[Federal Register Volume 64, Number 115 (Wednesday, June 16, 1999)]
[Rules and Regulations]
[Pages 32189-32196]
From the Federal Register Online via the Government Publishing Office [www.gpo.gov]
[FR Doc No: 99-14865]
-----------------------------------------------------------------------
ENVIRONMENTAL PROTECTION AGENCY
40 CFR Part 180
[OPP-300859; FRL-6080-9]
RIN 2070-AB78
Sethoxydim; Pesticide Tolerance
AGENCY: Environmental Protection Agency (EPA).
ACTION: Final rule.
-----------------------------------------------------------------------
SUMMARY: This regulation establishes tolerances for combined residues
of sethoxydim and its metabolites containing the 2-cyclohexen-1-one
moiety (calculated as the herbicide) in or on asparagus, carrot,
cranberry, horseradish, peppermint tops and spearmint tops. The
Interregional
[[Page 32190]]
Research Project Number 4 (IR-4) requested these tolerances under the
Federal Food, Drug, and Cosmetic Act, as amended by the Food Quality
Protection Act of 1996.
DATES: This regulation is effective June 16, 1999. Objections and
requests for hearings must be received by EPA on or before August 16,
1999.
ADDRESSES: Written objections and hearing requests, identified by the
docket control number, [OPP-300859], must be submitted to: Hearing
Clerk (1900), Environmental Protection Agency, Rm. M3708, 401 M St.,
SW., Washington, DC 20460. Fees accompanying objections and hearing
requests shall be labeled ``Tolerance Petition Fees'' and forwarded to:
EPA Headquarters Accounting Operations Branch, OPP (Tolerance Fees),
P.O. Box 360277M, Pittsburgh, PA 15251. A copy of any objections and
hearing requests filed with the Hearing Clerk identified by the docket
control number, [OPP-300859], must also be submitted to: Public
Information and Records Integrity Branch, Information Resources and
Services Division (7502C), Office of Pesticide Programs, Environmental
Protection Agency, 401 M St., SW., Washington, DC 20460. In person,
bring a copy of objections and hearing requests to Rm. 119, Crystal
Mall #2, 1921 Jefferson Davis Hwy., Arlington, VA.
A copy of objections and hearing requests filed with the Hearing
Clerk may be submitted electronically by sending electronic mail (e-
mail) to: [email protected]. Copies of objections and hearing requests
must be submitted as an ASCII file avoiding the use of special
characters and any form of encryption. Copies of objections and hearing
requests will also be accepted on disks in WordPerfect 5.1/6.1 file
format or ASCII file format. All copies of objections and hearing
requests in electronic form must be identified by the docket control
number [OPP-300859]. No Confidential Business Information (CBI) should
be submitted through e-mail. Electronic copies of objections and
hearing requests on this rule may be filed online at many Federal
Depository Libraries.
FOR FURTHER INFORMATION CONTACT: By mail: Hoyt Jamerson, Registration
Division (7505C), Office of Pesticide Programs, Environmental
Protection Agency, 401 M St., SW., Washington, DC 20460. Office
location, telephone number, and e-mail address: Rm. 272, Crystal Mall
#2, 1921 Jefferson Davis Hwy., Arlington, VA, (703) 308-9368,
[email protected].
SUPPLEMENTARY INFORMATION: In the Federal Register of December 30, 1998
(63 FR 71920) (FRL-6050-1), EPA issued a notice pursuant to section 408
of the Federal Food, Drug, and Cosmetic Act (FFDCA), 21 U.S.C. 346a as
amended by the Food Quality Protection Act of 1996 (FQPA) (Pub. L. 104-
170) announcing the filing of pesticide petitions (PP 3E4162, 2E4092,
0E3909, and 2E4052) for tolerances by Interregional Research Project
Number 4 (IR-4), New Jersey Agricultural Experiment Station, Rutgers
University, New Brunswick, New Jersey 08903. The notice included a
summary of the petitions prepared by BASF Corporation, the registrant.
There were no comments received in response to the notice of filing.
The petitions requested that 40 CFR 180.412 be amended by removing
the time limitations (expiration dates) on established tolerances for
combined residues of the herbicide sethoxydim (2-[1-
(ethoxyimino]butyl)-5-[2-(ethylthio)propyl]-3-hydroxy-2-cyclohexen-1-
one) and its metabolites containing the 2-cyclohexen-1-one moiety
(calculated as the herbicide), in or on asparagus (PP 3E4162) at 4.0
parts per million (ppm), carrot (PP 2E4092) at 1.0 ppm, cranberry (PP
0E3909) at 2.0 ppm, and peppermint and spearmint tops (PP 2E4052) at 30
ppm. Since the tolerances for asparagus, carrot, cranberry, peppermint
and spearmint tops expired December 31, 1998, after the notice of
filing was published in the Federal Register, this rule establishes the
tolerances without time limitations. In addition, in the Federal
Register of January 29, 1999 (64 FR 4650) (FRL-6055-8), PP 9E5049
proposed to amend 40 CFR 180.412 by establishing a tolerance for
residues of sethoxydim and its metabolites in or on horseradish at 4
ppm.
I. Background and Statutory Findings
Section 408(b)(2)(A)(i) of the 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) 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)
requires EPA to give special consideration to exposure of infants and
children to the pesticide chemical residue in establishing a tolerance
and to ``ensure that there is a reasonable certainty that no harm will
result to infants and children from aggregate exposure to the pesticide
chemical residue....''
EPA performs a number of analyses to determine the risks from
aggregate exposure to pesticide residues. For further discussion of the
regulatory requirements of section 408 and a complete description of
the risk assessment process, see the final rule on Bifenthrin Pesticide
Tolerances (62 FR 62961, November 26, 1997) (FRL-5754-7).
II. Aggregate Risk Assessment and Determination of Safety
Consistent with 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
sethoxydim and to make a determination on aggregate exposure,
consistent with section 408(b)(2), for a tolerance for combined
residues of (2-[1-(ethoxyimino]butyl)-5-[2-(ethylthio)propyl]-3-
hydroxy-2-cyclohexen-1-one) and its metabolites containing the 2-
cyclohexen-1-one moiety (calculated as the herbicide) in or on
asparagus, carrot, cranberry, horseradish, and peppermint and spearmint
tops. EPA's assessments of the dietary exposures and risks associated
with establishing the tolerances are as 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 nature of the toxic effects caused by sethoxydim are
discussed in this unit.
1. Acute toxicity. Based on the available acute toxicity data,
sethoxydim does not pose any acute dietary risks. A summary of the
acute toxicity studies follows:
i. Acute oral toxicity, rat: Toxicity Category III;
LD50=3,125 milligrams/kilograms (mg/kg) (male), 2,676 mg/kg
(female).
ii. Acute dermal toxicity, rat: Toxicity Category III;
LD50 >5,000 mg/kg (male and female).
iii. Acute inhalation toxicity, rat: Toxicity Category III;
LC50 (4-hour)=6.03 mg/liter (L) (male), 6.28 mg/L (female).
[[Page 32191]]
iv. Primary eye irritation, rabbit: Toxicity Category IV; no
irritation.
v. Primary dermal irritation, rabbit: Toxicity Category IV; no
irritation.
vi. Dermal sensitization, guinea pig: Waived because no
sensitization was seen in guinea pigs dosed with the end-use product
Poast (18% active ingredient).
2. Genotoxicity. Ames assays were negative for gene mutation in
Salmonella typhimurium strains TA98, TA100, TA1535, and TA 1537, with
and without metabolic activity. A Chinese hamster bone marrow
cytogenetic assay was negative for structural chromosomal aberrations
at doses up to 5,000 mg/kg in Chinese hamster bone marrow cells in
vivo. Recombinant assays and forward mutations tests in Bacillus
subtilis, Escherichia coli, and S. typhimurium were all negative for
genotoxic effects at concentrations of greater than or equal to 100%.
3. Reproductive and developmental toxicity. A 2-generation
reproduction study with rats fed diets containing 0, 150, 600, or 3,000
ppm (approximately 0, 7.5, 30, or 150 mg/kg/day) with no reproductive
effects observed under the conditions of the study.
A developmental toxicity study in rats fed dosages of 0, 50, 180,
650, or 1,000 mg/kg/day with a maternal no-observed-adverse-effect
level (NOAEL) of 180 mg/kg/day and a maternal lowest-adverse-effect
level (LAEL) of 650 mg/kg/day (irregular gait, decreased activity,
excessive salivation, and anogenital staining); and a developmental
NOAEL of 180 mg/kg/day, and a developmental LAEL of 650 mg/kg/day,
based on a 21 to 22% decrease in fetal weights, filamentous tail, and
lack of tail due to the absence of sacral and/or caudal vertebrae, and
delayed ossification in the hyoids, vertebral centrum and/or transverse
processes, sternebrae and/or metatarsal, and pubes). A developmental
toxicity study in rabbits fed doses of 0, 80, 160, 320, or 400 mg/kg/
day with a maternal NOAEL of 320 mg/kg/day and a maternal lowest-
observed-adverse-effect level (LOAEL) of 400 mg/kg/day (37% reduction
in body weight gain without significant differences in group mean body
weights and decreased food consumption during dosing); and a
developmental NOAEL greater than 400 mg/kg/day highest dose tested
(HDT).
4. Subchronic toxicity. A 21-day dermal study in rabbits with a
NOAEL of >1,000 mg/kg/day (limit dose). The only dose-related finding
was slight epidermal hyperplasia at the dosing site in nearly all males
and females dosed at 1,000 mg/kg/day. This was probably an adaptive
response.
5. Chronic toxicity. A 1-year feeding study with dogs fed diets
containing 0, 8.86/9.41, 17.5/19.9, and 110/129 mg/kg/day (males/
females) with a NOAEL of 8.86/9.41 mg/kg/day (males/females) based on
equivocal anemia in male dogs at the 17.5-mg/kg/day dose level.
A 2-year chronic feeding/carcinogenicity study with mice fed diets
containing 0, 40, 120, 360, and 1,080 ppm (equivalent to 0, 6, 18, 54,
and 162 mg/kg/day) with a systemic NOAEL of 120 ppm (18 mg/kg/day)
based on non-neoplastic liver lesions in male mice at the 360-ppm (54
mg/kg/day) dose level. There were no carcinogenic effects observed
under the conditions of the study. The maximum tolerated dose (MTD) was
not achieved in female mice. The need for a new study will be based on
the adequacy of the rat study currently under review.
A 2-year chronic feeding/carcinogenic study with rats fed diets
containing 0, 2, 6, and 18 mg/kg/day with a systemic NOAEL greater than
or equal to 18 mg/kg/day HDT. There were no carcinogenic effects
observed under the conditions of the study. This study was reviewed
under current guidelines and was found to be unacceptable because the
doses used were insufficient to induce a toxic response and the MTD was
not achieved.
A second chronic feeding/carcinogenic study with rats fed diets
containing 0, 360, or 1,080 ppm (equivalent to 18.2/23.0, or 55.9/71.8
mg/kg/day (males/females). The dose levels were too low to elicit a
toxic response in the test animals and failed to achieve the MTD or to
define a LAEL. Slight decreases in body weight in rats at the 1,080-ppm
dose level, although not biologically significant, support a free-
standing NOAEL of 1,080 ppm (55.9/71.8 mg/kg/day (males/females)).
There were no carcinogenic effects observed under the conditions of the
study.
A third chronic feeding/carcinogenicity study in rats has been
submitted. Male and female rats were dosed at nominal concentrations of
0, 300, 1,000, or 3,000 ppm. Clinical findings at the high-dose
included changes in food consumption, food efficiency, body weight, and
liver pathology. Upon initial review, it appears that the dose
selection was adequate, and that there was no evidence of
carcinogenicity.
6. Animal metabolism. In a rat metabolism study, excretion was
extremely rapid and tissue accumulation was negligible.
B. Toxicological Endpoints
1. Acute toxicity. In a rat developmental study rats received doses
of 0, 50, 180, 650, and 1,000 mg/kg/day. The maternal toxicity NOAEL
was 180 mg/kg/day and the LOAEL was 650 mg/kg/day based on irregular
gait, decreased activity, excessive salivation, and ano-genital
staining. For developmental toxicity the NOAEL was 180 mg/kg/day and
the LOAEL was 650 mg/kg/day based on 21-22% decrease in fetal weights,
filamentous tail and lack of tail due to the absence of accral and /or
caudal vertebrae, and delayed ossification in the hyoids, vertebral
centrum and/or transverse processes, sternebrae and/or metatarsal, and
pubes. The end point for use in the risk assessment is the maternal
NOAEL of 180 mg/kg/day. The end point is set on maternal effects
because the NOAEL for developmental effects is also 180 mg/kg/day.
2. Short- and intermediate-term toxicity. No short or intermediate
dermal or inhalation endpoints were identified. In a 21-day dermal
study with rabbits dosed at 0, 40, 200, or 1,000 mg/kg/day, there was
no evidence of compound related toxicity on clinical signs, body
weights, food consumption, food efficiency, eye health, clinical
pathology, organ weights, or gross pathology. The NOAEL was greater
than 1,000 mg/kg/day (limit dose). In the acute inhalation study with
rats the LC50 was 6.03 mg/L (males) and 6.28 mg/L (females
placing sethoxydim in category IV.
3. Chronic toxicity. EPA has established the Reference Dose (RfD)
for sethoxydim at 0.9 mg/kg/day. This RfD is based on a finding of
equivocal anemia in the 1-year dog study. The NOAEL was 8.86 mg/kg in
males and 9.41 mg/kg in females.
4. Carcinogenicity. Sethoxydim is not classified. Available studies
show no evidence of carcinogenicity in rats or mice.
C. Exposures and Risks
1. From food and feed uses. Tolerances have been established (40
CFR 180.412) for the combined residues of (2-[1-(ethoxyimino]butyl)-5-
[2-(ethylthio)propyl]-3-hydroxy-2-cyclohexen-1-one) and its metabolites
containing the 2-cyclohexen-1-one moiety (calculated as the herbicide),
in or on a variety of raw agricultural commodities. Risk assessments
conducted by EPA to assess dietary exposures from sethoxydim are as
follows:
i. Acute exposure and risk. Acute dietary risk assessments are
performed
[[Page 32192]]
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. The acute dietary endpoint is 180 mg/kg/day based on
NOAEL's of 180 mg/kg/day for maternal and developmental effects in the
rabbit developmental study. The FQPA safety factor of 3x was applied to
females 13+ only because the endpoint (based on decrease in fetal
weights, filamentous tail and lack of tail due to absence of sacral
and/or caudal vertebrae, delayed ossification in the hyoids, vertebral
centrum and/or transverse processes, sternebrae and/or metatarsal)
occurs only during in urtero exposure and is not a postnatal effect.
Since the effects occur during in urtero exposure, it is not an
appropriate endpoint for acute dietary risk assessment of infants and
children.
In conducting this acute dietary risk assessment, the Agency made
very conservative assumptions--100% of all commodities having
sethoxydim tolerances will contain sethoxydim regulable residues and
those residues will be at the level of the tolerance which result in an
over estimation of human dietary exposure.
From the acute dietary (food only) risk assessment, a high-end
exposure estimate of 0.2 mg/kg/day was calculated. This exposure
yielded dietary (food only) margins of exposure (MOEs) ranging from 420
for children (1-6 years old) to 622 for female 13+ and greater than 500
for all other subgroups.
ii. Chronic exposure and risk. The FQPA Safety Factor will not be
applied for chronic dietary risk assessment because the endpoint is
based on anemia in male dogs. The endpoint for which the FQPA safety
factor is based is an in utero effect and cannot result from postnatal
exposure. There was no indication of increased susceptibility in the
prenatal developmental study in rabbits following in utero exposure. In
the 2-generation reproduction study in rats, effects in offspring were
observed only at above treatment levels which resulted in evidence of
appreciable parental toxicity. No increased susceptibility was
demonstrated in the developmental toxicity study with rats when the
maternal and developmental NOAELs/LOAELs were compared. In conducting
this chronic dietary risk assessment, the Agency has made very
conservative assumptions no percent crop-treated data were used and all
commodities having sethoxydim tolerances will contain sethoxydim
residues and those residues will be at the level of the tolerance which
will result in an overestimate of human dietary exposure.
The sethoxydim tolerances (published and pending) result in a
Theoretical Maximum Residue Contribution (TMRC) that is equivalent to
the following percentages of the RfD:
------------------------------------------------------------------------
Subgroup TMRC %RFD
------------------------------------------------------------------------
U.S. Population......................... 0.039187 44
Nursing Infants......................... 00.018957 21
Non-Nursing Infants (<1 year old)....... 00.072949 81
Children (1-6 years old)................ 00.085308 95
Children (7-12 years old)............... 00.058101 65
Female (13+, nursing)................... 00.040144 45
Males (13-19 years old)................. 00.040429 45
U.S Population (Summer Season).......... 00.039408 44
Hispanics............................... 00.039428 44
Non-Hispanic Others..................... 00.040452 45
Non-Hispanic Whites..................... 00.039238 44
------------------------------------------------------------------------
The subgroups listed above are: (1) the U.S. population (48
states); and (2) those for infants, children, females, 13+ nursing; and
other subgroups for which the percentage of RfD occupied is greater
than occupied by the subgroup U.S. population.
2. Carcinogenic risk. Sethoxydim has not been classified. At the
present time, studies do not show evidence of carcinogenicity in rats
or mice.
3. From drinking water. Limited monitoring data of ground water and
surface water are available for sethoxydim. The modeling data estimates
maximum concentrations in ground water of 0.84 microgram (g)/
liter (L) and in surface water 59.4 g/L and 56-day EECs of
37.3 g/L. The modeling data were compared to the results of
the following equations used to calculate acute and chronic drinking
water level of concern (DWLOC) for sethoxydim in ground and surface
water (Standard Operating Procedures for Drinking Water Exposure and
Risk Assessments, November 20, 1997). Models used were SCI-GROW and
GENEC to provide estimates of ground and surface water contamination
respectively from sethoxydim, but did not consider the behavior of
degradates. Agency default weights and water consumption used in the
calculations were 70 kg(2L) for adult males, 60 kg(2L) for adult
females, and 10 kg (1L) for child.
i. Acute exposure and risk. Based on acute dietary exposure and
using default body weights and water consumption values stated above,
acute DWLOC were calculated using the following equation.
DWLOC (acute) = (NOAEL divided by uncertainty factor) - (acute food
+ residential exposure (mg/kg/day) x (body weight) divided by
consumption(L) x 10-3 mg/g.
Acute dietary water levels of concern were calculated to be 525,000
g/L for the U.S. population, 56,000 g/L for adult
males 13+, 12,000 g/L for adult females 13+ (including 3x
safety factor) and 14,000 g/L for child (infant < 1 year old).
ii. Chronic exposure and risk. Based on acute dietary exposure and
using default body weights and water consumption values stated above,
acute DWLOC were calculated using the following equation.
DWLOC (chronic) = (NOEL divided by uncertainty factor) - (chronic
food + residential exposure (mg/kg/day) x (body weight) divided by
consumption(L) x 10-3 mg/g.
Chronic DWLOCs were calculated to be 1,760 g/L for the
U.S. population, 1,780 g/L for adult males 13+, 1,700
g/L for adult females 13+ (including 3x safety factor) and
14,000 g/L for child (infant < 1 year old).
4. From non-dietary exposure. Sethoxydim is currently registered
for use on the following residential non-food sites: ornamentals and
flowering plants, recreational areas, and buildings/structures (outdoor
non-agricultural). These residential uses comprise a short- and
intermediate-term exposure scenario, but do not comprise a chronic
exposure scenario.
i. Acute exposure and risk. There is a potential for exposure to
sethoxydim by homeowner mixers/applicators. However, since no endpoints
for dermal or inhalation were selected, the use on residential non-food
sites is not
[[Page 32193]]
expected to pose an unacceptable acute risk.
ii. Chronic exposure and risk. The registered uses for sethoxydim
do not comprise a chronic exposure scenario. A chronic non-dietary
endpoint was not selected; therefore, the use on residential non-food
sites is not expected to pose an unacceptable chronic risk.
iii. Short- and intermediate-term exposure and risk. Short-term or
intermediate term endpoints were not identified. However, the following
scenarios may result if herbicides containing sethoxydim are applied to
residential turf, and/or ornamental plants: incidental non-dietary
ingestion of residues on lawns from hand-to-mouth transfer, ingestion
of pesticide-treated turfgrass, and incidental ingestion of soil from
treated lawns. A residential exposure estimate and risk assessment was
conducted for postapplication exposure following the application of
sethoxydim on turf and ornamental gardens. The acute dietary endpoint
was used for this risk assessment because the acute dietary endpoint
provides the worst case estimate of risk and exposure for these use
patterns. The assessment was performed using Draft SOPs for Residential
Exposure Assessments (December 18, 1998). The proposed postapplication
aggregate exposure assessment takes into account chronic dietary
exposure plus outdoor residential exposures. These exposure assessments
assume that 20% of the application rate is available from the turf
grass as dislodgeable residue and 2 hours as the duration of exposure.
These assumptions are considered conservative and protective.
Exposures and MOEs were calculated to be 0.053 mg/kg/day (MOE of
3,400) for hand to mouth transfer for treated lawns (toddlers), 0.0012
mg/kg/day (MOE of 15,000) for ingestion of treated turf grass
(toddler), and 0.000025 (MOE of 7,000,000) for incidental ingestion of
soil (toddlers). MOEs exceeded 100 for all three scenarios. MOEs
greater or equal to 100 do not exceed the Agency's level of concern.
5. Cumulative exposure to substances with common mechanism of
toxicity. Section 408(b)(2)(D)(v) 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 does not have, at this time, available data to determine
whether sethoxydim has a common mechanism of toxicity with other
substances or how to include this pesticide in a cumulative risk
assessment. Unlike other pesticides for which EPA has followed a
cumulative risk approach based on a common mechanism of toxicity,
sethoxydim does not appear to produce a toxic metabolite produced by
other substances. For the purposes of this tolerance action; therefore,
EPA has not assumed that sethoxydim has a common mechanism of toxicity
with other substances. For information regarding EPA's efforts to
determine which chemicals have a common mechanism of toxicity and to
evaluate the cumulative effects of such chemicals, see the final rule
for Bifenthrin Pesticide Tolerances (62 FR 62961, November 26, 1997).
D. Aggregate Risks and Determination of Safety for U.S. Population
1. Acute risk. Using the published and pending tolerances, the
dietary (food only) acute MOEs range from 420 for children (1-6 year)
to 622 for females 13+ years. The level of concern for females 13+
years is 300 (includes 3x safety factor) for acute sethoxydim exposure
and 100 for all other population subgroups. This risk estimate should
be viewed as highly conservative; refinement using anticipated residue
values and percent crop treated data in conjunction with Monte Carlo
analysis will result in a lower acute dietary exposure estimate. The
dietary exposure does not exceed the Agency's level of concern.
Sethoxydim is a nonpersistent, but highly mobile compound in soil
and water environments. The modeling data for sethoxydim in drinking
water indicate levels less than OPP`s DWLOC for acute exposure. Since a
refined acute risk for food only would not exceed EPA's levels of
concern for acute dietary exposures and the monitoring and modeling
levels in water are less than the acute DWLOC, EPA does not expect
aggregate acute exposure to sethoxydim will pose an unacceptable risk
to human health.
2. Chronic risk. Using the TMRC exposure assumptions described in
this unit, EPA has concluded that aggregate exposure to sethoxydim from
food will utilize 44% of the RfD for the U.S. population. The major
identifiable subgroup with the highest aggregate exposure is 95% for
children 1 to 6 years; discussed below. EPA generally has no concern
for exposures below 100% of the RfD because the RfD represents the
level at or below which daily aggregate dietary exposure over a
lifetime will not pose appreciable risks to human health. Despite the
potential for exposure to sethoxydim in drinking water and from non-
dietary, non-occupational exposure, EPA does not expect the aggregate
exposure to exceed 100% of the RfD. EPA concludes that there is a
reasonable certainty that no harm will result from aggregate exposure
to sethoxydim residues.
3. Short- and intermediate-term risk. Short- and intermediate-term
aggregate exposure takes into account chronic dietary food and water
(considered to be a background exposure level) plus indoor and outdoor
residential exposure.
Endpoints for short or intermediate term were not selected. An
aggregate exposure estimate and risk assessment was conducted for
postapplication exposure to sethoxydim on turf and ornamental plants
taking into account chronic exposure from food and the acute dietary
NOAEL. The resulting MOEs (1,390-2,350) are not of concern to the
Agency.
4. Aggregate cancer risk for U.S. population. Sethoxydim has not
been classified. Available studies do not show evidence of
carcinogenicity in rats or mice.
5. Determination of safety. Based on these risk assessments, EPA
concludes that there is a reasonable certainty that no harm will result
from aggregate exposure to sethoxydim residues.
E. Aggregate Risks and Determination of Safety for Infants and Children
1. Safety factor for infants and children-- i. In general. In
assessing the potential for additional sensitivity of infants and
children to residues of sethoxydim, EPA considered data from
developmental toxicity studies in the rat and rabbit and a 2-generation
reproduction study in the rat. The developmental toxicity studies are
designed to evaluate adverse effects on the developing organism
resulting from maternal pesticide exposure gestation. Reproduction
studies provide information relating to effects from exposure to the
pesticide on the reproductive capability of mating animals and data on
systemic toxicity.
FFDCA section 408 provides that EPA shall apply an additional
tenfold margin of safety for infants and children in the case of
threshold effects to account for pre- and postnatal toxicity and the
completeness of the data base unless EPA determines that a different
margin of safety will be safe for infants and children. Margins of
safety are incorporated into EPA risk assessments either directly
through use of a margin of exposure (MOE) analysis or through using
uncertainty (safety) factors in calculating a dose level that poses no
[[Page 32194]]
appreciable risk to humans. EPA believes that reliable data support
using the standard uncertainty factor (usually 100 for combined inter-
and intra-species variability) and not the additional tenfold MOE/
uncertainty factor when EPA has a complete data base under existing
guidelines and when the severity of the effect in infants or children
or the potency or unusual toxic properties of a compound do not raise
concerns regarding the adequacy of the standard MOE/safety factor.
ii. Pre- and postnatal sensitivity. There was no indication of
increased susceptibility in the prenatal developmental toxicity study
in rabbits following in utero exposure. In the 2-generation
reproduction study in rats, effects in the offspring were observed only
at or above treatment levels which resulted in evidence of appreciable
parental toxicity. No increased susceptibility was demonstrated in the
developmental toxicity studies; however developmental toxic effects,
were observed at the HDT.
Acceptable developmental toxicity studies have been performed in
rats and rabbits; an acceptable 2-generation reproduction study has
also been performed in rats. A chronic feeding/carcinogenicity
guideline study in rats has been submitted and is currently undergoing
review. An initial examination of the study supports the current
findings of no evidence of carcinogenicity. There is a complete
toxicity data base for sethoxydim and exposure data are complete or are
estimated based on data that reasonably accounts for potential
exposures.
The FQPA Safety Factor is to be retained in case of developmental
toxicity in the absence of maternal toxicity. Since malformations were
seen in the rat study at levels that produced minimal maternal
toxicity. The Agency concluded that an FQPA factor is needed. However,
it was determined that the 10x factor need not be retained, instead
should be reduced to 3x based on the following weight of evidence
considerations: (1) developmental toxicity was seen in only one
species, in the presence of maternal toxicity, and at a very high dose
(650 mg/kg/day) that approached the Limit-Dose of 1,000 mg/kg/day; (2)
no developmental toxicity was observed in the rabbit study at the HDT
(400 mg/kg/day); (3) there was no increased susceptibility seen in the
2-generation reproduction study in rats at doses up to 150 mg/kg/day
HDT; and (4) lack of concern for structure activity relationship (i.e.,
no significant developmental or reproductive toxicity was seen with the
structural analog, clethodim.)
Exposure assessments do not indicate a concern for potential risk
to infants and children based on: (1) the dietary exposure assessments
use field study data and assume 100% crop treated which results in an
overestimate of dietary exposure; (2) limited monitoring data are used
for ground and surface source drinking water exposure assessments,
resulting in estimates considered to be reasonable upper-bound
concentrations; (3) there is a potential for postapplication hand-to-
mouth exposure to toddlers associated with lawn use; however, the use
of conservative models and/or assumptions in the residential exposure
assessment provide adequate protection of infants and children.
The FQPA safety factor is applicable for acute dietary risk
assessment for females 13+ because the endpoint occurs only during in
urtero exposure and is not a postnatal effect. Since the effects occur
during in urtero exposure, it is not an appropriate endpoint for acute
dietary risk assessment of infants and children. The FQPA safety factor
is not applied for chronic risk assessment because the endpoint is an
in urtero effect and cannot result from postnatal exposure. The FQPA
safety factor is not applicable to the postapplication hand-to-mouth
exposure associated with the lawn use since this exposure scenario
would only be expected for toddlers and not for females 13+.
iii. Conclusion. Acceptable developmental toxicity studies have
been performed in rats and rabbits; an acceptable 2-generation
reproduction study has also been performed in rats. A chronic feeding/
carcinogenicity guideline study in rats has been submitted and is
currently undergoing review. An initial examination of the study
supports the current findings of no evidence of carcinogenicity. There
is a complete toxicity data base for sethoxydim and exposure data are
complete or are estimated based on data that reasonably accounts for
potential exposures.
2. Acute risk. Using the conservative exposure assumptions that
100% of the commodities having sethoxydim tolerances will contain
sethoxydim regulable residues and that those residues will be at the
level of the tolerance, EPA calculated acute dietary (food only) MOEs
ranging from 420 for children (1-6 years old) to 622 for females 13+
years. The level of concern is 300 (3x safety factor x 100) for females
13+ years and 100 for all other subgroups.
3. Chronic risk. Using the exposure assumptions described in this
unit, EPA has concluded that aggregate exposure to sethoxydim from food
will utilize less than 100% of the RfD for nursing infants, non-nursing
infants (<1 years old), children (1-6 years old), and children (7-12
years old). EPA generally has no concern for exposures below 100% of
the RfD because the RfD represents the level at or below which daily
aggregate dietary exposure over a lifetime will not pose appreciable
risks to human health. Despite the potential for exposure to sethoxydim
in drinking water and from non-dietary, non-occupational exposure, EPA
does not expect the aggregate exposure to exceed 100% of the RfD.
4. Short- or intermediate-term risk. An aggregate exposure estimate
and risk assessment was conducted for postapplication exposure to
sethoxydim on turf and ornamental plants taking into account chronic
exposure from food and the acute dietary NOAEL. The resulting MOEs
(1,390-2,350) are not of concern to EPA.
5. Determination of safety. Based on these risk assessments, EPA
concludes that there is a reasonable certainty that no harm will result
to infants and children from aggregate exposure to sethoxydim residues.
III. Other Considerations
A. Metabolism In Plants and Animals
The metabolism of sethoxydim in plants and animals is understood,
the tolerances for plant and animal commodities are expressed as the
combined residues of sethoxydim and its metabolites containing the 2-
cyclohexen-1-one moiety (calculated as the herbicide).
B. Analytical Enforcement Methodology
BASF Method 30 as published in PAM Vol. II is adequate for
tolerance enforcement in all raw agricultural commodities. Quantitation
is accomplished by gas chromatography with flame photometric detection
in the sulfur mode. Sethoxydim and its metabolites are not recovered or
not likely to be recovered by FDA multiresidue methods.
C. Magnitude of Residues
The available crop field data support the established tolerances
for asparagus at 4.0 ppm, carrot at 1.0 ppm, cranberry at 2.0 ppm, and
peppermint and spearmint tops at 30 ppm. Residue data submitted in
support of existing tolerances for carrot at 1.0 ppm, potato at 4.0
ppm, sugar beet at 1.0 ppm, and sweet potato at 4.0 ppm support the
establishment of a tolerance for horseradish at 4.0 ppm.
[[Page 32195]]
D. International Residue Limits
Maximum Residue Levels (MRLs) have not been established for
residues of sethoxydim on asparagus, carrot, cranberry, horseradish,
peppermint, or spearmint tops.
IV. Conclusion
Therefore, the tolerances are established for combined residues of
(2-[1-(ethoxyimino]butyl)-5-[2-(ethylthio)propyl]-3-hydroxy-2-
cyclohexen-1-one) and its metabolites containing the 2-cyclohexen-1-one
moiety (calculated as the herbicide) in or on asparagus at 4.0 ppm,
carrot at 1.0 ppm, cranberry at 2.0 ppm, horseradish at 4.0 ppm, and
peppermint and spearmint tops at 30 ppm. at ppm.
V. Objections and Hearing Requests
The new FFDCA section 408(g) provides essentially the same process
for persons to ``object'' to a tolerance regulation as was provided in
the old section 408 and in section 409. However, the period for filing
objections is 60 days, rather than 30 days. EPA currently has
procedural regulations which govern the submission of objections and
hearing requests. These regulations will require some modification to
reflect the new law. However, until those modifications can be made,
EPA will continue to use those procedural regulations with appropriate
adjustments to reflect the new law.
Any person may, by August 16, 1999, file written objections to any
aspect of this regulation and may also request a hearing on those
objections. Objections and hearing requests must be filed with the
Hearing Clerk, at the address given under the ``ADDRESSES'' section (40
CFR 178.20). A copy of the objections and/or hearing requests filed
with the Hearing Clerk should be submitted to the OPP docket for this
regulation. The objections submitted must specify the provisions of the
regulation deemed objectionable and the grounds for the objections (40
CFR 178.25). Each objection must be accompanied by the fee prescribed
by 40 CFR 180.33(i). EPA is authorized to waive any fee requirement
``when in the judgement of the Administrator such a waiver or refund is
equitable and not contrary to the purpose of this subsection.'' For
additional information regarding tolerance objection fee waivers,
contact James Tompkins, Registration Division (7505C), Office of
Pesticide Programs, Environmental Protection Agency, 401 M St., SW.,
Washington, DC 20460. Office location, telephone number, and e-mail
address: Rm. 239, Crystal Mall #2, 1921 Jefferson Davis Hwy.,
Arlington, VA, (703) 305-5697, [email protected]. Requests for
waiver of tolerance objection fees should be sent to James Hollins,
Information Resources and Services Division (7502C), Office of
Pesticide Programs, Environmental Protection Agency, 401 M St., SW.,
Washington, DC 20460.
If a hearing is requested, the objections must include a statement
of the factual issues on which a hearing is requested, the requestor's
contentions on such issues, and a summary of any evidence relied upon
by the requestor (40 CFR 178.27). A request for a hearing will be
granted if the Administrator determines that the material submitted
shows the following: There is genuine and substantial issue of fact;
there is a reasonable possibility that available evidence identified by
the requestor would, if established, resolve one or more of such issues
in favor of the requestor, taking into account uncontested claims or
facts to the contrary; and resolution of the factual issues in the
manner sought by the requestor would be adequate to justify the action
requested (40 CFR 178.32). Information submitted in connection with an
objection or hearing request may be claimed confidential by marking any
part or all of that information as CBI. Information so marked will not
be disclosed except in accordance with procedures set forth in 40 CFR
part 2. A copy of the information that does not contain CBI must be
submitted for inclusion in the public record. Information not marked
confidential may be disclosed publicly by EPA without prior notice.
VI. Public Record and Electronic Submissions
EPA has established a record for this regulation under docket
control number [OPP-300859] (including any comments and data submitted
electronically). A public version of this record, including printed,
paper versions of electronic comments, which does not include any
information claimed as CBI, is available for inspection from 8:30 a.m.
to 4 p.m., Monday through Friday, excluding legal holidays. The public
record is located in Room 119 of the Public Information and Records
Integrity Branch, Information Resources and Services Division (7502C),
Office of Pesticide Programs, Environmental Protection Agency, Crystal
Mall #2, 1921 Jefferson Davis Hwy., Arlington, VA.
Objections and hearing requests may be sent by e-mail directly to
EPA at:
[email protected]
E-mailed objections and hearing requests must be submitted as an
ASCII file avoiding the use of special characters and any form of
encryption.
The official record for this regulation, as well as the public
version, as described in this unit will be kept in paper form.
Accordingly, EPA will transfer any copies of objections and hearing
requests received electronically into printed, paper form as they are
received and will place the paper copies in the official record which
will also include all comments submitted directly in writing. The
official record is the paper record maintained at the Virginia address
in ``ADDRESSES'' at the beginning of this document.
VII. Regulatory Assessment Requirements
A. Certain Acts and Executive Orders
This final rule establishes a tolerance under section 408(d) of the
FFDCA in response to a petition submitted to the Agency. The Office of
Management and Budget (OMB) has exempted these types of actions from
review under Executive Order 12866, entitled Regulatory Planning and
Review (58 FR 51735, October 4, 1993). 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., or impose any enforceable
duty or contain any unfunded mandate as described under Title II of the
Unfunded Mandates Reform Act of 1995 (UMRA) (Pub. L. 104-4). Nor does
it require any prior consultation as specified by Executive Order
12875, entitled Enhancing the Intergovernmental Partnership (58 FR
58093, October 28, 1993), or special considerations as required by
Executive Order 12898, entitled Federal Actions to Address
Environmental Justice in Minority Populations and Low-Income
Populations (59 FR 7629, February 16, 1994), or require OMB review in
accordance with Executive Order 13045, entitled Protection of Children
from Environmental Health Risks and Safety Risks (62 FR 19885, April
23, 1997).
In addition, since tolerances and exemptions that are established
on the basis of a petition under FFDCA section 408(d), such as the
tolerance in this final rule, do not require the issuance of a proposed
rule, the requirements of the Regulatory Flexibility Act (RFA) (5
U.S.C. 601 et seq.) do not apply. Nevertheless, the Agency previously
assessed whether establishing tolerances, exemptions from tolerances,
raising tolerance levels or expanding exemptions might adversely impact
small entities and concluded, as a
[[Page 32196]]
generic matter, that there is no adverse economic impact. The factual
basis for the Agency's generic certification for tolerance actions
published on May 4, 1981 (46 FR 24950), and was provided to the Chief
Counsel for Advocacy of the Small Business Administration.
B. Executive Order 12875
Under Executive Order 12875, entitled Enhancing the
Intergovernmental Partnership (58 FR 58093, October 28, 1993), EPA may
not issue a regulation that is not required by statute and that creates
a mandate upon a State, local or tribal government, unless the Federal
government provides the funds necessary to pay the direct compliance
costs incurred by those governments. If the mandate is unfunded, EPA
must provide to OMB a description of the extent of EPA's prior
consultation with representatives of affected State, local, and tribal
governments, the nature of their concerns, copies of any written
communications from the governments, and a statement supporting the
need to issue the regulation. In addition, Executive Order 12875
requires EPA to develop an effective process permitting elected
officials and other representatives of State, local, and tribal
governments ``to provide meaningful and timely input in the development
of regulatory proposals containing significant unfunded mandates.''
Today's rule does not create an unfunded Federal mandate on State,
local, or tribal governments. The rule does not impose any enforceable
duties on these entities. Accordingly, the requirements of section 1(a)
of Executive Order 12875 do not apply to this rule.
C. Executive Order 13084
Under Executive Order 13084, entitled Consultation and Coordination
with Indian Tribal Governments (63 FR 27655, May 19, 1998), EPA may not
issue a regulation that is not required by statute, that significantly
or uniquely affects the communities of Indian tribal governments, and
that imposes substantial direct compliance costs on those communities,
unless the Federal government provides the funds necessary to pay the
direct compliance costs incurred by the tribal governments. If the
mandate is unfunded, EPA must provide OMB, in a separately identified
section of the preamble to the rule, a description of the extent of
EPA's prior consultation with representatives of affected tribal
governments, a summary of the nature of their concerns, and a statement
supporting the need to issue the regulation. In addition, Executive
Order 13084 requires EPA to develop an effective process permitting
elected officials and other representatives of Indian tribal
governments ``to provide meaningful and timely input in the development
of regulatory policies on matters that significantly or uniquely affect
their communities.''
Today's rule does not significantly or uniquely affect the
communities of Indian tribal governments. This action does not involve
or impose any requirements that affect Indian tribes. Accordingly, the
requirements of section 3(b) of Executive Order 13084 do not apply to
this rule.
VIII. Submission to Congress and the Comptroller General
The Congressional Review Act, 5 U.S.C. 801 et seq., as added by the
Small Business Regulatory Enforcement Fairness Act of 1996, generally
provides that before a rule may take effect, the Agency promulgating
the rule must submit a rule report, which includes a copy of the rule,
to each House of the Congress and the Comptroller General of the United
States. EPA will submit a report containing this rule and other
required information to the U.S. Senate, the U.S. House of
Representatives and the Comptroller General of the United States prior
to publication of the rule in the Federal Register. This rule is not a
``major rule'' as defined by 5 U.S.C. 804(2).
List of Subjects in 40 CFR Part 180
Environmental protection, Administrative practice and procedure,
Agricultural commodities, Pesticides and pests, Reporting and
recordkeeping requirements.
Dated: May 20, 1999.
Peter Caulkins,
Acting Director, Registration Division, Office of Pesticide Programs.
Therefore, 40 CFR chapter I is amended as follows:
PART 180-[AMENDED]
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. 180.412(a), by removing the expiration date for the
entries asparagus, carrot, cranberry, peppermint, tops and spearmint
tops and inserting None in each place and adding
a new entry for horseradish at 4.0 ppm to read as follows:
Sec. 180.412 Sethoxydim; tolerances for residues.
(a) * * *
------------------------------------------------------------------------
Parts Expiration/
Commodity per Revocation
million Date
------------------------------------------------------------------------
* * * * *
Horseradish....................................... 4.0 None
* * * * *
------------------------------------------------------------------------
* * * * *
[FR Doc. 99-14865 Filed 6-15-99; 8:45 am]
BILLING CODE 6560-50-F