[Federal Register Volume 63, Number 176 (Friday, September 11, 1998)]
[Proposed Rules]
[Pages 48664-48670]
From the Federal Register Online via the Government Publishing Office [www.gpo.gov]
[FR Doc No: 98-24338]
-----------------------------------------------------------------------
ENVIRONMENTAL PROTECTION AGENCY
40 CFR Part 180
[OPP-300710; FRL-6026-8]
RIN 2070-AB78
Azoxystrobin; Pesticide Tolerance
AGENCY: Environmental Protection Agency (EPA).
ACTION: Proposed rule.
-----------------------------------------------------------------------
SUMMARY: This is a proposed regulation to establish a temporary
tolerance for 1 year for the combined residues of azoxystrobin [methyl
(E)-2-{2-[6-(2-cyanophenoxy)pyrimidin-4-yloxy]phenyl}-3-
methoxyacrylate)] and its Z isomer in or on potatoes. This action is in
response to Wisconsin potato growers and University extension
specialists, Zeneca Ag Products and EPA's combined efforts to generate
the information necessary for registration of the reduced risk
pesticide, azoxystrobin, on late blight and early blight of potatoes.
This proposed temporary tolerance supports a non-crop destruct
experimental use permit (EUP) under section 5 of the Federal
Insecticide, Fungicide, and Rodenticide Act authorizing use of
azoxystrobin on potatoes in Wisconsin. This regulation proposes to
establish a maximum permissible level for residues of azoxystrobin in
this food commodity pursuant to section 408(e) of the Federal Food,
Drug, and Cosmetic Act, as amended by the Food Quality Protection Act
of 1996.
DATES: Comments must be received on or before September 28, 1998.
ADDRESSES: By mail, submit written comments in triplicate 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,
deliver comments to: Rm. 119, CM #2, 1921 Jefferson Davis Highway,
Arlington, VA.
Comments and data may also be submitted electronically to: docket@epamail.epa.gov. Follow the instructions under Unit VII. of this
document. No Confidential Business Information (CBI) should be
submitted through e-mail.
Information submitted as a comment concerning this document 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 comment that
does not contain CBI must be submitted for inclusion in the public
record. Information not marked confidential will be included in the
public docket by EPA without prior notice. The public docket is
available for public inspection in Rm. 119 at the Virginia address
given above, from 8:30 a.m. to 4 p.m., Monday through Friday, excluding
legal holidays.
FOR FURTHER INFORMATION CONTACT: By mail: John Bazuin, Registration
Division 7505C, Office of Pesticide Programs, Environmental Protection
Agency, 401 M St., SW., Washington, DC 20460. Office location,
telephone number, and e-mail address: Crystal Mall #2, 1921 Jefferson
Davis Hwy., Arlington, VA, (703) 305-7381, e-mail:
bazuin.john@epamail.epa.gov.
SUPPLEMENTARY INFORMATION: EPA, in cooperation with Wisconsin potato
growers, University extension specialists, and Zeneca Ag Products,
Inc., and pursuant to section 408(e) and (r) of the Federal Food, Drug,
and Cosmetic Act (FFDCA), 21 U.S.C. 346a(e) and (r), is proposing to
establish a temporary tolerance for 1 year for the combined residues of
the fungicide azoxystrobin and its Z isomer, in or on potatoes at 0.03
parts per million (ppm).
[[Page 48665]]
I. Background and Statutory Authority
The Food Quality Protection Act of 1996 (FQPA) (Pub. L. 104-170)
was signed into law August 3, 1996. FQPA amends both the Federal Food,
Drug, and Cosmetic Act (FFDCA), 21 U.S.C. 301 et seq., and the Federal
Insecticide, Fungicide, and Rodenticide Act (FIFRA), 7 U.S.C. 136 et
seq. The FQPA amendments went into effect immediately. Among other
things, FQPA amends FFDCA to bring all EPA pesticide tolerance-setting
activities under a new section 408 with a new safety standard and new
procedures. These activities are described below and discussed in
greater detail in the final rule establishing the time-limited
tolerance associated with the emergency exemption for use of
propiconazole on sorghum (61 FR 58135, November 13, 1996) (FRL-5572-9).
New section 408(b)(2)(A)(i) of 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. . . .''
Section 5 of FIFRA authorizes EPA to issue an experimental use
permit for a pesticide. This provision was not amended by FQPA. EPA has
established regulations governing such experimental use permits in 40
CFR part 172. Section 408(r) of FFDCA authorizes EPA to issue temporary
tolerances for pesticide residues resulting from FIFRA experimental use
permits.
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. The Agency has determined that
azoxystrobin is a reduced risk pesticide for use on potatoes.
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 adverse effect level'' or
``NOAEL'').
Once a study has been evaluated and the observed effects have been
determined to be threshold effects, EPA generally divides the NOAEL
from the study with the lowest NOAEL 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 NOAEL from the
appropriate animal study. Commonly, EPA finds MOEs lower than 100 to be
unacceptable. This 100-fold MOE is based on the same rationale as the
100-fold uncertainty factor.
Lifetime feeding studies in two species of laboratory animals are
conducted to screen pesticides for cancer effects. When evidence of
increased cancer is noted in these studies, the Agency conducts a
weight of the evidence review of all relevant toxicological data
including short-term and mutagenicity studies and structure activity
relationship. Once a pesticide has been classified as a potential human
carcinogen, different types of risk assessments (e.g., linear low dose
extrapolations or MOE calculation based on the appropriate NOAEL) 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 is typically assumed.
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
[[Page 48666]]
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/NOAEL 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 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 ground water
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 is 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 is 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 (non-nursing infants (<1 year="" old))="" was="" not="" regionally="" based.="" iii.="" 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="" azoxystrobin="" and="" to="" make="" a="" determination="" on="" aggregate="" exposure,="" consistent="" with="" section="" 408(b)(2),="" for="" a="" temporary="" tolerance="" for="" 1="" year="" for="" combined="" residues="" of="" azoxystrobin="" and="" its="" z="" isomer)="" on="" potatoes="" at="" 0.03="" ppm.="" epa's="" assessment="" of="" the="" dietary="" exposures="" and="" risks="" associated="" with="" establishing="" the="" tolerance="" follows.="" a.="" toxicological="" profile="" epa="" has="" evaluated="" the="" available="" toxicity="" data="" and="" considered="" its="" validity,="" completeness,="" and="" reliability="" as="" well="" as="" the="" relationship="" of="" the="" results="" of="" the="" studies="" to="" human="" risk.="" epa="" has="" also="" considered="" available="" information="" concerning="" the="" variability="" of="" the="" sensitivities="" of="" major="" identifiable="" subgroups="" of="" consumers,="" including="" infants="" and="" children.="" the="" nature="" of="" the="" toxic="" effects="" and="" the="" agency's="" selection="" of="" toxicological="" endpoints="" upon="" which="" to="" assess="" risk="" caused="" by="" azoxystrobin="" are="" discussed="" below.="" 1.="" acute="" toxicity.="" the="" agency="" evaluated="" the="" existing="" toxicology="" data="" base="" for="" azoxystrobin.="" no="" acute="" dietary="" endpoint="" was="" identified,="" no="" developmental="" toxicity="" was="" observed="" in="" the="" rabbit="" and="" rat="" studies="" reviewed,="" and="" no="" primary="" neurotoxicity="" was="" seen="" in="" the="" acute="" neurotoxicity="" study.="" therefore,="" no="" risk="" has="" been="" identified="" for="" this="" scenario="" and="" a="" risk="" assessment="" is="" not="" needed.="" 2.="" short="" -="" and="" intermediate-term="" toxicity.="" the="" agency="" evaluated="" the="" existing="" toxicology="" data="" base="" for="" short-="" and="" intermediate-term="" dermal="" and="" inhalation="" exposure="" and="" determined="" that="" this="" risk="" assessment="" is="" also="" not="" required.="" in="" a="" 21-day="" dermal="" toxicity="" study="" the="" noael="" was="" 1,000="" milligrams/kilograms/day="" (mg/kg/day)="" at="" the="" highest="" dose="" tested="" (acute="" inhalation="" toxicity="" category="" iii).="" 3.="" chronic="" toxicity.="" epa="" has="" established="" the="" rfd="" for="" azoxystrobin="" at="" 0.18="" mg/kg/day.="" this="" rfd="" is="" based="" on="" a="" chronic="" toxicity="" study="" in="" rats="" with="" a="" noael="" of="" 18.2="" mg/kg/day.="" the="" endpoint="" effects="" were="" reduced="" body="" weights="" and="" bile="" duct="" lesions="" at="" the="" lowest="" effect="" level="" (lel)="" of="" 34="" mg/kg/day.="" an="" uncertainty="" factor="" (uf)="" of="" 100="" was="" used="" to="" account="" for="" both="" the="" interspecies="" extrapolation="" and="" the="" intraspecies="" variability.="" 4.="" carcinogenicity.="" carcinogenicity="" testing="" of="" azoxystrobin="" in="" two="" appropriate="" species="" of="" mammals="" revealed="" no="" evidence="" that="" this="" fungicide="" is="" carcinogenic.="" therefore,="" epa="" classifies="" azoxystrobin="" as="" ``not="" likely''="" to="" be="" a="" human="" carcinogen="" in="" line="" with="" the="" proposed="" revised="" cancer="" guidelines.="" b.="" exposures="" and="" risks="" 1.="" from="" food="" and="" feed="" uses.="" permanent="" tolerances="" have="" been="" established="" (40="" cfr="" 180.507(a))="" for="" the="" combined="" residues="" of="" azoxystrobin="" and="" its="" z="" isomer,="" in="" or="" on="" a="" variety="" of="" raw="" agricultural="" commodities="" at="" levels="" ranging="" from="" 0.01="" ppm="" in="" pecans="" to="" 1.0="" ppm="" in="" grapes.="" in="" addition,="" time-limited="" tolerances="" have="" been="" established="" (40="" cfr="" 180.507(b)="" at="" levels="" ranging="" from="" 0.006="" ppm="" in="" milk="" to="" 20="" ppm="" in="" rice="" hulls)="" in="" conjunction="" with="" section="" 18="" requests.="" risk="" assessments="" were="" conducted="" by="" epa="" to="" assess="" dietary="" exposures="" and="" risks="" from="" azoxystrobin="" as="" follows:="" i.="" acute="" exposure="" and="" risk.="" acute="" dietary="" risk="" assessments="" are="" performed="" for="" a="" food-use="" pesticide="" if="" a="" toxicological="" study="" has="" indicated="" the="" possibility="" of="" an="" effect="" of="" concern="" occurring="" as="" a="" result="" of="" a="" 1="" day="" or="" single="" exposure.="" the="" agency="" did="" not="" conduct="" an="" acute="" risk="" assessment="" because="" no="" toxicological="" endpoint="" of="" concern="" was="" identified="" during="" review="" of="" available="" data.="" ii.="" chronic="" exposure="" and="" risk.="" in="" conducting="" this="" chronic="" dietary="" risk="" assessment,="" the="" agency="" has="" made="" very="" conservative="" assumptions--="" 100%="" of="" potatoes="" and="" all="" other="" commodities="" having="" azoxystrobin="" tolerances="" will="" contain="" azoxystrobin="" residues="" and="" those="" residues="" would="" be="" at="" the="" level="" of="" the="" tolerance--which="" result="" in="" an="" overestimation="" of="" human="" dietary="" exposure.="" thus,="" in="" making="" a="" safety="" determination="" for="" this="" tolerance,="" epa="" is="" taking="" into="" account="" this="" conservative="" [[page="" 48667]]="" exposure="" assessment.="" the="" existing="" azoxystrobin="" tolerances="" (published,="" pending,="" and="" including="" the="" necessary="" section="" 18="" tolerance(s))="" result="" in="" a="" theoretical="" maximum="" residue="" contribution="" (tmrc)="" that="" is="" equivalent="" to="" the="" following="" percentages="" of="" the="" rfd:="" ------------------------------------------------------------------------="" population="" sub-group="" tmrc="" (mg/kg/day)="" %="" rfd="" ------------------------------------------------------------------------="" u.s.="" population="" (48="" states)="" 0.003="" 1.8%="" nursing="" infants=""><1 year="" old)="" 0.004="" 2%="" non-nursing="" infants=""><1 year="" 0.011="" 8%="" old)="" children="" (1-6="" years="" old)="" 0.007="" 4%="" children="" (7-12="" years="" old)="" 0.004="" 2%="" hispanics="" 0.004="" 2%="" non-hispanics="" others="" 0.005="" 3%="" u.s.="" population="" (summer="" season)="" 0.003="" 2%="" u.s.="" population="" (northeast="" 0.003="" 2%="" region)="" u.s.="" population="" (western="" region)="" 0.003="" 2%="" u.s.="" population="" (pacific="" region)="" 0.003="" 2%="" females="" (13+,="" nursing)="" 0.003="" 2%="" females="" (13-19,="" not="" pregnant="" or="" 0.002="" 1%="" nursing)="" ------------------------------------------------------------------------="" neither="" the="" u.s.="" population="" as="" a="" whole="" nor="" any="" of="" the="" subgroups="" whose="" food="" consumption="" patterns="" were="" analyzed="" for="" dietary="" exposure="" and="" risk="" to="" azoxystrobin="" reached="" even="" one-twelfth="" of="" the="" rfd="" under="" these="" assumed="" theoretical="" maximum="" exposures="" to="" azoxystrobin="" for="" all="" published,="" pending,="" and="" proposed="" tolerances.="" moreover,="" real-world="" exposure="" is="" likely="" to="" be="" substantially="" lower="" than="" this.="" 2.="" from="" drinking="" water.="" there="" is="" no="" established="" maximum="" contaminant="" level="" for="" residues="" of="" azoxystrobin="" in="" drinking="" water.="" no="" health="" advisory="" levels="" for="" azoxystrobin="" in="" drinking="" water="" have="" been="" established.="" i.="" acute="" exposure="" and="" risk.="" an="" acute="" risk="" assessment="" was="" not="" appropriate="" since="" no="" toxicological="" endpoint="" of="" concern="" was="" identified="" for="" this="" scenario="" during="" review="" of="" the="" available="" data.="" ii.="" chronic="" exposure="" and="" risk.="" based="" on="" the="" chronic="" dietary="" (food)="" exposure="" estimates,="" chronic="" drinking="" water="" levels="" of="" concern="" (dwloc)="" for="" azoxystrobin="" were="" calculated="" and="" are="" summarized="" in="" the="" following="" table.="" estimated="" environmental="" concentrations="" (eecs)="" using="" geneec="" for="" azoxystrobin="" on="" bananas,="" grapes,="" peaches,="" peanuts,="" pecans,="" tomatoes,="" and="" wheat="" are="" listed="" in="" swat="" team="" second="" interim="" report="" (june="" 20,="" 1997).="" the="" highest="" eec="" for="" azoxystrobin="" in="" surface="" water="" is="" from="" the="" application="" of="" azoxystrobin="" on="" grapes="" (39="">g/L) and is
substantially lower than the DWLOCs calculated. Therefore, chronic
exposure to azoxystrobin residues in drinking water do not exceed the
Agency's level of concern.
----------------------------------------------------------------------------------------------------------------
TMRC [Food Maximum Water
RfD (mg/kg/day) Exposure] (mg/kg/ Exposure1 (mg/kg/ DWLOC2,3,4 (g/L)
----------------------------------------------------------------------------------------------------------------
U.S. Population (48 States) 0.18 0.0027 0.178 6,200
Females (13 + years old, not 0.18 0.0019 0.178 5,300
pregnant or nursing)
Non-nursing Infants (<1 year="" 0.18="" 0.0113="" 0.169="" 1,680="" old)="" ----------------------------------------------------------------------------------------------------------------="">1 Maximum water exposure (mg/kg/day) = RfD (mg/kg/day) - TMRC from DRES (mg/kg/day)
2 DWLOC (g/L) = Max water exposure (mg/kg/day) * body wt (kg)/[(10-3 mg/g)*water consumed
daily (L/day)]
3 HED default body wts for males, females, and children are 70 kg, 60 kg, and 10 kg respectively
4 HED default daily drinking rates are 2 L/day for adults and 1 L/day for children
3. From non-dietary exposure. Azoxystrobin is not currently
registered for use on residential non-food sites.
4. Cumulative exposure to substances with common mechanism of
toxicity. Azoxystrobin is related to the naturally occurring
strobilurins. There are no other members of this class of fungicides
registered with the Agency. 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 azoxystrobin has a common mechanism of toxicity with other
substances or how to include this pesticide in a cumulative
[[Page 48668]]
risk assessment. Unlike other pesticides for which EPA has followed a
cumulative risk approach based on a common mechanism of toxicity,
azoxystrobin 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 azoxystrobin has a common mechanism of
toxicity with other substances.
C. Aggregate Risks and Determination of Safety for U.S. Population
1. Acute risk. This risk assessment is not necessary since no acute
toxicological end-point of concern was identified for this exposure
scenario during review of the available data.
2. Chronic risk. Using the conservative TMRC exposure assumptions
described above, and taking into account the completeness and
reliability of the toxicity data, the Agency has estimated that
exposure to azoxystrobin from food will utilize 2% of the RfD for the
U.S. population as a whole. The Agency generally is not concerned about
exposures below 100% of the RfD because the RfD represents the level at
or below which daily aggregate dietary exposure over a lifetime will
not pose appreciable risks to human health. Despite the potential for
exposure to azoxystrobin in drinking water, the Agency does not expect
the aggregate exposure to exceed 100% of the RfD. Under current Agency
guidelines, the registered non-dietary uses of azoxystrobin do not
constitute a chronic exposure scenario and EPA concludes that there is
a reasonable certainty that no harm will result from aggregate exposure
to currently registered azoxystrobin residues.
3. Short- and intermediate-term risk. Short- and intermediate-term
aggregate exposure takes into account chronic dietary food and water
(considered to be a background exposure level) plus indoor and outdoor
residential exposure. This risk assessment is not needed because no
dermal or systemic effects were seen in the repeated dose dermal study
at the limit dose. Additionally, no indoor or outdoor residential
exposure uses are currently registered for azoxystrobin.
D. Aggregate Cancer Risk for U.S. Population
This risk assessment is also not needed. Azoxystrobin is classified
as ``not likely'' to be a carcinogen under the proposed revised
carcinogenicity guidelines because carcinogenicity testing was
performed on two appropriate species and no evidence of carcinogenicity
was found.
E. Aggregate Risks and Determination of Safety for Infants and Children
1. Safety factor for infants and children-- i. In general. In
assessing the potential for additional sensitivity of infants and
children to residues of azoxystrobin, EPA considered data from
developmental toxicity studies in the rat and rabbit and a 2-generation
reproduction study in the rat. The developmental toxicity studies are
designed to evaluate adverse effects on the developing organism
resulting from maternal pesticide exposure 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 data base unless EPA determines that a different
margin of safety will be safe for infants and children. Margins of
safety are incorporated into EPA risk assessments either directly
through use of a 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 MOE
and uncertainty factor (usually 100 for combined inter- and intra-
species variability) and not the additional tenfold MOE/uncertainty
factor when EPA has a complete data base under existing guidelines and
when the severity of the effect in infants or children or the potency
or unusual toxic properties of a compound do not raise concerns
regarding the adequacy of the standard MOE/safety factor.
ii. Developmental toxicity studies--a. Rabbit. In the developmental
toxicity study in rabbits, developmental NOAEL was 500 mg/kg/day, at
the highest dose tested (HDT). Because there were no treatment-related
effects, the developmental LEL was 500 mg/kg/day. The
maternal NOAEL was 150 mg/kg/day. The maternal LEL of 500 mg/kg/day was
based on decreased body weight gain during dosing.
b. Rat. In the developmental toxicity study in rats, the maternal
(systemic) NOAEL was not established. The maternal LEL of 25 mg/kg/day
at the lowest dose tested (LDT) was based on increased salivation. The
developmental (fetal) NOAEL was 100 mg/kg/day (HDT).
iii. Reproductive toxicity study--a. Rat. In the reproductive
toxicity study (MRID No. 43678144) in rats, the parental (systemic)
NOAEL was 32.3 mg/kg/day. The parental LEL of 165.4 mg/kg/day was based
on decreased body weights in males and females, decreased food
consumption and increased adjusted liver weights in females, and
cholangitis. The reproductive NOAEL was 32.3 mg/kg/day. The
reproductive LEL of 165.4 mg/kg/day was based on increased weanling
liver weights and decreased body weights for pups of both generations.
iv. Conclusion. The pre- and post-natal toxicology data base for
azoxystrobin is complete with respect to current toxicological data
requirements. The results of these studies indicate that infants and
children are no more sensitive to exposure to azoxystrobin than are
adults, based on the results of the rat and rabbit developmental
toxicity studies and the 2-generation reproductive toxicity study in
rats. Accordingly, EPA has determined that the standard margin of
safety will protect the safety of infants and children and the
additional tenfold safety factor can therefore be removed.
2. Chronic risk. Using the conservative exposure assumptions
described above, EPA has concluded that aggregate exposure to
azoxystrobin from food will utilize 2 to 8% of the RfD for infants and
children. EPA generally has no concern for exposures below 100% of the
RfD because the RfD represents the level at or below which daily
aggregate dietary exposure over a lifetime will not pose appreciable
risks to human health. Despite the potential for exposure to
azoxystrobin in drinking water and from non-dietary, non-occupational
exposure, EPA does not expect the aggregate exposure to exceed 100% of
the RfD. EPA concludes that there is a reasonable certainty that no
harm will result to infants and children from aggregate exposure to
azoxystrobin residues.
IV. Other Considerations
A. Metabolism in Plants and Animals
a. The metabolism of azoxystrobin as well as the nature of the
residues is adequately understood for purposes of the temporary
tolerance. Plant metabolism has been evaluated in three diverse crops;
grapes, wheat, and peanuts, which is required to define similar
metabolism of azoxystrobin in a wide range of crops. Parent
azoxystrobin is the major component found in crops. Azoxystrobin does
not accumulate in crop seeds or fruits. Metabolism of azoxystrobin in
plants is complex, with more than 15 metabolites identified. These
metabolites are present at low
[[Page 48669]]
levels, typically much less than 5% of the total radioactive residue
level.
b. The qualitative nature of the residue in animals is adequately
understood for the purposes of this proposed 1 year temporary
tolerance. Establishment of a temporary tolerance of 0.03 ppm for
azoxystrobin in/on potatoes is not expected to lead to detectable
azoxystrobin residues in animal commodities.
B. Analytical Enforcement Methodology
An analytical method, gas chromatography with nitrogen-phosphorus
detection (GC-NDP) or, in mobile phase, by high performance liquid
chromatography with ultraviolet detection (HPLC-UV), is available for
enforcement purposes with a limit of detection that allows monitoring
of food with residues at or above the level proposed for this temporary
tolerance. The Agency has concluded that the method is adequate for
enforcement of tolerances in/on other non-oily raw agricultural
commodities. The Agency concludes this method is adequate for
enforcement of the proposed temporary tolerance in/on potatoes.
C. Magnitude of Residues
Residues of azoxystrobin and its Z isomer are not expected to
exceed 0.03 ppm in/on potatoes as a result of the EUP use. A temporary
tolerance should be established at this level.
D. International Residue Limits
There are no CODEX, Canadian, or Mexican Maximum Residue Limits for
azoxystrobin in/on potatoes.
E. Rotational Crop Restrictions
Rotational crop data were previously submitted. Based on this
information, a 45-day plantback interval is appropriate for all crops
other than those with azoxystrobin tolerances.
V. Conclusion
A 15-day comment period is being allowed for this proposed rule
because of the speed of growth and of resistance development of early
and late blight, and because these fungal diseases are so devastating
to potato crops once they become established. The Agency desires to be
supportive of efforts by potato growers to combat these diseases and to
protect their crops. The Agency also desires to be supportive of
efforts by researchers to find control methods for the pests early and
late blight. Additionally, the Agency feels that there is strong
evidence in support of the safety of this proposed action.
Therefore, a temporary tolerance is proposed for 1 year for the
combined residues of azoxystrobin and its Z isomer in/on potatoes at
0.03 ppm.
VI. Public Record and Electronic Submissions
The official record for this rulemaking, as well as the public
version, has been established for this rulemaking under docket control
number ``OPP-300710'' (including comments and data submitted
electronically as described below). 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 official rulemaking record is located at the Virginia
address in ``ADDRESSES'' at the beginning of this document.
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. Comment and data
will also be accepted on disks in Wordperfect 5.1/6.1 or ASCII file
format. All comments and data in electronic form must be identified by
the docket control number ``OPP-300710.'' Electronic comments on this
proposed rule may be filed online at many Federal Depository Libraries.
VII. Regulatory Assessment Requirements
A. Certain Acts and Executive Orders
This document proposes establishing a temporary tolerance under
FFDCA section 408(d). EPA is proposing this regulation in cooperation
with Wisconsin potato growers, University extension specialists, and
Zeneca Ag Products, Inc. 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 action 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 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).
Pursuant to the requirements of the Regulatory Flexibility Act
(Pub. L. 96-354, 94 Stat. 1164, 5 U.S.C. 601-612), the Agency
previously assessed whether establishing tolerances, exemptions from
tolerances, raising tolerance levels or expanding exemptions might
adversely impact small entities and concluded, as a generic matter,
that there is no adverse economic impact. The factual basis for the
Agency's generic certification for tolerance actions published on May
4, 1981 (46 FR 24950), and was provided to the Chief Counsel for
Advocacy of the Small Business Administration.
B. Executive Order 12875
Under Executive Order 12875, ``entitled Enhancing Intergovernmental
Partnerships (58 FR 58093, October 28, 1993), EPA may not issue a
regulation that is not required by statute and that creates a mandate
upon a State, local or tribal government, unless the Federal government
provides the funds necessary to pay the direct compliance costs
incurred by those governments. If the mandate is unfunded, EPA must
provide to the Office of Management and Budget (OMB) a description of
the extent of EPA's prior consultation with representatives of affected
State, local and Tribal governments, the nature of their concerns,
copies of any written communications from the governments, and a
statement supporting the need to issue the regulation. In addition,
Executive Order 12875 requires EPA to develop an effective process
permitting elected officials and other representatives of State, local
and Tribal governments ``to provide meaningful and timely input in the
development of regulatory proposals containing significant unfunded
mandates.''
Today's proposed rule does not create an unfunded Federal mandate
on State, local or Tribal governments. The proposed rule does not
impose any enforceable duties on these entities. Accordingly, the
requirements of section 1(a) of Executive Order 12875 do not apply to
this proposed rule.
C. Executive Order 13084
Under Executive Order 13084, entitled ``Consultation and
Coordination with Indian Tribal Governments'' (63 FR 27655, May 19,
1998), EPA may not issue a regulation that is not required by statute,
that significantly or uniquely affects the communities of Indian tribal
[[Page 48670]]
governments, and that imposes substantial direct compliance costs on
those communities, unless the Federal government provides the funds
necessary to pay the direct compliance costs incurred by the Tribal
governments. If the mandate is unfunded, EPA must provide OMB, in a
separately identified section of the preamble to the rule, a
description of the extent of EPA's prior consultation with
representatives of affected Tribal governments, a summary of the nature
of their concerns, and a statement supporting the need to issue the
regulation. In addition, Executive Order 13084 requires EPA to develop
an effective process permitting elected and other representatives of
Indian tribal governments ``to provide meaningful and timely input in
the development of regulatory policies on matters that significantly or
uniquely affect their communities.''
Today's proposed rule does not significantly or uniquely affect the
communities of Indian tribal governments. This action does not involve
or impose any requirements that affect Indian Tribes. Accordingly, the
requirements of section 3(b) of Executive Order 13084 do not apply to
this proposed rule.
List of Subjects in 40 CFR Part 180
Environmental protection, Administrative practice and procedure,
Agricultural commodities, Pesticides and pests, Feed additives, Food
additives, Reporting and recordkeeping requirements.
Dated: September 2, 1998.
Stephen L. Johnson,
Acting Director, Office of Pesticide Programs.
Therefore, it is proposed that 40 CFR chapter I be 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 180.507(a) is amended by redesignating the existing text
as paragraph (a)(1) and adding paragraph (a)(2) to read as follows:
Sec. 180.507 Azoxystrobin; tolerances for residues.
(a)(1) * * *
(2) Temporary tolerance. A tolerance to expire on September 13,
1999 is established for the combined residues of azoxystrobin [methyl
(E)-2-{2-[6-(2-cyanophenoxy)pyrimidin-4-yloxy]phenyl}-3-
methoxyacrylate)] and its Z isomer in or on potatoes at 0.03 parts per
million (ppm) .
* * * * *
[FR Doc. 98-24338 Filed 9-10-98; 8:45 am]
BILLING CODE 6560-50-F
