[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]


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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.

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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: opp-
[email protected]. 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: 
[email protected].

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:
    [email protected]


    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