[Federal Register Volume 63, Number 67 (Wednesday, April 8, 1998)]
[Rules and Regulations]
[Pages 17101-17108]
From the Federal Register Online via the Government Publishing Office [www.gpo.gov]
[FR Doc No: 98-9392]
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ENVIRONMENTAL PROTECTION AGENCY
40 CFR Parts 180, 185, and 186
[OPP-300642; FRL-5784-9]
RIN 2070-AB78
Clethodim; Time-Limited Pesticide Tolerance
AGENCY: Environmental Protection Agency (EPA).
ACTION: Final rule.
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SUMMARY: This regulation establishes time-limited tolerances for
combined residues of clethodim and its metabolites containing the 5-(2-
ethylthiopropyl)cyclohexene-3-one and 5-(2-ethylthiopropyl)-5-
hydroxycyclohexene-3-one moieties and their sulphoxides and sulphones,
all expressed as clethodim in or on alfalfa, forage; alfalfa, hay; dry
beans; peanuts; peanut, hay; peanut, meal; tomatoes; tomato, puree;
tomato, paste. Valent U.S.A. Corporation requested this tolerance under
the Federal Food, Drug and Cosmetic Act (FFDCA), as amended by the Food
Quality Protection Act of 1996 (Pub. L. 104-170). The tolerances will
expire on April 30, 2001.
DATES: This regulation is effective April 8, 1998. Objections and
requests for hearings must be received byEPA on or before June 8, 1998.
ADDRESSES: Written objections and hearing requests, identified by the
docket control number, [OPP-300620], 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-300620], 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, CM #2, 1921
Jefferson Davis Hwy., Arlington, VA.
A copy of objections and hearing requests filed with the Hearing
Clerk may also 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-300620]. 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: Joanne I. Miller,
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: Crystal Mall #2,
1921 Jefferson Davis Hwy., Arlington, VA, 703-305-6224, e-mail:
[email protected].
SUPPLEMENTARY INFORMATION: In the Federal Register of February 12, 1997
(62 FR 6530-6534) (FRL-5586-3), EPA, issued a notice pursuant to
section 408 of the Federal Food, Drug, and Cosmetic Act (FFDCA), 21
U.S.C. 346a(e) announcing the filing of a pesticide petition (PP) for
tolerance by Valent U.S.A. Corporation, 1333 N. California Blvd.,
Walnut Creek, CA 94596. This notice included a summary of the petition
prepared by Valent, the registrant. There were no comments
[[Page 17102]]
received in response to the notice of filing.
The petition requested that 40 CFR 180.458 be amended by
establishing time-limited tolerances for combined residues of the
herbicide clethodim and its metabolites containing the 5-(2-
ethylthiopropyl)cyclohexene-3-one and 5-(2-ethylthiopropyl)-5-
hydroxycyclohexene-3-one moieties and their sulphoxides and sulphones,
all expressed as clethodim, in or on alfalfa, forage at 6 part per
million (ppm); alfalfa, hay at 10 ppm; dry beans at 2 ppm; peanuts at 3
ppm; peanut, hay at 3 ppm; peanut, meal at 5 ppm; tomatoes at 1 ppm;
tomato, puree at 2 ppm; and tomato, paste at 3 ppm. This tolerance will
expire on April 30, 2001.
I. Risk Assessment and Statutory Findings
New 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. First, EPA determines the
toxicity of pesticides based primarily on toxicological studies using
laboratory animals. These studies address many adverse health effects,
including (but not limited to) reproductive effects, developmental
toxicity, toxicity to the nervous system, and carcinogenicity. Second,
EPA examines exposure to the pesticide through the diet (e.g., food and
drinking water) and through exposures that occur as a result of
pesticide use in residential settings.
A. Toxicity
1. Threshold and non-threshold effects. For many animal studies, a
dose response relationship can be determined, which provides a dose
that causes adverse effects (threshold effects) and doses causing no
observed effects (the ``no-observed effect level'' or ``NOEL'').
Once a study has been evaluated and the observed effects have been
determined to be threshold effects, EPA generally divides the NOEL from
the study with the lowest NOEL by an uncertainty factor (usually 100 or
more) to determine the Reference Dose (RfD). The RfD is a level at or
below which daily aggregate exposure over a lifetime will not pose
appreciable risks to human health. An uncertainty factor (sometimes
called a ``safety factor'') of 100 is commonly used since it is assumed
that people may be up to 10 times more sensitive to pesticides than the
test animals, and that one person or subgroup of the population (such
as infants and children) could be up to 10 times more sensitive to a
pesticide than another. In addition, EPA assesses the potential risks
to infants and children based on the weight of the evidence of the
toxicology studies and determines whether an additional uncertainty
factor is warranted. Thus, an aggregate daily exposure to a pesticide
residue at or below the RfD (expressed as 100% or less of the RfD) is
generally considered acceptable by EPA. EPA generally uses the RfD to
evaluate the chronic risks posed by pesticide exposure. For shorter
term risks, EPA calculates a margin of exposure (MOE) by dividing the
estimated human exposure into the NOEL from the appropriate animal
study. Commonly, EPA finds MOEs lower than 100 to be unacceptable. This
100-fold MOE is based on the same rationale as the 100-fold uncertainty
factor.
Lifetime feeding studies in two species of laboratory animals are
conducted to screen pesticides for cancer effects. When evidence of
increased cancer is noted in these studies, the Agency conducts a
weight of the evidence review of all relevant toxicological data
including short-term and mutagenicity studies and structure activity
relationship. Once a pesticide has been classified as a potential human
carcinogen, different types of risk assessments (e.g., linear low dose
extrapolations or MOE calculation based on the appropriate NOEL) will
be carried out based on the nature of the carcinogenic response and the
Agency's knowledge of its mode of action.
2. Differences in toxic effect due to exposure duration. The
toxicological effects of a pesticide can vary with different exposure
durations. EPA considers the entire toxicity data base, and based on
the effects seen for different durations and routes of exposure,
determines which risk assessments should be done to assure that the
public is adequately protected from any pesticide exposure scenario.
Both short and long durations of exposure are always considered.
Typically, risk assessments include ``acute,'' ``short-term,''
``intermediate term,'' and ``chronic'' risks. These assessments are
defined by the Agency as follows.
Acute risk, by the Agency's definition, results from 1-day
consumption of food and water, and reflects toxicity which could be
expressed following a single oral exposure to the pesticide residues.
High end exposure to food and water residues are typically assumed.
Short-term risk results from exposure to the pesticide for a period
of 1-7 days, and therefore overlaps with the acute risk assessment.
Historically, this risk assessment was intended to address primarily
dermal and inhalation exposure which could result, for example, from
residential pesticide applications. However, since enaction of FQPA,
this assessment has been expanded to include both dietary and non-
dietary sources of exposure, and will typically consider exposure from
food, water, and residential uses when reliable data are available. In
this assessment, risks from average food and water exposure, and high-
end residential exposure, are aggregated. High-end exposures from all
three sources are not typically added because of the very low
probability of this occurring in most cases, and because the other
conservative assumptions built into the assessment assure adequate
protection of public health. However, for cases in which high-end
exposure can reasonably be expected from multiple sources (e.g.
frequent and widespread homeowner use in a specific geographical area),
multiple high-end risks will be aggregated and presented as part of the
comprehensive risk assessment/characterization. Since the toxicological
endpoint considered in this assessment reflects exposure over a period
of at least 7 days, an additional degree of conservatism is built into
the assessment; i.e., the risk assessment nominally covers 1-7 days
exposure, and the toxicological endpoint/NOEL is selected to be
adequate for at least 7 days of exposure. (Toxicity results at lower
levels when the dosing duration is increased.)
Intermediate-term risk results from exposure for 7 days to several
months. This assessment is handled in a manner similar to the short-
term risk assessment.
Chronic risk assessment describes risk which could result from
several months
[[Page 17103]]
to a lifetime of exposure. For this assessment, risks are aggregated
considering average exposure from all sources for representative
population subgroups including infants and children.
B. Aggregate Exposure
In examining aggregate exposure, FFDCA section 408 requires that
EPA take into account available and reliable information concerning
exposure from the pesticide residue in the food in question, residues
in other foods for which there are tolerances, residues in groundwater
or surface water that is consumed as drinking water, and other non-
occupational exposures through pesticide use in gardens, lawns, or
buildings (residential and other indoor uses). Dietary exposure to
residues of a pesticide in a food commodity are estimated by
multiplying the average daily consumption of the food forms of that
commodity by the tolerance level or the anticipated pesticide residue
level. The Theoretical Maximum Residue Contribution (TMRC) is an
estimate of the level of residues consumed daily if each food item
contained pesticide residues equal to the tolerance. In evaluating food
exposures, EPA takes into account varying consumption patterns of major
identifiable subgroups of consumers, including infants and children.The
TMRC is a ``worst case'' estimate since it is based on the assumptions
that food contains pesticide residues at the tolerance level and that
100% of the crop is treated by pesticides that have established
tolerances. If the TMRC exceeds the RfD or poses a lifetime cancer risk
that is greater than approximately one in a million, EPA attempts to
derive a more accurate exposure estimate for the pesticide by
evaluating additional types of information (anticipated residue data
and/or percent of crop treated data) which show, generally, that
pesticide residues in most foods when they are eaten are well below
established tolerances.
Percent of crop treated estimates are derived from Federal and
private market survey data. Typically, a range of estimates are
supplied and the upper end of this range is assumed for the exposure
assessment. By using this upper end estimate of percent of crop
treated, the Agency is reasonably certain that exposure is not
understated for any significant subpopulation group. Further, regional
consumption information is taken into account through EPA's computer-
based model for evaluating the exposure of significant subpopulations
including several regional groups, to pesticide residues. For this
pesticide, the most highly exposed population subgroup was not
regionally based.
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 clethodim
and to make a determination on aggregate exposure, consistent with
section 408(b)(2), for time-limited tolerances for combined residues of
clethodim and its metabolites containing the 5-(2-
ethylthiopropyl)cyclohexene-3-one and 5-(2-ethylthiopropyl)-5-
hydroxycyclohexene-3-one moieties and their sulphoxides and sulphones,
all expressed as clethodim on alfalfa, forage at 6 ppm; alfalfa, hay at
10 ppm; dry beans at 2 ppm; peanuts at 3 ppm; peanut, hay at 3 ppm;
peanut, meal at 5 ppm; tomatoes at 1 ppm; tomato, puree at 2 ppm; and
tomato, paste at 3 ppm. EPA's assessment of the dietary exposures and
risks associated with establishing the tolerance 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 clethodim are
discussed below.
1. Several acute toxicology studies places the technical-grade
herbicide in Toxicity Category II.
2. A 2-year rat chronic toxicity/carcinogenicity study found the
compound to be noncarcinogenic to rats under the conditions of the
study. The systemic no-observed-effect level (NOEL) was 500 ppm
(approximately 19 milligram/kilograms/day (mg/kg/day)), and the
systemic lowest-observed-effect-level (LOEL) was 2,500 ppm
(approximately 100 mg/kg/day) based on the observed body weight gain,
the increases in liver weights, and the presence of centrilobular
hepatic hypertrophy.
3. An 18-month mouse carcinogenicity study which showed the
compound to be noncarcinogenic to mice under the conditions of the
study. The systemic NOEL was 200 ppm (8 mg/kg/day), and the systemic
LOEL was 1,000 ppm (50 mg/kg/day) based on treatment-related effects on
survival, red cell mass, absolute and relative liver weights, and
microscopic findings in liver and lung.
4. A 1-year feeding study in dogs with a systemic NOEL of 1 mg/kg/
day in both sexes and an LOEL of 75 mg/kg/day based on increased
absolute and relative liver weights, and alteration and clinical
chemistry.
5. A developmental toxicity study in rats with a developmental and
maternal NOEL and LOEL of 100 and 350 mg/kg/day, respectively. The NOEL
and LOEL for developmental toxicity were based on reductions in fetal
body weight and increases in skeletal anomalies.
6. A developmental toxicity study in rabbits with a maternal
toxicity NOEL and LOEL of 25 and 100 mg/kg/day, respectively. Maternal
toxicity was manifested as clinical signs of toxicity and reduced
weight gain and food consumption during treatment. Developmental
toxicity was not observed, and therefore the developmental toxicity
NOEL was 300 mg/kg/day, highest dose tested (HDT).
7. A two-generation reproduction study in the rat with parental
toxicity NOEL and LOEL of 500 and 2,500 ppm (51 and 263 mg/kg/day),
respectively, based on reductions in body weight in males, and
decreased food consumption in both generations. The NOEL for
reproductive toxicity was 2,500 ppm (263 mg/kg/day, HDT).
8. A mutagenicity test with Salmonella Ames assay showed
nonmutagenicity in three strains. Clethodim imine sulfone was negative
for reverse gene mutation in Salmonella and E. Coli exposed up to
10,000 ug/plate with or without activation. Clethodim was negative for
chromosomal damage in bone marrow cells of rats treated orally up to
toxic dose (1,500 mg/kg).
B. Toxicological Endpoints
1. Acute toxicity. There were no effects observed in oral
developmental toxicity studies in rats or rabbits that could be
attributable to a single dose (exposure). Therefore, a dose and an
endpoint were not selected.
2. Short - and intermediate - term toxicity-- i. Dermal
absorption. In a dermal penetration study, groups of 12 male Sprague-
Dawley rats received a single dermal application of [14C]-
clethodim in deionized water at 0.05, 0.5, or 5 mg/rat onto an area of
10 cm2. Dermal absorption was assessed in 4 rats/dose/time
period after 2, 10 and 24 hours post-treatment. A dermal absorption
factor of 30% was selected for risk assessment based on the results
observed at 10 hours in rats administered the 0.05 mg/rat dose.
[[Page 17104]]
ii. Short-term toxicity . A dermal equivalent dose was calculated
as 350 mg/kg/day. This dermal equivalent dose was estimated by applying
the 30% dermal absorption (DA) rate to the oral NOEL of 100 mg/kg/day
in a rat developmental toxicity study (oral NOEL 100 / 30% DA x 100 =
333 mg/kg/day, dermal equivalent dose). Similarly, when the 30% DA is
applied to the oral LOEL of 350 mg/kg/day in that study, the resulting
dermal equivalent dose of 1167 mg/kg/day (oral LOEL 350 / 30% DA x 100)
approximates the LOEL of 1,000 mg/kg/day established in the 21-day
dermal study.
In a 21-day dermal toxicity study with technical clethodim, there
was a wide range between the mid (100 mg/kg/day) and the high (1,000
mg/kg/day) doses. This broad range obscured the detection of a true
NOEL which could have been anywhere in between these doses which were
the study NOEL (100 mg/kg/day) and the LOEL (1,000 mg/kg/day). The
Office of Pesticide's Health Effects Division's Hazard Identification
Review Committee (HAZID Committee) also noted the 10-fold difference
between the LOELs established with the Technical (1,000 mg/kg/day) and
Formulated (100 mg/kg/day) products in the 21-day dermal toxicity
studies. Therefore, based on these factors, the HAZID Committee
calculated a dermal equivalent dose for short-term occupational and
residential risk assessments.
iii. Intermediate-term toxicity. A dermal equivalent dose was
calculated as 75 mg/kg/day. This dermal equivalent dose was estimated
by applying the 30% dermal absorption (DA) rate to the oral NOEL of 25
mg/kg/day in the dog oral toxicity study (oral NOEL/30% DA x 100 = 75
mg/kg/day, dermal equivalent dose).
This dose (25 mg/kg/day) is supported by the NOEL of 30 mg/kg/day
established in the 90-day oral feeding study in rats. In that study,
the LOEL of 134 mg/kg/day was based on increased absolute and relative
liver weights as well as increases in centrilobular hypertrophy. Liver
was shown to be the target organ for clethodim-induced toxicity at
comparable doses in two species, dogs and rats.
Since an oral dose was identified, a dermal absorption (DA) rate of
30% should be used for risk assessments. Application of the 30% DA is
applied to the oral NOEL in the dog (25 mg/kg/ day) and rat (30 mg/kg/
day), and yields dermal equivalent doses of 75 and 100 mg/kg/day (25/30
mg/kg/day / 30% x 100 = 75/100 mg/kg/day), which approximates the NOEL
of 100 mg/kg/day established in the 21-day dermal toxicity study with
the technical product.
3. Chronic toxicity. EPA has established the RfD for clethodim at
0.01 mg/kg/day. This RfD is based on alterations in hematology, a
clinical chemistry parameter and increased absolute and relative liver
weights at 75 mg/kg/day observed in a chronic toxicity study in dogs
with a NOEL of 1 mg/kg/day. An uncertainty factor of 100 was used in
calculating the RfD to account for both inter- and intra-species
variations.
4. Carcinogenicity. The Office of Pesticide Programs' Health
Effects Division's Carcinogenicity Peer Review Committee (CPRC) has
classified clethodim in Group E carcinogen (no evidence of
carcinogenicity) under the Agency's ``Guidelines for Carcinogen Risk
Assessment,'' published in the Federal Register of September 24, 1986
(51 FR 33992). In its evaluation, CPRC gave consideration to the weight
change in the 2-year feeding study in rats and the 18 month feeding
study in mice.
C. Exposures and Risks
1. From food and feed uses. Tolerances have been established (40
CFR 180.458) for the combined residues of clethodim and its metabolites
containing the 5-(2-ethylthiopropyl)cyclohexene-3-one and 5-(2-
ethylthiopropyl)-5-hydroxycyclohexene-3-one moieties and their
sulphoxides and sulphones, all expressed as clethodim, in or on a
variety of raw agricultural commodities. Risk assessments were
conducted by EPA to assess dietary exposures and risks from clethodim
as follows:
i. Acute exposure and risk. Acute dietary 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 one day or single exposure. No acute dietary endpoint was
determined for clethodim, so an acute risk assessment was not required.
ii. Chronic exposure and risk. The chronic dietary exposure
analysis from food sources was conducted using the reference dose (RfD)
of 0.01 mg/kg/day and an uncertainty factor (UF) of 100 applicable to
all population subgroups. In conducting this chronic dietary (food)
risk assessment, residues were used for alfalfa, dry beans, peanuts and
tomatoes, and all other commodities with published or pending,
permanent or time-limited clethodim tolerances. Residues were used at
tolerance levels for some of these crops and at anticipated residue
levels for others. Thus, this risk assessment should be viewed as
partially refined. Further refinement using additional anticipated
residue levels and percent crop-treated information would result in a
lower estimate of chronic dietary exposure.
The estimated exposure levels for existing and proposed clethodim
uses vary between 0.001034 and 0.008411 mg/kg/day for the population
subgroups (the U.S. population (48 states)), those for infants and
children, females (13 to 19 years old, not pregnant and not nursing),
and the other subgroups for which the percentage of the RfD occupied is
greater than that occupied by the subgroup U.S. population (48 states);
and occupied between 10% and 84% of the RfD.
When EPA establishes, modifies, or leaves in effect a tolerance,
section 408(b)(2)(E) authorizes EPA to use available data and
information on the anticipated residue levels of pesticide residues in
food and the actual levels of pesticide chemicals that have been
measured in food. If EPA relies on such information, EPA must require
that data be provided five years after the tolerance is established,
modified, or left in effect, demonstrating that the levels in food are
not above the levels anticipated. As required by section 408(b)(2)(E),
EPA will issue a data call-in for information relating to anticipated
residues to be submitted no later than five years from the date of
issuance of this tolerance.
2. From drinking water. Based on the chronic dietary (food)
exposure and using default body weights and water consumption figures,
chronic drinking water levels of concern (DWLOC) for drinking water
were calcualted. To calculate the DWLOC, the chronic dietary food
exposure (from the DRES analysis) was subtracted from the RfD.
For chronic exposure, based on an adult body weight of 70 kg and 2L
consumption of water per day, the level of concern from chronic
exposure estimates for the U.S. population is 212 ppb and 1031 ppb for
females 13 years and older, not pregnant or nursing. For infants and
children (10 kg and 1L water/day) our level of concern for drinking
water is 16 ppb. Agency estimates for contamination of drinking water
from the registered uses of clethodim is 10 ppb. This level is lower
than the chronic DWLOCs for the U.S. population (212 ppb) and females
13 years and older, not pregnant or nursing (1,031 ppb), and infants
and children (16 ppb). Therefore, EPA concludes with reasonable
certainty that the chronic exposure to clethodim in surface water is
less than our level of concern.
[[Page 17105]]
3. From non-dietary exposure. Clethodim is currently registered for
use on the following residential non-food sites: ornamental plants,
wooden containers for growing plants, along driveways, patios, golf
course turf, walkways, trails, and paths. There are no indoor uses
registered for clethodim. It is conceivable that these outdoor uses
could result in residential exposure. However, under current EPA
criteria, the registered and proposed uses of clethodim would not
constitute a chronic residential exposure scenario. Clethodim does not
control broadleaf weeds and therefore is registered for use on edges
and walkways, thus greatly reducing the risk of residential exposure.
The short- and intermediate aggregate MOEs for residential
applicators using a low pressure handwand ranged from 7,300 to 1,600.
The post-application aggregate short- and intermediate-term MOEs for
the U.S. population ranged from 520 to 110. The post-application
aggregate short- and intermediate-term MOEs for infants/children range
from 540 to 115. Short- and intermediate-term aggregate exposure takes
into account chronic dietary exposure plus indoor and outdoor
residential exposures. These exposure assessments assumed the maximum
application rate for turf and garden uses and two hours as the duration
of exposure, and a 20% dislodgeable foliar residue. These assumptions
are considered conservative and protective.
4. 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.'' The Agency believes that ``available
information'' in this context might include not only toxicity,
chemistry, and exposure data, but also scientific policies and
methodologies for understanding common mechanisms of toxicity and
conducting cumulative risk assessments. For most pesticides, although
the Agency has some information in its files that may turn out to be
helpful in eventually determining whether a pesticide shares a common
mechanism of toxicity with any other substances, EPA does not at this
time have the methodologies to resolve the complex scientific issues
concerning common mechanism of toxicity in a meaningful way. EPA has
begun a pilot process to study this issue further through the
examination of particular classes of pesticides. The Agency hopes that
the results of this pilot process will increase the Agency's scientific
understanding of this question such that EPA will be able to develop
and apply scientific principles for better determining which chemicals
have a common mechanism of toxicity and evaluating the cumulative
effects of such chemicals. The Agency anticipates, however, that even
as its understanding of the science of common mechanisms increases,
decisions on specific classes of chemicals will be heavily dependent on
chemical specific data, much of which may not be presently available.
Although at present the Agency does not know how to apply the
information in its files concerning common mechanism issues to most
risk assessments, there are pesticides as to which the common mechanism
issues can be resolved. These pesticides include pesticides that are
toxicologically dissimilar to existing chemical substances (in which
case the Agency can conclude that it is unlikely that a pesticide
shares a common mechanism of activity with other substances) and
pesticides that produce a common toxic metabolite (in which case common
mechanism of activity will be assumed).
EPA does not have, at this time, available data to determine
whether clethodim 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,
clethodim 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 clethodim has a common mechanism of toxicity
with other substances.
D. Aggregate Risks and Determination of Safety for U.S. Population
1. Acute risk. There were no effects observed in oral developmental
toxicity studies in rats or rabbits that could be attributable to a
single dose (exposure). Therefore, a dose and an endpoint were not
selected, and EPA concludes that there is a reasonable certainty that
no harm will result from aggregate acute exposure to clethodim
residues.
2. Chronic risk. Using the ARC exposure assumptions described
above, EPA has concluded that aggregate exposure to clethodim from food
will utilize 39% of the RfD for the U.S. population. The major
identifiable subgroup with the highest aggregate exposure is children
one to six years of age and is 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 clethodim 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 chronic
exposure to clethodim 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.
Clethodim is registered for uses that could result in short- and
intermediate-term exposures. The short- and intermediate aggregate
margins of exposure (MOEs) for residential applicators using a low
pressure handwand ranged from 7,300 to 1,600. The postapplication
aggregate short- and intermediate-term MOEs for the U.S. population
ranged from 520 to 110. The postapplication aggregate short- and
intermediate-term MOEs for infants/children range from 540 to 115.
Short- and intermediate-term aggregate exposure takes into account
chronic dietary exposure plus indoor and outdoor residential exposures.
These exposure assessments assumed the maximum application rate for
turf and garden uses and two hours as the duration of exposure, and a
20% dislodgeable foliar residue. These assumptions are considered
conservative and protective. Short- and intermediate term MOEs for
occupational workers ranged from 620 for aerial mixer/loaders to 60,000
for ground applicators. These estimates do not exceed EPA's level of
concern. EPA concludes that there is a reasonable certainty that no
harm will result from aggregate short- and intermediate-term exposure
to clethodim residues.
E. Aggregate Cancer Risk for U.S. Population
Clethodim has been classified as a Group E chemical (no evidence of
carcinogenicity), and EPA concludes that there is a reasonable
certainty that no harm will result from aggregate exposure to clethodim
residues.
F. Aggregate Risks and Determination of Safety for Infants and Children
1. Safety factor for infants and children-- i. In general. In
assessing the
[[Page 17106]]
potential for additional sensitivity of infants and children to
residues of clethodim, EPA considered data from developmental toxicity
studies in the rat and rabbit and a two-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 post-natal toxicity and the
completeness of the database 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 MOE analysis or through using uncertainty (safety)
factors in calculating a dose level that poses no 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. Developmental toxicity studies. In a prenatal developmental
toxicity study in Sprague-Dawley rats, clethodim (82.6%) was
administered at doses of 0, 10, 100, 350, or 700 mg/kg/day by gavage in
10 mg/kg of 0.7% carboxy methylcellulose and Tween 80 on gestation days
6-15. For maternal toxicity, the NOEL was 100 mg/kg/day and the LOEL
was 350 mg/kg/day based upon decreased body weight gain and clinical
signs of toxicity (salivation). The developmental NOEL was 100 mg/kg/
day and the developmental LOEL was 350 mg/kg/day, based upon reductions
in fetal body weight and an increase in the incidence of skeletal
anomalies.
A prenatal developmental toxicity study was conducted in pregnant
New Zealand white rabbits in which clethodim (82.6%) was administered
by gavage in 5 ml/kg at doses of 0, 25, 100, or 300 mg/kg/day in 0.7%
carboxy methylcellulose and Tween 80 on gestation days 7-19. For
maternal toxicity, the NOEL was 25 mg/kg/day and the LOEL was 100 mg/
kg/day, based on clinical signs of toxicity (dried feces and blood in
the cage pan) and reduced body weight and food consumption during
treatment. There was no developmental toxicity noted. For developmental
toxicity, the NOEL was 300; a LOEL was not established.
iii. Reproductive toxicity study. In a two-generation reproductive
study, Sprague-Dawley rats received clethodim (83.2%) in the diet at 0,
5, 20, 500, or 2,500 ppm. The parental systemic NOEL was 500 ppm (51
mg/kg/day) and the parental systemic LOEL was 2,500 ppm (263 mg/kg/
day), based on decreased body weights (particularly in males) and food
consumption for both generations. There were no effects on
reproduction, nor was there evidence of toxicity to the offspring
(offspring NOEL 2,500 ppm).
iv. Pre- and post-natal sensitivity. The data base is complete. The
oral perinatal and prenatal data demonstrated no indication of
increased sensitivity of rats or rabbits to in utero exposure to
clethodim. Therefore, EPA concludes that reliable data show that the
standard uncertainty factor of 100 will be safe for infants and
children.
2. Acute risk. There were no effects observed in oral developmental
toxicity studies in rats or rabbits that could be attributable to a
single dose (exposure). Therefore, a dose and an endpoint were not
selected, and EPA concludes that there is a reasonable certainty that
no harm will result from aggregate acute exposure to clethodim
residues.
3. Chronic risk. Using the conservative exposure assumptions
described above, EPA has concluded that aggregate exposure to clethodim
from food will utilize 45% of the RfD for non-nursing infants less than
one year old, and 84% for children ages one through six years of age.
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 clethodim 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
to infants and children from aggregate exposure to clethodim residues.
4. Short- or intermediate-term risk. The postapplication aggregate
short- and intermediate-term MOEs for infants/children range from 540
to 115. Short- and intermediate-term aggregate exposure takes into
account chronic dietary exposure plus indoor and outdoor residential
exposures. These exposure assessments assumed the maximum application
rate for turf and garden uses and two hours as the duration of
exposure, and a 20% dislodgeable foliar residue. These assumptions are
considered conservative and protective. These estimates do not exceed
EPA's level of concern. EPA concludes that there is a reasonable
certainty that no harm will result from aggregate short- and
intermediate-term exposure to clethodim residues.
III. Other Considerations
A. Metabolism In Plants and Animals
The nature of clethodim residues in plants, ruminants, and poultry
is adequately understood for the purposes of these subject petitions.
The residues of concern are as defined in 40 CFR 180.485(b).
B. Analytical Enforcement Methodology
Analytical methods are available for enforcement. Method EPA-RM-
26D-2 [HPLC-UV], ``Confirmatory Method for the Determination of
Clethodim and Clethodim Metabolites in Crops, Animal Tissues, and Mail
and Eggs,'' which distinguishes clethodim residues from residues of the
structurally similar herbicide sethoxydim, and Method RM-26B-2 [GLC-
FPD-S], ``Analytical Method for the Determination of Clethodim
Residues,'' the common moiety method, have undergone successful EPA
Method Validation. Revisions to EPA-RM-26D-2 are requested prior to
establishment of permanent tolerances on these subject crops. The
method may be obtained from: Calvin Furlow, PRRIB, IRSD, (7502C),
Office of Pesticide Programs, Environmental Protection Agency, 401 M
St., SW., Washington, DC 20460. Office location and telephone number:
Rm. 119FF, CM #2, 1921 Jefferson Davis Hwy., Arlington, VA 22202, (703-
305-5229).
C. Magnitude of Residues
The crop field trial data are adequate for the purposes of these
time-limited tolerances. To support future permanent tolerances, Valent
U.S.A. Corp. must submit three additional dry bean field trials from
Region 5, four additional peanut field trials from Region 2, and four
additional tomato field trials from California, each conducted at the
maximum use rates and proposed pre-harvest intervals. Field trial
regions are defined in EPA OPPTS Guideline 860.1500.
D. International Residue Limits
There are no Codex, Canadian or Mexican tolerances or maximum
residue limits established for clethodim
[[Page 17107]]
on tomatoes, alfalfa, peanuts, or dry beans. There are no conflicts
between this proposed action and international residue limits.
E. Rotational Crop Restrictions
A confined rotational crop study of [ring-4,6-14C]-
clethodim with carrots, lettuce, and wheat was reported. Results
indicate there is no need for field rotational crop trials.
IV. Conclusion
Therefore, the time-limited tolerances are is established for
combined residues of clethodim and its metabolites containing the 5-(2-
ethylthiopropyl)cyclohexene-3-one and 5-(2-ethylthiopropyl)-5-
hydroxycyclohexene-3-one moieties and their sulphoxides and sulphones,
all expressed as clethodim in alfalfa, forage at 6 ppm; alfalfa, hay at
10 ppm; dry beans at 2 ppm; peanuts at 3 ppm; peanut, hay at 3 ppm;
peanut, meal at 5 ppm; tomatoes at 1 ppm; tomato, puree at 2 ppm; and
tomato, paste at 3 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 issued by EPA under
new section 408(e) and (l)(6) 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 June 8, 1998, 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 above (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 rulemaking. 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). 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
Confidential Business Information (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 Docket
EPA has established a record for this rulemaking under docket
control number [OPP-300620] (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.
Electronic comments may be sent directly to EPA at:
[email protected].
Electronic comments must be submitted as an ASCII file avoiding the
use of special characters and any form of encryption.
The official record for this rulemaking, as well as the public
version, as described above 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 rulemaking record which
will also include all comments submitted directly in writing. The
official rulemaking record is the paper record maintained at the
Virginia address in ``ADDRESSES'' at the beginning of this document.
VII. Regulatory Assessment Requirements
This final rule establishes time-limited 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). 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 these tolerances and exemptions that are
established on the basis of a petition under FFDCA section 408(d), such
as the time-limited 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.
Nevertheless, the Agency has previously assessed whether establishing
tolerances, exemptions from tolerances, raising tolerance levels or
expanding exemptions might adversely impact small entities and
concluded, as a 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.
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
[[Page 17108]]
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 to
the Comptroller General of the United States. EPA will submit a report
containing this rule and other required information to the U.S. Senate,
the U.S. House of Representatives, and the Comptroller General of the
United States prior to publication of 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
40 CFR Part 180
Environmental protection, Administrative practice and procedure,
Agricultural commodities, Pesticides and pests, Reporting and
recordkeeping requirements.
40 CFR Part 185
Environmental protection, Food additives, Pesticides and pests.
40 CFR Part 186
Environmental protection, Animal feeds, Pesticides and pests.
Dated: April 3, 1998.
James Jones,
Director, Registration Division, Office of Pesticide Programs.
Therefore, 40 CFR chapter I is amended as follows:
PART 180--[AMENDED]
1. In part 180:
a. The authority citation for part 180 continues to read as
follows:
Authority: 21 U.S.C. 346a and 371.
b. Section 180.458 is amended as follows:
i. By adding a heading to paragraph (a) and designating the text as
paragraph (a)(1).
ii. By adding paragraph (a)(2).
iii. By redesignating paragraph (b) as paragraph (a)(3).
iv. By adding with headings and reserving paragraphs (b), (c), and
(d).
The added text reads as follows:
Sec. 180.458 Clethodim ((E)-()-2-[1-[[(3-chloro-2-
propenyl)oxy]imino]propyl]-5-[2(ethylthio)propyl]-3-hydroxy-2-
cyclohexen-1-one); tolerances for residues.
(a) General. * * *
(2) Time-limited tolerances are established for the combined
residues of clethodim ((E)-()-2-[1-[[(3-chloro-2-
propenyl)oxy]imino]propyl]-5-[2- (ethylthio)propyl]-3-hydroxy-2-
cyclohexen-1-one) and its metabolites containing the 5-(2-
ethylthiopropyl)cyclohexene-3-one and 5-(2-ethylthiopropyl)-5-
hydroxycyclohexene-3-one moieties and their sulphoxides and sulphones,
expressed as clethodim, in or on the following raw agricultural
commodities:
------------------------------------------------------------------------
Expiration/
Commodity Parts per Revocation
million Date
------------------------------------------------------------------------
Alfalfa, forage............................... 6 4/30/01
Alfalfa, hay.................................. 10 4/30/01
Dry beans..................................... 2 4/30/01
Peanut, hay................................... 3 4/30/01
Peanut, meal.................................. 5 4/30/01
Peanuts....................................... 3 4/30/01
Tomatoes...................................... 1 4/30/01
Tomato, paste................................. 3 4/30/01
Tomato, puree................................. 2 4/30/01
------------------------------------------------------------------------
* * * * *
(b) Section 18 emergency exemptions. [Reserved]
(c) Tolerances with regional registrations. [Reserved]
(d) Indirect or inadvertent residues. [Reserved]
PART 185--[AMENDED]
2. In part 185:
a. The authority citation for part 185 continues to read as
follows:
Authority: 21 U.S.C. 346a and 348.
Sec. 185.1075 [Removed]
b. In Sec. 185.1075:
i. By transferring the text and table to Sec. 180.458 and
redesignating as paragraph (a)(4).
ii. The remainder of Sec. 185.1075 is removed.
PART 186--[AMENDED]
3. In part 186:
a. The authority citation for part 186 continues to read as
follows:
Authority: 21 U.S.C. 342, 348, and 701.
Sec. 186.1075 [Removed]
b. In Sec. 186.1075:
i. Paragraphs (a) and (b) are transferred to Sec. 180.458 and
redesignated as paragraphs (a)(5) and (a)(6) respectively.
ii. The remainder of Sec. 186.1075 is removed.
[FR Doc. 98-9392 Filed 4-7--98; 8:45 am]
BILLING CODE 6560-50-F