Analytical Method
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.
C. International Tolerances
The Agency is not aware of any
country requiring a tolerance for ADAA
nor have any CODEX Maximum Residue
Levels (MRLs) been established for any
food crops at this time.
jlentini on DSKJ8SOYB1PROD with RULES
IX. Conclusions
Based on the information in this
preamble, EPA concludes that there is a
reasonable certainty of no harm from
aggregate exposure to residues of
ADAA. Accordingly, EPA finds that
exempting ADAA (at a maximum of
VerDate Nov<24>2008
16:13 Apr 13, 2010
Jkt 220001
X. Statutory and Executive Order
Reviews
This final rule establishes a tolerance
under section 408(d) of FFDCA in
response to a petition submitted to the
Agency. The Office of Management and
Budget (OMB) has exempted these types
of actions from review under Executive
Order 12866, entitled Regulatory
Planning and Review (58 FR 51735,
October 4, 1993). Because this final rule
has been exempted from review under
Executive Order 12866, this final rule is
not subject to Executive Order 13211,
entitled Actions Concerning Regulations
That Significantly Affect Energy Supply,
Distribution, or Use (66 FR 28355, May
22, 2001) or Executive Order 13045,
entitled Protection of Children from
Environmental Health Risks and Safety
Risks (62 FR 19885, April 23, 1997).
This final rule does not contain any
information collections subject to OMB
approval under the Paperwork
Reduction Act (PRA), 44 U.S.C. 3501 et
seq., nor does it require any special
considerations under Executive Order
12898, entitled Federal Actions to
Address Environmental Justice in
Minority Populations and Low-Income
Populations (59 FR 7629, February 16,
1994).
Since tolerances and exemptions that
are established on the basis of a petition
under section 408(d) of FFDCA, such as
the tolerance in this final rule, do not
require the issuance of a proposed rule,
the requirements of the Regulatory
Flexibility Act (RFA) (5 U.S.C. 601 et
seq.) do not apply.
This final rule directly regulates
growers, food processors, food handlers,
and food retailers, not States or tribes,
nor does this action alter the
relationships or distribution of power
and responsibilities established by
Congress in the preemption provisions
of section 408(n)(4) of FFDCA. As such,
the Agency has determined that this
action will not have a substantial direct
effect on States or tribal governments,
on the relationship between the national
government and the States or tribal
governments, or on the distribution of
power and responsibilities among the
various levels of government or between
the Federal Government and Indian
tribes. Thus, the Agency has determined
that Executive Order 13132, entitled
Federalism (64 FR 43255, August 10,
1999) and Executive Order 13175,
PO 00000
Frm 00083
Fmt 4700
Sfmt 4700
19267
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).
XI. 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: April 1, 2010.
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, in the table add
alphabetically the following inert
ingredient to read as follows:
■
§ 180.920 Inert ingredients used preharvest; exemptions from the requirement
of a tolerance.
*
E:\FR\FM\14APR1.SGM
*
*
14APR1
*
*
19268
Federal Register / Vol. 75, No. 71 / Wednesday, April 14, 2010 / Rules and Regulations
Inert ingredients
Limits
Uses
*
*
*
Alkyl (C12-C16) dimethyl ammonio acetate (CAS Reg. Nos. 683–10–
3, 2601–33–4 and 693–33–4
*
*
*
*
*
*
*
20% by weight in pesticide formulation
*
*
*
*
§ 180.930 Inert ingredients applied to
animals; exemptions from the requirement
of a tolerance.
3. In §180.930, in the table add
alphabetically the following inert
ingredient to read as follows:
■
*
*
*
*
*
Inert ingredients
Limits
*
*
*
Alkyl (C12-C16) dimethyl ammonio acetate (CAS Reg. Nos. 683–10–
3, 2601–33–4 and 693–33–4
*
*
*
*
*
*
*
20% by weight in pesticide formulation
*
*
*
*
[FR Doc. 2010–8298 Filed 4–13–10; 8:45 am]
BILLING CODE 6560–50–S
ENVIRONMENTAL PROTECTION
AGENCY
40 CFR Part 180
[EPA–HQ–OPP–2008–0695; FRL–8808–7]
Kasugamycin; Pesticide Tolerances for
Emergency Exemptions
AGENCY: Environmental Protection
Agency (EPA).
ACTION: Final rule.
This regulation establishes a
time-limited tolerance for residues of
kasugamycin, 3-O-[2-amino-4[(carboxyiminomethyl)amino]-2,3,4,6tetradeoxy-a-D-arabino-hexopyranosyl]D-chiro-inositol in or on apples. This
action is in response to EPA’s granting
of an emergency exemption under
section 18 of the Federal Insecticide,
Fungicide, and Rodenticide Act (FIFRA)
authorizing use of the agricultural
bactericide on apples. This regulation
establishes a maximum permissible
level for residues of kasugamycin in this
food commodity. The time-limited
tolerance expires and is revoked on
December 31, 2012.
DATES: This regulation is effective April
14, 2010. Objections and requests for
hearings must be received on or before
June 14, 2010, 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–2008–0695. All documents in the
docket are listed in the docket index
available in https://www.regulations.gov.
SUMMARY:
jlentini on DSKJ8SOYB1PROD with RULES
Surfactant
VerDate Nov<24>2008
16:13 Apr 13, 2010
Jkt 220001
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
https://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:
Andrew Ertman, Registration Division
(7505P), Office of Pesticide Programs,
Environmental Protection Agency, 1200
Pennsylvania Ave., NW., Washington,
DC 20460–0001; telephone number:
(703) 308–9367; e-mail address:
ertman.andrew@epa.gov.
SUPPLEMENTARY INFORMATION:
I. General Information
A. Does This Action Apply to Me?
You may be potentially affected by
this action if you are an agricultural
producer, food manufacturer, or
pesticide manufacturer. Potentially
affected entities may include, but are
not limited to:
• Crop production (NAICS code 111).
• Animal production (NAICS code
112).
• Food manufacturing (NAICS code
311).
• Pesticide manufacturing (NAICS
code 32532).
PO 00000
Frm 00084
Fmt 4700
Sfmt 4700
Uses
Surfactant
This listing is not intended to be
exhaustive, but rather provides a guide
for readers regarding entities likely to be
affected by this action. Other types of
entities not listed in this unit could also
be affected. The North American
Industrial Classification System
(NAICS) codes have been provided to
assist you and others in determining
whether this action might apply to
certain entities. If you have any
questions regarding the applicability of
this action to a particular entity, consult
the person listed under FOR FURTHER
INFORMATION CONTACT.
B. How Can I Get Electronic Access to
Other Related Information?
You may access a frequently updated
electronic version of 40 CFR part 180
through the Government Printing
Office’s e-CFR site at https://
www.gpoaccess.gov/ecfr. To access the
OPPTS harmonized test guidelines
referenced in this document
electronically, please go to https://
www.epa.gov/oppts and select ‘‘Test
Methods and Guidelines.’’
C. Can I File an Objection or Hearing
Request?
Under section 408(g) of the Federal
Food, Drug, and Cosmetic Act (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. The EPA procedural
regulations which govern the
submission of objections and requests
for hearings appear in 40 CFR part 178.
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–2008–0695 in the subject line on
the first page of your submission. All
E:\FR\FM\14APR1.SGM
14APR1
Agencies
[Federal Register Volume 75, Number 71 (Wednesday, April 14, 2010)]
[Rules and Regulations]
[Pages 19261-19268]
From the Federal Register Online via the Government Printing Office [www.gpo.gov]
[FR Doc No: 2010-8298]
-----------------------------------------------------------------------
ENVIRONMENTAL PROTECTION AGENCY
40 CFR Part 180
[EPA-HQ-OPP-2009-0479; FRL-8816-5]
Alkyl (C12-C16) Dimethyl Ammonio Acetate; 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 Alkyl (C12-C16)
dimethyl ammonio acetate, herein referred to in this document as ADAA,
when used as an inert ingredient (surfactant) in pesticide formulations
for pre-harvest uses under 40 CFR 180.920 or applied to animals under
40 CFR 180.930 at a maxiumum concentration of 20% in pesticide product
formulations. Technology Sciences Group, Inc., on behalf of Rhodia,
Inc., 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 ADAA.
DATES: This regulation is effective April 14, 2010. Objections and
requests for hearings must be received on or before June 14, 2010, 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-2009-0479. All documents in the
docket are listed in the docket index available at https://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 https://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: Elizabeth Fertich, Registration
Division (7505P), Office of Pesticide Programs, Environmental
Protection Agency, 1200 Pennsylvania Ave., NW., Washington, DC 20460-
0001; telephone number: (703) 347-8560; e-mail address:
fertich.elizabeth@epa.gov.
SUPPLEMENTARY INFORMATION:
I. General Information
A. Does This Action Apply to Me?
You may be potentially affected by this action if you are an
agricultural producer, food manufacturer, or pesticide manufacturer.
Potentially affected entities may include, but are not limited to:
Crop production (NAICS code 111).
Animal production (NAICS code 112).
Food manufacturing (NAICS code 311).
Pesticide manufacturing (NAICS code 32532).
This listing is not intended to be exhaustive, but rather provides
a guide for readers regarding entities likely to be affected by this
action. Other types of entities not listed in this unit could also be
affected. The North American Industrial Classification System (NAICS)
codes have been provided to assist you and others in determining
whether this action might apply to certain entities. If you have any
questions regarding the applicability of this action to a particular
entity, consult the person listed under FOR FURTHER INFORMATION
CONTACT.
B. How Can I Get Electronic Access to Other Related Information?
You may access a frequently updated electronic version of 40 CFR
part 180 through the Government Printing Office's e-CFR cite at https://www.gpoaccess.gov/ecfr. To access the OPPTS harmonized test quidelines
referenced in this document electronically, please go to https://www.epa.gov/oppts and select ``Test Methods and Guidelines.''
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. The EPA procedural regulations which
govern the submission of objections and requests for hearings appear in
40 CFR part 178. 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-2009-0479 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 on or before June 14, 2010.
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 your copies, identified by docket ID
number EPA-HQ-OPP-2009-0479, by one of the following methods:
Federal eRulemaking Portal: https://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 and Statutory Findings
In the Federal Register of August 19, 2009 (74 FR 41895) (FRL-8429-
9), EPA issued a notice pursuant to section 408 of FFDCA, 21 U.S.C.
346a, announcing the filing of a pesticide petition (PP 9E7557) by
Rhodia, Inc., 5171 Glenwood Avenue, Suite 402, Raleigh, NC 27612. The
petition requested that 40 CFR 180.920 and 40 CFR 180.930 be amended by
establishing an exemption from the requirement of a tolerance for
residues of Alkyl (C12-C16) dimethyl ammonio
acetate, herein referred to in this document as ADAA. That notice
included a summary of the petition prepared by the petitioner. There
were no comments received in response to the notice of filing.
[[Page 19262]]
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 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 section 408(b)(2)(D) of FFDCA, and the factors
specified in section 408(b)(2)(D) of FFDCA, 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 ADAA when
used as inert ingredients in pesticide formulations for pre-harvest
uses and on animals at a maximum of 20% by weight in pesticide
formulations. EPA's assessment of exposures and risks associated with
establishing tolerances follows.
A. Toxicological Profile
Consistent with section 408(b)(2)(D) of FFDCA, EPA has reviewed the
available scientific data and other relevant information in support of
this action and considered its validity, completeness and reliability
and the relationship of this information 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 nature of the toxic effects caused by ADAA
are discussed in this unit.
Acute oral toxicity studies were performed using C12-
ADAA and C16-ADAA. ADAA has moderate to low acute toxicity
via the oral and dermal routes of exposure. Low acute toxicity is
generally associated with C16-ADAA while moderate acute
toxicity is associated with C12-ADAA. In acute dermal and
eye irritation studies, C12-ADAA was severely irritating to
the skin and eyes. A mixture of C12-C16 ADAA was
used in a local lymph node assay (LLNA) to evaluate the potential to
cause skin sensitization, C12-C16 ADAA was found
to be a sensitizer; however, it gave a negative response for skin
sensitization in in vivo guinea pigs as determined by Magnusson-Kligman
test.
Two developmental studies were available; an oral toxicity study in
the rat and a screening level developmental dermal toxicity study in
the rabbit. In the developmental toxicity study in the rat, maternal
toxicity was manifested as reduced body weight gain, stained and matted
haircoats, and respiratory rates at 50 milligrams/kilograms/day (mg/kg/
day) and above. Offspring toxicity was manifested as reduced or absent
ossification of the skull, sternebrae 5 and/or 6, and
other sternebrae at 250 mg/kg/day. The NOAEL for developmental toxicity
in rats was 150 mg/kg/day. In the screening level developmental dermal
toxicity study in rabbits, maternal toxicity manifested as skin
irritation, inhibition of body weight gain, decreased food consumption
and resorptions at doses of 100 mg/kg/day and above while offspring
toxicity was manifested as increased incidence of resorptions and
decreased average litter size at >= 100 mg/kg/day. The NOAEL for
systemic and developmental toxicity in rabbits via dermal route was 40
mg/kg/day.
A dose range-finding and a main study of Combined Repeated Dose
Toxicity Study with the Reproduction/Developmental Toxicity Screening
Test according to the OPPTS Harmonized Test Guideline 870.3650 study
were available in the rat. In the range-finding study, at >= 100 mg/kg/
day, a reduction was observed in mean food consumption, body weight,
and body weight gain during the pre-pairing period in all animals.
Also, animals pushed their heads through the bedding throughout the
treatment period at doses >= 100 mg/kg/day. At 1,000 mg/kg/day,
mortality was observed in all animals within 24 hours. In the main
OPPTS Harmonized Test Guideline 870.3650 study, parental toxicity was
manifested as microscopic lesions (squamous hyperplasia,
hyperkeratosis, submucosal inflammation and edema) in the forestomach
at the lowest dose tested (50 mg/kg/day). Reproductive and
developmental toxicity was manifested as increased implantation losses,
decreased birth and viability indices, and decreased pup weight at 300
mg/kg/day (highest dose tested). The NOAEL for reproductive/
developmental toxicity was 150 mg/kg/day.
Several mutagenicity studies (two Ames assays and chromosome
aberration assay) were available for review. The results for these
studies were negative. No animal carcinogenicity studies are available
in the database. Based on Structure Activity Relationship (SAR)
analysis, no structural alerts for carcinogenicity were identified.
Two in vitro dermal absorption studies were available in hairless
mice. The dermal absorption factor of C12-ADAA and
C16-ADAA was estimated to be <1%.
The Agency notes the surfactants are surface-active materials that
can damage the structural integrity of cellular membranes at high dose
levels. Thus, surfactants are often corrosive and irritating in
concentrated solutions. The observed toxicity seen in the repeated dose
studies, such as microscopic stomach lesions or decreased body weight
gain, are attributed to the corrosive and irritating nature of these
surfactants.
There are no published or unpublished ADAA metabolism studies.
However, ADAA are expected to metabolized via three potential metabolic
pathways:
[[Page 19263]]
1. Omega oxidation followed by beta oxidation of the carbon chain,
2. Conjugation of ADAA at the carboxylic acid portion of the
molecule by any of a number of amino acids, or
3. Glucuronidation at the same site on ADAA, followed by
elimination.
Specific information on the studies received and the nature of the
adverse effects caused by ADAA, as well as, the no-observed-adverse-
effect-level (NOAEL) and the lowest-observed-adverse-effect-level
(LOAEL) from the toxicity studies can be found at https://www.regulations.gov in document ``Decision Document for Alkyl
(C12-C16) dimethyl ammonio acetate (CAS Reg. Nos.
683-10-3, 2601-33-4 and 693-33-4),'' pages 8-16 in docket ID number
EPA-HQ-OPP-2009-0479.
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 https://www.epa.gov/pesticides/factsheets/riskassess.htm.
For the purpose of this risk assessment, a protective overall NOAEL
of 40 mg/kg/day was selected for all exposure scenarios based on
weight-of-evidence from three studies in which systemic toxicity was
observed at doses of 100 mg/kg/day or above. The different NOAELs
observed in these studies are due to the dose selection process. For
example, a NOAEL of 33 mg/kg/day and LOAEL of 100 mg/kg/day (based on
pushing head through bedding, decreased food consumption and weight
gain) were established in a range finding study for a combined
reproduction/ developmental toxicity screening test. In the main study,
Organization for Economic Cooperation and Development (OECD) combined
repeated dose toxicity study with the reproduction/developmental
toxicity screening test, the LOAEL was established at 50 mg/kg/day
(lowest dose tested). However, the LOAEL was based on irritation in the
forestomach of rats due to the physical/chemical properties of ADAA,
which was not considered relevant for human risk assessments. Also the
NOAEL of 40 mg/kg/day is considered to be protective of marginal
decreases in body weights seen at the LOAEL of 50 mg/kg/day in the oral
development toxicity study in rats because body weight effects were not
observed in the OECD 422 study (main study) at a dose level of 150 mg/
kg/day. Additionally, this NOAEL is supported by the developmental
dermal toxicity study in the rabbit. In this study, a NOAEL of 40 was
established based on the effects (uncoordinated movement, partial
paralysis and increased incidence of resorptions) observed at 100 mg/
kg/day in the presence of severe skin irritation.
A summary of the toxicological endpoints for ADAA used for human
risk assessment is shown in the Table of this unit.
Table.--Summary of Toxicological Doses and Endpoints for ADAA for Use in Human Health Risk Assessment
----------------------------------------------------------------------------------------------------------------
Point of Departure and
Exposure/Scenario Uncertainty/Safety RfD, PAD, LOC for Risk Study and Toxicological
Factors Assessment Effects
----------------------------------------------------------------------------------------------------------------
Acute dietary The Agency notes the surfactants are surface-active materials that can
(all populations).................... damage the structural integrity of cellular membranes at high dose
levels. Moderate acute toxicity is associated with C12-ADAA. However,
these effects are considered local irritations rather than systemic
toxicity. Therefore this endpoint is not appropriate for risk
assessment. In addition, no endpoint of concern attributed to a single
dose was identified in the database.
----------------------------------------------------------------------------------------------------------------
Chronic dietary NOAEL = 40 mg/kg/day Chronic RfD = 0.40 mg/ Overall NOAEL based on
(all populations).................... UFA = 10x.............. kg/day three studies
UFH = 10x.............. cPAD = 0.40 mg/kg/day.. OECD 422 range finding
FQPA SF = 1x........... and main study
Developmental toxicity
study in rabbits via
dermal route,
Oral developmental
toxicity study in rats
----------------------------------------------------------------------------------------------------------------
Incidental Oral, dermal and NOAEL= 40 mg/kg/day LOC for MOE = 100 Overall NOAEL based on
inhalation (Short- and Intermediate- UFA = 10x.............. three studies
Term) UFH = 10x.............. OECD 422 range finding
FQPA SF = 1x........... and main study
Developmental toxicity
study in rabbits via
dermal route,
Oral developmental
toxicity study in rats
----------------------------------------------------------------------------------------------------------------
[[Page 19264]]
Dermal short- and intermediate term NOAEL= 40 mg/kg/day LOC for MOE = 100 Overall NOAEL based on
(1 to 30 days) (1 to 6 months) UFA = 10x.............. three studies
UFH = 10x.............. OECD 422 range finding
FQPA SF = 1x........... and main study
10% dermal absorption Developmental toxicity
factor. study in rabbits via
dermal route,
Oral developmental
toxicity study in rats
----------------------------------------------------------------------------------------------------------------
Inhalation short- and intermediate 100% inhalation LOC for MOE = 100 Overall NOAEL based on
term (1 to 30 days) (1 to 6 months) absorption three studies
OECD 422 range finding
and main study
Developmental toxicity
study in rabbits via
dermal route,
Oral developmental
toxicity study in rats
----------------------------------------------------------------------------------------------------------------
Cancer (oral, dermal, inhalation) Not necessary. No cancer concerns were identified.
----------------------------------------------------------------------------------------------------------------
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 = FQPA Safety Factor. RfD = reference dose. MOE = margin of exposure. LOC =
level of concern. N/A = not applicable.
V. Aggregate Exposures
A. Dietary Exposure
1. Dietary exposure from food and feed uses. In evaluating dietary
exposure to the ADAA, EPA considered exposure under the petitioned-for
exemptions from the requirement of a tolerance. EPA assessed dietary
exposures from ADAA in food as follows:
i. Acute exposure. The Agency notes the surfactants are surface-
active materials that can damage the structural integrity of cellular
membranes at high dose levels. Moderate acute toxicity is associated
with C12-ADAA. However, these effects are considered local
irritations rather than systemic toxicity. Therefore this endpoint is
not appropriate for risk assessment. In addition, no endpoint of
concern attributed to a single dose was identified in the database.
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 ADAA. 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 https://www.regulations.gov in docket ID number EPA-HQ-OPP-2008-0738.
In the dietary exposure assessment, the Agency assumed that the
residue level of the inert ingredient would be no higher than the
highest tolerance for a given commodity. Implicit in this assumption is
that there would be similar rates of degradation (if any) between the
active and inert ingredient and that the concentration of inert
ingredient in the scenarios leading to these highest levels of
tolerances would be no higher than the concentration of the active
ingredient.
The Agency believes the assumptions used to estimate dietary
exposures lead to an extremely conservative assessment of dietary risk
due to a series of compounded conservatisms. First, assuming that the
level of residue for an inert ingredient is equal to the level of
residue for the active ingredient will overstate exposure. The
concentrations of active ingredient in agricultural products are
generally at least 50 percent 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 ADAA, EPA made a specific
adjustment to the dietary exposure assessment to account for the use
limitations of the amount of ADAA that may be in formulations (to no
more than 20% by weight in pesticide products) and assumed that the
ADAA are 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
[[Page 19265]]
conservatism is EPA's assumption that all foods contain the inert
ingredient at the highest tolerance level. In other words, EPA assumed
100 percent 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. ADAA is not expected to be carcinogenic since there
was no evidence of carcinogenicity in the available studies. Since the
Agency has not identified any concerns for carcinogenicity relating to
ADAA, a cancer dietary exposure assessment was not conducted.
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 ADAA, a conservative
drinking water concentration value of 100 ppb based on screening level
modeling was used to assess the contribution to drinking water for
chronic dietary risk assessments for ADAA. 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). ADAA may be used as
inert ingredients in pesticide products that are registered for
specific uses that may result in both indoor and outdoor residential
exposures. A screening level residential exposure and risk assessment
was completed for products containing ADAA as inert ingredients. The
ADAA inerts are used in pesticide formulations that may be used around
the home in pesticide formulations used on lawn, turf, or gardens. In
addition, these inerts may be present in personal care products. The
Agency selected representative scenarios and conducted an assessment to
represent worst-case residential exposure by assessing ADAA in
pesticide formulations (outdoor scenarios) and ADAA in disinfectant-
type uses (indoor scenarios). Based on information contained in the
petition, ADAA can be present in personal care products (maximum
concentration 5%). Therefore, the Agency assessed the personal care
products containing ADAA using exposure scenarios used by OPP's
Antimicrobials Division to represent worst-case residential handler
exposure. The Agency conducted an assessment to represent worst-case
residential exposure by assessing post application exposures and risks
from ADAA in pesticide formulations (Outdoor Scenarios) and ADAA in
disinfectant-type uses (Indoor Scenarios). Further details of this
residential exposure and risk analysis can be found at https://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.
VI. Cumulative Effects
Section 408(b)(2)(D)(v) of FFFDCA 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.''
Unlike other pesticide ingredients for which EPA has followed as
cumulative risk approach based on a common mechanism of toxicity, EPA
has not made a common mechanism of toxicity finding as to ADAA acetate
and any other substances and, ADAA does not appear to produce a toxic
metabolite produced by other substances. For the purposes of this
tolerance action, therefore, EPA has not assumed that ADAA has 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
the policy statements released by EPA's Office of Pesticide Programs
concerning common mechanism determinations and procedures for
cumulating effects from substances found to have a common mechanism on
EPA's website at https://www.epa.gov/pesticides/cumulative/.
VII. Additional Safety Factor for the Protection of 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 Food Quality
Protection Act (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 is available to EPA support
the choice of a different factor. EPA concluded that the FQPA safety
factor should be reduced to 1X for ADAA.
2. Prenatal and postnatal sensitivity. There was no evidence of
increased susceptibility of infants and children in the available
developmental toxicity studies via dermal and oral routes of exposure.
In these studies developmental toxicity was observed in the presence of
maternal toxicity and/or at one dose level higher. There was no
evidence of increased susceptibility of infants and children in the
OPPTS 870.3650 study (OECD 422) study. In this study, the maternal
toxicity was manifested as body weight changes and microscopic changes,
while the fetal toxicity was manifested as increased implantation
losses and decreased pup weight. The maternal and developmental NOAEL
was 150 mg/kg/day.
3. Conclusion. EPA has determined that reliable data show that 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 database is considered adequate for FQPA assessment. The
following acceptable studies are available:
Developmental toxicity study in rats (1)
Developmental dermal toxicity study in rabbits
Combined development/reproduction repeated dose toxicity study (1)
ii. Fetal susceptibility was not observed in the oral developmental
toxicity study in the rat, the
[[Page 19266]]
developmental dermal toxicity study in the rabbit or in the OPPTS
Harmonized Test Guideline 870.3650 study. In these studies fetal
toxicity was observed at doses that were higher than the dose that
caused maternal toxicity. Therefore, there are low concerns and no
residual uncertainties concerning prenatal and postnatal toxicity.
iii. Clinical signs of neurotoxicity (uncoordinated movement,
partial paralysis) were observed in the developmental dermal study in
the rabbit. However, no effects on Functional Observation Battery (FOB)
parameters were observed at doses up to and including 300 mg/kg/day in
the OPPTS 870.3650 study (OECD 422 study). Therefore, EPA concluded
that the developmental neurotoxicity study is not required.
iv. No evidence of immunotoxicity was observed in the database.
v. No chronic toxicity or carcinogenicity studies are available in
the database, however the Agency notes that surfactants are surface-
active materials that can damage the structural integrity of cellular
membranes at high dose levels. Thus, surfactants are often corrosive
and irritating in concentrated solutions. The observed toxicity seen in
the repeated dose studies, such as microscopic lesions or decreased
body weight gain, are attributed to the corrosive and irritating nature
of these surfactants. The Agency has considerable toxicity information
on surfactants which indicates that the effects do not progressively
increase in severity over time. In addition, use of the full 10X
interspecies factor will actually provide an additional margin of
safety because it is not expected that humans' response to local
irritation/corrosiveness effects would be markedly different from
animals. The database on ADAA indicates that the target organ toxicity
is occurring at relatively high doses. Based on the consideration in
this unit, the Agency concluded that an additional FQPA safety factor
for the lack of a chronic study is not necessary.
vi. The dietary food exposure assessment utilizes highly
conservative default assumptions and would not underestimate the
dietary risk to all populations. For the purpose of the screening level
dietary risk assessment to support this request for an exemption from
the requirement of a tolerance for ADAA, a value of 100 ppb based on
screening level modeling was used for the chronic dietary risk
assessment. The value of 100 ppb is considered to be a high end,
conservative assumption that is not likely to underestimate drinking
water risks.
Taking into consideration the available information, EPA concludes
the additional 10X FQPA safety factor can be reduced to 1X.
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. The Agency notes the surfactants are surface-active
materials that can damage the structural integrity of cellular
membranes at high dose levels. Moderate acute toxicity is associated
with C12-ADAA. However, these effects are considered local
irritations rather than systemic toxicity. Therefore this endpoint is
not appropriate for risk assessment. In addition, no endpoint of
concern attributed to a single dose was identified in the database.
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 limitation of not more than 20% by
weight in pesticide formulations, the chronic dietary exposure from
food and water to ADAA is 19.5% of the cPAD for the U.S. population and
62.9% 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).
ADAA are used as inert ingredients 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 ADAA. 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 110 for adult males and adult females. Adult
residential exposure combines high end dermal and inhalation handler
exposure from indoor hard surface wiping with a high end post
application dermal exposure from contact with treated lawns. EPA has
concluded the combined short-term aggregated food, water, and
residential exposures result in an aggregate MOE of 130 for children.
Children's residential exposure includes total exposures associated
with contact with treated lawns (dermal and hand-to-mouth exposures).
As the level of concern is for MOEs that are lower than 100, 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).
ADAA are 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 ADAA. Using the
exposure assumptions described in this unit, EPA has concluded that the
combined intermediate-term aggregated food, water, and residential
exposures result in aggregate MOEs of 450 for adult males and adult
females. Adult residential exposure includes high end post application
dermal exposure from contact with treated lawns. EPA has concluded the
combined intermediate-term aggregated food, water, and residential
exposures result in an aggregate MOE of 150 for children. Children's
residential exposure includes total exposures associated with contact
with treated lawns (dermal and hand-to-mouth exposures). As the level
of concern is for MOEs that are lower than 100, this MOE is not of
concern.
5. Aggregate cancer risk for U.S. population. The Agency has not
identified any concerns for carcinogenicity relating to ADAA.
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 ADAA when used as inert ingredients in
pesticide formulations for pre-harvest uses and on animals at a maximum
of 20% by weight in pesticide formulations.
[[Page 19267]]
VIII. Other Considerations
A. Endocrine Disruptors
EPA is required under the Federal Food, Drug and Cosmetic Act
(FFDCA), as amended by FQPA, to develop a screening program to
determine whether certain substances (including all pesticide active
and other ingredients) ``may have an effect in humans that is similar
to an effect produced by a naturally occurring estrogen, or other such
endocrine effects as the Administrator may designate.'' Following
recommendations of its Endocrine Disruptor and Testing Advisory
Committee (EDSTAC), EPA determined that there was a scientific basis
for including, as part of the program, the androgen and thyroid hormone
systems, in addition to the estrogen hormone system. EPA also adopted
EDSTAC's recommendation that the Program include evaluations of
potential effects in wildlife. For pesticide chemicals, EPA will use
FIFRA and, to the extent that effects in wildlife may help determine
whether a substance may have an effect in humans, FFDCA authority to
require the wildlife evaluations. As the science develops and resources
allow, screening of additional hormone systems may be added to the
Endocrine Disruptor Screening Program (EDSP).
When additional appropriate screening and/or testing protocols
being considered under the Agency's EDSP have been developed, ADAA may
be subjected to further screening and/or testing to better characterize
effects related to endocrine disruption.
B. Analytical Method
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.
C. International Tolerances
The Agency is not aware of any country requiring a tolerance for
ADAA nor have any CODEX Maximum Residue Levels (MRLs) been established
for any food crops at this time.
IX. Conclusions
Based on the information in this preamble, EPA concludes that there
is a reasonable certainty of no harm from aggregate exposure to
residues of ADAA. Accordingly, EPA finds that exempting ADAA (at a
maximum of 20% by weight in formulation) from the requirement of a
tolerance will be safe.
X. Statutory and Executive Order Reviews
This final rule establishes a tolerance under section 408(d) of
FFDCA in response to a petition submitted to the Agency. The Office of
Management and Budget (OMB) has exempted these types of actions from
review under Executive Order 12866, entitled Regulatory Planning and
Review (58 FR 51735, October 4, 1993). Because this final rule has been
exempted from review under Executive Order 12866, this final rule is
not subject to Executive Order 13211, entitled Actions Concerning
Regulations That Significantly Affect Energy Supply, Distribution, or
Use (66 FR 28355, May 22, 2001) or Executive Order 13045, entitled
Protection of Children from Environmental Health Risks and Safety Risks
(62 FR 19885, April 23, 1997). This final rule does not contain any
information collections subject to OMB approval under the Paperwork
Reduction Act (PRA), 44 U.S.C. 3501 et seq., nor does it require any
special considerations under Executive Order 12898, entitled Federal
Actions to Address Environmental Justice in Minority Populations and
Low-Income Populations (59 FR 7629, February 16, 1994).
Since tolerances and exemptions that are established on the basis
of a petition under section 408(d) of FFDCA, such as the tolerance in
this final rule, do not require the issuance of a proposed rule, the
requirements of the Regulatory Flexibility Act (RFA) (5 U.S.C. 601 et
seq.) do not apply.
This final rule directly regulates growers, food processors, food
handlers, and food retailers, not States or tribes, nor does this
action alter the relationships or distribution of power and
responsibilities established by Congress in the preemption provisions
of section 408(n)(4) of FFDCA. As such, the Agency has determined that
this action will not have a substantial direct effect on States or
tribal governments, on the relationship between the national government
and the States or tribal governments, or on the distribution of power
and responsibilities among the various levels of government or between
the Federal Government and Indian tribes. Thus, the Agency has
determined that Executive Order 13132, entitled Federalism (64 FR
43255, August 10, 1999) and Executive Order 13175, entitled
Consultation and Coordination with Indian Tribal Governments (65 FR
67249, November 9, 2000) do not apply to this final rule. In addition,
this final rule does not impose any enforceable duty or contain any
unfunded mandate as described under Title II of the Unfunded Mandates
Reform Act of 1995 (UMRA) (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).
XI. 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: April 1, 2010.
Lois Rossi,
Director, Registration Division, Office of Pesticide Programs.
0
Therefore, 40 CFR chapter I is amended as follows:
PART 180--[AMENDED]
0
1. The authority citation for part 180 continues to read as follows:
Authority: 21 U.S.C. 321(q), 346a and 371.
0
2. In Sec. 180.920, in the table add alphabetically the following inert
ingredient to read as follows:
Sec. 180.920 Inert ingredients used pre-harvest; exemptions from the
requirement of a tolerance.
* * * * *
[[Page 19268]]
------------------------------------------------------------------------
Inert ingredients Limits Uses
------------------------------------------------------------------------
* * * * * * *
Alkyl (C12-C16) dimethyl ammonio 20% by weight in Surfactant
acetate (CAS Reg. Nos. 683-10- pesticide
3, 2601-33-4 and 693-33-4 formulation
* * * * * * *
------------------------------------------------------------------------
0
3. In Sec. 180.930, in the table add alphabetically the following inert
ingredient to read as follows:
Sec. 180.930 Inert ingredients applied to animals; exemptions from
the requirement of a tolerance.
* * * * *
------------------------------------------------------------------------
Inert ingredients Limits Uses
------------------------------------------------------------------------
* * * * * * *
Alkyl (C12-C16) dimethyl ammonio 20% by weight in Surfactant
acetate (CAS Reg. Nos. 683-10- pesticide
3, 2601-33-4 and 693-33-4 formulation
* * * * * * *
------------------------------------------------------------------------
[FR Doc. 2010-8298 Filed 4-13-10; 8:45 am]
BILLING CODE 6560-50-S