N,N-diethyl-2-(4-methylbenzyloxy)ethylamine hydrochloride (PT 807-HCL) Pesticide Petition Filing 11/99
[Federal Register: November 10, 1999 (Volume 64, Number 217)]
>From the Federal Register Online via GPO Access [wais.access.gpo.gov]
ENVIRONMENTAL PROTECTION AGENCY
Notice of Filing Pesticide Petitions to Establish a Tolerance for
Certain Pesticide Chemicals in or on Food
AGENCY: Environmental Protection Agency (EPA).
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
FOR FURTHER INFORMATION CONTACT: The product manager listed in the
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
Shaja Brothers..................... Rm. 237, CM #2, 703-308- Do. PP 9E3810, 9E3813,
3194, e-mail: OE3912, 9E5075, and
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:
Categories NAICS potentially
Industry 111 Crop production
112 Animal production
311 Food 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
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
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@example.com ,'' 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
E. What Should I Consider as I Prepare My Comments for EPA?
You may find the following suggestions helpful for preparing your
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
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
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
Dated: November 1, 1999.
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
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
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
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
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
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
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
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
[FR Doc. 99-29184 Filed 11-9-99; 8:45 am]
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