[Federal Register Volume 81, Number 155 (Thursday, August 11, 2016)]
[Rules and Regulations]
[Pages 53019-53025]
From the Federal Register Online via the Government Publishing Office [www.gpo.gov]
[FR Doc No: 2016-19118]


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ENVIRONMENTAL PROTECTION AGENCY

40 CFR Part 180

[EPA-HQ-OPP-2012-0919; FRL-9946-30]


Halauxifen-methyl; Pesticide Tolerances

AGENCY: Environmental Protection Agency (EPA).

ACTION: Final rule.

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SUMMARY: This regulation establishes tolerances for residues of 
halauxifen-methyl and its metabolite, XDE-729 acid, in or on multiple 
commodities which are identified and discussed later in this document. 
Dow AgroSciences LLC requested these tolerances under the Federal Food, 
Drug, and Cosmetic Act (FFDCA).

DATES: This regulation is effective August 11, 2016. Objections and 
requests for hearings must be received on or before October 11, 2016, 
and must be filed in accordance with the instructions provided in 40 
CFR part 178 (see also Unit I.C. of the SUPPLEMENTARY INFORMATION).

ADDRESSES: The docket for this action, identified by docket 
identification (ID) number EPA-HQ-OPP-2012-0919, 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: Susan Lewis, 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: [email protected].

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 the Government 
Printing 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-2012-0919 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 
October 11, 2016. 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-2012-0919, 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 February 15, 2013 (78 FR 11126) (FRL-
9378-4), 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 
2F8086) by Dow AgroSciences, 9330 Zionsville Road, Indianapolis, IN 
46268. The petition requested that 40 CFR part 180 be amended by 
establishing tolerances for residues of the herbicide, halauxifen-
methyl (methyl 4-amino-3-chloro-6-(4-chloro-2-fluoro-3-
methoxyphenyl)pyridine-2-carboxylate) and its major metabolite, XDE-729 
acid, expressed as halauxifen-methyl (parent) equivalents, in or on 
barley, grain at 0.01 parts per million (ppm); barley, hay at 0.01 ppm; 
barley, straw at 0.01 ppm; cattle, fat at 0.01 ppm; cattle, meat at 
0.01 ppm; cattle, meat byproducts at 0.01 ppm; goat, fat at 0.01 ppm; 
goat, meat at 0.01 ppm; goat, meat byproducts at 0.01 ppm; horse, fat 
at 0.01 ppm; horse, meat at 0.01 ppm; horse, meat byproducts at 0.01 
ppm; milk at 0.01 ppm; sheep, fat at 0.01 ppm; sheep, meat at 0.01 ppm; 
sheep, meat byproducts at 0.01 ppm; wheat, forage at 0.5 ppm; wheat, 
grain at 0.01 ppm; wheat, hay at 0.04 ppm; and wheat, straw at 0.015 
ppm. That document referenced a summary of the petition

[[Page 53020]]

prepared by Dow AgroSciences LLC, the registrant, which is available in 
the docket, http://www.regulations.gov. There were no comments received 
in response to the notice of filing.
    Based upon review of the data supporting the petition, EPA has 
determined that livestock commodity tolerances are not required for the 
proposed uses. In addition, the proposed ``wheat, hay'' tolerance level 
of 0.04 ppm will be set at a reduced tolerance level of 0.03 ppm. The 
reason 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 halauxifen-methyl and its acid 
metabolite, including exposure resulting from the tolerances 
established by this action. EPA's assessment of exposures and risks 
associated with halauxifen-methyl and its major metabolite, XDE-729 
acid, 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.
    The toxicology database for halauxifen-methyl is considered 
adequate at this time. Following oral exposure and absorption, the 
liver is exposed pre-systemically to halauxifen-methyl, where it is 
hydrolyzed to its major metabolite, XDE-729 acid, before entering the 
systemic circulation. Therefore, systemic exposure to organs and 
tissues other than the liver is to XDE-729 acid, whereas the liver is 
also exposed to the parent prior to its metabolism. The guideline 
studies were conducted on XDE-729 acid and identified the kidney as the 
main target organ. Bridging studies on halauxifen-methyl identified the 
liver as the target organ, but the data could not bridge to the acid 
metabolite because liver toxicity from exposure to halauxifen-methyl 
occurred at lower doses than the kidney toxicity resulting from 
exposure to XDE-729 acid. In lieu of conducting long-term oral studies 
on halauxifen-methyl, mechanistic studies were performed to 
characterize the mode of action (MOA) for liver toxicity. These studies 
identified activation of the liver aryl hydrocarbon receptor (AhR) as 
the MOA, and the molecular initiating event (MIE), for liver toxicity, 
for which increased liver Cyp1a1 gene expression serves as a biomarker. 
In the absence of this MIE, liver toxicity from parent halauxifen-
methyl, including induction of hepatocellular proliferation, will not 
be observed. A point of departure (POD) of 3 mg/kg/day for increased 
Cyp1a1 expression (observed at 10 mg/kg/day, the study NOAEL) was 
identified in the rat 90-day dietary study on halauxifen-methyl and was 
selected for chronic dietary risk assessment, since it protects for the 
initial step in liver toxicity, regardless of exposure duration. 
Therefore, the bridging and mechanistic studies were considered along 
with the guideline studies in selection of the dose and endpoint for 
halauxifen-methyl. Based on the abundance of guideline and mechanistic 
data available, a MOA approach was used for the identification and 
characterization of hazard. Due to the distinct toxicities of the two 
compounds and the unique MOA for liver toxicity of halauxifen-methyl, 
risk from the two compounds was assessed separately.
    There is no evidence of neurotoxicity or immunotoxicity for either 
compound. Inhalation studies (including the acute LD50 
study) were waived because MOEs for inhalation exposure, calculated 
using a highly conservative endpoint from oral data, were high 
(>=2,500), and the available oral and dermal studies did not indicate 
the potential for portal of entry effects. In addition, halauxifen-
methyl has a low vapor pressure and adequate particle sizes for test 
atmospheres could not be generated. Guideline rat or rabbit dermal 
toxicity, rat two-generation reproductive toxicity, dog chronic 
toxicity, rat chronic toxicity/carcinogenicity, mouse carcinogenicity, 
rat acute and subchronic neurotoxicity studies on halauxifen-methyl 
were also waived. The waivers were granted because adequate data were 
available for XDE-729 acid, to which systemic exposure would occur. The 
available data, when combined with the bridging and MOE data on 
halauxifen-methyl, allowed identification of a protective POD for AhR-
mediated liver toxicity. Therefore, an additional database uncertainty 
factor (UFDB) is not required for either compound. Both are 
mild eye irritants (Category III) but not dermal irritants or 
sensitizers. XDE-729 acid is classified as ``not likely to be 
carcinogenic to humans.'' Halauxifen-methyl is classified as ``not 
likely to be carcinogenic to humans at doses that do not induce Cyp1a1 
expression,'' based on the premise that AhR activation and subsequent 
promotion of hepatocellular tumors (via a prolonged increase in 
hepatocellular proliferation), a well-known non-genotoxic mechanism of 
liver carcinogenesis that has been previously described for other 
chemicals, depend upon this molecular initiating event (MIE). Moreover, 
based on its rapid metabolism to XDE-729 acid, halauxifen-methyl is not 
expected to persist in the body; therefore, progression of liver 
toxicity (including carcinogenic potential) from sustained AhR 
activation is not expected. Neither compound showed evidence of 
genotoxicity.
    There is no evidence of increased prenatal susceptibility to either 
compound in developmental toxicity studies in two species. No 
developmental toxicity was observed in the presence of maternal 
toxicity for rats exposed to halauxifen-methyl or rabbits exposed to 
XDE-729 acid. In rats exposed to XDE-729 acid, mild fetal effects 
(decreased body weight and delayed ossification of the thoracic centra) 
were observed in the presence of more significant maternal toxicity 
(moribund sacrifice due to excessively decreased body weight and food 
consumption, along with increased relative kidney weight). In rabbits 
exposed to halauxifen-methyl, the fetal effects (decreased body weight, 
increases in delayed ossification of the pubis) were observed in the 
presence of maternal liver histopathology and

[[Page 53021]]

increased liver weight, at a dose greater than the maternal LOAEL, and 
were therefore not considered indicative of greater sensitivity. In a 
rat two-generation reproductive toxicity study on XDE-729 acid, there 
was no evidence of increased postnatal susceptibility. Parental 
toxicity in the rat two-generation reproductive toxicity study was 
observed at 443 mg/kg/day (NOAEL 103 mg/kg/day), but no offspring or 
reproductive toxicity was reported. A reproductive toxicity study was 
not conducted on halauxifen-methyl. Residual concerns for postnatal 
susceptibility to halauxifen-methyl in the absence of this study are 
low, due to selection of a highly conservative endpoint and assumptions 
for dietary exposure, as well as the low level of exposure expected 
from proposed use patterns.
    Specific information on the studies received and the nature of the 
adverse effects caused by halauxifen-methyl and its metabolite, XDE-729 
acid, 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 Halauxifen-
methyl--New Active Ingredient Human Health Risk Assessment for Proposed 
Uses on Cereal Grains (Barley, Wheat, and Triticale) at page 42 in 
docket ID number EPA-HQ-OPP-2012-0919.

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://www.epa.gov/pesticides/factsheets/riskassess.htm.
    A summary of the toxicological endpoints for halauxifen-methyl used 
in the Agency's human health risk assessment is shown in Table 1(a) of 
this unit. No hazard from a single exposure was identified in the 
available database; therefore, no risk is expected from acute dietary 
exposure to halauxifen-methyl. For chronic dietary exposure, the rat 
90-day oral study was selected. Although long-term oral toxicity 
studies are not available for halauxifen-methyl, a dose and an endpoint 
protective of long-term toxicity could be identified using the 
subchronic data together with the MOA data. The rat 90-day study NOAEL 
of 10.3 mg/kg/day was based on increased liver weight, hypertrophy and 
vacuolization consistent with fatty change at the LOAEL of 53.4 mg/kg/
day. Liver effects at the LOAEL were of low severity but were 
considered treatment-related. A marked increase (1,500-fold above 
controls) in Cyp1a1 expression was also observed at the LOAEL. As 
previously noted, mechanistic studies on halauxifen-methyl identified 
activation of liver AhR as the MOA for liver toxicity, for which 
increased expression of Cyp1a1 in the liver is a biomarker for AhR 
activation, the MIE. In the absence of AhR activation, liver toxicity 
will not occur. Although there were no liver effects observed at the 
study NOAEL, a 52-fold increase in Cyp1a1 expression was observed. This 
increase is well below the increase that was associated which mild 
liver toxicity. Long-term effects on the liver from this lower level 
increase are not known in the absence of chronic data, but the lowest 
dose in the study, 3 mg/kg/day, showed essentially no Cyp1a1 
activation. Cyp1a1 expression at 3 mg/kg/day was comparable to controls 
in both the 28- and 90-day studies (1.2- and 3.6-fold higher than 
controls, respectively), indicating that there is not expected to be 
significant activation of the AhR receptor at this dose level over 
time. Therefore, in order to be protective of potential adverse effects 
on the liver following long-term exposure, the point of departure (POD) 
of 3 mg/kg/day was selected, based on increased expression of liver 
Cyp1a1 (52-fold) at 10 mg/kg/day. The selected dose and endpoint are 
considered conservative, since the dose is below the study NOAEL, but 
protective of residual uncertainty due to the lack of chronic data 
because liver toxicity may not occur in the absence of the MIE, 
regardless of exposure duration. They are also protective of chronic 
effects from XDE-729 acid, which are observed at higher doses. A UF of 
100 is based on the combined interspecies (10x) and intraspecies (10x) 
UFs. An additional 10x UF for lack of chronic data was not applied for 
the following reasons: (1) Progression of toxicity was not observed in 
the 28- and 90-day dietary studies in the rat: the NOAELs and LOAELs 
for both studies were the same, and the severity of the findings was 
minimal at both exposure durations; (2) evaluation of Cyp1a1 expression 
in the rat 28- and 90-day studies indicated that at the selected POD of 
3 mg/kg/day, which is below the NOAELs for these studies, there is no 
expectation of significant AhR activation that could lead to liver 
toxicity. Observable liver toxicity in these studies was only 
associated with significantly greater levels of Cyp1a1; (3) halauxifen-
methyl is rapidly metabolized to the acid, and neither bioaccumulate; 
and (4) based on comparative in vitro studies, humans are not 
anticipated to be more sensitive to liver effects of halauxifen-methyl 
than rats.
    Carcinogenicity studies on halauxifen-methyl were not conducted. 
Systemic exposure from halauxifen-methyl is primarily to XDE-729 acid, 
which showed no evidence of carcinogenicity. However, pre-systemic 
exposure of the liver to halauxifen-methyl was shown to activate the 
AhR receptor, an effect that induces an increase in hepatocellular 
proliferation and, subsequently, may promote an increased incidence of 
liver tumors with long-term exposure. The molecular marker for AhR 
activation, the MIE for liver toxicity, is increased expression of 
hepatic Cyp1a1, which was observed at a dose below the LOAEL for 
observable adverse effects of any type. The chronic dietary endpoint 
for halauxifen-methyl is based on the point of departure (POD) from the 
rat subchronic study for Cyp1a1 induction, as described above. The 
selected POD is considered very conservative because it is below the 
study NOAEL (the LOAEL was based on mild liver effects). Since Cyp1a1 
induction is one of the early key events in the MOA leading to 
hepatotoxicity and promotion of hepatocellular proliferation, a dose 
that is protective of this event will be protective of the potential 
risk for liver cancer with chronic exposure, based on the rapid onset 
of AhR activation following initiation of exposure, and the lack of 
evidence of temporal progression of

[[Page 53022]]

liver toxicity in the available studies (28- and 90-day). The MOA is 
considered relevant to human health risk assessment, but in vitro data 
suggest that humans are unlikely to be more sensitive than the rat. 
Based on a weight-of-the-evidence consideration, halauxifen-methyl is 
classified as ``not likely to be carcinogenic to humans'' at doses that 
do not induce liver Cyp1a1 expression.

   Table 1(a)--Summary of Toxicological Doses and Endpoints for Halauxifen-methyl 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
----------------------------------------------------------------------------------------------------------------
Acute dietary (General population  No hazard from a single exposure was identified in the available database;
 including infants and children     therefore, no risk is expected from this exposure scenario.
 and females age 13-49).
rrrrrrrrrrrrrrrrrrrrrrrrrrrrrrrrrr
Chronic dietary (All populations)  POD = 3.0 mg/kg/day.  Chronic RfD = 0.03   90-day oral toxicity in the rat
                                   UFA = 10x...........   mg/kg/day.           (halauxifen-methyl).
                                   UFH = 10x...........  cPAD = 0.03 mg/kg/   NOAEL = 10 mg/kg/day.
                                   FQPA SF = 1x........   day.                At the NOAEL, increased Cyp1a1
                                                                               expression was observed (endpoint
                                                                               selected for risk assessment).
                                                                               The lowest dose of 3.0 mg/kg/day
                                                                               was selected to be protective of
                                                                               potential long-term effects from
                                                                               increased AhR expression in the
                                                                               liver.\1\
                                                                              LOAEL = 52 mg/kg/day based on mild
                                                                               liver enlargement and pathology.
                                  ------------------------------------------------------------------------------
Cancer (Oral, dermal, inhalation)  Classification: Not likely to be carcinogenic to humans at dose levels that
                                    do not induce Cyp1a1 expression. The cRfD is considered protective of
                                    potential cancer effects because it protects for the MIE for hepatocellular
                                    proliferation (AhR activation) that, over time, may result in promotion of
                                    liver tumors.
----------------------------------------------------------------------------------------------------------------
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). FQPA SF = FQPA Safety Factor.
  PAD = population adjusted dose (a = acute, c = chronic). RfD = reference dose. MIE = molecular initiating
  event.
1. The POD selected for risk assessment was based on a non-adverse finding, increased liver Cyp1a1 expression in
  a rat 90-day dietary study, which was observed below the study NOAEL of 10 mg/kg/day for liver toxicity. This
  effect is a biomarker for activation of AhR, which causes liver toxicity and hepatocellular proliferation. The
  POD was selected to be protective of potential liver effects resulting from chronic dietary exposure to
  halauxifen-methyl. Other tissues and organs will not be exposed to halauxifen-methyl due to rapid conversion
  to XDE-729 acid. The POD is protective of effects from exposure to XDE-729 acid.

    A summary of the toxicological endpoints for XDE-729 acid used for 
human risk assessment is shown in Table 1(b) of this unit. No hazard 
from a single exposure was identified in the available database; 
therefore, no risk is expected from acute dietary exposure to XDE-729 
acid. The chronic toxicity/carcinogenicity study using the rat was 
chosen to assess chronic dietary risk to XDE-729 acid. A NOAEL of 20.3 
was chosen based on hyperplasia of the renal pelvic epithelium in 
females observed at 101 mg/kg/day. This NOAEL is protective of 
developmental effects, observed in the rat at 526 mg/kg/day (NOAEL = 
140 mg/kg/day), and of maternal toxicity in both the rat (LOAEL = 526 
mg/kg/day) and rabbit (LOAEL 1094 mg/kg/day).
    There was no evidence of carcinogenicity in rat and mouse cancer 
studies on XDE-729 acid, which is classified as ``not likely to be 
carcinogenic to humans.''

     Table 1(b)--Summary of Toxicological Doses and Endpoints for XDE-729 Acid for Use in Human Health Risk
                                                   Assessment
----------------------------------------------------------------------------------------------------------------
                                    Point of departure
        Exposure/Scenario            and uncertainty/     RfD, PAD, LOC for     Study and toxicological effects
                                      safety factors       risk assessment
----------------------------------------------------------------------------------------------------------------
Acute dietary (General population  No hazard from a single exposure was identified in the available database;
 including infants and children     therefore, no risk is expected from this exposure scenario.
 and females age 13-49).
                                  ------------------------------------------------------------------------------
Chronic dietary (All populations)  NOAEL = 20.3 mg/kg/   Chronic RfD = 0.20   Rat two-year dietary chronic
                                    day (females).        mg/kg/day.           toxicity/carcinogenicity study
                                                                              NOAEL = 101/20.3 mg/kg/day [M/F].
                                   UFA = 10x...........  cPAD = 0.20 mg/kg/   LOAEL = 404/101 mg/kg/day [M/F]
                                   UFH = 10x...........   day.                 based on increased mortality,
                                   FQPA SF = 1x........                        altered urinalysis parameters,
                                                                               decreased body weight, increased
                                                                               kidney weights, adrenal zone
                                                                               glomerulosa hypertrophy,
                                                                               increased degeneration and
                                                                               regeneration of renal tubules and
                                                                               kidney stones, and bladder
                                                                               pathology in males; in females,
                                                                               hyperplasia of pelvic epithelium
                                                                               of the kidney.
                                  ------------------------------------------------------------------------------

[[Page 53023]]

 
Cancer (Oral, dermal, inhalation)  Classification: Not likely to be carcinogenic to humans.
----------------------------------------------------------------------------------------------------------------
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). FQPA SF = FQPA Safety Factor.
  PAD = population adjusted dose (a = acute, c = chronic). RfD = reference dose. MOE = margin of exposure.

C. Exposure Assessment

    1. Dietary exposure from food and feed uses. In evaluating dietary 
exposure to halauxifen-methyl and the XDE-729 acid metabolite, EPA 
considered exposure under the petitioned-for tolerances. EPA assessed 
dietary exposures to these compounds 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. No such effects were 
identified in the toxicological studies for halauxifen-methyl or XDE-
729 acid; therefore, quantitative acute dietary exposure assessments 
were determined unnecessary.
    ii. Chronic exposure. In conducting individual chronic dietary 
exposure assessments for these two compounds, EPA used the food 
consumption data collected between 2003 and 2008 for USDA's National 
Health and Nutrition Survey/What We Eat in America (NHANES/WWEIA). As 
to residue levels in food, EPA used tolerance-level residues and 
assumed 100 percent of all wheat, barley and triticale acres are 
treated. No processing factors were used due to the lack of residue 
concentration in processed commodities. Residue chemistry data indicate 
that halauxifen-methyl (parent compound) converts to the XDE-729 acid 
metabolite so quickly in the environment that dietary exposure to 
halauxifen-methyl is expected to be minimal.
    iii. Cancer. Based on the data summarized in Unit III.A., EPA has 
concluded that halauxifen-methyl does not pose a cancer risk to humans 
at dose levels that do not induce liver toxicity or Cypla1 expression. 
EPA has also concluded that its XDE-729 acid metabolite does not pose a 
cancer risk to humans. Therefore, separate dietary exposure assessments 
for the purpose of assessing cancer risk are determined to be 
unnecessary.
    iv. Anticipated residue and percent crop treated (PCT) information. 
EPA did not use anticipated residue and/or PCT information in the 
dietary assessment for halauxifen-methyl. Tolerance-level residues and 
100% CT 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 halauxifen-methyl and its metabolites (primarily XDE-729 
acid) in drinking water. These simulation models take into account data 
on the physical, chemical, and fate/transport characteristics of 
halauxifen-methyl and its metabolites. Further information regarding 
EPA drinking water models used in pesticide exposure assessment can be 
found at http://www.epa.gov/oppefed1/models/water/index.htm.
    Based on the Pesticide Root Zone Model/Exposure Analysis Modeling 
System (PRZM/EXAMS) and Pesticide Root Zone Model Ground Water (PRZM 
GW), the estimated drinking water concentrations (EDWCs) of halauxifen-
methyl were estimated for chronic exposure in a non-cancer assessment. 
Based on the Screening Concentration in Groundwater (SCI-GROW) model, 
the EDWCs of the XDE-729 acid metabolite were estimated for chronic 
exposure in a non-cancer assessment. Modeled estimates of drinking 
water concentrations were directly entered into the dietary exposure 
model. For chronic dietary risk assessment of halauxifen-methyl only, 
the water concentration value of 0.007 ppb was used to assess the 
contribution to drinking water. For chronic dietary risk assessment of 
XDE-729 acid, a drinking water concentration value of 19.5 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). Halauxifen-methyl is 
not used, nor is it being proposed for use in any specific use patterns 
that would result in residential exposure.
    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 
halauxifen-methyl or XDE-729 acid to share a common mechanism of 
toxicity with any other substances, nor do they appear to produce any 
toxic metabolites produced by other substances. For the purposes of 
this tolerance action, therefore, EPA has assumed that neither of these 
compounds have a common mechanism of toxicity with other substances. 
For information regarding EPA's efforts to determine which chemicals 
have a common mechanism of toxicity and to evaluate the cumulative 
effects of such chemicals, see EPA's Web site at http://www.epa.gov/pesticides/cumulative.

D. Safety Factor for Infants and Children

    1. In general. Section 408(b)(2)(C) of FFDCA provides that EPA 
shall apply an additional tenfold (10X) margin of safety for infants 
and children in the case of threshold effects to account for prenatal 
and postnatal toxicity and the completeness of the database on toxicity 
and exposure unless EPA determines based on reliable data that a 
different margin of safety will be safe for infants and children. This 
additional margin of safety is commonly referred to as the FQPA Safety 
Factor (SF). In applying this provision, EPA either retains the default 
value of 10X, or uses a different additional safety factor when 
reliable data available to EPA support the choice of a different 
factor.

[[Page 53024]]

    2. Prenatal and postnatal sensitivity. There was no evidence of 
increased prenatal susceptibility to either compound and no evidence of 
postnatal susceptibility to XDE-729 acid. Residual concerns for 
postnatal susceptibility to halauxifen-methyl in the absence of 
reproductive toxicity data are low, due to selection of a conservative 
endpoint and assumptions for dietary exposure, as well as the low level 
of exposure expected from proposed use patterns.
    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 halauxifen-methyl and XDE-729 acid are 
complete.
    ii. There is no indication that halauxifen-methyl or XDE-729 acid 
are neurotoxic chemicals and there is no need for developmental 
neurotoxicity studies or additional UFs to account for neurotoxicity.
    iii. There is no evidence to suggest that exposure to halauxifen-
methyl or XDE-729 acid results in increased in utero susceptibility in 
rats or rabbits in the prenatal developmental studies or in young rats 
in the 2-generation reproduction study.
    iv. There are no residual uncertainties identified in the exposure 
databases. The chronic dietary food exposure assessment was based on 
100 PCT and tolerance-level residues. EPA also made conservative 
assumptions in the ground and surface water modeling used to assess 
exposure to halauxifen-methyl and XDE-729 acid in drinking water. These 
assessments will not underestimate the exposure and risks posed by 
these compounds.

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. An acute aggregate risk assessment takes into 
account acute exposure estimates from dietary consumption of food and 
drinking water. No adverse effect resulting from a single oral exposure 
was identified and no acute dietary endpoint was selected. Therefore, 
neither halauxifen-methyl, nor XDE-729 acid are expected to pose an 
acute risk.
    2. Chronic risk. Using the exposure assumptions described in this 
unit for chronic exposure, EPA has concluded that chronic exposure to 
halauxifen-methyl from food and water will utilize < 1% of the cPAD for 
all infants, the population group receiving the greatest exposure. In 
addition, EPA has concluded that chronic exposure to XDE-729 acid from 
drinking water will also utilize < 1% of the cPAD for all infants. XDE-
729 is not a residue of concern in food; therefore, the chronic 
assessment was based on drinking water only for this acid metabolite. 
There are no residential uses for halauxifen-methyl being proposed at 
this time; therefore chronic aggregate risk reflects only dietary 
exposure to potential residues in food and drinking water.
    3. Short-term risk. Short-term risk is assessed based on short-term 
residential exposure plus chronic dietary exposure. Because there is no 
short-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 short-term risk), no 
further assessment of short-term risk is necessary.
    4. Intermediate-term risk. 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, no further assessment of intermediate-
term risk is necessary.
    5. Aggregate cancer risk for U.S. population. Long-term dietary 
studies conducted with XDE-729 acid in the rat and the mouse showed no 
evidence of carcinogenicity. Based on the MOA and bridging data on 
halauxifen-methyl, which allowed identification of a POD for liver 
cancer, halauxifen-methyl is not expected to pose a cancer risk to 
humans at dose levels below those that induce liver Cyp1a1 expression. 
Genotoxicity studies were negative for both compounds.
    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 halauxifen-methyl and XDE-729 acid residues.

IV. Other Considerations

A. Analytical Enforcement Methodology

    Adequate enforcement methodology (LC-MS/MS) with a limit of 
quantitation of 0.01 ppm is available to enforce the tolerance 
expression. The multi-residue method, QuEChERS, is adequate for the 
determination of both residues of halauxifen-methyl and XDE-729 acid in 
crop commodities. 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: 
[email protected].

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.
    No MRLs have been established by Codex for halauxifen-methyl on the 
commodities affected by this action.

C. Revisions to Petitioned-For Tolerances

    As noted in Unit II, the petitioned-for livestock commodity 
tolerances (milk; fat, meat, meat byproducts of cattle, goat, horse, 
and sheep) are not being established due to the lack of quantifiable 
residues in livestock commodities associated with the proposed uses in 
wheat, barley and triticale. In addition, although the petitioner 
proposed a tolerance of 0.04 ppm for wheat, hay, EPA has determined 
that a tolerance of 0.03 ppm is appropriate. When the petitioner 
determined the proposed tolerances, the metabolite XDE-729 acid was 
included as a residue of concern. EPA has subsequently determined that 
this metabolite is not a residue of concern for tolerance enforcement. 
Residues of metabolite XDE-729 acid were not

[[Page 53025]]

quantifiable in any of the residue field trials. Therefore, the values 
for measuring compliance with these tolerances only include residues of 
halauxifen-methyl. With the exception of wheat, hay, this revision to 
the residues of concern for tolerance enforcement had no impact on the 
plant commodity tolerances.

V. Conclusion

    Therefore, tolerances are established for residues of halauxifen-
methyl, (methyl 4-amino-3-chloro-6-(4-chloro-2-fluoro-3-methoxyphenyl) 
pyridine-2-carboxylate) and its major metabolite, XDE-729 acid, 
expressed as halauxifen-methyl (parent) equivalents, in or on barley, 
(grain, hay, straw) and wheat, grain at 0.01 ppm; wheat, forage at 0.50 
ppm; wheat, hay at 0.03 ppm; and wheat, straw at 0.015 ppm.

VI. Statutory and Executive Order Reviews

    This action establishes 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). 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: July 28, 2016.
Jack E. Housenger,
Director, 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. Add Sec.  180.691 to subpart C to read as follows:


Sec.  [emsp14]180.691  Halauxifen-methyl; tolerances for residues.

    (a) General. Tolerances are established for residues of the 
herbicide, halauxifen-methyl, including its metabolites and degradates, 
in or on the commodities in the table below. Compliance with the 
tolerance levels specified below is to be determined by measuring only 
halauxifen-methyl (methyl (4-amino-3-chloro-6-(4-chloro-2-fluoro-3-
methoxyphenyl)-2-pyridine carboxylate).

------------------------------------------------------------------------
                                                            Parts per
                       Commodity                             million
------------------------------------------------------------------------
Barley, grain.........................................              0.01
Barley, hay...........................................              0.01
Barley, straw.........................................              0.01
Wheat, forage.........................................              0.50
Wheat, grain..........................................              0.01
Wheat, hay............................................              0.03
Wheat, straw..........................................             0.015
------------------------------------------------------------------------

    (b) Section 18 emergency exemptions. [Reserved]
    (c) Tolerances with regional registrations. [Reserved]
    (d) Indirect or inadvertent residues. [Reserved]

[FR Doc. 2016-19118 Filed 8-10-16; 8:45 am]
 BILLING CODE 6560-50-P