Document ID: EPA-HQ-OPP-2018-0561-0004
Agency: epa
Document Type: Rule
Title: Pesticide Tolerances: Indaziflam
Posted Date: 2019-10-10T04:00Z

[Federal Register Volume 84, Number 197 (Thursday, October 10, 2019)]
[Rules and Regulations]
[Pages 54510-54516]
From the Federal Register Online via the Government Publishing Office [www.gpo.gov]
[FR Doc No: 2019-21715]

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ENVIRONMENTAL PROTECTION AGENCY

40 CFR Part 180

[EPA-HQ-OPP-2018-0561; FRL-9999-70]

Indaziflam; Pesticide Tolerances

AGENCY: Environmental Protection Agency (EPA).

ACTION: Final rule.

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SUMMARY: This regulation establishes tolerances for residues of 
indaziflam in or on the tropical and subtropical fruit (edible peel) 
group 23 and tropical and subtropical fruit (inedible peel) group 24. 
Interregional Research Project Number 4 (IR-4) requested these 
tolerances under the Federal Food, Drug, and Cosmetic Act (FFDCA).

DATES: This regulation is effective October 10, 2019. Objections and 
requests for hearings must be received on or before December 9, 2019, 
and must be filed in accordance with the instructions provided in 40 
CFR part 178 (see also Unit I.C. of the SUPPLEMENTARY INFORMATION).

ADDRESSES: The docket for this action, identified by docket 
identification (ID) number EPA-HQ-OPP-2018-0561, is available at http://www.regulations.gov or at the Office of Pesticide Programs Regulatory 
Public Docket (OPP Docket) in the Environmental Protection Agency 
Docket Center (EPA/DC), West William Jefferson Clinton Bldg., Rm. 3334, 
1301 Constitution Ave. NW, Washington, DC 20460-0001. The Public 
Reading Room is open from 8:30 a.m. to 4:30 p.m., Monday through 
Friday, excluding legal holidays. The telephone number for the Public 
Reading Room is (202) 566-1744, and the telephone number for the OPP 
Docket is (703) 305-5805. Please review the visitor instructions and 
additional information about the docket available at http://www.epa.gov/dockets.

FOR FURTHER INFORMATION CONTACT: Michael Goodis, Registration Division 
(7505P), Office of Pesticide Programs, Environmental Protection Agency, 
1200 Pennsylvania Ave. NW, Washington, DC 20460-0001; main telephone 
number: (703) 305-7090; email address: RDFRNotices@epa.gov.

SUPPLEMENTARY INFORMATION: 

I. General Information

A. Does this action apply to me?

    You may be potentially affected by this action if you are an 
agricultural producer, food manufacturer, or pesticide manufacturer. 
The following list of North American Industrial Classification System 
(NAICS) codes is not intended to be exhaustive, but rather provides a 
guide to help readers determine whether this document applies to them. 
Potentially affected entities may include:

     Crop production (NAICS code 111).
     Animal production (NAICS code 112).
     Food manufacturing (NAICS code 311).
     Pesticide manufacturing (NAICS code 32532).

B. How can I get electronic access to other related information?

    You may access a frequently updated electronic version of EPA's 
tolerance regulations at 40 CFR part 180 through

[[Page 54511]]

the Government Publishing Office's e-CFR site at http://www.ecfr.gov/cgi-bin/text-idx?&c=ecfr&tpl=/ecfrbrowse/Title40/40tab_02.tpl.

C. How can I file an objection or hearing request?

    Under FFDCA section 408(g), 21 U.S.C. 346a, any person may file an 
objection to any aspect of this regulation and may also request a 
hearing on those objections. You must file your objection or request a 
hearing on this regulation in accordance with the instructions provided 
in 40 CFR part 178. To ensure proper receipt by EPA, you must identify 
docket ID number EPA-HQ-OPP-2018-0561 in the subject line on the first 
page of your submission. All objections and requests for a hearing must 
be in writing and must be received by the Hearing Clerk on or before 
December 9, 2019. Addresses for mail and hand delivery of objections 
and hearing requests are provided in 40 CFR 178.25(b).
    In addition to filing an objection or hearing request with the 
Hearing Clerk as described in 40 CFR part 178, please submit a copy of 
the filing (excluding any Confidential Business Information (CBI)) for 
inclusion in the public docket. Information not marked confidential 
pursuant to 40 CFR part 2 may be disclosed publicly by EPA without 
prior notice. Submit the non-CBI copy of your objection or hearing 
request, identified by docket ID number EPA-HQ-OPP-2018-0561, by one of 
the following methods:

     Federal eRulemaking Portal: http://www.regulations.gov. 
Follow the online instructions for submitting comments. Do not submit 
electronically any information you consider to be CBI or other 
information whose disclosure is restricted by statute.
     Mail: OPP Docket, Environmental Protection Agency Docket 
Center (EPA/DC), (28221T), 1200 Pennsylvania Ave. NW, Washington, DC 
20460-0001.
     Hand Delivery: To make special arrangements for hand 
delivery or delivery of boxed information, please follow the 
instructions at http://www.epa.gov/dockets/contacts.html. Additional 
instructions on commenting or visiting the docket, along with more 
information about dockets generally, is available at http://www.epa.gov/dockets.

II. Summary of Petitioned-For Tolerance

    In the Federal Register of December 21, 2018 (83 FR 65660) (FRL-
9985-67), EPA issued a document pursuant to FFDCA section 408(d)(3), 21 
U.S.C. 346a(d)(3), announcing the filing of a pesticide petition (PP 
8E8686) by IR-4, IR-4 Project Headquarters, Rutgers, The State 
University of New Jersey, 500 College Road East, Suite 201 W, 
Princeton, NJ 08540. The petition requested that 40 CFR part 180 be 
amended by establishing tolerances for residues of indaziflam, N-
[(1R,2S)-2,3-dihydro-2,6-dimethyl-1H-inden-1-yl]-6-(1-fluoroethyl)-
1,3,5-triazine-2,4-diamine, including its metabolites and degradates, 
in or on the raw agricultural commodities Fruit, tropical and 
subtropical, edible peel, group 23 at 0.01 ppm and Fruit, tropical and 
subtropical, inedible peel, group 24 at 0.01 ppm. The petition also 
requested to amend 40 CFR 180.653 by removing the established tolerance 
for residues of indaziflam in or on the raw agricultural commodity 
Fruit, tropical and subtropical, small fruit, edible peel, subgroup 23A 
at 0.01 ppm. That document referenced a summary of the petition 
prepared by Bayer CropScience, the registrant, which is available in 
the docket, http://www.regulations.gov. There were no comments received 
in response to the notice of filing.
    Although not requested, EPA is removing the tolerance for 
``banana'' since it is covered by the new group 24 tolerance. Also, the 
tolerance expression is being modified as well. The reasons for these 
changes are explained in Unit IV.C.

III. Aggregate Risk Assessment and Determination of Safety

    Section 408(b)(2)(A)(i) of FFDCA allows EPA to establish 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. . . 
.''
    Consistent with FFDCA section 408(b)(2)(D), and the factors 
specified in FFDCA section 408(b)(2)(D), EPA has reviewed the available 
scientific data and other relevant information in support of this 
action. EPA has sufficient data to assess the hazards of and to make a 
determination on aggregate exposure for indaziflam including exposure 
resulting from the tolerances established by this action. EPA's 
assessment of exposures and risks associated with indaziflam follows.

A. Toxicological Profile

    EPA has evaluated the available toxicity data and considered its 
validity, completeness, and reliability as well as the relationship of 
the results of the studies to human risk. EPA has also considered 
available information concerning the variability of the sensitivities 
of major identifiable subgroups of consumers, including infants and 
children.
    Metabolism studies with rats indicate that indaziflam is rapidly 
and completely (>90%) absorbed by the oral route, although absorption 
may become saturated at higher doses. Following absorption, indaziflam 
is distributed to multiple tissues, with the highest levels found in 
the liver, skin, and thyroid. Metabolism of indaziflam was extensive 
and occurred primarily via oxidation to form carboxylic acid and 
hydroxylated metabolites. Based on in vivo dermal absorption data from 
rats and comparative in vitro absorption data from rat and human skin, 
dermal absorption for humans is estimated to be 7.3%.
    The nervous system is the major target for toxicity in rats and 
dogs. Evidence of neurotoxicity (e.g., decreased motor activity, 
clinical signs, and/or neuropathology) was observed in both species 
throughout the database, which included the dog subchronic and chronic 
toxicity studies; the rat acute, subchronic, and developmental 
neurotoxicity (DNT) studies; the rat two-generation reproduction study; 
the rat chronic toxicity study; and the rat combined carcinogenicity/
chronic toxicity study. In repeated-dose studies, the dog was the more 
sensitive species, showing the lowest no observed adverse effects 
levels (NOAELs) and lowest observed adverse effects levels (LOAELs) 
among all available studies, based on neuropathology (degenerative 
nerve fibers in the brain, spinal cord, and sciatic nerve). At higher 
doses, three dogs in the subchronic study were prematurely terminated 
due to excessive clinical signs including ataxia, tremors, decreased 
pupil response, seizures, and other findings.
    In the rat, a marginal decrease in motor/locomotor activity was 
observed in females in the acute neurotoxicity study. Decreases in 
motor/locomotor

[[Page 54512]]

activity were also seen in the subchronic neurotoxicity study in 
females and in the DNT study in male offspring at post-natal day (PND) 
21. Clinical signs of neurotoxicity were observed in the acute, 
subchronic, and developmental neurotoxicity studies and consisted 
primarily of tremors, changes in activity and reactivity, repetitive 
chewing, dilated pupils, and oral, perianal, and nasal staining. 
Similar clinical signs of neurotoxicity were observed in the 2-
generation reproduction study, the rat chronic toxicity study, and the 
combined rat carcinogenicity/chronic toxicity study. Neuropathology 
findings were also observed in the rat manifested as focal/multifocal 
vacuolation of the median eminence of the brain and the pituitary pars 
nervosa and degenerative nerve fibers in the Gasserian ganglion, 
sciatic nerve, and tibial nerve. Evidence of neurotoxicity was not seen 
in the mouse following subchronic or chronic exposure.
    Other organs affected by indaziflam in mice and rats included the 
kidney, liver, thyroid, stomach, seminal vesicles, and ovaries. Effects 
on the kidney were observed following chronic exposure in rats and mice 
while effects on the liver were observed following chronic exposure in 
the rat. Effects on the thyroid were only observed in multiple dose rat 
studies and usually in the male only. Increased thyroid stimulating 
hormone (TSH) measured at 3 and 14 weeks in the 90-day and 1-year 
studies showed an increase in males at week 3. Histopathological 
alterations (thyroid follicular cell hypertrophy at 90 days and 1 year, 
as well as colloid alterations at chronic exposure times) were 
observed, but no increases in thyroid weight were noted. Thyroid 
histopathology was observed at a lower dose in the two-year study, 
compared to the 90-day and 1-year studies. Chronic exposures also led 
to atrophied or small seminal vesicles in male rats and glandular 
erosion/necrosis in the stomach and blood-filled ovarian cysts/
follicles in female mice. In rats, effects observed on the liver, 
thyroid, kidney, and seminal vesicles occurred at doses that were 
similar to or higher than those that produced neurotoxicity. However, 
these effects in the rat occurred at higher doses than those at which 
neurotoxicity was observed in the dog. Decreased body weight was also 
observed in most subchronic and chronic studies following oral exposure 
to indaziflam. There was no evidence of immunotoxicity in the available 
studies, which included a guideline immunotoxicity study in the rat. No 
systemic effects were observed in the rat following a 28-day dermal 
exposure period.
    Since the previous assessment, the maternal findings in the rat 
developmental toxicity study have been revised because the decreases in 
maternal weight gain and food consumption did not result in reduced 
mean maternal body weight at any dose tested and no other maternal 
findings were reported. Decreased mean fetal weight was observed at the 
highest dose tested, indicating increased quantitative susceptibility. 
However, no evidence of increased quantitative or qualitative 
susceptibility was seen in developmental toxicity studies in rabbits, a 
developmental neurotoxicity study in rats, or in a 2-generation 
reproduction study in rats. No developmental effects were observed in 
rabbits up to maternally toxic dose levels. Decreased pup weight and 
delays in sexual maturation (preputial separation in males and vaginal 
patency in females) were observed in the rat two-generation 
reproductive toxicity study, along with clinical signs of toxicity, at 
a dose causing parental toxicity that included coarse tremors, renal 
toxicity, and decreased weight gain. In the developmental neurotoxicity 
study, transiently decreased motor activity (PND 21 only) in male 
offspring was observed and was considered a potential neurotoxic 
effect. It was observed at a dose that also caused clinical signs of 
neurotoxicity along with decreased body weight in maternal animals.
    Indaziflam showed no evidence of carcinogenicity in the two-year 
dietary rat and mouse bioassays. All genotoxicity studies that were 
conducted on indaziflam were negative.
    Specific information on the studies received and the nature of the 
adverse effects caused by indaziflam as well as the NOAEL and the LOAEL 
from the toxicity studies can be found at http://www.regulations.gov in 
the document titled ``Indaziflam--Aggregate Human Health Risk 
Assessment of the Proposed New Use on Lowbush Blueberry, and Crop Group 
Expansions to Tropical and Subtropical Fruit, Edible Peel, Group 23 and 
Tropical and Subtropical Fruit, Inedible Peel, Group 24'' on pages 29-
39 in docket ID number EPA-HQ-OPP-2018-0561.

B. Toxicological Points of Departure/Levels of Concern

    Once a pesticide's toxicological profile is determined, EPA 
identifies toxicological points of departure (POD) and levels of 
concern to use in evaluating the risk posed by human exposure to the 
pesticide. For hazards that have a threshold below which there is no 
appreciable risk, the toxicological POD is used as the basis for 
derivation of reference values for risk assessment. PODs are developed 
based on a careful analysis of the doses in each toxicological study to 
determine the dose at which no adverse effects are observed (the NOAEL) 
and the lowest dose at which adverse effects of concern are identified 
(the LOAEL). Uncertainty/safety factors are used in conjunction with 
the POD to calculate a safe exposure level--generally referred to as a 
population-adjusted dose (PAD) or a reference dose (RfD)--and a safe 
margin of exposure (MOE). For non-threshold risks, the Agency assumes 
that any amount of exposure will lead to some degree of risk. Thus, the 
Agency estimates risk in terms of the probability of an occurrence of 
the adverse effect expected in a lifetime. For more information on the 
general principles EPA uses in risk characterization and a complete 
description of the risk assessment process, see http://www2.epa.gov/pesticide-science-and-assessing-pesticide-risks/assessing-human-health-risk-pesticide.
    A summary of the toxicological endpoints for indaziflam used for 
human risk assessment is shown in Table 1 of this unit.

[[Page 54513]]

  Table 1--Summary of Toxicological Doses and Endpoints for Indaziflam for Use in Human Health Risk Assessment
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                                    Point of departure
        Exposure/scenario            and uncertainty/     RfD, PAD, LOC for     Study and toxicological effects
                                      safety factors       risk assessment
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Acute dietary (General population  NOAEL = 7.5 mg/kg/    Acute RfD = 0.075    Subchronic Gavage Toxicity Study
 including infants and children     day.                  mg/kg/day aPAD =     in Dogs.
 and females 13 to 49 years old).  UFA = 10x...........   0.075 mg/kg/day.    LOAEL = 15 mg/kg/day, based on
                                   UFH = 10x...........                        axonal degenerative microscopic
                                   FQPA SF = 1x........                        findings in the brain, spinal
                                                                               cord, and sciatic nerve.
Chronic dietary (All populations)  NOAEL= 2 mg/kg/day..  Chronic RfD = 0.02   Chronic Dietary Toxicity Study in
                                   UFA = 10x...........   mg/kg/day cPAD =     Dogs.
                                   UFH = 10x...........   0.02 mg/kg/day.     LOAEL = \6/7\ mg/kg/day M/F, based
                                   FQPA SF = 1x........                        on nerve fiber degenerative
                                                                               lesions in the brain, spinal
                                                                               cord, and sciatic nerve.
Incidental oral short-term (1 to   NOAEL= 7.5 mg/kg/day  LOC for MOE = 100..  Subchronic Gavage Toxicity Study
 30 days).                         UFA = 10x...........                        in Dogs.
                                   UFH = 10x...........                       LOAEL = 15 mg/kg/day, based on
                                   FQPA SF = 1x........                        axonal degenerative microscopic
                                                                               findings in the brain, spinal
                                                                               cord, and sciatic nerve.
Dermal short-term (1 to 30 days).  Oral study NOAEL =    LOC for MOE = 100..  Subchronic Gavage Toxicity Study
                                    7.5 mg/kg/day                              in Dogs.
                                    (dermal absorption                        LOAEL = 15 mg/kg/day, based on
                                    rate = 7.3%).                              axonal degenerative microscopic
                                   UFA = 10x...........                        findings in the brain, spinal
                                   UFH = 10x...........                        cord, and sciatic nerve.
                                   FQPA SF = 1x........
Inhalation short-term (1 to 30     Oral study NOAEL=     LOC for MOE = 100..  Subchronic Gavage Toxicity Study
 days).                             7.5 mg/kg/day                              in Dogs.
                                    (inhalation                               LOAEL = 15 mg/kg/day, based on
                                    absorption rate =                          axonal degenerative microscopic
                                    100%).                                     findings in the brain, spinal
                                   UFA = 10x...........                        cord, and sciatic nerve.
                                   UFH = 10x...........
                                   FQPA SF = 1x........
                                  ------------------------------------------------------------------------------
Cancer (Oral, dermal, inhalation)  No Evidence of Carcinogenicity. Classified as ``Not Likely to be Carcinogenic
                                    to Humans.''
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FQPA SF = Food Quality Protection Act Safety Factor. LOAEL = lowest-observed-adverse-effect-level. LOC = level
  of concern. mg/kg/day = milligram/kilogram/day. MOE = margin of exposure. NOAEL = no-observed-adverse-effect-
  level. PAD = population adjusted dose (a = acute, c = chronic). RfD = reference dose. UF = uncertainty factor.
  UFA = extrapolation from animal to human (interspecies). UFH = potential variation in sensitivity among
  members of the human population (intraspecies).

C. Exposure Assessment

    1. Dietary exposure from food and feed uses. In evaluating dietary 
exposure to indaziflam, EPA considered exposure under the petitioned-
for tolerances as well as all existing indaziflam tolerances in 40 CFR 
180.653. EPA assessed dietary exposures from indaziflam in food as 
follows:
    i. Acute exposure. Quantitative acute dietary exposure and risk 
assessments are performed for a food-use pesticide, if a toxicological 
study has indicated the possibility of an effect of concern occurring 
as a result of a 1-day or single exposure.
    Such effects were identified for indaziflam. In estimating acute 
dietary exposure, EPA used 2003-2008 food consumption information from 
the U.S. Department of Agriculture's (USDA's) National Health and 
Nutrition Examination Survey, What We Eat in America, (NHANES/WWEIA). 
As to residue levels in food, the acute assessment was based on 
tolerance-level residues and 100 percent crop treated (PCT).
    ii. Chronic exposure. In estimating chronic dietary exposure, EPA 
used 2003-2008 food consumption information from the USDA's NHANES/
WWEIA. As to residue levels in food, the chronic assessment was based 
on tolerance-level residues and 100 PCT.
    iii. Cancer. Based on the data summarized in Unit III.A., EPA has 
concluded that indaziflam does not pose a cancer risk to humans. 
Therefore, a dietary exposure assessment for the purpose of assessing 
cancer risk is unnecessary.
    iv. Anticipated residue and PCT information. EPA did not use 
anticipated residue estimates or PCT information in the dietary 
assessment for indaziflam. Tolerance level residues and 100 PCT were 
assumed for all food commodities.
    2. Dietary exposure from drinking water. The Agency used screening 
level water exposure models in the dietary exposure analysis and risk 
assessment for indaziflam in drinking water. These simulation models 
take into account data on the physical, chemical, and fate/transport 
characteristics of indaziflam. Further information regarding EPA 
drinking water models used in pesticide exposure assessments can be 
found at http://www2.epa.gov/pesticide-science-and-assessing-pesticide-risks/about-water-exposure-models-used-pesticide.
    Residues of concern in drinking water are indaziflam, triazine 
indanone, indaziflam-carboxylic acid, indaziflam-olefin, indaziflam-
hydroxyethyl, and fluoroethyl diaminotriazine (FDAT). With the 
exception of FDAT, all of the metabolites are assumed to have 
comparable toxicity to the parent due to structural similarity (i.e., 
both rings intact). However, FDAT, a single-ring metabolite, is not 
expected to be more toxic than the parent indaziflam based on FDAT's 
non-neurotoxic mode of action. The Agency calculated total indaziflam 
estimated drinking water

[[Page 54514]]

concentrations (EDWCs) for residues of concern that are structurally 
similar to indaziflam (i.e., indaziflam, triazine-indanone, indaziflam-
carboxylic acid, indaziflam-hydroxyethyl, and indaziflam-olefin), and 
separate EDWCs for total FDAT, including its fluoroethyl-
triazinanedione (ROI1) degradate. The Agency combined the total 
indaziflam and total FDAT EDWCs for use in the dietary assessments.
    Based on the Pesticide in Water Calculator (PWC), the EDWCs of 
combined residues of indaziflam for acute exposures are estimated to be 
84 parts per billion (ppb) for surface water and 3.7 ppb for ground 
water, and for chronic exposures are estimated to be 26 ppb for surface 
water and 3.7 ppb for ground water.
    Modeled estimates of drinking water concentrations were directly 
entered into the dietary exposure model. For the acute dietary risk 
assessment, the water concentration value of 84 ppb was used to assess 
the contribution to drinking water. For the chronic dietary risk 
assessment, the water concentration value of 26 ppb was used to assess 
the contribution to drinking water.
    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).
    Indaziflam is currently registered for the following uses that 
could result in residential exposures: Turf, gardens, and trees. EPA 
assessed residential exposure using the following assumptions: Short-
term dermal and inhalation handler exposure is expected for adults as a 
result of applying products containing indaziflam to lawns/turf and 
gardens/trees using a variety of application equipment. Short-term 
post-application dermal exposure is expected for adults, children 11 to 
less than 16 years old, and children 6 to less than 11 years old as a 
result of playing, mowing, and/or golfing on treated turf. Short-term 
dermal and incidental oral exposure (hand to mouth, object to mouth, 
incidental soil ingestion) is expected for children 1 to less than 2 
years old as a result from playing on treated turf/lawns. Lastly, 
short-term post-application dermal exposure is expected for adults and 
children 6 to less than 11 years old as result of application to 
gardens and trees.
    The Agency selected only the most conservative, or worst case, 
residential adult and child scenarios to be included in the aggregate 
estimates, based on the lowest overall MOE (i.e., highest risk 
estimates). The worst-case residential exposure scenario for both 
adults and children resulted from short-term dermal and incidental oral 
(for children only) post-application exposure to treated turf. Further 
information regarding EPA standard assumptions and generic inputs for 
residential exposures may be found at http://www2.epa.gov/pesticide-science-and-assessing-pesticide-risks/standard-operating-procedures-residential-pesticide.
    4. Cumulative effects from substances with a common mechanism of 
toxicity. Section 408(b)(2)(D)(v) of FFDCA requires that, when 
considering whether to establish, modify, or revoke a tolerance, the 
Agency consider ``available information'' concerning the cumulative 
effects of a particular pesticide's residues and ``other substances 
that have a common mechanism of toxicity.''
    EPA has not found indaziflam to share a common mechanism of 
toxicity with any other substances, and indaziflam does not appear to 
produce a toxic metabolite produced by other substances. For the 
purposes of this tolerance action, therefore, EPA has assumed that 
indaziflam does not have a common mechanism of toxicity with other 
substances. For information regarding EPA's efforts to determine which 
chemicals have a common mechanism of toxicity and to evaluate the 
cumulative effects of such chemicals, see EPA's website at http://www2.epa.gov/pesticide-science-and-assessing-pesticide-risks/cumulative-assessment-risk-pesticides.

D. Safety Factor for Infants and Children

    1. In general. Section 408(b)(2)(C) of FFDCA provides that EPA 
shall apply an additional tenfold (10X) margin of safety for infants 
and children in the case of threshold effects to account for prenatal 
and postnatal toxicity and the completeness of the database on toxicity 
and exposure unless EPA determines based on reliable data that a 
different margin of safety will be safe for infants and children. This 
additional margin of safety is commonly referred to as the FQPA Safety 
Factor (SF). In applying this provision, EPA either retains the default 
value of 10X, or uses a different additional safety factor when 
reliable data available to EPA support the choice of a different 
factor.
    2. Prenatal and postnatal sensitivity. Since the previous 
assessment, the maternal findings in the rat developmental toxicity 
study have been revised because the decreases in maternal weight gain 
and food consumption did not result in reduced mean maternal body 
weight at any dose tested and no other maternal findings were reported. 
Decreased mean fetal weight was observed at the highest dose tested, 
indicating increased quantitative susceptibility. However, no evidence 
of increased quantitative or qualitative susceptibility was seen in 
developmental toxicity studies in rabbits, a developmental 
neurotoxicity study in rats, or in a 2-generation reproduction study in 
rats. No developmental effects were observed in rabbits up to 
maternally toxic dose levels. Decreased pup weight and delays in sexual 
maturation (preputial separation in males and vaginal patency in 
females) were observed in the rat two-generation reproductive toxicity 
study, along with clinical signs of toxicity, at a dose causing 
parental toxicity that included coarse tremors, renal toxicity and 
decreased weight gain. In the developmental neurotoxicity study, 
transiently decreased motor activity (PND 21 only) in male offspring 
was observed and was considered a potential neurotoxic effect. It was 
observed at a dose that also caused clinical signs of neurotoxicity 
along with decreased body weight in maternal animals.
    3. Conclusion. EPA has determined that reliable data show the 
safety of infants and children would be adequately protected if the 
FQPA SF were reduced to 1x. That decision is based on the following 
findings:
    i. The toxicity database for indaziflam is complete.
    ii. Evidence of neurotoxicity was observed in dogs and rats 
throughout the database, which included the dog subchronic toxicity 
study; the rat subchronic toxicity; the rat acute, subchronic, and 
developmental neurotoxicity screening batteries; the rat two-generation 
reproduction study; the rat chronic toxicity study; and the rat 
combined carcinogenicity/chronic toxicity study. Evidence of 
neurotoxicity was manifested as neuropathology in dogs and as decreased 
motor activity and clinical signs (e.g., tremors) in rats. Evidence of 
neurotoxicity was the most consistent effect (seen in dogs and rats), 
the most sensitive toxicological finding (based on neuropathology in 
dogs) and is being used as the basis for the risk assessment.
    iii. No developmental effects were observed in rabbits up to 
maternally toxic dose levels. Offspring effects in the DNT study in 
rats and multi-generation toxicity studies only occurred in the 
presence of maternal toxicity and were not considered more severe than 
the parental effects. However, decreased

[[Page 54515]]

fetal weight was observed in the rat developmental toxicity study in 
the absence of adverse maternal effects. Therefore, the Agency 
concluded that there is evidence of increased quantitative 
susceptibility to rat fetuses exposed in utero to indaziflam. In all 
studies, clear NOAELs/LOAELs were identified for maternal/parental and 
fetal/offspring effects.
    iv. There are no residual uncertainties identified in the exposure 
databases. The dietary food exposure assessments were performed based 
on 100 PCT and tolerance-level residues. EPA made conservative 
(protective) assumptions in the ground and surface water modeling used 
to assess exposure to indaziflam in drinking water. EPA used similarly 
conservative assumptions to assess post-application exposure of 
children as well as incidental oral exposure of toddlers. These 
assessments will not underestimate the exposure and risks posed by 
indaziflam.

E. Aggregate Risks and Determination of Safety

    EPA determines whether acute and chronic dietary pesticide 
exposures are safe by comparing aggregate exposure estimates to the 
acute PAD (aPAD) and chronic PAD (cPAD). For linear cancer risks, EPA 
calculates the lifetime probability of acquiring cancer 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 appropriate PODs to ensure that an 
adequate MOE exists.
    1. Acute risk. Using the exposure assumptions discussed in this 
unit for acute exposure, the acute dietary exposure from food and water 
to indaziflam will occupy 19% of the aPAD for all infants less than 1 
year old, the population group receiving the greatest exposure.
    2. Chronic risk. Using the exposure assumptions described in this 
unit for chronic exposure, EPA has concluded that chronic exposure to 
indaziflam from food and water will utilize 7.8% of the cPAD for all 
infants less than 1 year old, the population group receiving the 
greatest exposure. Based on the explanation in Unit III.C.3., regarding 
residential use patterns, chronic residential exposure to residues of 
indaziflam is not expected.
    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). Indaziflam is 
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 indaziflam. Using the exposure 
assumptions described in this unit for short-term exposures, EPA has 
concluded the combined short-term food, water, and residential 
exposures result in aggregate MOEs of 1,400 for adults and 580 for 
children 1 to less than 2 years old. Because EPA's level of concern for 
indaziflam is an MOE of 100 or below, 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).
    An intermediate-term adverse effect was identified; however, 
indaziflam is not registered for any use patterns that would result in 
intermediate-term residential exposure. Intermediate-term risk is 
assessed based on intermediate-term residential exposure plus chronic 
dietary exposure. Because there is no intermediate-term residential 
exposure and chronic dietary exposure has already been assessed under 
the appropriately protective cPAD (which is at least as protective as 
the POD used to assess intermediate-term risk), no further assessment 
of intermediate-term risk is necessary, and EPA relies on the chronic 
dietary risk assessment for evaluating intermediate-term risk for 
indaziflam.
    5. Aggregate cancer risk for U.S. population. Based on the lack of 
evidence of carcinogenicity in two adequate rodent carcinogenicity 
studies, indaziflam is not expected to pose a cancer risk to humans.
    6. Determination of safety. Based on these risk assessments, EPA 
concludes that there is a reasonable certainty that no harm will result 
to the general population, or to infants and children from aggregate 
exposure to indaziflam residues.

IV. Other Considerations

A. Analytical Enforcement Methodology

    Adequate enforcement methodology (liquid chromatography with tandem 
mass spectrometry detection (LC/MS/MS) method (DH-003-P07-02) for fruit 
and nut tree matrices for indaziflam and FDAT) is available to enforce 
the tolerance expression. The method may be requested from: Chief, 
Analytical Chemistry Branch, Environmental Science Center, 701 Mapes 
Rd., Ft. Meade, MD 20755-5350; telephone number: (410) 305-2905; email 
address: residuemethods@epa.gov.

B. International Residue Limits

    In making its tolerance decisions, EPA seeks to harmonize U.S. 
tolerances with international standards whenever possible, consistent 
with U.S. food safety standards and agricultural practices. EPA 
considers the international maximum residue limits (MRLs) established 
by the Codex Alimentarius Commission (Codex), as required by FFDCA 
section 408(b)(4). The Codex Alimentarius is a joint United Nations 
Food and Agriculture Organization/World Health Organization food 
standards program, and it is recognized as an international food safety 
standards-setting organization in trade agreements to which the United 
States is a party. EPA may establish a tolerance that is different from 
a Codex MRL; however, FFDCA section 408(b)(4) requires that EPA explain 
the reasons for departing from the Codex level.
    The Codex has not established any MRLs for indaziflam.

C. Revisions to Petitioned-For Tolerances

    Although not requested, EPA is also removing the existing tolerance 
for ``banana'' because it is superseded by the new crop group 24 
tolerance. Also, EPA is amending the tolerance expression for 
indaziflam to correct the residues that should be measured in 
determining compliance with the established tolerance levels. The 
Agency has determined that residues of the FDAT metabolite should be 
aggregated with residues of indaziflam when evaluating compliance with 
established tolerance levels. This revision does not require any 
changes in tolerance levels because those tolerance levels were 
established based on aggregated residues of FDAT and indaziflam. In 
accordance with its policy to improve the consistency and clarity of 
its tolerance expressions, EPA is revising the tolerance expression in 
this rulemaking.

V. Conclusion

    Therefore, tolerances are established for residues of indaziflam in 
or on Fruit, tropical and subtropical, edible peel, group 23 at 0.01 
ppm and Fruit, tropical and subtropical, inedible peel, group 24 at 
0.01 ppm.
    Additionally, the existing tolerances for both the tropical and 
subtropical, small fruit, edible peel, subgroup 23A and banana are 
removed as unnecessary due to the establishment of the above 
tolerances.

[[Page 54516]]

    Lastly, the tolerance expression in paragraph (a) is modified to 
read as follows: ``General. Tolerances are established for residues of 
the herbicide indaziflam, N-[(1R,2S)-2,3-dihydro-2,6-dimethyl-1H-inden-
1-yl]-6-(1-fluoroethyl)-1,3,5-triazine-2,4-diamine, including its 
metabolites and degradates, in or on the commodities in the following 
table. Compliance with the tolerance levels specified in the table 
below is to be determined by measuring only indaziflam and FDAT, 6-
[(1R)-1-fluoroethyl]-1,3,5-triazine-2,4-diamine, calculated as the 
stoichiometric equivalent of indaziflam, in or on the commodity.''

VI. Statutory and Executive Order Reviews

    This action establishes and modifies tolerances under FFDCA section 
408(d) in response to a petition submitted to the Agency. The Office of 
Management and Budget (OMB) has exempted these types of actions from 
review under Executive Order 12866, entitled ``Regulatory Planning and 
Review'' (58 FR 51735, October 4, 1993). Because this action has been 
exempted from review under Executive Order 12866, this action 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), nor is it considered a 
regulatory action under Executive Order 13771, entitled ``Reducing 
Regulations and Controlling Regulatory Costs'' (82 FR 9339, February 3, 
2017). This action does not contain any information collections subject 
to OMB approval under the Paperwork Reduction Act (PRA) (44 U.S.C. 3501 
et seq.), nor does it require any special considerations under 
Executive Order 12898, entitled ``Federal Actions to Address 
Environmental Justice in Minority Populations and Low-Income 
Populations'' (59 FR 7629, February 16, 1994).
    Since tolerances and exemptions that are established on the basis 
of a petition under FFDCA section 408(d), such as the tolerances 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 action directly regulates growers, food processors, food 
handlers, and food retailers, not States or tribes, nor does this 
action alter the relationships or distribution of power and 
responsibilities established by Congress in the preemption provisions 
of FFDCA section 408(n)(4). As such, the Agency has determined that 
this action will not have a substantial direct effect on States or 
tribal governments, on the relationship between the national government 
and the States or tribal governments, or on the distribution of power 
and responsibilities among the various levels of government or between 
the Federal Government and Indian tribes. Thus, the Agency has 
determined that Executive Order 13132, entitled ``Federalism'' (64 FR 
43255, August 10, 1999) and Executive Order 13175, entitled 
``Consultation and Coordination with Indian Tribal Governments'' (65 FR 
67249, November 9, 2000) do not apply to this action. In addition, this 
action does not impose any enforceable duty or contain any unfunded 
mandate as described under Title II of the Unfunded Mandates Reform Act 
(UMRA) (2 U.S.C. 1501 et seq.).
    This action does not involve any technical standards that would 
require Agency consideration of voluntary consensus standards pursuant 
to section 12(d) of the National Technology Transfer and Advancement 
Act (NTTAA) (15 U.S.C. 272 note).

VII. Congressional Review Act

    Pursuant to the Congressional Review Act (5 U.S.C. 801 et seq.), 
EPA will submit a report containing this rule and other required 
information to the U.S. Senate, the U.S. House of Representatives, and 
the Comptroller General of the United States prior to publication of 
the rule in the Federal Register. This action is not a ``major rule'' 
as defined by 5 U.S.C. 804(2).

List of Subjects in 40 CFR Part 180

    Environmental protection, Administrative practice and procedure, 
Agricultural commodities, Pesticides and pests, Reporting and 
recordkeeping requirements.

    Dated: September 18, 2019.
Michael Goodis,
Director, Registration Division, Office of Pesticide Programs.

    Therefore, 40 CFR chapter I is amended as follows:

PART 180--[AMENDED]

0
1. The authority citation for part 180 continues to read as follows:

    Authority:  21 U.S.C. 321(q), 346a and 371.

0
2. Section 180.653(a) is amended as follows:
0
a. Revise the introductory text; and
0
b. In the table:
0
i. Add a heading for the table;
0
ii. Remove the entry for ``Banana'';
0
iii. Add alphabetically the entries ``Fruit, tropical and subtropical, 
edible peel, group 23'' and ``Fruit, tropical and subtropical, inedible 
peel, group 24'';
0
iv. Remove the entry for ``Fruit, tropical and subtropical, small 
fruit, edible peel, subgroup 23A''; and
0
v. Remove footnote 2 to the table.
    The revision and additions read as follows:

Sec.  180.653  Indaziflam; tolerances for residues.

    (a) General. Tolerances are established for residues of the 
herbicide indaziflam, N-[(1R,2S)-2,3-dihydro-2,6-dimethyl-1H-inden-1-
yl]-6-(1-fluoroethyl)-1,3,5-triazine-2,4-diamine, including its 
metabolites and degradates, in or on the commodities in the following 
table. Compliance with the tolerance levels specified in the following 
table is to be determined by measuring only indaziflam and FDAT, 6-
[(1R)-1-fluoroethyl]-1,3,5-triazine-2,4-diamine, calculated as the 
stoichiometric equivalent of indaziflam, in or on the commodity.

                        Table 1 to Paragraph (a)
------------------------------------------------------------------------
                                                               Parts per
                          Commodity                             million
------------------------------------------------------------------------
 
                                * * * * *
Fruit, tropical and subtropical, edible peel, group 23......        0.01
Fruit, tropical and subtropical, inedible peel, group 24....        0.01
 
                                * * * * *
------------------------------------------------------------------------

* * * * *
[FR Doc. 2019-21715 Filed 10-9-19; 8:45 am]
 BILLING CODE 6560-50-P