[Federal Register Volume 64, Number 217 (Wednesday, November 10, 1999)]
[Notices]
[Pages 61336-61343]
From the Federal Register Online via the Government Publishing Office [www.gpo.gov]
[FR Doc No: 99-29184]


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ENVIRONMENTAL PROTECTION AGENCY

[PF-896; FRL-6388-3]


Notice of Filing Pesticide Petitions to Establish a Tolerance for 
Certain Pesticide Chemicals in or on Food

AGENCY: Environmental Protection Agency (EPA).

ACTION: Notice.

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SUMMARY: This notice announces the initial filing of pesticide 
petitions proposing the establishment of regulations for residues of 
certain pesticide chemicals in or on various food commodities.

DATES: Comments, identified by docket control number PF-896, must be 
received on or before December 10, 1999.

ADDRESSES: Comments may be submitted by mail, electronically, or in 
person. Please follow the detailed instructions for each method as 
provided in Unit I.C. of the ``SUPPLEMENTARY INFORMATION'' section. To 
ensure proper receipt by EPA, it is imperative that you identify docket 
control number PF-896 in the subject line on the first page of your 
response.

FOR FURTHER INFORMATION CONTACT: The product manager listed in the 
table below:

----------------------------------------------------------------------------------------------------------------
                                      Office location/telephone
          Product Manager               number/e-mail address             Address           Petition number(s)
----------------------------------------------------------------------------------------------------------------
Cynthia Giles-Parker (PM 22).......  Rm. 247, CM #2, 703-305-     1921 Jefferson Davis    PP 8F4998
                                      7740, e-mail: giles-         Hwy, Arlington, VA
                                      [email protected].
Shaja Brothers.....................  Rm. 237, CM #2, 703-308-     Do.                     PP 9E3810, 9E3813,
                                      3194, e-mail:                                        OE3912, 9E5075, and
                                      [email protected]                           9E6061
                                      .gov.
----------------------------------------------------------------------------------------------------------------


SUPPLEMENTARY INFORMATION:

I. General Information

A. Does this Action Apply to Me?

    You may be affected by this action if you are an agricultural 
producer, food manufacturer or pesticide manufacturer. Potentially 
affected categories and entities may include, but are not limited to:

 
------------------------------------------------------------------------
                                                          Examples of
           Categories                    NAICS            potentially
                                                       affected entities
------------------------------------------------------------------------
Industry                          111                 Crop production
 
                                  112                 Animal production
 
                                  311                 Food manufacturing
                                  32532               Pesticide
                                                       manufacturing
------------------------------------------------------------------------

    This listing is not intended to be exhaustive, but rather provides 
a guide for readers regarding entities likely to be affected by this 
action. Other types of entities not listed in the table could also be 
affected. The North American Industrial Classification System (NAICS) 
codes have been provided to assist you and others in determining 
whether or not this action might apply to certain entities. If you have 
questions regarding the applicability of this action to a particular 
entity, consult the person listed in the ``FOR FURTHER INFORMATION 
CONTACT'' section.

B. How Can I Get Additional Information, Including Copies of this 
Document and Other Related Documents?

    1. Electronically. You may obtain electronic copies of this 
document, and certain other related documents that might be available 
electronically, from the EPA Internet Home Page at http://www.epa.gov/. 
To access this document, on the Home Page select ``Laws and 
Regulations'' and then look up the entry for this document under the 
``Federal Register--Environmental Documents.'' You can also go directly 
to the Federal Register listings at http://www.epa.gov/fedrgstr/.
    2. In person. The Agency has established an official record for 
this action under docket control number PF-896. The official record 
consists of the documents specifically referenced in this action, any 
public comments received during an applicable comment period, and other 
information related to this action, including any information claimed 
as confidential business information (CBI). This official record 
includes the documents that are physically located in the docket, as 
well as the documents that are referenced in those documents. The 
public version of the official record does not include any information 
claimed as CBI. The public version of the official record, which 
includes printed, paper versions of any electronic comments submitted 
during an applicable comment period, is available for inspection in the 
Public Information and Records Integrity Branch (PIRIB), Rm. 119, 
Crystal Mall #2, 1921 Jefferson Davis Highway, Arlington, VA, from 8:30 
a.m. to 4 p.m., Monday through Friday, excluding legal holidays. The 
PIRIB telephone number is (703) 305-5805.

C. How and to Whom Do I Submit Comments?

    You may submit comments through the mail, in person, or 
electronically. To ensure proper receipt by EPA, it is imperative that 
you identify docket control number PF-896 in the subject line on the 
first page of your response.
    1. By mail. Submit your comments to: Public Information and Records 
Integrity Branch (PIRIB), Information Resources and Services Division 
(7502C), Office of Pesticide Programs, Environmental Protection Agency, 
401 M St., SW., Washington, DC 20460.
    2. In person or by courier. Deliver your comments to: Public 
Information and Records Integrity Branch (PIRIB), Information Resources 
and Services Division (7502C), Office of Pesticide Programs (OPP), 
Environmental Protection Agency, Rm. 119, Crystal

[[Page 61337]]

Mall #2, 1921 Jefferson Davis Highway, Arlington, VA. The PIRIB is open 
from 8:30 a.m. to 4 p.m., Monday through Friday, excluding legal 
holidays. The PIRIB telephone number is (703) 305-5805.
    3. Electronically. You may submit your comments electronically by 
E-mail to: ``[email protected] ,'' or you can submit a computer disk 
as described above. Do not submit any information electronically that 
you consider to be CBI. Avoid the use of special characters and any 
form of encryption. Electronic submissions will be accepted in 
Wordperfect 6.1/8.0 or ASCII file format. All comments in electronic 
form must be identified by docket control number PF-896. Electronic 
comments may also be filed online at many Federal Depository Libraries.

D. How Should I Handle CBI That I Want to Submit to the Agency?

    Do not submit any information electronically that you consider to 
be CBI. You may claim information that you submit to EPA in response to 
this document as CBI 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. In addition to one complete 
version of the comment that includes any information claimed as CBI, a 
copy of the comment that does not contain the information claimed as 
CBI must be submitted for inclusion in the public version of the 
official record. Information not marked confidential will be included 
in the public version of the official record without prior notice. If 
you have any questions about CBI or the procedures for claiming CBI, 
please consult the person identified in the ``FOR FURTHER INFORMATION 
CONTACT'' section.

E. What Should I Consider as I Prepare My Comments for EPA?

    You may find the following suggestions helpful for preparing your 
comments:
     1. Explain your views as clearly as possible.
     2. Describe any assumptions that you used.
     3. Provide copies of any technical information and/or data you 
used that support your views.
     4. If you estimate potential burden or costs, explain how you 
arrived at the estimate that you provide.
     5. Provide specific examples to illustrate your concerns.
     6. Make sure to submit your comments by the deadline in this 
notice.
     7. To ensure proper receipt by EPA, be sure to identify the docket 
control number assigned to this action in the subject line on the first 
page of your response. You may also provide the name, date, and Federal 
Register citation.

II. What Action is the Agency Taking?

    EPA has received pesticide petitions as follows proposing the 
establishment and/or amendment of regulations for residues of certain 
pesticide chemicals in or on various food commodities under section 408 
of the Federal Food, Drug, and Comestic Act (FFDCA), 21 U.S.C. 346a. 
EPA has determined that these petitions contain data or information 
regarding the elements set forth in section 408(d)(2); however, EPA has 
not fully evaluated the sufficiency of the submitted data at this time 
or whether the data supports granting of the petition. Additional data 
may be needed before EPA rules on the petition.

List of Subjects

    Environmental protection, Agricultural commodities, Feed additives, 
Food additives, Pesticides and pests, Reporting and recordkeeping 
requirements.

    Dated: November 1, 1999.

James Jones,

Director, Registration Division, Office of Pesticide Programs.

Summaries of Petitions

    The petitioner summaries of the pesticide petitions are printed 
below as required by section 408(d)(3) of the FFDCA. The summaries of 
the petitions were prepared by the petitioners and represent the views 
of the petitioners. EPA is publishing the petition summaries verbatim 
without editing them in any way. The petition summary announces the 
availability of a description of the analytical methods available to 
EPA for the detection and measurement of the pesticide chemical 
residues or an explanation of why no such method is needed.

1. GMJA Specialties

 8F4998

    EPA has received a pesticide petition (8F4998) from GMJA 
Specialties, 10001 13th Avenue, East Bradenton, FL proposing, pursuant 
to section 408(d) of the Federal Food, Drug, and Cosmetic Act (FFDCA), 
21 U.S.C. 346a(d), to amend 40 CFR part 180 by establishing a tolerance 
for residues of PT807-HCl N,N-Diethyl-N-2-(4-methybenzyloxy)ethylamine 
hydrochloride in or on the raw agricultural commodity (RAC) oranges at 
0.01 parts per million (ppm). EPA has determined that the petition 
contains data or information regarding the elements set forth in 
section 408(d)(2) of the FFDCA; however, EPA has not fully evaluated 
the sufficiency of the submitted data at this time or whether the data 
supports granting of the petition. Additional data may be needed before 
EPA rules on the petition.

A. Residue Chemistry

    1. Plant metabolism. The metabolism of PT807-HCl in plants and 
animals is understood. In plants (oranges), unchanged parent is the 
only residue identified in fruit. Valencia orange trees were treated 
with 14C PT807-HCl at a nominal rate of 1,000 ppm 
(approximately 60x the maximum recommended application rate). Fruit 
from the previous season's crop present on the tree at the time of 
application was harvested 50 days after treatment (DAT) and mature 
fruit (not present on the tree at application) was harvested 370 DAT. 
Total radioactive residue (TRR) levels were 0.538 ppm in 50 DAT orange 
samples and were 0.051 ppm in 370 DAT orange samples. Most of the 
radioactivity was present on the peel (88.63% TRR or 0.475 ppm in the 
50 DAT fruit, and 64.19% TRR or 0.033 ppm in the 370 DAT fruit). 
Unchanged parent PT807-HCl was detected in 50 DAT mature fruit (0.386 
ppm), but not in the 370 DAT mature fruit (less than 0.001 ppm).
    The metabolism of PT807-HCl in oranges has been determined. The 
only significant metabolite is unchanged parent. No detectable residues 
of PT807-HCl are anticipated in oranges treated at the recommended 
application rate.
    14C PT807-HCl was extensively metabolized and readily 
eliminated in the urine and feces following oral administration to a 
lactating goat. The efficient elimination process resulted in neglible 
to modest retention of radioactive residues in milk and tissues (less 
than 0.2% of the administered dose). No residues of unchanged parent 
were identified in tissues or milk. The rapid elimination of PT807-HCl 
and its metabolites coupled with the highly exaggerated dose 
(approximately 3,600x the dietary burden) clearly indicate that no 
detectable residues of PT807-HCl will accumulate in milk and tissues.
    2. Analytical method. An analyticial method capable of extracting 
PT807-HCl from whole oranges, juice, and dried pulp using organic 
solvents has been validated. Extracted PT807-HCl residues are analyzed 
using high performance liquid chromatography (HPLC) with a ultraviolet 
(UV) detector. The limit of

[[Page 61338]]

quantitation (LOQ) of the method is 0.01 ppm.
    3. Magnitude of residues. Seventeen field trials were conducted 
using various varieties of oranges in California (4 trials), Florida 
(12 trials), and Texas (1 trial). Two of the trials (1 in California 
and 1 in Florida) were declined studies with sampling intervals of 0, 
7, 14, 30, and 60 days after application. For all other trials, oranges 
were harvested at the earliest possible time for normal commercial 
harvest after a single application with PT807-HCl at the maximum 
recommended application rate, 6 gram active ingredient per acre (g/ai/
A). At some of the test sites (depending on the variety of oranges), 
the previous season's crop was present on the tree at application for 
these trials, oranges were collected 0 to 68 DAT. In all other trials, 
fruit were not present on the trees at applications and mature oranges 
were collected at normal harvest (197 to 359 DAT). Samples were 
analyzed for residues of PT807-HCl by HPLC with UV detection. Residues 
of PT807-HCl were nondetectable (less than 0.01ppm) in all treated and 
control samples.
    A processing study was conducted using oranges treated at 5x the 
maximum application rate in California. The harvested oranges were from 
the previous season's crop and were on the tree at the time of 
application. Therefore, the application represents the maximum possible 
residues. No detectable residues were measured in whole oranges, juice, 
or oil. Residues of PT807-HCl were detected in dried pulp at 0.015 and 
0.017 ppm (average 0.016 ppm). Correcting the measured residues for the 
exaggerated application rate, no detectable residues are likely in any 
processed product of oranges.
    Residues of PT807-HCl were determined to be stable in whole orange, 
fruit, oil, juice, and dried pulp stored frozen up to 113 days.

B. Toxicological Profile

    1. Acute toxicity. PT807-HCl exhibits low acute oral and dermal 
toxicity (Toxicity Category III, LD50 of 531 milligrams/
kilograms (mg/kg) and greater than 2,525 mg/kg, respectively) and 
inhalation toxicity (Toxicity Category IV, LC50 of greater 
than 2.08 milligrams per liter (mg/L). PT807-HCl is minimally 
irritating to the eyes, only slightly irritating to the skin (Toxicity 
Categories III and IV, respectively), and is not a dermal sensitizer. 
An acute neurotoxicity study in rats showed no specific evidence of 
neurotoxicity; transient non-specific signs of toxicity were observed 
in this study.
    2. Genotoxicity. The genotoxic potential of PT807-HCl has been 
assessed in an Ames Salmonella assay, a Chinese hampster ovary (CHO) 
hypoxanthine guanine phophoribosyl transferase (HGPRT) gene mutation 
assay, mouse micronucleus assay, an in vitro CHO assay for chromosomal 
aberrations, and an in vivo unscheduled DNA synthesis (UDS) assay. The 
in vitro chromosomal aberration assay was positive with and without 
metabolic activation; however, all of the remaining assays were 
negative, indicating very low genotoxic potential of PT807-HCl. The 
contribution of the positive in vitro chromosomal aberration assay is 
weakened by the negative finding in an in vivo study (mouse 
micronucleus) measuring a similar endpoint.
    3. Reproductive and developmental toxicity. Based on currently 
available data, PT807-HCl does not present a unique hazard to infants 
or children and there is no evidence that children are likely to be 
more sensitive to the toxic effects of PT807-HCl. A 2-generation 
reproductive toxicity study with PT807-HCl in rats showed developmental 
delays in pups associated with decreased weight gain at 2,000 and 4,000 
ppm, doses which were also toxic to the adult animals. PT807-HCl showed 
evidence of developmental effects in rats only at a severely maternally 
toxic dose level. No evidence of developmental toxicity was seen in 
rabbits.
    4. Subchronic toxicity. Studies have been conducted with PT807-HCl 
in mice, rats, and dogs. In dietary studies in rats and dogs, the most 
notable findings include decreased food consumptions and a consequent 
decrease in body weight gain (resulting primarily from poor 
palatability of the test material). Dogs also showed a trend toward 
anemia, and males showed arrested or delayed sexual maturation at the 
high dose (equivalent to approximately 222 mg/kg/day). Marked weight 
loss and decreased weight gain was observed at this dose, and this dose 
level is considered to have exceeded, a maximum tolerance dose (MTD). 
Rats dosed by gavage showed signs of neurotoxic effects (tremors in 
coordination changes in activity) at doses greater than or equal to 300 
mg/kg/day. These clinical signs disappeared 2-4 hours post-dosing. Rats 
receiving dietary administration of up to 5,000 ppm PT807-HCl for 13 
weeks did not exhibit any neurotoxic effects. In mice, treatment-
related decreased food consumption and body weight gain were seen in 
males at 7,000 ppm highest dose tested (HDT). No treatment-related 
toxicity was evident at dietary doses up to 3,500 ppm (479 and 635 mg/
kg/day for males and females respectively).
    5. Chronic toxicity. Ecolyst is not oncogenic when administered to 
rats at dietary concentration of up to 10,000 ppm for 24 months, and 
when administered to mice at doses up to 7,000 ppm (equivalent to 1,050 
mg/kg/day/(male) 1,250 mg/kg/day(female) for 18 months. In the rat, 
survival was increased in the treated animals. Systemic toxicity was 
evident from decreased body weight gains and increased incidences of 
hepatocellular hypertrophy and foci cellular alteration of hepatocytes 
in both rats and mice receiving dietary levels of 5,000 and 10,000 ppm 
of PT807-HCl. In the mouse, decreased body weights were noted in males 
at 7,000 ppm (1,050 mg/kg/day) HDT. No other treatment-related effects 
were noted. There were no treatment-related effects of dietary 
administration of PT807-HCl to dogs at doses up to 5,000 ppm 
(equivalent to 152 male/136 female mg/kg/day) except for a transient 
decrease in body weight and food consumption in the first few weeks of 
the study, and food consumption in the first few weeks of the study, 
primarily at the 5,000 ppm level, due to poor palatability of the test 
diet.
    6. Plant and animal metabolism. Valencia orange trees treated with 
approximately 470 mg 14C PT807-HCl in 400 ml spray solution/
tree. Samples were extracted and radioactivity was partitioned into 
organic, aqueous, and non-extractable fractions. Extractable, 
radioactivity was analyzed by HPLC to separate parent and metabolites. 
Unchanged parent PT807-HCl was detected in leaves (14.191 ppm), 
immature fruit (0.093), and mature fruit (0.386 ppm) from the previous 
season's crop that was harvested approximately 50 DAT, but not in 
mature fruit (less than 0.001 ppm) harvested 370 DAT. 14C 
PT807-HCl is extensively metabolized and readily eliminated by animals 
as indicated in a lactating goat study. A lactating goat was dosed with 
14C PT807-HCl once a day for 5 consecutive days at a target 
rate of 10 ppm in the diet. Approximately 100% of the total dose was 
recovered. Most of the radioactivity (approximately 100% of the total 
dose was recovered. Most of the radioactivity (approximately 93.8% of 
the administered dose) was excreted in the urine and approximately 5.6% 
of the dose was excreted in the feces. Tissues and milk contained less 
than 0.2% of the administered dose. Unchanged parent compound was not 
detected in any of the tissue. The rapid elimination of PT807-HCl and 
its metabolites coupled with the highly

[[Page 61339]]

exaggerated dose (approximately 3,600x the dietary burden) clearly 
indicates that no detectable residues of PT807-HCl will accumulate in 
milk and tissues.
    7. Metabolite toxicology. PT807-HCl was rapidly excreted from the 
rat following oral administration. Approximately 70-80% of the 
administered dose as excreted from the urine and 10-20% was excreted 
from the feces. Minimal radioactive residue remained in the tissue. A 
small quantity of the unchanged parent 14C PT807-HCl (M-14) 
was detected in urine and feces of the treated rats. The metabolism of 
PT807-HCl occurs through a variety of pathways, including oxidation, 
reduction, hydroxylation, deamination, N-dealkylation, and conjugation.
    8. Endocrine disruption. No evidence of endocrine disruption, 
including estrogenic or anti-estrogenic activity was present in the 
animal studies. The developmental toxicity studies showed no effects 
suggesting endocrine disruption (e.g., change in fetal sex ratios, or 
malformed or altered reproductive organ development). Maturational 
delays were seen in both sexes of pups in the reproductive toxicity 
study at high dose levels; these findings correlated with the decreased 
body weight gain at these doses. There were no effects on anogenital 
distance, estrous cyclicity of adult females or on reproduction and 
fertility. FO females at 2,000 and 4,000 ppm showed 
histopathological evidence of decreased cyclicity at weaning of their 
litters; no such findings were apparent in the F1 females 
which were necropsied 1-2 weeks after weaning. The findings in the 
FO females attributed to the combined stress of weaning and 
weight loss. As described below, high dose dogs given a dose exceeding 
an MTD and showing marked weight loss, showed evidence of maturational 
arrest of the germinal epithelium and absence of sperm in the 
epidydimides. All four high dose female dogs were in anestrus (as 
compared to two of the four control females). These findings are 
considered related to the marked weight loss and weight gain decrease 
in this study at the high dose level. No similar findings were seen in 
a chronic dog study at dose levels up to 5,000 ppm.

C. Aggregate Exposure

    1. Dietary exposure--i. Food. There are no anticipated dietary 
exposures to PT807-HCl outside of those requested in this tolerance 
petition. The chronic dietary exposure from the consumption of oranges 
and its processed products, treated with PT807-HCl is very low. The 
exposure is only 0.5% of the reference dose (RfD) (0.000063 mg/kg/day) 
for the most high exposed population, children 1 to 6 years old. The 
dietary exposure is only 0.17% of the reference dose (RfD) (0.000021 
mg/kg/day) for the U.S. population.
    ii. Drinking water. There are no registered uses of PT807-HCl at 
this time; thus, the only potential source of residues in drinking 
water is this requested use on oranges. Available data suggest that 
PT807-HCl will not be a ground water contaminant because it does not 
exhibit the mobility or persistence characteristics of pesticides that 
are normally found in ground water. As a worst-case screen, GMJA 
specialties used EPA's GENEEC model to estimate drinking water risk, 
although GENEEC is an inappropriate model for the purpose because it 
was designed to estimate surface water runoff for ecological risk 
assessment purposes and greatly overestimates likely residues in 
surface water. Nevertheless, it is the model EPA currently is using to 
estimate drinking water exposure in order to assess aggregate risk.
    Based on the results of the generic expected environmental 
concentration (GENEEC) model, the 56-day chronic EEC (calculated from 
the lowest Koc value measured for PT807-HCl) is 0.315 
g/L. Using the standard drinking water consumption scenarios 
of 2 liters per day for a 70 kg adult and 1 liter per day for a 10 kg 
child, the calculated consumption of PT807-HCl in drinking water is 
0.009 g/kg/day for an adult and 0.032 g/kg/day for a 
child. These consumption values correspond to 0.07% of the RfD for 
adults and 0.26% of the RfD for children ages 1 to 6 years old. As 
discussed above, drinking water concentrations calculated by the GENEEC 
procedure represent very conservative screening level assessments of 
drinking water exposure.
    2. Non-dietary exposure. There are currently no registered uses for 
PT807-HCl, and therefore, there is no anticipated non-occupational 
exposure to the chemical.

D. Cumulative Effects

    GMJA Specialities/Tropicana Products, Inc. is not aware of any 
currently registered products that are structurally similar to PT-807-
HCl or that would be likely to share a common mechanism of action. 
Therefore, no cummulative exposures are considered in the PT807-HCl 
dietary risk assessment.

E. Safety Determination

    1. U.S. population. The RfD was 0.0125 mg/kg/day based on a no 
observed adverse effect level (NOAEL) of 12.5 mg/kg/day and an 
uncertainty factor of 1,000. Although we do not believe there were any 
findings of concern in the toxicology studies that warrant a 1,000-fold 
safety factor, we used it as a very consecutive, worst-case screening 
value. NOAEL was obtained from the results of the rat reproduction 
study that showed developmental delay and decreased weight gain in pups 
at levels that were also toxic to adult rats.
    2. Infants and children. The chronic dietary exposure from the 
consumption of oranges and its processed products treated with PT807-
HCl is very low. The exposure is only 0.5% of the RfD (0.000063 mg/kg/
day) for the most highly exposed sub-population, children 1 to 6 years 
old. The dietary exposure is only 0.17% of the RfD (0.000021 mg/kg/day) 
for the U.S. population.

F. International Tolerance

    There are not Codex Maximum Residue Levels (MRLs) established for 
PT807-HCl.

2. Interregional Project Number 4

PP 9E3810, 9E3813, 0E3912, 9E5075, and 9E6061

    EPA has received pesticide petitions (9E3810, 9E3813, 0E3912, 
9E5075, and 9E6061) from the Interregional Project Number 4, Center for 
Minor Crop, Pest Management, Technology Centre of New Jersey, Rutgers 
University, 681 U.S. Highway No. 1 South, North Brunswick, NJ 08902-
3390 proposing, pursuant to section 408(d) of the Federal Food, Drug, 
and Cosmetic Act (FFDCA), 21 U.S.C. 346a(d), to amend 40 CFR part 180 
by establishing tolerances for residues of esfenvalerate,(S)-cyano-(3-
phenoxyphenyl)methyl(S)-4-chloro-alpha-(1-methylethyl) benzeneacetate 
in or on the raw agricultural commodities (RAC) as follows:
    1. PP 9E3810 proposes the establishment of a tolerance for bok choy 
at 1.0 ppm. Registration will be limited to areas east of the 
Mississippi River based on the geographical representation of the 
residue data submitted to EPA.
    2. PP 9E3813 proposes the establishment of a tolerance for sweet 
potatoes at 0.05 ppm.
    3. PP 0E3912 proposes the establishment of a tolerance for cardoon 
at 1.0 ppm. Registration will be limited to California based on the 
geographical representation of the residue data submitted to EPA.
    4. PP 9E5075 proposes the establishment of a tolerance for canola 
seed at 0.3 ppm.
    5. PP 9E6061 proposes the establishment of a tolerance for brussels

[[Page 61340]]

sprout at 0.2 ppm for regional registration only.
    Fenvalerate is a racemic mixture of four isomers (S,S; R,S; S,R; 
and R,R). Technical Asana (esfenvalerate) is enriched in the 
insecticidally active S,S-isomer (84%). Tolerance expressions are 
proposed for esfenvalerate based on the sum of all isomers.
    EPA has determined that the petitions contain data or information 
regarding the elements set forth in section 408(d)(2) of the FFDCA; 
however, EPA has not fully evaluated the sufficiency of the submitted 
data at this time or whether the data supports granting of the 
petitions. Additional data may be needed before EPA rules on the 
petitions. This notice includes a summary of the petitions prepared by 
E.I. du Pont Nemours and Company, Agricultural Products, Wilmington, 
Delaware 19898.

A. Residue Chemistry

    1. Plant metabolism. The metabolism and chemical nature of residues 
of esfenvalerate in plants is adequately understood. The fate of 
fenvalerate has been extensively studied using radioactive tracers in 
plant metabolism/nature of the residue studies previously submitted to 
the Agency. These studies have demonstrated that the parent compound is 
the only residue of toxicological significance. The registrant has 
concluded that the qualitative nature of the residue is the same for 
both fenvalerate and esfenvalerate.
    2. Analytical method. There is a practical analytical method 
utilizing gas chromatography with electron capture detection available 
for enforcement with a limit of detection (LOD) that allows monitoring 
food with residues at or above tolerance levels. The LOD for the 
updated method is the same as that of the current Pesticide Analytical 
Manual, Volume II (PAM II), which is 0.01 ppm.
    3. Magnitude of residues. The following tolerances have been 
proposed: cardoon at 1.0 ppm, bok choy at 1.0 ppm, sweet potatoes at 
0.05 ppm, canola at 0.3 ppm, and brussels sprout at 0.2 ppm. Magnitude 
of residue studies support the proposed tolerances.

B. Toxicological Profile

    1. Acute toxicity. A battery of acute toxicity studies places 
technical esfenvalerate in Toxicity Category II (Warning) for acute 
oral toxicity rat lethal dose (LD50 87.2 mg/kg), Category 
III (Caution) for acute dermal (rabbit LD50 > 2,000 mg/kg) 
and primary eye irritation (mild irritation in rabbits), and Category 
IV (Caution) for primary skin irritation (minimal skin irritation in 
rabbits that reversed within 72 hours after treatment). Acute 
inhalation on technical grade active ingredient (a.i.) was waived due 
to negligible vapor pressure. A dermal sensitization test on 
esfenvalerate in guinea pigs showed no sensitization.
    2. Genotoxicity. Esfenvalerate was not mutagenic in reverse 
mutation assays in S. typhimurium and E. Coli and did not induce 
mutations Chinese hamster V79 cells or chromosome aberrations in 
Chinese hamster ovary (CHO) cells. Esfenvalerate did not induce 
micronuclei in bone marrow of mice given up to 150 mg/kg 
intraperitoneally. Esfenvalerate did not induce unscheduled DNA 
synthesis (UDS) in HeLa cells. Other genetic toxicology studies 
submitted on racemic fenvalerate indicate that the mixture containing 
equal parts of the four stereoisomers is not mutagenic in bacteria. The 
racemic mixture was also negative in a mouse host mediated assay and in 
a mouse dominant lethal assay.
    3. Reproductive and developmental toxicity. Esfenvalerate was 
administered to pregnant female rats by gavage in a pilot developmental 
study at doses of 0, 1, 2, 3, 4, 5, or 20 mg/kg/day and a main study at 
0, 2.5, 5, 10, or 20 mg/kg/day. Maternal clinical signs (abnormal gait 
and mobility) were observed at 2.5 mg/kg/day and above. A no observed 
adverse effect level (NOAEL) of 2 mg/kg/day was established for the 
pilot study. The developmental NOAEL was > 20 mg/kg/day.
    Esfenvalerate was administered by gavage to pregnant female rabbits 
in a pilot developmental study at doses of 0, 2, 3, 4, 4.5, 5, or 20 
mg/kg/day and a main study at doses of 0, 3, 10, or 20 mg/kg/day. 
Maternal clinical signs (excessive grooming) were observed at 3 mg/kg/
day and above. A maternal NOAEL of 2 mg/kg/day was established on the 
pilot study. The developmental NOAEL was > 20 mg/kg/day.
    A 2-generation feeding study with esfenvalerate was conducted in 
the rat at dietary levels of 0, 75, 100, or 300 ppm. Skin lesions and 
minimal (non-biologically significant) parental body weight effects 
occurred at 75 ppm. The NOAEL for reproductive toxicity was 75 ppm 
(4.2-7.5 mg/kg/day) based on decreased pup weights at 100 ppm.
    4. Subchronic toxicity. Two 90-day feeding studies with 
esfenvalerate were conducted in rats, one at 50, 150, 300, or 500 ppm 
esfenvalerate, and a second at 0, 75, 100, 125, or 300 ppm to provide 
additional dose levels. The NOAEL was 125 ppm (6.3 mg/kg/day) based on 
clinical signs (jerky leg movements) observed at 150 ppm (7.5 mg/kg/
day) and above.
    A 90-day feeding study in mice was conducted at 0, 50, 150, or 500 
ppm esfenvalerate with a NOAEL of 150 ppm (30.5 mg/kg) based on 
clinical signs of toxicity at 500 ppm (106 mg/kg).
    A 21-day dermal study in rabbits with fenvalerate conducted at 100, 
300, or 1,000 mg/kg/day with a NOAEL of 1,000 mg/kg/day.
    5. Chronic toxicity. In a 1-year study, dogs were fed 0, 25, 50, or 
200 ppm esfenvalerate with no treatment related effects at any dietary 
level. The NOAEL was 200 ppm (5 mg/kg/day). An effect level for dietary 
administration of esfenvalerate for dogs of 300 ppm had been 
established earlier in a 3-week pilot study used to select dose levels 
for the chronic dog study.
    One chronic study with esfenvalerate and three chronic studies with 
fenvalerate have been conducted in mice.
    In an 18-month study, mice were fed 0, 35, 150, or 350 ppm 
esfenvalerate. Mice fed 350 ppm were sacrificed within the first 2 
months of the study after excessive self-trauma related to skin 
stimulation and data collected were not used in the evaluation of the 
carcinogenic potential of esfenvalerate. The NOAEL was 35 ppm (4.29 and 
5.75 mg/kg/day for males and females, respectively) based on lower body 
weight and body weight gain at 150 ppm. Esfenvalerate did not produce 
carcinogenicity.
    In a 2-year feeding study, mice were administered 0, 10, 50, 250, 
or 1,250 ppm fenvalerate in the diet. The NOAEL was 10 ppm (1.5 mg/kg/
day) based on granulomatous changes (related to fenvalerate only, not 
esfenvalerate) at 50 ppm (7.5 mg/kg/day). Fenvalerate did not produce 
carcinogenicity.
    In an 18-month feeding study, mice were fed 0, 100, 300, 1,000, or 
3,000 ppm fenvalerate in the diet. The NOAEL is 100 ppm (15.0 mg/kg/
day) based on fenvalerate-related microgranulomatous changes at 300 ppm 
(45 mg/kg/day). No compound related carcinogenicity occurred.
    Mice were fed 0, 10, 30, 100, or 300 ppm fenvalerate for 20 months. 
The NOAEL was 30 ppm (3.5 mg/kg/day) based on red blood cell effects 
and granulomatous changes at 100 ppm (15 mg/kg/day). Fenvalerate was 
not carcinogenic at any concentration tested.
    In a 2-year study, rats were fed 1, 5, 25, or 250 ppm fenvalerate. 
A 1,000 ppm group was added in a supplemental study to establish an 
effect level. The NOAEL was 250 ppm (12.5 mg/kg/day). At 1,000 ppm (50 
mg/kg/day), hind limb weakness, lower body weight, and higher organ-to-
body

[[Page 61341]]

weight ratios were observed. Fenvalerate was not carcinogenic at any 
concentration.
    EPA has classified esfenvalerate in Group E - evidence of 
noncarcinogenicity for humans.
    6. Animal metabolism. After oral dosing with fenvalerate, the 
majority of the administered radioactivity was eliminated in the 
initial 24 hours. The metabolic pathway involved cleavage of the ester 
linkage followed by hydroxylation, oxidation, and conjugation of the 
acid and alcohol moieties.
    7. Metabolite toxicology. The parent molecule is the only moiety of 
toxicological significance appropriate for regulation in plant and 
animal commodities.
    8. Endocrine disruption. Estrogenic effects have not been observed 
in any studies conducted on fenvalerate or esfenvalerate. In subchronic 
or chronic studies there were no lesions in reproductive systems of 
males or females. In the recent reproduction study with esfenvalerate, 
full histopathological examination of the pituitary and the 
reproductive systems of males and females was conducted. There were no 
compound-related gross or histopathological effects. There were also no 
compound-related changes in any measures of reproductive performance 
including mating, fertility, or gestation indices or gestation length 
in either generation. There have been no effects on offspring in 
developmental toxicity studies.

C. Aggregate Exposure

    1. Dietary exposure. Tolerances have been established for the 
residues of fenvalerate/esfenvalerate, in or on a variety of 
agricultural commodities. For purposes of assessing dietary exposure, 
chronic and acute dietary assessments have been conducted using all 
existing and pending tolerances for esfenvalerate. EPA recently 
reviewed the existing toxicology data base for esfenvalerate and 
selected the following toxicological endpoints. For acute toxicity, EPA 
established a NOAEL of 2.0 mg/kg/day from rat and rabbit developmental 
studies based on maternal clinical signs at higher concentrations. A 
margin of exposure (MOE) of 100 was required for chronic toxicity. EPA 
established the chronic population adjusted dose (cPAD) for 
esfenvalerate at 0.02 mg/kg/day. This cPAD was also based on the NOAEL 
of 2.0 mg/kg/day in the rat developmental study with an uncertainty 
factor of 100. Esfenvalerate is classified as a Group E carcinogen - no 
evidence of carcinogenicity in either rats or mice. Therefore, a 
carcinogenicity risk analysis for humans is not required.
    i. Food. A chronic dietary exposure assessment was conducted using 
Novigen's Dietary Exposure Estimate Model (DEEM). Anticipated residues 
and adjustment for percent crop treated were used in the chronic 
dietary risk assessment. The percentages of the cPAD utilized by the 
most sensitive sub-population, children 1-6 years old, was 4.6% based 
on a daily dietary exposure of 0.000911 mg/kg/day. Chronic exposure for 
the overall U.S. population was 1.9% of the cPAD based on a dietary 
exposure of 0.000376 mg/kg/day. Results of the chronic dietary risk 
assessment adding cardoon, bok choy, sweet potatoes, canola, and 
brussels sprout had no significant effect on chronic dietary exposure 
when compared to the previous chronic dietary risk assessment. EPA has 
no concern for exposures below 100% of the cPAD because the cPAD 
represents the level at or below which daily aggregate dietary exposure 
over a lifetime will not pose appreciable risks to human health.
    Potential acute exposures from food commodities were estimated 
using a Tier 3 (Monte Carlo) Analysis and appropriate processing 
factors for processed food and distribution analysis. This analysis 
used field trial data to estimate exposure, and federal and market 
survey information to derive the percent of crop treated. Regional 
consumption information was taken into account. The MOEs for the most 
sensitive sub-population (children 1-6 years old) were 202 and 103 at 
the 99th, and 99.9th percentile of exposure, 
respectively, based on daily exposures of 0.009914 and 0.019390 mg/kg/
day. The MOEs for the general population are 355 and 171 at the 
99th and 99.9th percentile of exposure, 
respectively, based on daily exposure estimates of 0.005638 and 
0.011710 mg/kg/day. The registrant has stated there is no cause for 
concern if total acute exposure calculated for the 99.9th 
percentile yields an MOE of 100 or larger. This acute dietary exposure 
estimate is considered conservative and EPA considered the MOEs 
adequate in a recent Final Rule (62 FR 63019) (FRL 5754-6) November 26, 
1997.
    ii. Drinking water. Esfenvalerate is immobile in soil and will not 
leach into ground water. Due to the insolubility and lipophilic nature 
of esfenvalerate, any residues in surface water will rapidly and 
tightly bind to soil particles and remain with sediment, therefore, not 
contributing to potential dietary exposure from drinking water.
    A screening evaluation of leaching potential of a typical 
pyrethroid was conducted using EPA's Pesticide Root Zone Model (PRZM). 
Based on this screening assessment, the potential concentrations of a 
pyrethroid in ground water at depths of 1 and 2 meters are essentially 
zero (much less than 0.001 parts per billion) (ppb).
    Surface water concentrations for pyrethroids were estimated using 
PRZM3 and Exposure Analysis Modeling System (EXAMS) using Standard EPA 
cotton runoff and Mississippi pond scenarios. The maximum concentration 
predicted in the simulated pond was 0.052 ppb. Concentrations in actual 
drinking water would be much lower than the levels predicted in the 
hypothetical, small, stagnant farm pond model since drinking water 
derived from surface water would be treated before consumption.
    Chronic drinking water exposure was estimated to be 0.000001 mg/kg/
day for both the United States general population and for non-nursing 
infants. Less than 0.1% of the cPAD was occupied by both population 
groups.
    Using these values, the contribution of water to the acute dietary 
risk estimate was estimated for the U.S. population to be 0.000019 mg/
kg/day at the 99th percentile and 0.000039 mg/kg/day at the 
99.9th percentile resulting in MOEs of 105,874 and 51,757, 
respectively. For the most sensitive subpopulation, non-nursing infants 
less than 1-year old, the exposure is 0.000050 mg/kg/day and 0.000074 
mg/kg/day at the 99th and 99.9th percentile, 
respectively, resulting in MOEs of 39,652 and 27,042, respectively.
    Therefore, the registrant concludes that there is reasonable 
certainty of no harm from drinking water.
    2. Non-dietary exposure. Esfenvalerate is registered for non-crop 
uses including spray treatments in and around commercial and 
residential areas, treatments for control of ectoparasites on pets, 
home care products including foggers, pressurized sprays, crack and 
crevice treatments, lawn and garden sprays, and pet and pet bedding 
sprays. For the non-agricultural products, the very low amounts of a.i. 
they contain, combined with the low vapor pressure (1.5 x 
10-9 mm Mercury at 25 deg.C.) and low dermal penetration, 
would result in minimal inhalation and dermal exposure.
    To assess risk from (nonfood) short- and intermediate-term 
exposure, the registrant selected a toxicological endpoint of 2.0 mg/
kg/day, the NOAEL from the rat and rabbit developmental studies. For 
dermal penetration/

[[Page 61342]]

absorption, the registrant selected 25% dermal absorption based on the 
weight-of-evidence available for structurally related pyrethroids. For 
inhalation exposure, the registrant used the oral NOAEL of 2.0 mg/kg/
day and assumed 100% absorption by inhalation.
    Individual non-dietary risk exposure analyses were conducted using 
a flea infestation scenario that included pet spray, carpet and room 
treatment, and lawn care, respectively. The total potential short- and 
intermediate-term aggregate non-dietary exposure including lawn, 
carpet, and pet uses are: 0.000023 mg/kg/day for adults, 0.00129 mg/kg/
day for children 1-6 years old and 0.00138 mg/kg/day for infants less 
than 1-year old.
    EPA concluded November 26, 1997 (62 FR 63019)(FRL 5754-6) that the 
potential non-dietary exposure for esfenvalerate are associated with 
substantial margins of safety.

D. Cumulative Effects

    Section 408(b)(2)(D)(v) requires that, when considering whether to 
establish, modify, or revoke a tolerance, the Agency considers 
``available information'' concerning the cumulative effects of a 
particular pesticide's residues and ``other substances that have a 
common mechanism of toxicity.'' In a recent Final Rule on esfenvalerate 
(62 FR 63019), EPA concluded, ``Available information'' in this context 
might include not only toxicity, chemistry, and exposure data, but also 
scientific policies and methodologies for understanding common 
mechanism 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 mechanisms 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 less concerning common mechanism issues to most risk 
assessments, there are pesticides as to which the common mechanism 
issues can be resolved. These pesticides include those 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 a 
common mechanism of activity will be assumed). Although esfenvalerate 
is similar to other members of the synthetic pyrethroid class of 
insecticides, EPA does not have, at this time, available data to 
determine whether esfenvalerate has a common method 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, 
esfenvalerate does not appear to produce a toxic metabolite produced by 
other substances for the purposes of this tolerance action. Therefore 
for the purpose of this tolerance action, the registrant has not 
assumed that esfenvalerate has a common mechanism of toxicity with 
other substances.

E. Safety Determination

    Both the chronic and acute toxicological endpoints are derived from 
maternal NOAELs of 2.0 mg/kg/day in developmental studies in rats and 
rabbits. There were no fetal effects. In addition, no other studies 
conducted with fenvalerate or esfenvalerate indicate that immature 
animals are more sensitive than adults. Therefore, the registrant 
concludes that the safety factor used for protection of adults is fully 
appropriate for the protection of infants and children. No additional 
safety factor is necessary as described below.
    1. U.S. population. A chronic dietary exposure assessment using 
anticipated residues, monitoring information, and percent crop treated 
indicated the percentage of the cPAD utilized by the general population 
to be 1.9%. There is generally no concern for exposures below 100% of 
the cPAD because the cPAD represents the level at or below which daily 
aggregate dietary exposure over a lifetime will not pose appreciable 
risks to human health.
    For acute exposure, a MOE greater than 100 is considered adequate. 
A Tier 3 acute dietary exposure assessment found the general population 
to have MOEs of 355 and 171 at the 99th and 
99.9th percentile of exposure, respectively. These values 
were generated using actual field trial residues and market share data 
for percentage of crop treated. These results depict an accurate 
exposure pattern at an exaggerated daily dietary exposure rate.
    Short- and intermediate-term aggregate exposure risk from chronic 
dietary food and water plus indoor and outdoor residential exposure for 
the U.S. population is an exposure of 0.0082 mg/kg/day with an MOE of 
244. Therefore, the registrant concludes that there is a reasonable 
certainty that no harm will result from chronic dietary, acute dietary, 
non-dietary, or aggregate exposure to esfenvalerate residues.
    2. Infants and children. FFDCA section 408 provides that EPA shall 
apply an additional tenfold margin of safety for infants and children 
unless EPA determines that a different margin of safety will be safe 
for infants and children. EPA has stated that reliable data supports 
the use of the standard MOE and uncertainty factor (100 for combined 
interspecies and intraspecies 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. In a recent final rule (62 FR 63019), EPA concluded that 
reliable data support use of the standard 100-fold uncertainty factor 
for esfenvalerate, and that an additional uncertainty factor is not 
needed to protect the safety of infants and children. This decision was 
based on no evidence of developmental toxicity at doses up to 20 mg/kg/
day (10 times the maternal NOAEL) in prenatal developmental toxicity 
studies in both rats and rabbits; offspring toxicity only at dietary 
levels which were also found to be toxic to parental animals in the 2-
generation reproduction study; and no evidence of additional 
sensitivity to young rats or rabbits following prenatal or postnatal 
exposure to esfenvalerate.
    A chronic dietary exposure assessment found the percentages of the 
cPAD utilized by the most sensitive sub-population to be 4.6% for 
children 1-6 years old based on a dietary exposure of 0.000911 mg/kg/
day. The percent cPAD for nursing and non-nursing infants was 1.1% and 
2.7%, respectively. The registrant has no cause for concern if cPADs 
are below 100%.

[[Page 61343]]

    The most sensitive sub-population, children 1-6 years old, had 
acute dietary MOEs of 202 and 103 at the 99th and 
99.9th percentile of exposure, respectively. Nursing infants 
had MOEs of 198 and 146 at the 99th and 99.9th 
percentile of exposure, respectively. Non-nursing infants had MOEs of 
300 and 156 at the 99th and 99.9th percentile of 
exposure, respectively. The registrant has no cause for concern if 
total acute exposure calculated for the 99.9th percentile 
yields a MOE of 100 or larger.
    The potential short- or intermediate-term aggregate exposure of 
esfenvalerate from chronic dietary food and water plus indoor and 
outdoor residential exposure to children (1-6 years old) is 0.0113 mg/
kg/day with an MOE of 177. For infants (less than 1-year old) the 
exposure is 0.0098 mg/kg/day with an MOE of 204. Thus, the registrant 
concludes that there is a reasonable certainty that no harm will result 
to infants and children from aggregate exposure to esfenvalerate 
residues (62 FR 63019).

F. International Tolerances

    There are no Codex MRL values established for fenvalerate on 
cardoon, bok choy, sweet potatoes, canola, brussels sprout, and 
rapeseed; therefore, no harmonization is required.

[FR Doc. 99-29184 Filed 11-9-99; 8:45 am]
BILLING CODE 6560-50-F