[Federal Register Volume 83, Number 203 (Friday, October 19, 2018)]
[Rules and Regulations]
From the Federal Register Online via the Government Publishing Office [www.gpo.gov]
[FR Doc No: 2018-22862]
ENVIRONMENTAL PROTECTION AGENCY
40 CFR Part 180
Tetrahydrofurfuryl Alcohol; Exemption From the Requirement of a
AGENCY: Environmental Protection Agency (EPA).
ACTION: Final rule.
SUMMARY: This regulation amends the exemption from the requirement of a
tolerance for residues of tetrahydrofurfuryl alcohol (THFA) (CAS Reg.
No. 97-99-4) when used as an inert ingredient in pesticide formulations
to add one herbicide application prior to the preboot stage on
buckwheat, oats, rye, sorghum, triticale, rice and wild rice; extend
use on canola to the early bolting stage; extend use on soybeans prior
to the bloom growth stage; and allow use in herbicides with two
applications to field corn and popcorn prior to 36 inches tall (V8
stage). Toxcel, LLC, on behalf of Penn A Kem, LLC, submitted a petition
to EPA under the Federal Food, Drug, and Cosmetic Act (FFDCA),
requesting an amendment to an existing exemption from the requirement
of a tolerance. This regulation eliminates the need to establish a
maximum permissible level for residues of tetrahydrofurfuryl alcohol.
DATES: This regulation is effective October 19, 2018. Objections and
requests for hearings must be received on or before December 18, 2018,
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-2013-0098, 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.
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 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-
2013-0098 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 18, 2018. 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-2013-0098, 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
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. Petition for Exemption
In the Federal Register of February 27, 2013 (78 FR 13295) (FRL-
9380-2), EPA issued a document pursuant to FFDCA section 408, 21 U.S.C.
346a, announcing the filing of a pesticide petition (PP 2E8080) by
Toxcel, LLC, 7140 Heritage Village Plaza, Gainsville, VA 20156 on
behalf of Penn A Kem, LLC, 3324 Chelsea Avenue, Memphis, TN 38108. The
petition requested amendment of the exemption from the requirement of a
tolerance in 40 CFR 180.1263 for residues of tetrahydrofurfuryl alcohol
(THFA) (CAS Reg. No. 97-99-4) when used as an inert ingredient
(solvent/cosolvent) to include allowance of one herbicide application
prior to the preboot stage to all small cereal grains; extended use on
canola to the early bolting stage; and extended use on soybeans up to
the bloom growth stage. That document referenced a summary of the
petition prepared by Toxcel, LLC, on behalf of Penn A Kem, LLC, the
petitioner, which is available in the docket, http://www.regulations.gov. There were no comments received in response to the
notice of filing.
Toxcel, LLC, on behalf of Penn A Kem, LLC, submitted a revised
pesticide petition to supersede the previously submitted petition. EPA
issued a document in the Federal Register of April 6, 2015 (80 FR
18327) (FRL-9924-00), pursuant to FFDCA section 408, 21 U.S.C. 346a,
announcing the filing of this revised petition. The revised petition
requested that 40 CFR 180.1263 be amended to allow one herbicide
application prior to the preboot stage for wheat, buckwheat, barley,
oats, rye, sorghum, triticale, rice, and wild rice; extend the use on
canola to the early bolting stage; extend the use on soybeans up to the
bloom growth stage; and allow two herbicide applications to field corn
and popcorn up to 36 inches tall (V8 stage). That document referenced a
summary of the petition prepared by Toxcel, LLC, on behalf of Penn A
Kem, LLC, the petitioner, which is available in the docket, http://www.regulations.gov. There were no comments received in response to the
notice of filing.
III. Inert Ingredient Definition
Inert ingredients are all ingredients that are not active
ingredients as defined in 40 CFR 153.125 and include, but are not
limited to, the following types of ingredients (except when they have a
pesticidal efficacy of their own): Solvents such as alcohols and
hydrocarbons; surfactants such as polyoxyethylene polymers and fatty
acids; carriers such as clay and diatomaceous earth; thickeners such as
carrageenan and modified cellulose; wetting, spreading, and dispersing
agents; propellants in aerosol dispensers; microencapsulating agents;
and emulsifiers. The term ``inert'' is not intended to imply
nontoxicity; the ingredient may or may not be chemically active.
Generally, EPA has exempted inert ingredients from the requirement of a
tolerance based on the low toxicity of the individual inert
IV. Aggregate Risk Assessment and Determination of Safety
Section 408(c)(2)(A)(i) of FFDCA allows EPA to establish an
exemption from the requirement for a tolerance (the legal limit for a
pesticide chemical residue in or on a food) only if EPA determines that
the exemption is ``safe.'' Section 408(c)(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. In making this safety finding, EPA is required
to take into account the considerations set forth in section
408(b)(2)(C) and (D). 21 U.S.C. 346a(c)(2)(B). Section 408(b)(2)(C) of
FFDCA requires EPA to give special consideration to exposure of infants
and children to the pesticide chemical residue in establishing a
tolerance and to ``ensure that there is a reasonable certainty that no
harm will result to infants and children from aggregate exposure to the
pesticide chemical residue. . . .''
EPA establishes exemptions from the requirement of a tolerance only
in those cases where it can be clearly demonstrated that the risks from
aggregate exposure to pesticide chemical residues under reasonably
foreseeable circumstances will pose no appreciable risks to human
health. In order to determine the risks from aggregate exposure to
pesticide inert ingredients, the Agency considers the toxicity of the
inert in conjunction with possible exposure to residues of the inert
ingredient through food, drinking water, and through other exposures
that occur as a result of pesticide use in residential settings. If EPA
is able to determine that a finite tolerance is not necessary to ensure
that there is a reasonable certainty that no harm will result from
aggregate exposure to the inert ingredient, an exemption from the
requirement of a tolerance may be established.
Consistent with FFDCA section 408(c)(2)(A), and the factors
specified in FFDCA section 408(c)(2)(B), 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 tetrahydrofurfuryl alcohol
including exposure resulting from the exemption established by this
action. EPA's assessment of exposures and risks associated with
tetrahydrofurfuryl alcohol follows.
A. Toxicological Profile
EPA has evaluated the available toxicity data and considered their
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.
Specific information on the studies received and the nature of the
adverse effects caused by tetrahydrofurfuryl alcohol as well as the no-
observed-adverse-effect-level (NOAEL) and the lowest-observed-adverse-
effect-level (LOAEL) from the toxicity studies can be found at http://www.regulations.gov in the document ``Hazard Assessment for the
Tolerance Reassessment of Tetrahydrofurfuryl alcohol (THFA)(CAS Reg.
No. 97-99-4)'' at pp 8-12 in docket ID number EPA-HQ-OPP-2013-0098. A
summary of the toxicity of tetrahydrofurfuryl alcohol as given in that
Acute toxicity information is available for the oral route with an
LD50 for the rat of 1.6-3.2 g/kg. Tetrahydrofurfuryl alcohol
was not irritating to the skin of mice but was irritating to the eyes
of rabbits. Acute dermal and inhalation toxicity, as well as dermal
sensitization information, currently are not available. However, there
are reports that suggest tetrahydrofurfuryl alcohol may be moderately
irritating via the dermal and inhalation routes of exposure to humans.
Although data on chronic effects is unavailable, subchronic studies
indicate that systemic effects from repeated dermal and oral exposure
to tetrahydrofurfuryl alcohol include decreased body weight and body
weight gain. Tetrahydrofurfuryl alcohol also exhibits adverse
reproductive and developmental effects, and potential effects on the
Males are not only quantitatively more sensitive to the subchronic
effects of tetrahydrofurfuryl alcohol than females, but the male
reproductive system appears to be a target for tetrahydrofurfuryl
alcohol. Consistent decreases in male reproductive organ weights
(testicular, epididymal, and seminal vesicle) were observed in rats in
the 90-day dietary (LOAEL 339 mg/kg/day), dermal (LOAEL 300 mg/kg/day),
and inhalation (LOAEL <0.21 mg/L/day) toxicity studies. In addition, a
90-day oral (dietary) study in dogs revealed decreased testes weights
of males in all treated groups (1,000, 3,000, 6,000 ppm, equivalent to
approximately 25, 75, and 150 mg/kg/day), compared to controls, with
severe testicular atrophy in all males at the highest dose (6,000 ppm
or 150 mg/kg/day). Decreased spermatogenic activity was noted in males
of the 3,000 ppm group (75 mg/kg/day) and was interpreted as a
prodromal sign of atrophy.
A 28-day repeated oral (gavage) study in rats revealed significant
decreases in absolute testes and epididymal weights after 28 days at a
dose level of 600 mg/kg/day which continued through the 14-day recovery
period. Necrosis of the seminiferous tubular epithelium of the testes
was also observed in males of the 150 and 600 mg/kg/day group at 28
days. Necrosis of the testes was also observed in males of the 600 mg/
kg/day group at the end of the 14-day recovery period.
In the reproduction/developmental toxicity screening test in rats,
no reproductive parameters were affected except slightly increased
gestation length at the high dose of 150 mg/kg/day.
The endocrine system may also be a target for tetrahydrofurfuryl
alcohol. Alterations in pituitary, thymus, adrenal, and thyroid weights
have been reported after subchronic exposure (28 days) to 600 mg/kg/day
in male rats and pituitary weights at 150 mg/kg/day in female rats.
Decreased absolute and relative adrenal weights were observed in males
and females receiving 5,000 ppm (equivalent to 339 mg/kg/day males and
401 mg/kg/day females).
In one developmental toxicity study in rats a quantitative
susceptibility based on decreased fetal body weights and a qualitative
susceptibility based on increased incidence of filamentous tail was
observed. However, in a more recent reproduction/developmental toxicity
screening test (OECD 421 guideline study) in rats, an increased
incidence of filamentous tail was not evident nor was there any other
evidence of increased qualitative susceptibility. Based on the overall
weight of evidence for developmental toxicity, it is determined that
there is increased quantitative susceptibility but not increased
A neurotoxicity study is not available for tetrahydrofurfuryl
alcohol, however no neurotoxic effects were observed in the available
subchronic oral, dermal and inhalation toxicity studies.
Mutagenicity studies indicate tetrahydrofurfuryl alcohol is not
mutagenic in Salmonella typhimurium or E. coli with or without
metabolic activation. Tetrahydrofurfuryl alcohol was also negative for
causing structural chromosomal aberrations or polyploidy with or
without metabolic activation in cultured Chinese hamster lung cells.
There are currently no chronic toxicity or cancer studies available
for tetrahydrofurfuryl alcohol. The Agency used a qualitative structure
activity relationship (SAR) database, DEREK Nexus, to determine if
there were structural alerts for potential carcinogenicity for
tetrahydrofurfuryl alcohol. No structural alerts for carcinogenicity
were identified for tetrahydrofurfuryl alcohol. In the absence of any
structural alerts and lack of mutagenicity concerns, tetrahydrofurfuryl
alcohol is not expected to be carcinogenic.
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 discussion of the toxicological
endpoints for tetrahydrofurfuryl alcohol used for human risk assessment
can be found at http://www.regulations.gov in the document ``Hazard
Assessment for the Tolerance Reassessment of Tetrahydrofurfuryl alcohol
(THFA) (CAS Reg. No. 97-99-4) at pp. 6-8 in docket ID number EPA-HQ-
OPP-2013-0098''. A summary of the toxicological dose and endpoints for
Table 1--Summary of Toxicological Doses and Endpoints for Tetrahydrofurfuryl Alcohol for Use in Human Risk
Point of departure
Exposure/scenario and uncertainty/ RfD, PAD, LOC for Study and toxicological effects
safety factors risk assessment
Acute dietary (Females 13-50 NOAEL =  mg/kg/ Acute RfD = [0.5] [Developmental rat].
years of age). day. mg/kg/day. LOAEL =  mg/kg/day based on
UFA =  x........ aPAD = [0.05] mg/kg/ [decreased fetal body weight and
UFH = x......... day. increased incidence of
FQPA SF = x..... filamentous tail, complete
resorptions at 500 and 1,000 mg/
Acute dietary (General population None................ NA................. No acute effects relevant to the
including infants and children). general population were observed
in the available studies.
Chronic dietary (All populations) NOAEL=  mg/kg/ Chronic RfD = [0.5] [Developmental rat].
day. mg/kg/day. LOAEL =  mg/kg/day based on
UFA = x......... cPAD = [0.05] mg/kg/ [decreased fetal body weight and
UFH = x......... day. increased incidence of
FQPA SF = x..... filamentous tail, complete
resorptions at 500 and 1,000 mg/
Incidental oral short-term (1 to NOAEL=  mg/kg/ LOC for MOE = [Developmental, rat].
30 days). day. [1,000]. LOAEL =  mg/kg/day based on
UFA = x......... [decreased fetal body weight and
UFH = x......... increased incidence of
FQPA SF = x..... filamentous tail, complete
resorptions at 500 and 1,000 mg/
Dermal short-term (1 to 30 days). Dermal study NOAEL = LOC for MOE = [90-day dermal, rat].
 mg/kg/day. [1,000]. LOAEL = [300 and 1,000] mg/kg/day
UFA = x......... M/F respectively based on
UFH = x......... [decreased sperm count and sperm
FQPA SF = x..... production rate in males, lower
body weight/gains in females].
Inhalation short-term (1 to 30 Inhalation study LOC for MOE = [90-day inhalation, rat].
days). LOAEL=0.21 mg/l. . LOAEL = [0.21] mg/L (50 ppm;
UFA = x......... approx. 60 mg/kg/day) based on.
UFH = x......... Decreased body weight of males at
FQPA SF = x..... 150 and 500 ppm. Multiple effects
on sperm number, motility, and
morphology at interim and
terminal necropsy of males at
both 150 and 500 ppm].
Cancer (Oral, dermal, inhalation) Classification: No structural alerts for carcinogenicity were identified for
tetrahydrofurfuryl alcohol using a qualitative structure activity
relationship (SAR) database, DEREK Nexus. In the absence of any structural
alerts and lack of mutagenicity concerns, tetrahydrofurfuryl alcohol is not
expected to be carcinogenic.
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). UFDB = to account for the absence of data or other
data deficiency. UFH = potential variation in sensitivity among members of the human population
(intraspecies). UFL = use of a LOAEL to extrapolate a NOAEL. UFS = use of a short-term study for long-term
C. Exposure Assessment
1. Dietary exposure from food and feed uses. In evaluating dietary
exposure to tetrahydrofurfuryl alcohol, EPA considered exposure under
the proposed exemption from the requirement of a tolerance. EPA
assessed dietary exposures from tetrahydrofurfuryl alcohol in food as
2. Acute and chronic exposure. In conducting the acute and chronic
dietary exposure assessments using the Dietary Exposure Evaluation
Model DEEM-FCID\TM\, Version 3.18, EPA used food consumption
information from the U.S. Department of Agriculture's (USDA's) 2003-
2008 National Health and Nutrition Examination Survey, What We Eat in
In the absence of specific residue data, EPA has developed an
approach which uses surrogate information to derive upper-bound
exposure estimates for the subject inert ingredient. Upper-bound
exposure estimates are based on the highest tolerance for a given
commodity from a list of high-use insecticides, herbicides and
fungicides. A complete discussion of the general approach taken to
assess inert ingredient risks in the absence of residue data is
contained in the memorandum entitled ``Alkyl Amines Polyethoxylates
(Cluster 4): Acute and Chronic Aggregate (Food and Drinking Water)
Dietary Exposure and Risk Assessment for the Inerts'' (D361707, S.
Piper 2/25/09) and can be found at http://www.regulations.gov in docket
ID number EPA-HQ-OPP-2008-0738.
In the case of tetrahydrofurfuryl alcohol residues resulting from
foliar applications, EPA made specific adjustments to the dietary
exposure assessments to account for the use limitations of
tetrahydrofurfuryl alcohol as well as some residue chemistry data
(plant uptake data) submitted with the petition. The use of the dietary
estimated exposure model (DEEM) for upper-bound dietary risk
assessments as described above was modified to include only those
commodities on which pesticide formulations containing
tetrahydrofurfuryl alcohol are being
used or are proposed to be used. Specifically, the dietary exposure
assessment considered foliar uses of tetrahydrofurfuryl alcohol on
wheat, buckwheat, barley, oats, rye, sorghum, triticale, rice and wild
rice, canola, cotton, field corn, and popcorn as contained in the
existing tolerance exemption expression and that are the subject of the
present petitions. A residue chemistry study (a radiolabeled plant
uptake study with THFA in corn, tomato, and wheat) suggest that the
highest reported detectable level of tetrahydrofurfuryl alcohol
residues resulting from foliar application in these crops is 0.5 ppm
and this value is used in the dietary exposure assessment for the
commodities included in the tolerance exemption.
For seed treatment use, it was conservatively assumed that all of
the following commodities (which represent an agglomeration of all
commodities for which seed treatment pesticide products are approved
for use) could potentially be treated with a seed treatment pesticide
containing tetrahydrofurfuryl alcohol: barley, corn (field, pop, sweet
and corn for seed production), legume vegetables (dried shelled peas
and beans), brassica and bulb vegetables, alfalfa, cucurbits, rye,
wheat, cotton, sugar beets, and sunflowers. For seed treatment use, in
the absence of THFA-specific data, residue chemistry data for active
ingredients with seed treatment uses were utilized. Residue levels for
pesticide active ingredients used for seed treatment are all below the
limit of detection, so a highly conservative value of 0.05 ppm is used
in the dietary exposure assessment as a residue value for THFA for all
seed treatment commodities based on application of Agency policies for
assigning values to nondetected/nonquantified pesticide residues.
3. Dietary exposure from drinking water. For the purpose of the
screening level dietary risk assessment to support this request for an
exemption from the requirement of a tolerance for tetrahydrofurfuryl
alcohol a conservative drinking water concentration value of 100 ppb
based on screening level modeling was used to assess the contribution
to drinking water for the chronic dietary risk assessments for parent
compound. These values were directly entered into the dietary exposure
4. From non-dietary exposure. The term ``residential exposure'' is
used in this document to refer to non-occupational, non-dietary
exposure (e.g., textiles (clothing and diapers), carpets, swimming
pools, and hard surface disinfection on walls, floors, tables).
Tetrahydrofurfuryl alcohol is contained in a pesticide currently
registered for uses that could result in residential exposures. The use
pattern of the product includes application to dogs. EPA assessed this
residential exposure using the Agency's Standard Operating Procedures
for Residential Pesticide Exposure Assessment Residential Exposure
(Residential SOP). Based on the Treated Pets section of the Residential
SOP, the following assumptions are made: for residential handlers,
exposure (dermal and inhalation) is expected to be short-term only.
Residential post-application dermal exposure (short-term only) was
assessed for adults and children. Residential post-application
inhalation exposure is generally not assessed for pet treatment product
uses as such exposure is typically considered to be negligible.
Incidental oral post-application exposure was assessed for children 1
to 2 years old. All post-application exposures are expected to be
short-term in duration. Further information regarding EPA standard
assumptions and generic inputs for residential exposures may be found
5. 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 tetrahydrofurfuryl alcohol to share a common
mechanism of toxicity with any other substances, and tetrahydrofurfuryl
alcohol does not appear to produce a toxic metabolite produced by other
substances. For the purposes of this tolerance action, therefore, EPA
has assumed that tetrahydrofurfuryl alcohol 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://www.epa.gov/pesticides/cumulative.
D. Safety Factor for Infants and Children
1. In general. Section 408(b)(2)(C) of FFDCA provides that EPA
shall apply an additional tenfold (10X) margin of safety for infants
and children in the case of threshold effects to account for prenatal
and postnatal toxicity and the completeness of the database on toxicity
and exposure unless EPA determines based on reliable data that a
different margin of safety will be safe for infants and children. This
additional margin of safety is commonly referred to as the FQPA Safety
Factor (SF). In applying this provision, EPA either retains the default
value of 10X, or uses a different additional safety factor when
reliable data available to EPA support the choice of a different
2. Prenatal and postnatal sensitivity. The data available for
evaluation suggest there is evidence of increased quantitative
susceptibility of the offspring after in utero exposure to
tetrahydrofurfuryl alcohol. No reproductive parameters were affected
except slightly increased gestation length at the high dose of 150 mg/
kg/day in the OECD 421 study in rats. There is also a concern for the
effects of tetrahydrofurfuryl alcohol on the developing male
reproductive system. Subchronic and reproductive toxicity studies
consistently revealed decreased testicular epididymis and seminal
vesicle weights as well as atrophy of the epididymis and seminal
vesicles and abnormal morphology and motility of sperm. The level at
which tetrahydrofurfuryl alcohol may affect the reproductive system
during development is currently not known.
3. Conclusion. EPA has determined that based on evidence of
quantitative and qualitative susceptibility the safety of infants and
children would be adequately protected if the FQPA SF was retained at
10x for all scenarios. That decision is based on the following
i. The toxicity database for tetrahydrofurfuryl alcohol consists of
a 28-day and 90-day oral toxicity studies in rats, dogs, 90-day dermal
toxicity study in rats, 90-day inhalation toxicity study in rats,
several mutagenicity studies, developmental/reproductive toxicity
screening study in rats, and a developmental toxicity study and
reproductive toxicity study in rats.
ii. Slight atrophy of thymus was seen in high dose animal groups in
the 28-day oral toxicity study, which may be indicative of an immune
response, however no guideline immunotoxicity study is available.
iii. Evidence of increased quantitative susceptibility of offspring
is seen in the developmental toxicity study.
iv. Additionally, alterations in the male reproductive system from
subchronic exposure to tetrahydrofurfuryl alcohol does indicate
a concern for effects to the developing male reproductive system.
v. The FQPA factor of 10X is considered adequate to account for
potential immunotoxicity and uncertainty regarding the developing
reproductive system in males because clear NOAELs are established in
the available database.
vi. There are no residual uncertainties identified in the exposure
databases. As described earlier, EPA used highly conservative
assumptions for the dietary food exposure assessment. EPA made
conservative (protective) assumptions in the ground and surface water
modeling used to assess exposure to tetrahydrofurfuryl alcohol in
drinking water. EPA used similarly conservative assumptions to assess
residential exposures of children to tetrahydrofurfuryl alcohol. These
assessments will not underestimate the exposure and risks.
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, EPA has concluded that acute exposure to
tetrahydrofurfuryl alcohol from food and water will utilize 8.88% of
the aPAD for females 13-49 years old.
2. Chronic risk. Using the exposure assumptions described in this
unit for chronic exposure, EPA has concluded that chronic exposure to
tetrahydrofurfuryl alcohol from food and water will utilize 8.5% of the
cPAD for children 1-2 years 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
tetrahydrofurfuryl alcohol 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).
Tetrahydrofurfuryl alcohol is contained in a pesticide 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 tetrahydrofurfuryl alcohol.
Using the exposure assumptions described in this unit for short-
term exposures, EPA has concluded the combined chronic food, water, and
short-term residential exposures result in aggregate MOEs of 13,100 for
adults and 9,800 for children 1-2 years old. Because EPA's level of
concern for tetrahydrofurfuryl alcohol is a MOE of 1,000 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
An intermediate-term adverse effect was identified; however,
tetrahydrofurfuryl alcohol is not contained in any pesticide products
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 tetrahydrofurfuryl
5. Cancer. Based on the lack of genotoxicity and a DEREK assessment
of tetrahydrofurfuryl alcohol that revealed no structural alerts
suggestive of carcinogenicity, tetrahydrofurfuryl alcohol is therefore
not expected to pose a cancer risk to humans.
6. Determination of safety. Taking into consideration all available
information on tetrahydrofurfuryl alcohol, EPA has determined that
there is a reasonable certainty that no harm to any population subgroup
will result from aggregate exposure to tetrahydrofurfuryl alcohol
resulting from the limited uses contained in 40 CFR 180.1263.
Therefore, the amendment of the exemption from requirement of a
tolerance at 40 CFR 180.1263 for residues of tetrahydrofurfuryl alcohol
when used as an inert ingredient in pesticide formulations to include
allowance of one herbicide application prior to the pre-boot stage to
wheat, buckwheat, barley, oats, rye, sorghum, triticale, rice and wild
rice; extended use on canola to the early bolting stage; extended use
on soybeans up to the bloom stage; and allowance of two applications to
field corn and popcorn up to 36 inches tall (V8 stage) is safe under
FFDCA section 408.
V. Analytical Enforcement Methodology
An analytical method is not required for enforcement purposes since
the Agency is establishing an exemption from the requirement of a
tolerance without any numerical limitation.
Therefore, the exemption from the requirement of a tolerance under
40 CFR 180.1263 is amended to add exemption from the requirement of a
tolerance for residues of tetrahydrofurfuryl alcohol (CAS Reg. No. 97-
99-4) when used as an inert ingredient (solvent) in herbicides applied
to wheat, buckwheat, barley, oats, rye, sorghum, triticale, rice and
wild rice prior to the pre-boot stage; use on canola to the early
bolting stage; use on soybeans up to the bloom stage; and two
applications to field corn and popcorn up to 36 inches tall (V8 stage).
VII. Statutory and Executive Order Reviews
This final rule establishes exemptions from the requirement of a
tolerance 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 final rule has been exempted from review
under Executive Order 12866, this final rule is not subject to
Executive Order 13211, entitled ``Actions Concerning Regulations That
Significantly Affect Energy Supply, Distribution, or Use'' (66 FR
28355, May 22, 2001) or Executive Order 13045, entitled ``Protection of
Children from Environmental Health Risks and Safety Risks'' (62 FR
19885, April 23, 1997). This final rule does not contain any
information collections subject to OMB approval under the Paperwork
Reduction Act (PRA) (44 U.S.C. 3501 et seq.), nor does it require any
special considerations under Executive Order 12898, entitled ``Federal
Actions to Address Environmental Justice in Minority Populations and
Low-Income Populations'' (59 FR 7629, February 16, 1994).
Since tolerances and exemptions that are established on the basis
of a petition under FFDCA section 408(d), such as
the exemptions in this final rule, do not require the issuance of a
proposed rule, the requirements of the Regulatory Flexibility Act (RFA)
(5 U.S.C. 601 et seq.), do not apply.
This final rule directly regulates growers, food processors, food
handlers, and food retailers, not States or tribes, nor does this
action alter the relationships or distribution of power and
responsibilities established by Congress in the preemption provisions
of 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 final rule. In addition,
this final rule does not impose any enforceable duty or contain any
unfunded mandate as described under Title II of the Unfunded Mandates
Reform Act of 1995 (UMRA) (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 of 1995 (NTTAA) (15 U.S.C. 272 note).
VIII. 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
Dated: October 9, 2018.
Director, Registration Division, Office of Pesticide Programs.
Therefore, 40 CFR chapter I is amended as follows:
1. The authority citation for part 180 continues to read as follows:
Authority: 21 U.S.C. 321(q), 346a and 371.
2. In Sec. 180.1263, revise paragraphs (d) and (e), and add paragraphs
(f) and (g) to read as follows:
Sec. 180.1263 Tetrahydrofurfuryl alcohol; exemption from the
requirement of a tolerance.
* * * * *
(d) For use in herbicides with one application to wheat, buckwheat,
barley, oats, rye, sorghum, triticale, rice, and wild rice prior to the
(e) For use in herbicides with two applications to field corn and
popcorn up to 36 inches tall (V8 stage).
(f) For use in herbicides with two applications to canola prior to
the early bolting stage.
(g) For use in herbicides with two applications to soybeans prior
to the bloom growth stage.
[FR Doc. 2018-22862 Filed 10-18-18; 8:45 am]
BILLING CODE 6560-50-P