[Federal Register Volume 74, Number 193 (Wednesday, October 7, 2009)]
[Rules and Regulations]
From the Federal Register Online via the Government Publishing Office [www.gpo.gov]
[FR Doc No: E9-24055]
ENVIRONMENTAL PROTECTION AGENCY
40 CFR Part 180
C10-C18-Alkyl dimethyl amine oxides;
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 C10-C18-Alkyl
dimethyl amine oxides (ADAO) when used as the inert ingredient in
pesticide formulations applied to raw agricultural commodities pre- and
post-harvest. Exponent on behalf of Stepan Company and Rhodia submitted
petitions 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 ADAOs.
DATES: This regulation is effective October 7, 2009. Objections and
requests for hearings must be received on or before December 7, 2009,
and must be filed in accordance with the instructions provided in 40
CFR part 178 (see also Unit I.C. of the SUPPLEMENTARY INFORMATION).
ADDRESSES: EPA has established a docket for this action under docket
identification (ID) number EPA-HQ-OPP-2009-0690. All documents in the
dockets are listed in the docket index available at http://www.regulations.gov. Although listed in the index, some information is
not publicly available, e.g., Confidential Business Information (CBI)
or other information whose disclosure is restricted by statute. Certain
other material, such as copyrighted material, is not placed on the
Internet and will be publicly available only in hard copy form.
Publicly available docket materials are available in the electronic
docket at http://www.regulations.gov, or, if only available in hard
copy, at the OPP Regulatory Public Docket in Rm. S-4400, One Potomac
Yard (South Bldg.), 2777 S. Crystal Dr., Arlington, VA. The Docket
Facility is open from 8:30 a.m. to 4 p.m., Monday through Friday,
excluding legal holidays. The Docket Facility telephone number is (703)
FOR FURTHER INFORMATION CONTACT: Lisa Austin, Registration Division
(7505P), Office of Pesticide Programs, Environmental Protection Agency,
1200 Pennsylvania Ave., NW., Washington, DC 20460-0001; telephone
number: (703) 305-7894; e-mail address: email@example.com.
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
B. How Can I Access Electronic Copies of this Document?
In addition to accessing electronically available documents at
http://www.regulations.gov, you may access this Federal Register
document electronically through the EPA Internet under the ``Federal
Register'' listings at http://www.epa.gov/fedrgstr. You may also access
a frequently updated electronic version of 40 CFR part 180 through the
Government Printing Office's e-CFR cite at http://www.gpoaccess.gov/ecfr. To access the OPPTS Harmonized Guidelines referenced in this
document, go to the guidelines at http://www.epa.gov/opptsfrs/home/guidelin.htm.
C. Can I File an Objection or Hearing Request?
Under section 408(g) of FFDCA, 21 U.S.C. 346a, any person may file
an objection to any aspect of this regulation and may also request a
hearing on those objections. 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-2009-0690 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 December 7, 2009.
In addition to filing an objection or hearing request with the
Hearing Clerk as described in 40 CFR part 178, please submit a copy of
the filing that does not contain any CBI for inclusion in the public
docket that is described in ADDRESSES. Information not marked
confidential pursuant to 40 CFR part 2 may be disclosed publicly by EPA
without prior notice. Submit your copies, identified by docket ID
EPA-HQ-OPP-2009-0690, by one of the following methods:
Federal eRulemaking Portal: http://www.regulations.gov.
Follow the on-line instructions for submitting comments.
Mail: Office of Pesticide Programs (OPP) Regulatory Public
Docket (7502P), Environmental Protection Agency, 1200 Pennsylvania
Ave., NW., Washington, DC 20460-0001.
Delivery: OPP Regulatory Public Docket (7502P),
Environmental Protection Agency, Rm. S-4400, One Potomac Yard (South
Bldg.), 2777 S. Crystal Dr., Arlington, VA. Deliveries are only
accepted during the Docket Facility's normal hours of operation (8:30
a.m. to 4 p.m., Monday through Friday, excluding legal holidays).
Special arrangements should be made for deliveries of boxed
information. The Docket Facility telephone number is (703) 305-5805.
II. Background and Statutory Findings
EPA received two petitions requesting that 40 CFR part 180 be
amended by establishing an exemption from the requirement of a
tolerance for residues of ADAOs. These two petitions are grouped
together because they fall under the same general chemical description
In the Federal Register of February 1, 2006 (71 FR 5322) (FRL-7756-
5), EPA issued a notice pursuant to section 408 (d)(3)of FFDCA, 21
U.S.C. 346a(d)(3), announcing the filing of a pesticide petition (PP
5E7003) by Stepan Company, 951 Bankhead Hwy., Winder, GA
30680. The petition requested that 40 CFR 180.920 be amended by
establishing an exemption from the requirement of a tolerance for
residues of ADAOs (CAS Reg. Nos. 1643-20-5, 2571-88-2, 2605-79-0, 3332-
27-2, 61788-90-7, 68955-55-5, 70592-80-2, 7128-91-8, 85408-48-6, and
85408-49-7). Also, in the Federal Register of December 3, 2008 (73 FR
73644) (FRL-8390-4), EPA issued a notice pursuant to section 408 (d)(3)
of FFDCA, 21 U.S.C. 346a(d)(3), announcing the filing of a pesticide
petition (PP 5E7003) by Stepan Company, 951 Bankhead Hwy.,
Winder, GA 30680. This petition is an addendum to PP 5E7003
and included the submission of new data only. Both notices included a
summary of the petition prepared by the petitioner. There were no
comments received in response to the notices of filing.
Also, in the Federal Register of April 13, 2009 (74 FR 16869) (FRL-
8396-6), EPA issued a notice pursuant to section 408 (d)(3)of FFDCA, 21
U.S.C. 346a(d)(3), announcing the filing of a pesticide petition (PP
8E7316) by Rhodia Inc. c/o SciReg, Inc., 12733 Director's
Loop, Woodbridge, VA 22192. The petition requested that 40 CFR 180.920
be amended by establishing an exemption from the requirement of a
tolerance for residues of ADAOs. The notice included a summary of the
petition prepared by the petitioner. There were no substantial comments
received in response to the notice of filing.
Based upon review of the data supporting the petitions
(5E7003 and 8E7316), EPA has modified the exemptions
requested by limiting ADAOs to a maximum of 15% by weight in pesticide
formulations. In addition, the risk assessment supports the expansion
of the exemptions from a requirement of tolerance to include use in
pesticide formulations intended for post- harvest as well as pre-
harvest application under 40 CFR 180.910. Further details can be found
at http://www.regulations.gov in document Decision Document for
Petition Numbers 5E7003 and 8E7316 (C10-16);
C10-C18-Alkyldimethylamine oxides CAS Reg. No.
1643-20-5, 2571-88-2, 2605-79-0, 3332-27-2, 61788-90-7, 68955-55-5,
70592-80-2, 7128-91-8, 85408-48-6, 85408-49-7) in docket ID numbers
EPA-HQ-OPP-2005-0310 and EPA-HQ-OPP-2008-0858.
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 ploymers 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
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
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 ADAOs is
limited to no more than 15% by weight in pesticide formulations when
used as an inert ingredient in pesticide formulations for pre- and
post-harvest uses. EPA's assessment of exposures and risks associated
with establishing tolerances follows.
A. Toxicological Profile
EPA has evaluated the available toxicity data and considered its
validity, completeness, and reliability as well as the relationship of
the results of the studies to human risk. EPA has also considered
available information concerning the variability of the sensitivities
of major identifiable subgroups of consumers, including infants and
The available toxicology database includes an acute, subchronic
(rat and rabbit), 21 and 90 day dermal toxicity (rabbit), developmental
(rat and rabbit), reproduction and fertility effects study, an OPPTS
Harmonized Guideline 870.3650 combined repeated dose toxicity studies
with the reproduction/developmental toxicity screening tests, chronic
dermal toxicity (mouse), chronic/carcinogenicity (rat), mutagenicity,
and metabolism studies.
ADAOs have moderate acute toxicity via the oral routes and low
toxicity via the dermal and inhalation routes. It is moderately
irritating to the skin and severely irritating to the eye. It is not a
Subchronic studies were available in the rat and rabbit. Following
subchronic exposure to rats via the diet, a decrease in body weight was
observed in females only while cataracts were observed in males only.
In the rabbit, subchronic exposure via the diet resulted in decreased
alkaline phosphatase levels and increased liver/body weight ratio.
A 21/28 day study and 91-day dermal toxicity studies were available
in rabbits. Systemic toxicity was not observed at the limit dose in the
21/28 day study and was not observed at the highest dose (2.5
milligrams/kilogram/day (mg/kg bw/day)) tested in the 91-day study.
Three developmental studies were available for review (2-rat, 1-
rabbit). In one developmental toxicity study in the rat (Sprague-
Dawley), maternal (decreased body weight gain) and offspring (skeletal
variation-bifid centrum) toxicity were manifested at 100 mg/kg/day. The
NOAEL in this study was 25 mg/kg/day. In a second developmental
toxicity study in the rat (CD), maternal and offspring toxicity
occurred at the same dose (200 mg/kg/day), the highest dose tested.
Effects similar to the previous study were observed. Maternal toxicity
was manifested as decreased body weight, food intake and water
consumption and offspring toxicity was manifested as a slight reduction
in fetal ossification. The NOAEL in this study was 100 mg/kg/day. In
the rabbit, maternal and offspring toxicity were not observed at doses
up to 160 mg/kg/day (highest dose tested, HDT). In a reproduction and
fertility effects study in the rat, neither maternal nor offspring
systemic toxicity was not observed at doses up to 40 mg/kg bw/day
(HDT). No treatment-related effects were observed on reproductive
In an OPPTS Harmonized Test Guideline 870.3650 study designed to
evaluate developmental, reproduction and neurological parameters,
maternal toxicity in the rat [HanRcc:WIST(SPF)] was manifested as
hyperkeratosis, parakeratosis, squamous cell hyperplasia, submucosal
inflammation and submucosal edema in the forestomach at 100 mg/kg/day
(mid dose tested, MDT). Mortality and decreased body weight were
observed in the offspring at 250 mg/kg/day (HDT). Reproductive toxicity
(decreased gestation index) was also manifested at 250 mg/kg/day.
Reduced total locomotor activity was observed in females at 250 mg/kg/
day. However, this effect was considered a result of systemic toxicity
rather than a result of neurological toxicity since it was transient,
occurred at the high dose in one gender only, it was not observed at
the lower doses, neuropathologic lesions were not observed and signs of
neurotoxicity were not observed in other studies. Changes in absolute
and relative thymus weights and atrophy were observed in males at the
250 mg/kg/d (HDT). These were determined to be non-specific changes not
indicative of immunotoxicity. In addition, no blood parameters were
affected. Furthermore, these compounds do not belong to a class of
chemicals that would be expected to be immunotoxic.
Several mutagenicity studies (Ames, chromosome aberration,
micronucleus assay, cell transformation, and cell dominant lethal
assay) were available for review. The results for these studies were
There were two chronic studies available, a chronic dermal toxicity
study in the mouse, and a chronic/carcinogenicity study in the rat. In
the dermal toxicity study in the mouse, systemic toxicity and evidence
of increased tumors were not observed at the HDT (5.6 mg/kg/day). In
the chronic carcinogenicity study in the rat, systemic toxicity was
manifested as decreased body weight and cataracts at 107 mg/kg/day
(HDT). Evidence of increased tumors was not observed. Based on the lack
of evidence of carcinogenicity in these studies and the negative
response for mutagenicity ADAOs are not expected to be carcinogenic.
Metabolism studies demonstrated that C12 ADAO was
absorbed in rats and extensively and rapidly excreted. The distribution
of C12 ADMO was similar between males and females. Among all
the tissues analyzed, the largest amount and the highest concentration
of radioactivity were found in the liver. The fractions of dosed
radioactivity appearing in the liver, kidney, and blood reached maxima
within 1 hour after the oral dose. The excretion of radioactivity was
rapid with approximately 70% and greater excreted within 24 hours. The
major excretory pathway was urine followed by expired CO2
with much less found in feces and bile.
Specific information on the studies received and the nature of the
adverse effects caused by ADAOs, 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 http://www.regulations.gov in the document Decision Document for Petition
Numbers 5E7003 and 8E7316 (C10-16); C10-
C18-Alkyldimethylamine oxides CAS Reg. No. 1643-20-5, 2571-
88-2, 2605-79-0, 3332-27-2, 61788-90-7, 68955-55-5, 70592-80-2, 7128-
91-8, 85408-48-6, 85408-49-7) at pp 7-18 in docket ID numbers EPA-HQ-
OPP-2005-0310 and EPA-HQ-OPP-2008-0858.
B. Toxicological Endpoints
For hazards that have a threshold below which there is no
appreciable risk, a toxicological point of departure (POD) is
identified as the basis for derivation of reference values for risk
assessment. The POD may be defined as the highest dose at which no
adverse effects are observed (the NOAEL) in the toxicology study
identified as appropriate for use in risk assessment. However, if a
NOAEL cannot be determined, the lowest dose at which adverse effects of
concern are identified (the LOAEL) or a Benchmark Dose (BMD) approach
is sometimes used for risk assessment. Uncertainty/safety factors (UFs)
are used in conjunction with the POD to take into account uncertainties
inherent in the extrapolation from laboratory animal data to humans and
in the variations in sensitivity among members of the human population
as well as other unknowns. Safety is assessed for acute and chronic
dietary risks by comparing aggregate food and water exposure to the
pesticide to the acute population adjusted dose (aPAD) and chronic
population adjusted dose (cPAD). The aPAD and cPAD are calculated by
dividing the POD by all applicable UFs. Aggregate short-, intermediate-
, and chronic-term risks are evaluated by comparing food, water, and
residential exposure to the POD to ensure that the margin of exposure
(MOE) called for by the product of all applicable UFs is not exceeded.
This latter value is referred to as the Level of Concern (LOC).
For non-threshold risks, the Agency assumes that any amount of
exposure will lead to some degree of risk. Thus, the Agency estimates
risk in terms of the probability of an occurrence of the adverse effect
greater than that expected in a lifetime. For more information on the
general principles EPA uses in risk characterization and a complete
description of the risk assessment process, see http://www.epa.gov/pesticides/factsheets/riskassess.htm.
A summary of the toxicological endpoints for ADAOs used for human
health risk assessment is shown in Table 1 of this unit.
Table 1.--Summary of Toxicological Doses and Endpoints for ADAOs 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 No appropriate endpoints were identified for acute dietary risk
(all populations)................... assessment.
Chronic dietary (all populations) NOAEL = 42.3 mg inert/ Chronic RfD = .42 mg/kg/ Chronic toxicity/
kg/day day oncogenicity study-
UFA = 10x.............. cPAD = .42 mg/kg/day... rat (CAS Reg. No.
UFH = 10x.............. 70592-80-2)
FQPA SF = 1x........... .......................
LOAEL = 87.4 mg/kg/day
based on decreased
body weight and
Incidental Oral Short- and NOAEL= 42.3 mg/kg/day Residential/ Chronic toxicity/
Intermediate Term Dermal and UFA = 10x.............. Occupational LOC for oncogenicity study-
Inhalation UFH = 10x.............. MOE = 100. rat (CAS Reg. No.
FQPA SF = 1x (10% 70592-80-2)
Dermal absorption; .......................
100% inhalation and LOAEL = 87.4 mg/kg/day
oral toxicity assumed based on decreased
equivalent). body weight and
Cancer Classification: ADAOs are not expected to be carcinogenic based on the
(oral, dermal, inhalation)........... lack of evidence of carcinogenicity in the chronic feeding study in rats
or in the chronic dermal study in mice as well as the negative response
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.
C. Exposure Assessment
1. Dietary exposure from food and feed uses. In evaluating dietary
exposure to the ADAOs, EPA considered exposure under the petitioned-for
exemptions from the requirement of a tolerance. EPA assessed dietary
exposures from ADAOs in food as follows:
i. Acute exposure. No adverse effects attributable to a single
exposure of ADAOs were seen in the toxicity databases. Therefore, acute
dietary risk assessments for ADAOs are not necessary.
ii. Chronic exposure. In conducting the chronic dietary exposure
assessment, EPA used food consumption information from the U.S.
Department of Agriculture (USDA) [1994-1996 and 1998] Nationwide
Continuing Surveys of Food Intake by Individuals (CSFII). As to residue
levels in food, no residue data were submitted for ADAOs. In the
absence of specific residue data, EPA has developed an approach which
uses surrogate information to derive upper bound exposure estimates for
the subject inert ingredient. Upper bound exposure estimates are based
on the highest tolerance for a given commodity from a list of high-use
insecticides, herbicides, and fungicides. A complete description of the
general approach taken to assess inert ingredient risks in the absence
of residue data is contained in the memorandum entitled ``Alkyl Amines
Polyalkoxylates (Cluster 4): Acute and Chronic Aggregate (Food and
Drinking Water) Dietary Exposure and Risk Assessments for the Inerts,''
(D361707, S. Piper, 2/25/09) and can be found at http://www.regulations.gov in docket ID number EPA-HQ-OPP-2008-0738.
In the dietary exposure assessment, the Agency assumed that the
residue level of the inert ingredient would be no higher than the
highest tolerance for a given commodity. Implicit in this assumption is
that there would be similar rates of degradation (if any) between the
active and inert ingredient and that the concentration of inert
ingredient in the scenarios leading to these highest levels of
tolerances would be no higher than the concentration of the active
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 ADAOs, EPA made a specific
adjustment to the dietary exposure assessment to account for the use
limitations of the amount of ADAOs that may be in formulations (to no
more than 15% by weight in pesticide products) and assumed that the
ADAOs are present at the maximum limitation rather than at equal
quantities with the active ingredient.
Second, the conservatism of this methodology is compounded by EPA's
decision to assume that, for each commodity, the active ingredient
which will serve as a guide to the potential level of inert ingredient
residues is the active ingredient with the highest tolerance level.
This assumption overstates residue values because it would be highly
unlikely, given the high number of inert ingredients, that a single
inert ingredient or class of ingredients would be present at the level
of the active ingredient in the highest tolerance for every commodity.
Finally, a third compounding conservatism is EPA's assumption that all
foods contain the inert ingredient at the highest tolerance level. In
other words, EPA assumed 100 percent of all foods are treated with the
inert ingredient at the rate and manner necessary to produce the
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. ADAOs are not expected to be carcinogenic since there
was no evidence of carcinogenicity in the chronic feeding studies in
mice and rats or in the chronic dermal study in mice as well as the
negative response for mutagenicity. Since the Agency has not identified
any concerns for carcinogenicity relating to ADAOs, a cancer dietary
exposure assessment was not performed.
iv. Anticipated residue and percent crop treated (PCT) information.
EPA did not use anticipated residue and/or PCT information in the
dietary assessment for ADAOs. Tolerance level residues and/or 100% CT
were assumed for all food commodities.
2. Dietary exposure from drinking water. For the purpose of the
screening level dietary risk assessment to support this request for an
exemption from the requirement of a tolerance for ADAOs, a conservative
drinking water concentration value of 100 parts per billion (ppb) based
on screening level modeling was used to assess the contribution to
drinking water for chronic dietary risk assessments for ADAOs. 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). ADAOs may be used in
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 ADAOs as inert ingredients. The
ADAO 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 home cleaning products. The
Agency selected representative scenarios, based on end-use product
application methods and labeled application rates. The Agency conducted
an assessment to represent worst-case residential exposure by assessing
ADAOs in pesticide formulations (Outdoor Scenarios) and ADAOs in
disinfectant-type uses (Indoor Scenarios). Based on information
contained in the petition, ADAOs can be present in consumer cleaning
products (maximum concentration 4%). Therefore, the Agency assessed the
disinfectant-type products containing ADAOs 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 ADAOs in pesticide formulations (Outdoor
Scenarios) and ADAOs in disinfectant-type uses (Indoor Scenarios).
Further details of this residential exposure and risk analysis can be
found at http://www.regulations.gov in the memorandum entitled: ``JITF
Inert Ingredients. Residential and Occupational Exposure Assessment
Algorithms and Assumptions Appendix for the Human Health Risk
Assessments to Support Proposed Exemption from the Requirement of a
Tolerance When Used as Inert Ingredients in Pesticide Formulations,''
(D364751, 5/7/09, Lloyd/LaMay in docket ID number EPA-HQ-OPP-2008-0710.
4. Cumulative effects from substances with a common mechanism of
toxicity. Section 408(b)(2)(D)(v) of FFDCA requires that, when
considering whether to establish, modify, or revoke a tolerance, the
Agency consider``available information''concerning the cumulative
effects of a particular pesticide's residues and``other substances that
have a common mechanism of toxicity.'' Unlike other pesticides for
which EPA has followed a cumulative risk approach based on a common
mechanism of toxicity, EPA has not made a common mechanism of toxicity
finding as to ADAOs and any other substances and, this material 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 ADAOs have a common mechanism of toxicity with other
substances. For information regarding EPA's efforts to determine which
chemicals have a common mechanism of toxicity and to evaluate the
cumulative effects of such chemicals, see 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 http://www.epa.gov/pesticides/cumulative/.
D. Safety Factor for Infants and Children
1. In general. Section 408(b)(2)(C) of FFDCA provides that EPA
shall apply an additional tenfold (10X) margin of safety for infants
and children in the case of threshold effects to account for prenatal
and postnatal toxicity and the completeness of the database on toxicity
and exposure unless EPA determines based on reliable data that a
different margin of safety will be safe for infants and children. This
additional margin of safety is commonly referred to as the FQPA safety
factor (SF). In applying this provision, EPA either retains the default
value of 10X, or uses a different additional safety factor when
reliable data available to EPA support the choice of a different
2. Prenatal and postnatal sensitivity. Qualitative susceptibility
was observed in the developmental toxicity studies in the rat. Skeletal
variations were observed in rat fetuses at a dose (100 mg/kg/day) that
caused maternal toxicity (decreased body weight gain). In a second
developmental study in the rat, increased incidence of bifid centrum
occurred in fetuses at a dose (100 mg/kg/day) that caused maternal
toxicity (decreased body weight gain). However, the concern for
qualitative fetal susceptibility is low because NOAELs are well
established in these two studies and protective of fetuses. The NOAEL
of 25 mg/kg/day established in the developmental study in the rat
represents the lowest NOAEL in the database. However, the NOAEL of 42.3
mg/kg/day was selected from the chronic/carcinogenicity study for use
in risk assessment. This decision was based on the conclusion that the
NOAEL of 25 mg/kg/day is an artifact of dose spread. The doses tested
in the developmental study in the rat were 0, 25, 100, and 200 mg/kg/
day. The LOAEL for this study was 100 mg/kg/day. In a second rat
developmental study and a 2-generation reproduction study, fetal and
maternal effects were consistently seen at doses >100 mg/kg/day, the
maternal and fetal NOAELs
were established at 100 mg/kg/day (developmental study) and >40 mg/kg/
day (2-generation reproduction study, highest dose tested). In a
recently conducted combined developmental/reproduction screening study
(OPPTS Harmonized Guideline 870.3650), the maternal and offspring
NOAELs were 40 and 100 mg/kg/day, respectively, and effects were seen
at doses >100 mg/kg/day further supporting the higher NOAEL.
Additionally, in the chronic/carcinogenicity study, the NOAEL was 42.3
mg/kg/day, effects (decreased body weight and cataracts) were observed
at 87.4 mg/kg/day which is consistent with the dose at which other
effects were seen. Given this weight-of-evidence, it was concluded that
the NOAEL of 42.3 mg/kg/day most accurately reflected the true NOAEL.
Therefore, the established Chronic Reference Dose (cRfD) (0.42 mg/kg/
day) is protective of any developmental effects observed at doses as
low as 100 mg/kg/day in these studies. There are low concerns for
residual uncertainties concerning prenatal and postnatal toxicity.
3. Conclusion. EPA has determined that reliable data show the
safety of infants and children would be adequately protected if the
FQPA SF were reduced to 1X. That decision is based on the following
i. The toxicity database for the ADAOs inerts is considered
adequate for assessing the risks to infants and children. The toxicity
data available on the ADAOs is summarized in Unit IV.A.
ii. Although qualitative susceptibility was observed in the
developmental toxicity studies in the rat, the concern for qualitative
fetal susceptibility is low for the reasons noted in Unit IV.D.2.
iii. Evidence of neurotoxicity was noted in the combined
developmental/reproduction screening test in rats. Total locomotor
activity was reduced at the high dose (250 mg/kg/day) in females only.
However, EPA concluded that the reduction in locomotor activity was due
to excessive systemic toxicity at the high dose rather than due to
neurological origin. This conclusion is based on the following: effects
were seen only in one sex at the high dose, the effect was transient,
neurotoxicity was not observed at the lower doses in this study, there
were no neuropathological lesions in the study and clinical signs of
neurotoxicity and neuropathology were not observed in any other studies
in the database. Thus there is no need for a developmental
neurotoxicity study or additional UFs to account for neurotoxicity.
iv. The Agency noted changes in thymus weight and thymus atrophy
were observed in males at the high dose (250 mg/kg/day) only. These
were determined to be non-specific changes not indicative of
immunotoxicity. In addition, no blood parameters were affected.
Furthermore, these compounds do not belong to a class of chemicals that
would be expected to be immunotoxic. Therefore, these identified
effects do not raise a concern necessitating an additional uncertainty.
v. There are no residual uncertainties identified in the exposure
databases. The food and drinking water assessment is not likely to
underestimate exposure to any subpopulation, including those comprised
of infants and children. The food exposure assessments are considered
to be highly conservative as they are based on the use of the highest
tolerance level from the surrogate pesticides for every food and 100%
crop treated is assumed for all crops. EPA also made conservative
(protective) assumptions in the ground and surface water modeling used
to assess exposure to ADAOs in drinking water. These assessments will
not underestimate the exposure and risks posed by ADAOs.
E. Aggregate Risks and Determination of Safety
EPA determines whether acute and chronic pesticide exposures are
safe by comparing aggregate exposure estimates to the aPAD and cPAD.
The aPAD and cPAD represent the highest safe exposures, taking into
account all appropriate SFs. EPA calculates the aPAD and cPAD by
dividing the POD by all applicable UFs. For linear cancer risks, EPA
calculates the probability of additional cancer cases given the
estimated aggregate exposure. Short-, intermediate-, and chronic-term
risks are evaluated by comparing the estimated aggregate food, water,
and residential exposure to the POD to ensure that the MOE called for
by the product of all applicable UFs is not exceeded.
1. Acute risk.There was no hazard attributable to a single exposure
seen in the toxicity database for ADAOs. Therefore, the ADAOs are not
expected to pose an acute risk.
2. Chronic risk. A chronic aggregate risk assessment takes into
account exposure estimates from chronic dietary consumption of food and
drinking water Using the exposure assumptions discussed in this unit
for chronic exposure and the use limitations of not more than 15% by
weight in pesticide formulations, the chronic dietary exposure from
food and water to ADAO is 14% of the cPAD for the U.S. population and
45% of the cPAD for children 1 to 2 years old, the most highly exposed
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).
ADAOs 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 ADAOs. 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 250 for both adult males and females respectively.
Adult residential exposure combines high end dermal and inhalation
handler exposure from indoor hand 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 200 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
ADAOs 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 ADAOs. 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 840 for adult males and 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 210 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
5. Aggregate cancer risk for U.S. population. The Agency has not
identified any concerns for carcinogenicity relating to ADAOs.
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 ADAOs.
V. 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, ADAOs may
be subjected to further screening and/or testing to better characterize
effects related to endocrine disruption.
B. Analytical Method(s)
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
ADAOs nor have any CODEX Maximum Residue Levels (MRLs) been established
for any food crops at this time.
Based on the information in this preamble, EPA concludes that there
is a reasonable certainty of no harm from aggregate exposure to
residues of ADAOs. Accordingly, EPA finds that exempting ADAOs from the
requirement of a tolerance when used as an inert ingredient in
pesticide formulations applied to growing crops will be safe.
VII. Statutory and Executive Order Reviews
This final rule establishes a tolerance under section 408(d) of
FFDCA in response to a petition submitted to the Agency. The Office of
Management and Budget (OMB) has exempted these types of actions from
review under Executive Order 12866, entitled Regulatory Planning and
Review (58 FR 51735, October 4, 1993). Because this final rule has been
exempted from review under Executive Order 12866, this final rule is
not subject to Executive Order 13211, entitled Actions Concerning
Regulations That Significantly Affect Energy Supply, Distribution, or
Use (66 FR 28355, May 22, 2001) or Executive Order 13045, entitled
Protection of Children from Environmental Health Risks and Safety Risks
(62 FR 19885, April 23, 1997). This final rule does not contain any
information collections subject to OMB approval under the Paperwork
Reduction Act (PRA), 44 U.S.C. 3501 et seq., nor does it require any
special considerations under Executive Order 12898, entitled Federal
Actions to Address Environmental Justice in Minority Populations and
Low-Income Populations (59 FR 7629, February 16, 1994).
Since tolerances and exemptions that are established on the basis
of a petition under section 408(d) of FFDCA, such as the exemption 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
VIII. Congressional Review Act
The Congressional Review Act, 5 U.S.C. 801 et seq., generally
provides that before a rule may take effect, the agency promulgating
the rule must submit a rule report to each House of the Congress and to
the Comptroller General of the United States. EPA will submit a report
containing this rule and other required information to the U.S. Senate,
the U.S. House of Representatives, and the Comptroller General of the
United States prior to publication of this final rule in the Federal
Register. This final rule is not a ``major rule'' as defined by 5
List of Subjects in 40 CFR Part 180
Environmental protection, Administrative practice and procedure,
Agricultural commodities, Pesticides and pests, Reporting and
Dated: September 25, 2009.
Director, Registration Division, Office of Pesticide Programs.
Therefore, 40 CFR chapter I is amended as follows:
1. The authority citation for part 180 continues to read as follows:
Authority: 21 U.S.C. 321(q), 346a and 371.
2. In Sec. 180.910, the table is amended by adding alphabetically the
following inert ingredients:
Sec. 180.910 Inert ingredients used pre- and post-harvest; exemptions
from the requirement of a tolerance.
* * * * *
Inert ingredients Limits Uses
* * * * * * *
C10-C18-Alkyl dimethyl amine 15% by weight in Surfactant
oxides (CAS Reg. Nos. 1643-20- pesticide
5, 2571-88-2, 2605-79-0, 3332- formulation
27-2, 61788-90-7, 68955-55-5,
70592-80-2, 7128-91-8, 85408-48-
6, and 85408-49-7)
* * * * * * *
[FR Doc. E9-24055 Filed 10-06-09; 8:45 am]
BILLING CODE 6560-50-S