[Federal Register Volume 63, Number 87 (Wednesday, May 6, 1998)]
[Rules and Regulations]
[Pages 24941-24949]
From the Federal Register Online via the Government Publishing Office [www.gpo.gov]
[FR Doc No: 98-11764]
-----------------------------------------------------------------------
ENVIRONMENTAL PROTECTION AGENCY
40 CFR Part 180
[OPP-300653; FRL-5788-5]
RIN 2070-AB78
Cymoxanil; Pesticide Tolerance
AGENCY: Environmental Protection Agency (EPA).
ACTION: Final rule.
-----------------------------------------------------------------------
SUMMARY: This regulation establishes a tolerance for residues of the
fungicide, cymoxanil, 2-cyano-N-[(ethylamino)carbonyl]-2-(methoxyimino)
acetamide, in or on potatoes. E.I. DuPont de Nemours & Company
submitted a petition under the Federal Food, Drug and Cosmetic Act
(FFDCA), as amended by the Food Quality Protection Act of 1996 (Pub. L.
104-170) requesting this tolerance.
DATES: This regulation is effective May 6, 1998. Objections and
requests for hearings must be received by EPA on or before July 6,
1998.
ADDRESSES: Written objections and hearing requests, identified by the
docket control number, [OPP-300653], 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-300653], 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: opp-docket@epamail.epa.gov. 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-300653]. 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: Mary Waller, Acting Product
Manager (PM) 21, 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) 308-
9354, e-mail: waller.mary@epamail.epa.gov.
SUPPLEMENTARY INFORMATION: In the Federal Register of (July 25, 1997,
62 FR 40075)(FRL-5726-4), 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 pesticide petition (PP 7F4805) for a tolerance
by E.I. DuPont de Nemours and Company, E. I. DuPont Agricultural
Products, Walker's Mill,
[[Page 24942]]
Barley Mill Plaza, P.O. Box 80038, Wilmington, Deleware, 19880-0038.
This notice included a summary of the petition prepared by E.I. DuPont
de Nemours & Company, the registrant. No comments were received in
response to the notice of filing.
The petition requested that 40 CFR 180.503 be amended by
establishing a tolerance for residues of the fungicide cymoxanil, 2-
cyano-N-[(ethylamino)carbonyl]-2-(methoxyimino) acetamide, in or on
potatoes at 0.05 parts per million (ppm).
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 percent 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 hundredfold MOE is based on the same rationale as
the hundredfold 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 to a lifetime of exposure. For this assessment, risks
are aggregated considering average exposure from all sources for
representative population
[[Page 24943]]
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 percent 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 (children 1 to 6
years old) 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 cymoxanil
to make a determination on aggregate exposure, consistent with section
408(b)(2), for a tolerance for residues of cymoxanil 2-cyano-N-
[(ethylamino)carbonyl]-2-(methoxyimino) acetamide in or on potatoes.
EPA's assessment of the dietary exposures and risks associated with
establishing this 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 cymoxanil is
discussed below.
1. Acute toxicity. A battery of acute toxicity studies resulted in
an acute oral LD50 = 760 milligrams/kilograms (mg/kg) for
males and LD50 =1,200 mg/kg for females; an acute dermal
LD50 > 2,000 mg/kg for both sexes; an acute inhalation
LC50 > 5.06 for both sexes; no ocular irritation; slight
dermal irritation and a finding that the cymoxanil is not a dermal
sensitizer.
2. Subchronic toxicity. a. A subchronic oral toxicity/
neurotoxicity study in rats fed cymoxanil at dose levels of 0, 100,
750, 1,500, or 3,000 ppm (0, 6.54, 47.6, 102, or 224 mg/kg/day for
males, and 0, 8.0, 59.9, 137, or 333 mg/kg/day for females) for
approximately 97 days. A group of 10 rats/sex/dose were evaluated for
subchronic systemic toxicity and a group of 10 rats/sex/dose underwent
neurobehavioral testing at pre-test, 5, 9, and 13 weeks. The control
and high-dose groups were assessed for neuropathology. The LOEL for
subchronic systemic toxicity is 1,500 ppm based on decreases in body
weights, body weight gains, and food efficiency in the females, and
body weight decreases and testicular and epididymal changes in the
males. The no-observed-effect level (NOEL) for subchronic systemic
toxicity is 750 ppm.
b. A subchronic oral study in mice fed doses of 50, 500, 1,750,
3,500, or 7,000 ppm (average 8.25, 82.4, 294, 566, or 1,306 mg/kg/day,
for males; 11.3, 121, 433, 846, or 1,130 mg/kg/day, for females) for 98
days showed a decrease in body weight gains in males dosed at 500,
1,750, and 3,500 ppm. An increase in the absolute liver and spleen
weights was seen in females fed doses of 1,750 and 3,500 ppm. The NOEL
was established at 50 ppm for males and 500 ppm for females; the LOEL
was 500 ppm for males and 1,750 ppm for females.
c. A subchronic oral toxicity study was conducted in dogs fed
doses of 100 or 200 ppm (3 or 5 mg/kg/day) for 13 weeks, or at 250 ppm
(5 mg/kg/day) for 2 weeks followed by 500 ppm (11 mg/kg/day) for 11
weeks. The 250/500 ppm males had lower epididymal and testicular
weights, and aspermatogenesis was observed. The LOEL is 3 mg/kg body
weight/day (100 ppm) for dogs based on decreased body weights and food
consumption in females. The NOEL was not established.
d. In a 28-day dermal toxicity study, cymoxanil was applied to the
shaved backs of rats for 6 hrs/day at doses of 50, 500, and 1,000 mg/
kg/day. There were no demonstrated effects and no compound-related
histopathology. The NOEL for systemic toxicity and dermal irritation
was 1,000 mg/kg/day, the highest dose tested (HDT).
3. Chronic toxicity. a. A combined chronic/carcinogenicity study
was conducted in rats fed cymoxanil at doses of 0, 50, 100, 700, or
2,000 ppm (0, 1.98, 4.08, 30.3, and 90.1 mg/kg/day for males, and 0,
2.71, 5.36, 38.4, and 126 mg/kg/day for females) for 23 months. A
satellite group was included and terminated at 52 weeks. Because of
poor survival in controls and treated rats, the study was terminated
after 23 months. Survival was 24-45 percent and 21-40 percent in the
male and female groups, respectively.
Chronic toxicity observed at 126 mg/kg/day in females included
significant decreases in mean body weight and body weight gains, a
decrease in food efficiency, and increased incidences of non-neoplastic
lesions in several organ systems including the lungs, intestines, and
mesenteric lymph nodes. In females receiving 38.4 mg/kg/day, chronic
toxicity was characterized by increased incidences of non-neoplastic
lesions of the lungs, liver, sciatic nerve, and eyes (retinal atrophy).
Chronic toxicity in the males dosed at 30.3 or 90.1 mg/kg/day included
aggressiveness and/or hyperactivity, decreased mean body weight and
body weight gain, decreased food efficiency, and increased incidence of
elongate spermatid degeneration and retinal atrophy. No important
effects
[[Page 24944]]
were observed in the low- and low-mid-dose groups. No increases in the
incidences of any neoplasm was observed in dosed animals. The chronic
LOEL was 30.3 mg/kg/day for males and 38.4 mg/kg/day females based on
histologic changes detected in several organs of the females and
decreased body weight, body weight gains, and food efficiency observed
in the males and females. The chronic NOEL is 4.08 mg/kg/day for males
and 5.36 mg/kg/day for females. Under the conditions of this study,
there was no evidence of carcinogenic potential.
b. A chronic toxicity study was conducted in dogs fed cymoxanil at
doses of 25, 50, or 100 ppm for females (0.7, 1.6, or 3.1 mg/kg/day)
and 50, 100, or 200 ppm for males (1.8, 3.0, or 5.7 mg/kg/day) for 52
weeks. The only effect seen in females in the 100 ppm treatment group
was weight loss during the first week of the study. No effect was
observed in females in the 25 or 50 ppm group, or in males in the 50 or
100 ppm group. The LOEL was 200 ppm for males, based on depressed
weight gains through week 12 and changes in hematology and blood
chemistry. No LOEL was established for females. The NOEL was 100 ppm.
4. Carcinogenicity. a. A combined chronic/carcinogenicity study,
conducted in rats (described in the Chronic Toxicity Section, above,
Unit II.A.3.) showed no evidence of carcinogenic potential.
b. A carcinogenicity study was conducted in mice fed cymoxanil at
doses of 30, 300, 1,500, and 3,000 ppm (4.19, 42.0, 216, and 446 mg/kg/
day for males; 5.83, 58.1, 298, and 582 mg/kg/day for females) for
approximately 80 weeks. Two additional groups were sacrificed at 31-32
days for cell proliferation and biochemical evaluation.
Males and females dosed at 300 ppm and above exhibited alterations
in organ weights and microscopic pathology. Affected organs were the
testes and epididymis in males, the gastrointestinal tract in females,
and the liver in both sexes. Male mice fed 300 ppm exhibited treatment-
related increased frequency of sperm cyst/cystic dilation, tubular
dilation, and increased lymphoid aggregate. Centrilobular apoptotic
hepatocytes, pigment-containing macrophages, and granuloma were
detected in males dosed with 300 ppm. Elevated centrilobular
hepatocellular hypertrophy and associated significant increases in
liver weight in males dosed with 300 ppm was considered a pharmacologic
response to cymoxanil. Hyperplastic gastropathy increased significantly
in 300 ppm female mice and cystic enteropathy of the small intestine
showed a significant positive trend. At the 1,500 ppm dose, decreases
in body weight, body weight gain, and food efficiencies were observed
in males and females. In addition to the testicular and epididymal
abnormalities observed at the lower dose, the 1,500 ppm males exhibited
increased incidence of sperm granuloma and bilateral oligospermia.
Females at 1,500 ppm exhibited the microscopic liver abnormalities seen
in males at the lower dose. Cystic enteropathy was observed in males at
1,500 ppm. At 3,000 ppm, there were significant reductions in body
weight, body weight gain, food consumption, and food efficiencies in
males and females. Survival over 18 months was decreased in the 3,000
ppm females, 57 percent compared to 69 percent in controls. Early
deaths among high-dose females were attributed to pancreatic acinar
cell necrosis and/or stress, evidenced by splenal and thymic atrophy
and bone marrow congestion. The 3,000 ppm females exhibited increased
frequency of pallor, weakness, and hunching over. Male mice fed 3,000
ppm showed hematological signs of decreased circulating erythrocyte
mass at the 12-month evaluation. The high dose also resulted in gross
and microscopic pathology of the liver, gastrointestinal tract, and
testes. Dosing was considered adequate based on decreased body weight
gains and an increase in non-neoplastic lesions in both sexes relative
to the controls at the highest dose level.
The LOEL was 300 ppm, based on toxicity to the testes and
epididymides in males and toxicity to the gastrointestinal mucosa in
females. The NOEL was 30 ppm. Under the conditions of this study, there
was no evidence of a carcinogenic effect.
5. Developmental toxicity. a. A prenatal developmental toxicity
study was conducted in rats gavaged with cymoxanil on days 7-16 of
gestation at dose levels of 0, 10, 25, 75, or 150 mg/kg/day. The
maternal LOEL was 25 mg/kg/day, based upon reduced body weight, body
weight change, and food consumption. The maternal NOEL was 10 mg/kg/
day. The developmental LOEL was 25 mg/kg/day, based upon a significant
increase in overall malformations and a generalized dose-related delay
in skeletal ossification. Fetal body weights were significantly
decreased at 75, 150 and 150 mg/kg/day. Increased early resorptions
resulted in reduced litter sizes. The developmental NOEL was 10 mg/kg/
day.
b. A prenatal developmental toxicity study was conducted in
rabbits gavaged with cymoxanil on days 6-18 of gestation at dose levels
of 0, 4, 8, or 16 mg/kg/day. There was no evidence of treatment-related
maternal or developmental toxicity. A maternal and developmental LOEL
was not determined; the maternal and developmental NOEL was
16 mg/kg/day. When considered along with other prenatal developmental
toxicity studies in rabbits, this study provides acceptable information
that assists in determining the overall maternal and developmental NOEL
and LOEL for cymoxanil in a nonrodent species.
c. A prenatal developmental toxicity study was conducted in
rabbits gavaged with cymoxanil on days 6-18 of gestation at dose levels
of 8, 16, or 32 mg/kg/day. Uncertainties regarding the source of the
parental rabbits substantially reduced the confidence that any observed
skeletal effects were solely related to treatment.
d. A prenatal developmental toxicity study was conducted in rabbits
gavaged with cymoxanil on days 6-18 of gestation at dose levels of 0,
1, 4, 8, or 32 mg/kg/day. The females showed significant posttreatment
increases in body weight gain at 8 and 32 mg/kg/day. The maternal LOEL
was 8 mg/kg/day, based upon a significant dose-related rebound in
maternal body weight. The maternal NOEL was 4 mg/kg/day. The
developmental LOEL was 8 mg/kg/day, based upon an increase in skeletal
malformations of the cervical and thoracic vertebrae and ribs; and, at
32 mg/kg/day, cleft palate was observed. The developmental NOEL was 4
mg/kg/day.
6. Reproductive toxicity. A two-generation reproduction study was
conducted in rats fed cymoxanil at doses of 100, 500, or 1,500 ppm
(equivalent to 6.5, 32.1, or 97.9 mg/kg/day in males and 7.9, 40.6, or
130 mg/kg/day in females) over two consecutive generations. No effects
of treatment were observed at 100 ppm. The parental systemic LOEL was
500 ppm based upon reduced pre-mating body weight, body weight gain,
and food consumption for F1 males; and decreased gestation
and lactation body weight for F1 females. The parental
systemic NOEL was 100 ppm. The offspring LOEL was 500 ppm based upon
decreased F1 pup viability on postnatal days 0-4 and on a
significant reduction in F2b pup weight. The offspring NOEL
was 100 ppm.
7. Neurotoxicity. a. The neurotoxicity portion of the subchronic/
neurotoxicity study in rats demonstrated no effects on the functional
observation battery or on motor activity after 5, 9, and 13 weeks of
dietary doses of cymoxanil at 0, 100,
[[Page 24945]]
750, 1,500, or 3,000 ppm (0, 6.54, 47.6, 102, or 224 mg/kg/day for
males, and 0, 8.0, 59.9, 137, or 333 mg/kg/day for females) for 97
days. There were no treatment-related gross or microscopic findings
detected in the nervous system or skeletal muscles. Grip strength and
foot splay measurements were decreased (non-significantly) in males at
224 mg/kg/day in the 13-week subchronic neurotoxicity study in rats,
although these findings occurred in conjunction with decreased body
weight. A LOEL for neurobehavioral and neuropathic effects was not
established. The NOEL for neurotoxicity was 3,000 ppm.
b. In the combined chronic toxicity/carcinogenicity study in rats,
increased incidence of sciatic nerve axon/myelin degeneration was
observed in females fed cymoxanil at doses of 38.4 and 126 mg/kg/day
for 104 weeks. Also, increased incidence and severity of retinal
atrophy was observed in males at 30.3 and 90.1 mg/kg/day as well as in
females at 38.4 and 126 mg/kg/day. These two findings demonstrated a
dose-related effect. In addition, clinical observations of
hyperactivity and aggressiveness were reported in males at 700 and
2,000 ppm (30.3 and 90.1 mg/kg/day).
c. In the carcinogenicity study in mice, absolute brain weight was
decreased in both sexes at 1,500 and 3,000 ppm (216/298 mg/kg/day and
446/582 mg/kg/day for males/females, respectively).
d. No evidence of developmental anomalies of the fetal nervous
system were observed in the prenatal developmental toxicity studies in
either rats, or rabbits, at maternally toxic oral doses up to 25 and 32
mg/kg/day, respectively. In addition, there was no evidence of
behavioral or neurological effects on the offspring in the two-
generation reproduction study in rats.
e. There were no major data gaps for the assessment of potential
neurotoxicological effects due to cymoxanil. However, following a
weight-of-the evidence review of the database, which suggested that
neuropathological lesions, changes in brain weight, axon/myelin
degeneration, and retinal atrophy could result from long-term exposure
to cymoxanil, the Agency will require a confirmatory developmental
neurotoxicity study in rats.
8. Mutagenicity. Mutagenicity studies with cymoxanil included gene
mutation assays in bacterial and mammalian cells, a mouse micronucleus
assay and an in vivo/in vitro unscheduled DNA synthesis (UDS) assay in
rats. These studies did not demonstrate mutagenicity. An in vitro
unscheduled DNA synthesis assay-primary rat hepatocytes was positive
from 5-500 g/mL and cytotoxicity was seen at concentrations of
500 g/mL. A chromosome aberrations in human
lymphocytes assay was also positive at 100 - 1,500 g/mL,
positive at 1,250 and 1,500 g/mL -S9, and 850-1,500
g/mL +S9.
9. Metabolism. A metabolism study was conducted by gavaging rats
with single doses of radiolabeled cymoxanil at 2.5 or 120 mg/kg, or as
a single dose (2.5 mg/kg) following a 14-day pretreatment with
unlabeled cymoxanil (2.5 mg/kg/day). Radiolabeled cymoxanil was readily
absorbed through the intestinal tract. Maximum plasma concentrations
were attained within 3-5 hours of dosing, then declined steadily. Dose
rate and pretreatment did not appear to affect absorption.
Elimination was not dependent on sex or dosing regimen; occurring
predominantly in the urine (63.8-74.8 percent), during the first 24
hours (58-66 percent). Fecal excretion accounted for 15.7-23.6 percent
of the dose, and radioactivity in the tissues and carcasses accounted
for <1 percent="" of="" the="" dose="" at="" sacrifice="" for="" all="" three="" dosing="" regimens.="" a="" pilot="" study="" indicated="" that="" approximately="" 3="" percent="" of="" the="" dose="" would="" be="" expected="" to="" be="" respired="" as="">14CO2.
For each dosing regimen, there was also no difference between male
and female rats in the distribution of radioactivity in tissues. No
accumulation of radioactivity was observed over time in any tissues.
However, in comparison, concentrations of radioactivity were highest in
liver and kidney and lowest in brain tissue at 96 hours post-dosing
sacrifice.
Peak plasma concentrations for the low and high dose groups were
attained within 3-5 hours of dosing, and both dose groups had similar
elimination half-lives from plasma, suggesting that the metabolic
process was not saturated by the high dose. In addition, there was a
fortyfold difference in the area under the curve for plasma from the
low and high dose groups, approximating the 48-fold difference in the
dose levels.
The metabolite profile in urine and feces was similar between
sexes and among dose groups. In the urine, the majority of the
radioactivity (36.7-55 percent of the dose) was free and/or conjugated
[14C]glycine, and 2-cyano-2-methoxyiminoacetic acid (IN-
W3595) (6.5-33 percent of the dose) was also found. Intact
[14C]cymoxanil was not detected. In the feces, trace levels
(<1 percent="" of="" the="" dose)="" of="">14C]cymoxanil and IN-W3595 were
detected, but the majority of radioactivity was the free and conjugated
[14C]glycine (8.5-13.1 percent of the dose). The data
indicate that the principal pathway for the elimination of cymoxanil
from rats is via renal elimination.
Based on the data, the proposed metabolic pathway involves
hydrolysis of cymoxanil to IN-W3595, which is then degraded to glycine.
Subsequently, glycine is incorporated into natural constituents or
further metabolized.
10. Other toxicological considerations. The submitted mutagenicity
test battery satisfied the new mutagenicity initial testing battery
guidelines and the available studies indicate that cymoxanil is not
mutagenic in bacterial or cultured mammalian cells. There is, however,
confirmed evidence of clastogenic activity and UDS induction in vitro.
In contrast, cymoxanil was neither clastogenic nor aneurogenic in mouse
bone marrow cells and did not induce a genotoxic response in rat
somatic or germinal cells. Accordingly, the negative results from the
mouse bone marrow micronucleus assay support the lack of carcinogenic
effect in the rat and mouse long-term feeding study.
Similarity of clinical signs were observed in the micronucleus and
in vivo UDS assay, but the confidence in the negative findings of the
in vivo UDS assay was not high because of a failure to demonstrate that
test material reached either target tissue. It was concluded that the
test may have been inadequate because of the short interval between
dosing and cell harvest. Therefore, the Agency will be requiring that a
supplemental rat dominant lethal assay be conducted to determine if any
effects are noted which are associated with genetic damage to male
germinal cells.
B. Toxicological Endpoints
1. Acute toxicity-females 13+. To assess acute dietary exposure,
the Agency used a NOEL of 4 mg/kg/day from prenatal developmental
toxicity studies in rabbits based on an increase in skeletal
malformations of the cervical and thoracic vertebrae and ribs at 8 mg/
kg/day. EPA determined that the 10x factor to account for enhanced
sensitivity of infants and children (required by FQPA) should be
reduced to 3x. An MOE of 300 is required for the acute dietary
assessment to protect the sub-population of concern, ``Females 13+,''
due to neuropathological lesions seen in the chronic toxicity study in
rats and the need for an additional developmental neurotoxicity study.
Acute toxicity-general population. An acute dose and endpoint was
not selected for the general population and
[[Page 24946]]
the sub-population including ``infants and children'' because there
were no observable effects in oral toxicology studies, and no maternal
toxicity in the developmental toxicity studies in rats or rabbits
attributable to a single dose.
2. Short- and intermediate-term residential toxicity. The Agency
determined that this dose and endpoint was not applicable for risk
assessment because no dermal or systemic toxicity was seen in a 28 day
dermal toxicity study, at the limit dose.
3. Chronic residential toxicity. Based on the use pattern,
chronic dermal exposure is not anticipated and long-term dermal risk
assessment is not required.
4. Chronic dietary toxicity. An RfD of 0.013 mg/kg/day was
established based on a chronic feeding study in rats with a NOEL of
4.08 mg/kg/day and an uncertainty factor of 300.
5. Carcinogenicity. Based on the lack of evidence of
carcinogenicity in mice and rats, EPA has classified cymoxanil as a
``not likely'' human carcinogen, according to EPA's Proposed Guidelines
for Carcinogen Risk Assessment (April 10, 1996).
C. Exposures and Risks
1. From food and feed uses. Time-limited tolerances of 0.05 ppm
have been established in the 40 CFR 180.503(b) for residues of
cymoxanil in or on potatoes and tomatoes under section 18 of FIFRA. In
today's action, a tolerance will be established for residues of
cymoxanil in or on potatoes at 0.05 ppm under section 3 of FIFRA in 40
CFR 180.503(a) and the section 18 tolerance for potatoes will be
removed. Risk assessments were conducted by EPA to assess dietary
exposures and risks from cymoxanil as follows:
a. Acute exposure and risk. Acute dietary risk assessments are
performed for a food-use pesticide if a toxicological study indicates
an effect of concern may occur as a result of a 1-day or single
exposure. For the subpopulation of concern, females 13+, the estimated
acute MOE of 5,000 demonstrates no acute dietary concern.
b. Chronic exposure and risk. The chronic dietary risk analysis
used the RfD of 0.013 mg/kg/day. Chronic dietary exposure estimates
utilized tolerance level residues on potatoes and tomatoes and assumed
100 percent of the crops were treated. The risk assessment resulted in
use of <1 percent="" of="" the="" rfd="" for="" the="" general="" population,="" including="" infants="">< 1="" year="" old),="" and="">< 2="" percent="" of="" the="" rfd="" for="" children="" (1-6="" or="" 7-12="" years="" old).="" 2.="" from="" drinking="" water.="" no="" monitoring="" data="" are="" currently="" available="" to="" perform="" a="" quantitative="" drinking="" water="" risk="" assessment.="" cymoxanil="" appears="" to="" be="" mobile="" in="" soils,="" although="" its="" rapid="" environmental="" dissipation="" precludes="" extensive="" leaching.="" cymoxanil="" was="" not="" detected="" below="" 0-15="" cm="" of="" soil.="" degradates="" of="" cymoxanil="" are="" mobile,="" but="" short-="" lived,="" and="" are="" not="" expected="" to="" pose="" a="" threat="" to="" ground="" water.="" epa="" estimated="" surface="" water="" exposure="" using="" the="" generic="" expected="" environmental="" concentration="" (geneec)="" model,="" a="" screening="" level="" model="" for="" determining="" concentrations="" of="" pesticides="" in="" surface="" water.="" geneec="" uses="" the="" soil/water="" partition="" coefficient,="" hydrolysis="" half="" life,="" and="" maximum="" label="" rate="" to="" estimate="" surface="" water="" concentration.="" in="" addition,="" the="" model="" contains="" a="" number="" of="" conservative="" underlying="" assumptions.="" therefore,="" the="" drinking="" water="" concentrations="" derived="" from="" geneec="" for="" surface="" water="" are="" likely="" to="" be="" overestimated.="" surface="" water="" estimates="" derived="" from="" geneec="" assumed="" 7="" applications="" of="" 0.12="" lbs.="" active="" ingredient/acre="" would="" be="" applied.="" the="" model="" indicated="" that="" cymoxanil="" in="" surface="" water="" could="" reach="" 4.13="" parts="" per="" billion="" (ppb)="" (peak="" concentration)="" and="" 0.19="" ppb="" (average="" 56="" day="" concentration="" ).="" a.="" acute="" exposure="" and="" risk.="" epa="" calculated="" drinking="" water="" levels="" of="" concern="" (dwloc)="" for="" acute="" exposure="" by="" using="" the="" acute="" toxicity="" endpoint.="" the="" acute="" dietary="" food="" exposure="" (from="" the="" dres="" analysis)="" was="" subtracted="" from="" the="" ratio="" of="" the="" acute="" noel="" (used="" for="" acute="" dietary="" assessments)="" to="" the="" ``acceptable''="" moe="" for="" aggregate="" exposure="" to="" obtain="" the="" acceptable="" acute="" exposure="" to="" cymoxail="" in="" drinking="" water.="" epa="" has="" calculated="" dwlocs="" for="" acute="" exposure="" to="" cymoxanil="" in="" drinking="" water="" for="" females="" (13+="" years="" old)="" to="" be="" 380="" ppb.="" the="" maximum="" estimated="" concentrations="" of="" cymoxanil="" in="" surface="" and="" ground="" water="" are="" below="" epa's="" levels="" of="" concern="" for="" cymoxanil="" in="" drinking="" water="" as="" a="" contribution="" to="" acute="" aggregate="" exposure.="" therefore,="" epa="" concludes="" with="" reasonable="" certainty="" that="" residues="" of="" cymoxanil="" in="" drinking="" water="" do="" not="" contribute="" significantly="" to="" the="" aggregate="" acute="" human="" health="" risk.="" b.="" chronic="" exposure="" and="" risk.="" chronic="" (non-cancer),="" drinking="" water="" levels="" of="" concern="" are="" 450="" ppb="" for="" the="" u.s.="" population="" and="" 130="" ppb="" for="" children="" (1-6="" years="" old).="" the="" estimated="" average="" concentrations="" of="" cymoxanil="" in="" surface="" and="" ground="" water="" are="" less="" than="" epa's="" levels="" of="" concern="" for="" cymoxanil="" in="" drinking="" water="" as="" a="" contribution="" to="" chronic="" aggregate="" exposure.="" therefore,="" epa="" concludes="" with="" reasonable="" certainty="" that="" residues="" of="" cymoxanil="" in="" drinking="" water="" do="" not="" contribute="" significantly="" to="" the="" aggregate="" chronic="" human="" health="" risk.="" 3.="" from="" non-dietary="" exposure.="" cymoxanil="" is="" not="" registered="" for="" use="" on="" residential="" non-food="" sites.="" therefore,="" no="" non-occupational,="" non-="" dietary="" exposure="" and="" risk="" are="" expected.="" 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="" [[page="" 24947]]="" case="" common="" mechanism="" of="" activity="" will="" be="" assumed).="" at="" this="" time,="" epa="" does="" not="" have="" available="" data="" to="" determine="" whether="" cymoxanil="" has="" a="" common="" mechanism="" of="" toxicity="" with="" other="" substances="" or="" how="" to="" include="" this="" pesticide="" in="" a="" cumulative="" risk="" assessment.="" cymoxanil="" is="" structurally="" related="" to="" metazachlor,="" dimethenamid="" and="" amiphos.="" of="" these="" pesticides,="" only="" dimethenamid="" is="" currently="" registered="" for="" use="" in="" the="" united="" states.="" unlike="" other="" pesticides="" for="" which="" epa="" has="" followed="" a="" cumulative="" risk="" approach="" based="" on="" a="" common="" mechanism="" of="" toxicity,="" cymoxanil="" 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="" cymoxanil="" has="" a="" common="" mechanism="" of="" toxicity="" with="" other="" substances="" and="" that="" structurally-related="" chemicals="" will="" not="" have="" common="" toxic="" metabolites="" to="" cymoxanil.="" d.="" aggregate="" risks="" and="" determination="" of="" safety="" for="" u.s.="" population="" 1.="" acute="" risk.="" the="" moe="" for="" the="" acute="" dietary="" (food="" only)="" risk="" assessment="" for="" the="" population="" subgroup="" of="" concern,="" females="" 13+="" years,="" was="" estimated="" at="" 5,000.="" this="" risk="" estimate="" does="" not="" exceed="" the="" agency's="" level="" of="" concern.="" epa="" has="" calculated="" drinking="" water="" levels="" of="" concern="" (dwlocs)="" for="" acute="" exposure="" to="" cymoxanil="" in="" drinking="" water="" for="" females="" (13+="" years="" old)="" to="" be="" 380="" ppb.="" chronic="" (non-cancer),="" drinking="" water="" levels="" of="" concern="" are="" 450="" ppb="" for="" the="" u.s.="" population="" and="" 130="" ppb="" for="" children="" (1-6="" years="" old).="" therefore,="" epa="" concludes="" with="" reasonable="" certainty="" that="" the="" potential="" risks="" from="" aggregate="" acute="" exposure="" (food="" &="" water)="" would="" not="" exceed="" the="" agency's="" level="" of="" concern.="" 2.="" chronic="" risk.="" using="" the="" tmrc="" exposure="" assumptions="" described="" above,="" epa="" has="" concluded="" that="" aggregate="" exposure="" to="" cymoxanil="" from="" food="" will="" utilize=""><1 percent="" of="" the="" rfd.="" the="" estimated="" average="" concentrations="" of="" cymoxanil="" in="" surface="" and="" ground="" water="" are="" less="" than="" epa's="" levels="" of="" concern="" for="" cymoxanil="" in="" drinking="" water="" as="" a="" contribution="" to="" chronic="" aggregate="" exposure.="" therefore,="" epa="" concludes="" with="" reasonable="" certainty="" that="" residues="" of="" cymoxanil="" in="" drinking="" water="" do="" not="" contribute="" significantly="" to="" the="" potential="" aggregate="" chronic="" human="" health="" risk="" at="" the="" present="" time,="" considering="" the="" present="" uses="" and="" those="" proposed="" in="" this="" action.="" e.="" aggregate="" cancer="" risk="" for="" u.s.="" population="" epa="" has="" classified="" cymoxanil="" as="" a="" ``not="" likely''="" human="" carcinogen,="" based="" on="" the="" lack="" of="" evidence="" of="" carcinogenicity="" in="" mice="" and="" rats,="" and="" therefore="" has="" a="" reasonable="" certainty="" that="" no="" harm="" will="" result="" from="" exposure="" to="" residues="" of="" cymoxanil.="" f.="" aggregate="" risks="" and="" determination="" of="" safety="" for="" infants="" and="" children="" safety="" factor="" for="" infants="" and="" children="" -="" in="" general.="" in="" assessing="" the="" potential="" for="" additional="" sensitivity="" of="" infants="" and="" children="" to="" residues="" of="" cymoxanil,="" 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="" during="" 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.="" the="" agency="" determined="" that="" for="" cymoxanil,="" the="" 10x="" factor="" for="" the="" protection="" of="" infants="" and="" children="" (as="" required="" by="" fqpa)="" should="" be="" reduced="" to="" 3x,="" based="" on="" the="" following="" weight="" of="" the="" evidence="" considerations:="" (1)="" no="" increased="" sensitivity="" in="" fetuses="" as="" compared="" to="" maternal="" animals="" was="" observed="" following="" in="" utero="" exposures="" in="" developmental="" studies="" in="" rats="" and="" rabbits;="" (2)="" no="" increased="" sensitivity="" in="" pups="" when="" compared="" to="" adults="" was="" seen="" in="" the="" two-generation="" reproduction="" study="" in="" rats;="" (3)="" the="" toxicology="" data="" base="" is="" complete="" except="" for="" the="" requirement="" to="" submit="" a="" developmental="" neurotoxicity="" study;="" and="" (4)="" no="" frank="" neurotoxicity="" was="" seen="" in="" the="" 90-day="" neurotoxicity="" study.="" the="" agency="" has="" determined="" that="" a="" moe="" of="" 300="" is="" required="" because="" of="" the="" observance="" of="" neuropathological="" lesions="" in="" the="" chronic="" toxicity="" study="" in="" rats="" and="" the="" need="" for="" a="" developmental="" neurotoxicity="" study.="" iii.="" other="" considerations="" a.="" endocrine="" disrupter="" effects="" epa="" is="" required="" to="" develop="" a="" screening="" program="" to="" determine="" whether="" certain="" substances="" (including="" all="" pesticides="" and="" inerts)="" ``may="" have="" an="" effect="" in="" humans="" that="" is="" similar="" to="" an="" effect="" produced="" by="" a="" naturally="" occurring="" estrogen,="" or="" such="" other="" endocrine="" effect....''="" the="" agency="" is="" currently="" working="" with="" interested="" stakeholders,="" including="" other="" government="" agencies,="" public="" interest="" groups,="" industry="" and="" research="" scientists="" in="" developing="" a="" screening="" and="" testing="" program="" and="" a="" priority="" setting="" scheme="" to="" implement="" this="" program.="" congress="" has="" allowed="" 3="" years="" from="" the="" passage="" of="" fqpa="" (august="" 3,="" 1999)="" to="" implement="" this="" program.="" at="" that="" time,="" epa="" may="" require="" further="" testing="" of="" this="" active="" ingredient="" and="" end="" use="" products="" for="" endocrine="" disrupter="" effects.="" b.="" metabolism="" in="" plants="" and="" animals="" plants.="" based="" on="" a="" metabolism="" study="" on="" potatoes,="" the="" nature="" of="" the="" residue="" is="" adequately="" understood.="" only="" the="" parent="" cymoxanil="" compound="" is="" of="" regulatory="" concern.="" animals.="" based="" on="" a="" metabolism="" study="" in="" lactating="" goats,="" the="" nature="" of="" the="" residue="" in="" animals="" is="" adequately="" understood.="" only="" the="" parent="" cymoxanil="" compound="" is="" of="" regulatory="" concern.="" c.="" analytical="" enforcement="" methodology="" an="" adequate="" enforcement="" method,="" amr="" 3705-95,="" is="" available="" to="" enforce="" the="" tolerance="" on="" potatoes.="" quantitation="" is="" by="" hplc/uv.="" these="" methods="" have="" been="" submitted="" for="" publication="" in="" pam="" i.="" the="" methods="" are="" available="" to="" anyone="" who="" is="" interested="" in="" pesticide="" residue="" enforcement="" from:="" calvin="" furlow,="" information="" resources="" and="" services="" division="" (7502c),="" office="" of="" pesticide="" programs,="" environmental="" protection="" agency,="" 401="" m="" st.,="" sw.,="" washington,="" dc="" 20460.="" office="" location="" and="" telephone="" number:="" crystal="" mall="" #2,="" rm="" 101ff,="" 1921="" jefferson="" davis="" hwy.,="" arlington,="" va="" (703)="" 305-5229.="" d.="" magnitude="" of="" residues="" residues="" of="" cymoxanil="" resulting="" from="" the="" proposed="" use="" will="" not="" exceed="" 0.05="" ppm="" in="" potatoes.="" the="" tolerance="" on="" potatoes="" is="" for="" the="" raw="" agricultural="" commodity="" as="" defined="" in="" 40="" cfr="" 180.1(j)(1).="" for="" risk="" assessment="" purposes,="" it="" was="" concluded="" that="" [[page="" 24948]]="" residues="" resulting="" from="" the="" proposed="" use="" will="" not="" exceed="" 0.05="" ppm="" in="" potatoes.="" e.="" international="" residue="" limits="" there="" are="" no="" codex="" or="" canadian="" residue="" limits="" established="" for="" cymoxanil="" on="" potatoes="" but="" a="" mexican="" maximum="" residue="" limit="" (mrl)="" of="" 0.05="" ppm="" is="" established="" for="" potatoes.="" therefore,="" no="" compatibility="" problems="" exist="" for="" the="" proposed="" tolerance="" on="" potatoes.="" f.="" rotational="" crop="" restrictions="" the="" confined="" rotational="" crop="" studies="" provided="" adequate="" results="" to="" conclude="" that="" a="" 30-day="" plant="" back="" interval="" is="" sufficient="" for="" all="" crops.="" iv.="" conclusion="" therefore,="" the="" tolerance="" is="" established="" for="" residues="" of="" cymoxanil,="" 2-cyano-n-[(ethylamino)carbonyl]-2-(methoxyimino)="" acetamide,="" in="" or="" on="" the="" raw="" agricultural="" commodity,="" potatoes,="" at="" 0.05="" 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="" july="" 6,="" 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="" epa="" docket="" for="" this="" rule="" making.="" 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="" and="" electronic="" submissions="" epa="" has="" established="" a="" record="" for="" this="" rulemaking="" under="" docket="" control="" number="" [opp-300653]="" (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="" highway,="" arlington,="" va.="" electronic="" comments="" may="" be="" sent="" directly="" to="" epa="" at:="">opp-docket@epamail.epa.gov.
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 a tolerance under FFDCA section 408(d)
in response to a petition submitted to the Agency. The Office of
Management and Budget (OMB) has exempted these types of actions from
review under Executive Order 12866, entitled Regulatory Planning and
Review (58 FR 51735, October 4, 1993). 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 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 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 was 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 General Accounting Office
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
[[Page 24949]]
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 in 40 CFR Part 180
Environmental protection, Administrative practice and procedure,
Agricultural commodities, Pesticides and pests, Reporting and
recordkeeping requirements.
Dated: April 22, 1998.
Stephen L. Johnson,
Acting Director, 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. 346a and 371.
2. Section 180.503 is amended by adding text to paragraph (a) to
read as follows and by removing the entry for ``potatoes'' in paragraph
(b) .
Sec. 180.503 Cymoxanil; tolerances for residues.
(a) General . A tolerance is established for residues of the
fungicide, cymoxanil, 2-cyano-N-[(ethylamino)carbonyl]-2-(methoxyimino)
acetamide, in or on the following food commodity.
------------------------------------------------------------------------
Commodity Parts per million
------------------------------------------------------------------------
Potatoes.................................. 0.05
------------------------------------------------------------------------
* * * * *
[FR Doc. 98-11764 Filed 5-5-98; 8:45 am]
BILLING CODE 6560-50-F
