Document ID: EPA-HQ-OPP-2009-0479-0003
Agency: epa
Document Type: Rule
Title: Exemption from the Requirement of a Tolerance: Alkyl (C12-C16) Dimethyl Ammonio Acetate
Posted Date: 2010-04-14T04:00Z

[Federal Register: April 14, 2010 (Volume 75, Number 71)]
[Rules and Regulations]               
[Page 19261-19268]
From the Federal Register Online via GPO Access [wais.access.gpo.gov]
[DOCID:fr14ap10-17]                         

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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.

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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 http://
www.regulations.gov. Although listed in the index, some information is 
not publicly available, e.g., Confidential Business Information (CBI) 
or other information whose disclosure is restricted by statute. Certain 
other material, such as copyrighted material, is not placed on the 
Internet and will be publicly available only in hard copy form. 
Publicly available docket materials are available in the electronic 
docket at http://www.regulations.gov, or, if only available in hard 
copy, at the OPP Regulatory Public Docket in Rm. S-4400, One Potomac 
Yard (South Bldg.), 2777 S. Crystal Dr., Arlington, VA. The Docket 
Facility is open from 8:30 a.m. to 4 p.m., Monday through Friday, 
excluding legal holidays. The Docket Facility telephone number is (703) 
305-5805.

FOR FURTHER INFORMATION CONTACT: 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 http://
www.gpoaccess.gov/ecfr. To access the OPPTS harmonized test quidelines 
referenced in this document electronically, please go to http://
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: 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

    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 http://
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 http://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 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 
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 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.

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 http://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