[Federal Register Volume 62, Number 100 (Friday, May 23, 1997)]
[Rules and Regulations]
[Pages 28350-28355]
From the Federal Register Online via the Government Publishing Office [www.gpo.gov]
[FR Doc No: 97-13645]
[[Page 28350]]
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ENVIRONMENTAL PROTECTION AGENCY
40 CFR Part 180
[OPP-300496; FRL-5719-8]
RIN 2070-AB78
Cyclanilide; Pesticide Tolerances
AGENCY: Environmental Protection Agency (EPA).
ACTION: Final rule.
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SUMMARY: This regulation establishes tolerances for residues of the
plant growth regulator, cyclanilide, in or on the food commodities
cottonseed, cotton gin byproducts, milk, fat, meat, meat by-products,
and kidney of cattle, goats, horses, hogs and sheep. Rhone-Poulenc Ag
Company submitted a petition to EPA under the Federal Food, Drug, and
Cosmetic Act (FFDCA) as amended by the Food Quality Protection Act of
1996 (Pub. L. 104-170) requesting the tolerances.
DATES: This regulation becomes effective May 23, 1997. Written
objections and requests for hearings must be received on or before July
22, 1997.
ADDRESSES: Written objections and hearing requests, identified by the
docket control number, [OPP-300496], may 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 should be identified by the
docket control number and submitted to: Public Information and Records
Integrity Branch, Information Resources and Services (7506C), Office of
Pesticide Programs, Environmental Protection Agency, 401 M St., SW.,
Washington, DC 20460. In person, bring copy of objections and hearing
requests to: Rm. 1132, 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 in 5.1
file format or ASCII file format. All copies of objections and hearing
requests in electronic form must be identified by the docket number
[OPP-300496]. 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: Cynthia Giles-Parker, Team
Leader (22), Registration Division, Environmental Protection Agency,
401 M St., SW., Washington, DC 20460. Office location and telephone
number and e-mail address: Room 227, CM#2, 1921 Jefferson Davis
Highway, Arlington, VA (703-305-7740). e-mail: parker.cynthia@epamail.epa.gov.
SUPPLEMENTARY INFORMATION: In the Federal Register of December 23, 1996
(61 FR 67544)(FRL-5577-1), EPA issued a notice pursuant to section
408(d)of the Federal Food, Drug, and Cosmetic Act (FFDCA), 21 U.S.C.
346a(d), announcing the filing of a pesticide tolerance petition (PP
6F4643) by Rhone-Poulenc AG Company, P.O. Box 12014, Research Triangle
Park, NC 27709 to EPA requesting that the Administrator amend 40 CFR
part 180 by establishing tolerances for residues of the plant growth
regulator, cyclanilide [1-(2,4-dichlorophenylaminocarbonyl)-
cyclopropane carboxylic acid] determined as 2,4-dichloroaniline
(calculated as cyclanilide) in or on the food commodities cottonseed at
0.60 parts per million (ppm); cotton gin byproducts at 25.0 ppm; milk
at 0.04 ppm; fat of cattle, goats, horses, hogs and sheep at 0.10 ppm;
meat of cattle, goats, horses, hogs and sheep at 0.02 ppm; meat by-
products (except kidney) of cattle, goats, horses, hogs and sheep at
0.20 ppm; and kidney of cattle, goats, horses, hogs and sheep at 2.0
ppm. There were no comments received in response to the notice of
filing.
I. Statutory Background
Section 408 of the Federal Food, Drug, and Cosmetic Act (FFDCA), 21
U.S.C. 301 et seq., as amended by the Food Quality Protection Act of
1996, Pub. L. 104-170) authorizes the establishment of tolerances
(maximum residue levels), exemptions from the requirement of a
tolerance, modifications in tolerances, and revocation of tolerances
for residues of pesticide chemicals in or on food commodities and
processed foods. Without a tolerance or exemption, food containing
pesticide residues is considered to be unsafe and therefore
``adulterated'' under section 402(a) of the FFDCA, and hence may not
legally be moved in interstate commerce. For a pesticide to be sold and
distributed, the pesticide must not only have appropriate tolerances
under the FFDCA, but also must be registered under section 3 of the
Federal Insecticide, Fungicide, and Rodenticide Act (FIFRA, 7 U.S.C.
136 et seq.).
Section 408 was substantially amended by the Food Quality
Protection Act of 1996 (FQPA). Among other things, the FQPA amends the
FFDCA to bring all EPA pesticide tolerance-setting activities under a
new section 408 with a new safety standard and new procedures. New
section 408(b)(2)(A)(i) 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 food, drinking water, and from pesticide use in
gardens, lawns, or buildings (residential and other indoor uses) 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....''
II. Risk Assessment and Statutory Findings
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
[[Page 28351]]
(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
hundredfold margin of exposure 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 margin of exposure (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''. These assessments are defined
by the Agency as follows.
i. Acute risk. 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.
ii. Short-term risk. Short-term risk results from exposure to the
pesticide for a period of 1 to 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 to 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.)
iii. Intermediate-term risk. 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.
iv. Chronic 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 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
[[Page 28352]]
for evaluating the exposure of significant subpopulations including
several regional groups, to pesticide residues. For this pesticide, the
most highly exposed population subgroup (non-nursing infants < 1="" year="" old)="" was="" not="" regionally="" based.="" iii.="" 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="" cyclanilide="" is="" discussed="" below.="" 1.="" acute="" toxicity.="" the="" acute="" oral="" toxicity="" study="" resulted="" in="" a="">50 of 315 milligrams/kilogram (mg/kg) for males and 208
mg/kg for females. The acute dermal toxicity in rabbits resulted in an
LD50 in either sex of greater than 2,000 mg/kg. The acute
inhalation study in rats resulted in a LC50 greater than
2.64 mg/liter. In an acute oral neurotoxicity study in rats fed 0, 15,
50 and 150 mg/kg, the NOEL was 50 mg/kg and the LOEL was 150 mg/kg
based on gait abnormalities, increased abdominal muscle tone, and
slightly decreased motor activity test.
2. Mutagenicity. Cyclanilide was negative for mutagenic activity in
the bacterial reverse mutation tests (duplicate tests), forward gene
mutation (CHO/HGPRT) test and mouse micronucleus test (duplicate
tests). Positive findings (clastogenicity) were seen in the in vitro
chromosomal aberrations study with Chinese hamster ovary cells at high
doses near the limit of cytotoxicity. Since cyclanilide caused liver
toxicity in several studies, a confirmatory rat unscheduled DNA
synthesis (UDS) test needs to be conducted with cyclanilide.
3. Rat metabolism. In the rat metabolism study radioactive
cyclanilide was rapidly absorbed after oral administration. The
principal route of elimination was by renal excretion of the parent
compound and amino acid conjugates. Methylation was a minor metabolic
pathway.
4. Sub-chronic toxicity. i. In a rat 90-day feeding study the No
Observed Effect Level (NOEL) was 54.6 mg/kg/day for males and 62.4 mg/
kg/day for females. The Lowest Observed Effect Level (LOEL) for males
was 113.2 mg/kg/day and for females it was 121.4 mg/kg/day based on
reductions in body weight, body weight gain, and food consumption,
clinical signs, and increased liver weight in males and females.
ii. In a 90-day mouse feeding study the NOEL for males was 38 mg/
kg/day and 43 mg/kg/day for females. The LOEL was 364 mg/kg/day for
males and 416 mg/kg/day for females based on mortality, elevated
alkaline phosphatase, increased absolute, relative liver weights, focal
hepatocellular necrosis, and handling induced rigidity.
iii. In a 21-day rabbit dermal toxicity study the NOEL was equal or
greater than 1,000 mg/kg/day. The LOEL was greater than 1,000 mg/kg/
day.
iv. In a 90-day mammalian neurotoxicity study the NOEL for males
was equal or greater than 78.6 mg/kg/day and for females was 4.0 mg/kg/
day. The LOEL was greater than 78.6 mg/kg/day for males and was 35.8
mg/kg/day for females based on increased motor activity and decreased
body weight.
5. Chronic feeding toxicity and carcinogenicity. i. In a 1-year
feeding study in dogs fed diets containing 0, 40, 160, or 640 ppm
(equivalent to 0, 1.5, 5.3, and 21.2 mg/kg/day for males and 0, 1.3,
5.2, and 21.5 mg/kg/day for females) the NOEL was 5.3 mg/kg/day for
males and 5.2 mg/kg/day for females. The LOEL was 21.2 mg/kg/day for
males and 21.5 mg/kg/day for females based on decreased body weight
gain, elevated enzymes and gross and histopathological liver lesions.
ii. In a chronic feeding and carcinogenicity study in rats fed
diets containing 0, 50, 150, 450, or 1,000 ppm (equivalent to 0, 2.0,
6.2, 18.9 and 43.1 mg/kg/day for males and 0, 2.6, 8.1, 25.5, and 58.6
mg/kg/day for females) the chronic NOEL was equal or greater than 43.1
mg/kg/day for males and was 8.1 mg/kg/day for females. The chronic LOEL
was greater than 43.1 mg/kg/day for males and was 25.5 mg/kg/day for
females based on decreased body weight gains and histopathological
changes in liver. The study was negative for carcinogenicity.
iii. In a carcinogenicity study in mice fed diets containing 0, 50,
250, or 1,000 ppm (equivalent to 0, 8.4, 41.8, and 168 mg/kg/day for
males and 0, 10.6, 52.4, and 206 mg/kg/day for females) the chronic
NOEL was 41.8 mg/kg/day for males and was 52.4 mg/kg/day for females.
The chronic LOEL was 168 mg/kg/day for males based on decreased weight
gain and was 206 mg/kg/day for females based on decreased weight gain.
The study was negative for carcinogenicity.
According to the new proposed guidelines for Carcinogen Risk
Assessment (April, 1996), the appropriate descriptor for human
carcinogenic potential of cyclanilide is ``Not Likely''. The
appropriate subdescriptor is ``has been evaluated in at least two well
conducted studies in two appropriate species without demonstrating
carcinogenic effects''.
6. Developmental toxicity. i. In a developmental toxicity study in
rats fed 0, 3, 10, and 30 mg/kg/day the maternal NOEL was 10 mg/kg/day
and the maternal LOEL was 30 mg/kg/day based on decreased body weight
gain and food consumption. The developmental NOEL was 30 mg/kg/day
(Highest Dose Tested).
ii. In a developmental toxicity study in rabbits fed 0, 3, 10, and
30 mg/kg/day the maternal NOEL was 10 mg/kg/day and the maternal LOEL
was 30 mg/kg/day based on wobbly gait, partial hindlimb paralysis and
emaciation. The developmental NOEL was 30 mg/kg/day (Highest Dose
Tested).
iii. In a 2 generation reproduction study in rats fed 0, 30, 300 or
1,000 ppm (equivalent to 0, 1.9, 19.0 or 64.1 mg/kg/day for P
(Parental) Males; 0, 2.0. 20.2, or 70.4 mg/kg/day for F1 males; 0, 2.3,
21.8, or 84.5 mg/kg/day for P females; and 0, 2.4, 25.9, or 85.7 mg/kg/
day for F1 females), the systemic NOEL was less than 2.0 mg/kg/day for
males and less than 2.4 mg/kg/day for females. The systemic LOEL was
2.0 mg/kg/day for males based on reduced early post-weaning weight
gains. The systemic NOEL for females was 2.4 mg/kg/day based on reduce
early post-weaning body weight gains and increased renal
mineralization. The reproduction NOEL is 2.3 mg/kg/day and the
reproduction LOEL is 21.8 mg/kg/day based on decreased mean pup weight.
IV. Aggregate Exposures
1. From food and feed uses. The primary source for human exposure
to cyclanilide will be from ingestion of both raw and processed
agricultural commodities from cotton, milk, and meat. A DRES chronic
exposure analysis was conducted using tolerance level residues and 100%
crop treated information to estimate the Theoretical Maximum Residue
Contribution (TMRC) for the general population and 22 subgroups.
2. From potable water. As a worst case screen, upper bound
estimates (acute/chronic) of the concentration of cyclanilide that
might be found in surface water have been calculated with the generic
expected environmental concentrations (GENEEC) screening model program.
For cotton, based on the assumption of one application aerially at the
maximum application rate 0.25 lb active ingredient/acre), GENEEC
calculates the peak (acute)
[[Page 28353]]
concentration in runoff water adjacent to the application area to be
8.4 ppb and the chronic concentration to be 7.7 ppb.
3. From non-dietary uses. There are no non-food uses of cyclanilide
registered under the Federal Insecticide, Fungicide and Rodenticide
Act, as amended. No non-dietary exposures are expected for the general
population.
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 cyclanilide 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,
cyclanilide does not appear to produce a toxic metabolite produced by
other substances. The Agency has determined that there are no
metabolites of toxicological concern associated with cyclanilide.
Cyclanilide appears to be the only know pesticide member of its class
of chemistry and there are no reliable data to indicate that this
chemical is structurally or toxicologically similar to existing
chemical substances at this time. Therefore it appear unlikely that
cyclanilide bears a common mechanism of activity with other substances.
For the purposes of this tolerance action, therefore, EPA has not
assumed that cyclanilide has a common mechanism of toxicity with other
substances.
V. Determination of Safety
A. Chronic Risk
The Reference Dose (RfD) for cyclanilide is 0.007 mg/kg/day. This
value is based on the systemic LOEL of 30 ppm (2.0 mg/kg/day in males
and 2.4 mg/kg/day in females) from the rat reproductive study. The NOEL
was not achieved (less than 30 ppm the Lowest Dose Tested). Reduced
body weights in young post-weaning F1 males and females and increased
renal mineralization in adult F1 females were observed at this level.
An Uncertainty Factor (UF) of 300 was applied to the LOEL based on an
Uncertainty Factor of 100 to account for interspecies extrapolation and
intraspecies variability and an additional Uncertainty Factor of 3 to
account for the lack of a NOEL in the reproductive toxicity study.
The chronic analysis showed that exposure from the proposed new
tolerances in or on cottonseed, cotton gin trash, milk, and meat for
non-nursing infants (the subgroup with the highest exposure) would be
77% of the Reference Dose (RfD). The exposure for the general U.S.
population would be 15% of the RfD. Based on the estimated exposures to
cyclanilide from drinking water, the percentage of the RfD utilized for
non-nursing infants (the subgroup with the highest exposure) would be
10% of the Reference Dose (RfD). The exposure for the general U.S.
population would be 6% of the RfD. There is no established Maximum
Concentration Level or Health Advisory Level for cyclanilide under the
Safe Drinking Water Act. For the aggregate dietary exposures from food
and drinking water, the percentage of the RfD utilized for non-nursing
infants (the subgroup with the highest exposure) would be 91% of the
Reference Dose (RfD). The exposure for the general U.S. population
would be 21% of the RfD.
The analysis for cyclanilide is a worst case estimate of dietary
exposure with all residues at tolerance levels and 100% of the
commodities assumed to be treated with cyclanilide.
B. Acute Risk
An acute dietary analysis was conducted to determine the Margin of
Exposure from how close the high end exposure comes to the lowest
observed effect level of 150 mg/kg/day in the rat acute oral
neurotoxicity study. Generally acute dietary margins of exposure
greater than 100 tend to cause no dietary concern. The high end MOE for
cyclanilide for all population subgroups was greater than 5,000 and is
above the acceptable level and demonstrates no acute dietary concerns.
The Acute MOE for drinking water is estimated to be greater than
47,000 for all population subgroups. The acute dietary MOE greater than
100 indicates that there is not acute dietary risk concern from acute
drinking water cyclanilide exposure.
The aggregate acute MOE for non-nursing infants (the subgroup with
the highest exposure) would be greater than 8,000. The acute MOE for
the general U.S. population would be greater than 11,000.
C. Conclusion
Based on these risk estimates EPA concludes that there is a
reasonable certainty of no harm from aggregate exposure to cyclanilide
for consumers, including major identifiable subgroups and infants and
children.
VI. Additional Safety Factor for Infants and Children
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 margin of exposure analysis or through using
[[Page 28354]]
uncertainty (safety) factors in calculating a dose level that poses no
appreciable risk to humans. In either case, EPA generally defines the
level of appreciable risk as exposure that is greater than 1/100 of the
no observed effect level in the animal study appropriate to the
particular risk assessment. This hundredfold uncertainty (safety)
factor/margin of exposure (safety) is designed to account for combined
inter- and intra-species variability. EPA believes that reliable data
support using the standard hundredfold margin/factor not the additional
tenfold margin/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 margin/factor.
An additional Uncertainty Factor of 10 was not used for cyclanilide
because (1) the experimental data provided no indication of increased
sensitivity of fetal animals to in utero exposure to cyclanilide or of
neonates to pre-weaning exposure to cyclanilide; (2) the endpoint upon
which the RfD was set, decreased body weight gain in young post-weaning
rats, was observed in young, growing animals and therefore already
considered the increased sensitivity of young animals in the
determination for the LOEL; and (3) treatment related effects seen in
other animals did not indicate potential pre or post-natal effects of
concern to infants or small children. An additional safety factor of 3
was incorporated to account for the fact that a NOEL was not determined
in the study used to establish the RfD.
VII. Other Considerations
1. Endocrine effects. No evidence of endocrine effects on the
systems of mammals was reported in the toxicology studies described
above. There was no observed pathology of the endocrine organs in these
studies. There is no evidence at this time that cyclanilide causes
endocrine effects.
2. Metabolism in plants and animals. The metabolism of cyclanilide
in plants and animals is adequately understood for purposes of these
tolerances. There are no Codex Alimentarius Commission (Codex) Maximum
Residue Levels (MRLs) for cyclanilide. An adequate analytical method,
gas chromatography with electron-capture detection, is available for
enforcement purposes. Because of the long lead time from establishing
these tolerances to publication of the enforcement methodology in the
Pesticide Analytical Manual, Vol. II, the analytical methodology is
being made available in the interim to anyone interested in pesticide
enforcement when requested from: Calvin Furlow, Public Information
Branch, Field Operations Division (7506C), Office of Pesticide
Programs, Environmental Protection Agency, 401 M St., SW., Washington,
DC 20460. Office location and telephone number: Room 1130A, CM#2, 1921
Jefferson Davis Highway, Arlington, VA (703-305-5937).
VIII. Summary of Findings
The analysis for cyclanilide for all population subgroups examined
by EPA shows the proposed uses on cotton will not cause exposure at
which the Agency believes there is an appreciable risk.
Based on the information cited above, the Agency has determined
that the establishment of the tolerances by amending 40 CFR part 180
will be safe; therefore, the tolerances are established as set forth
below.
IX. 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 (1)(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 governs 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 22, 1997, 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 issue(s) on which a hearing is requested, the
requestor's contentions on such issues, and a summary of any evidence
relied upon by the objector (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 a 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 issue(s) in the manner sought by the requestor would be
adequate to justify the action requested (40 CFR 178.32). Information
submitted in connection with an objection or hearing request may be
claimed confidential by marking any part or all of that information as
CBI. Information so marked will not be disclosed except in accordance
with procedures set forth in 40 CFR part 2. A copy of the information
that does not contain CBI must be submitted for inclusion in the public
record. Information not marked confidential may be disclosed publicly
by EPA without prior notice.
X. Public Docket
A record has been established for this rulemaking under the docket
number [OPP-300496] (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 1132 Public Information and Records Integrity
Branch, Information Resources and Services Division (7506C), Office of
Pesticide Programs, Environmental Protection Agency, Crystal Mall #2,
1921 Jefferson Davis Highway, Arlington, VA.
Electronic comments can 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 rule-making record
which will also include all comments submitted directly in writing. The
official rulemaking record is the paper record maintained at the
address in ``ADDRESSES'' at the beginning of this document.
[[Page 28355]]
XI. Regulatory Assessment Requirements
This final rule establishes a tolerance under section 408 of the
FFDCA and is in response to a petition received by the Agency
requesting the establishment of such a tolerance. 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). In addition, 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, because tolerances that are established on the basis
of a petition under section 408(d) of FFDCA, such as the tolerance in
this final rule, do not require the issuance of a proposed rwule, the
requirements of the Regulatory Flexibility Act (RFA) (5 U.S.C. 601 et
seq.) do not apply. Prior to the recent amendments to the FFDCA,
however, EPA had treated such actions as subject to the RFA. The
amendments to the FFDCA clarify that no proposed rule is required for
such regulatory actions, which makes the RFA inapplicable to these
actions. 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 (46 FR 24950, May 4, 1981). In accordance with Small Business
Administration (SBA) policy, this determination will be provided to the
Chief Counsel for Advocacy of the SBA upon request.
XII. Submission to Congress and the General Accounting Office
Under 5 U.S.C. 801(a)(1)(A), as added by the Small Business
Regulatory Enforcement Fairness Act of 1996, the Agency has submitted 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 General Accounting Office prior to publication of this rule in
today's Federal Register. This is not a ``major rule'' as defined by 5
U.S.C. 804(2).
List of Subjects in 40 CFR Part 180
Administrative practice and procedure, Agricultural commodities,
Pesticides and pests, Recording and recordkeeping requirements.
Dated: May 16, 1997.
Stephen L. Johnson,
Acting Director, Office of Pesticide Programs.
Therefore, 40 CFR part 180 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. By adding Sec. 180.506 to read as follows:
Sec. 180.506 Cyclanilide; tolerances for residues.
(a) General. Tolerances are established for residues of the plant
growth regulator, cyclanilide, [1-(2,4-dichlorophenylaminocarbonyl)-
cyclopropane carboxylic acid] determined as 2,4-dichloroaniline
(calculated as cyclanilide) in or on the following food commodities and
processed feed:
------------------------------------------------------------------------
Parts Per
Commodity Million
------------------------------------------------------------------------
Cattle, fat................................................ 0.10
Cattle, meat............................................... 0.20
Cattle, mbyp (except kidney)............................... 0.2
Cattle, kidney............................................. 2.0
Cottonseed................................................. 0.60
Cotton gin byproducts...................................... 25.0
Goats, fat................................................. 0.10
Goats, meat................................................ 0.20
Goats, mbyp (except kidney)................................ 0.20
Goats, kidney.............................................. 2.0
Horses, fat................................................ 0.10
Horses, meat............................................... 0.20
Horses, mbyp (except kidney)............................... 0.20
Horses, kidney............................................. 2.0
Hogs, fat.................................................. 0.10
Hogs, meat................................................. 0.20
Hogs, mbyp (except kidney)................................. 0.20
Hogs, kidney............................................... 2.0
Milk....................................................... 0.04
Sheep, fat................................................. 0.10
Sheep, meat................................................ 0.20
Sheep, mbyp (except kidney)................................ 0.20
Sheep, kidney.............................................. 2.0
------------------------------------------------------------------------
(b) Section 18 emergency exemptions. [Reserved]
(c) Tolerances with regional registrations. [Reserved]
(d) Indirect or inadvertent residues. [Reserved]
[FR Doc. 97-13645 Filed 5-22-97; 8:45 am]
BILLING CODE 6560-50-F
