[Federal Register: June 30, 2005 (Volume 70, Number 125)]
[Notices]
[Page 37847-37851]
From the Federal Register Online via GPO Access [wais.access.gpo.gov]
[DOCID:fr30jn05-92]
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ENVIRONMENTAL PROTECTION AGENCY
[OPP-2005-0141; FRL-7719-4]
2-amino-4,5-dihydro-6-methyl-4-propyl-s-triazolo(1,5-
alpha)pyrimidin-5-one (PP796); Notice of Filing a Pesticide Petition to
Amend the Existing Tolerance Exemption
AGENCY: Environmental Protection Agency (EPA).
ACTION: Notice.
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SUMMARY: This notice announces the initial filing of a pesticide
petition by Syngenta Crop Protection, Inc. proposing to amend the
established exemption from the requirement of a tolerance under 40 CFR
180.1065 for 2-amino-4,5-dihydro-6-methyl-4-propyl-s-triazolo(1,5-
alpha)pyrimidin-5-one, which is also known as PP796, by increasing the
amount that can be used to not more than 0.3 percent in formulation of
paraquat dichloride.
DATES: Comments, identified by docket identification (ID) number OPP-
2005-0141, must be received on or before August 1, 2005.
ADDRESSES: Comments may be submitted electronically, by mail, or
through hand delivery/courier. Follow the detailed instructions as
provided in Unit I. of the SUPPLEMENTARY INFORMATION.
FOR FURTHER INFORMATION CONTACT: Karen Angulo, Registration Division
(7505C), Office of Pesticide Programs, Environmental Protection Agency,
1200 Pennsylvania Ave., NW., Washington, DC 20460-0001; telephone
number: (703) 306-0404; e-mail address: angulo.karen@epa.gov.
SUPPLEMENTARY INFORMATION:
I. General Information
A. Does this Action Apply to Me?
You may be potentially affected by this action if you an
agricultural producer, food manufacturer, or pesticide manufacturer.
Potentially affected entities may include, but are not limited to:
Crop production (NAICS 111)
Animal production (NAICS 112)
Food manufacturing (NAICS 311)
Pesticide manufacturing (NAICS 32532)
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 this unit could also be
affected. The North American Industrial Classification System (NAICS)
codes have been provided to assist you and others in determining
whether this action might apply to certain entities. If you have any
questions regarding the applicability of this action to a particular
entity, consult the person listed under FOR FURTHER INFORMATION
CONTACT.
B. How Can I Get Copies of this Document and Other Related Information?
1. Docket. EPA has established an official public docket for this
action under docket ID number OPP-2005-0141. The official public docket
consists of the documents specifically referenced in this action, any
public comments received, and other information related to this action.
Although a part of the official docket, the public docket does not
include Confidential Business Information (CBI) or other information
whose disclosure is restricted by statute. The official public docket
is the collection of materials that is available for public viewing at
the Public Information and Records Integrity Branch (PIRIB), Rm. 119,
Crystal Mall 2, 1801 S. Bell St., Arlington, VA. This docket
facility is open from 8:30 a.m. to 4 p.m., Monday through Friday,
excluding legal holidays. The docket telephone number is (703) 305-
5805.
2. Electronic access. You may access this Federal Register document
electronically through the EPA Internet under the ``Federal Register''
listings at http://www.epa.gov/fedrgstr/.
An electronic version of the public docket is available through
EPA's electronic public docket and comment system, EPA Dockets. You may
use EPA Dockets at http://www.epa.gov/edocket/ to submit or view public
comments, access the index listing of the contents of the official
public docket, and to access those documents in the public docket that
are available electronically. Although not all docket materials may be
available electronically, you may still access any of the publicly
available docket materials through the docket facility identified in
Unit I.B.1. Once in the system, select ``search,'' then key in the
appropriate docket ID number.
Certain types of information will not be placed in the EPA Dockets.
Information claimed as CBI and other information whose disclosure is
restricted by statute, which is not included in the official public
docket, will not be available for public viewing in EPA's electronic
public docket. EPA's policy is that copyrighted material will not be
placed in EPA's electronic public docket but will be available only in
printed, paper form in the official public docket. To the extent
feasible, publicly available docket materials will be made
[[Page 37848]]
available in EPA's electronic public docket. When a document is
selected from the index list in EPA Dockets, the system will identify
whether the document is available for viewing in EPA's electronic
public docket. Although not all docket materials may be available
electronically, you may still access any of the publicly available
docket materials through the docket facility identified in Unit I.B.
EPA intends to work towards providing electronic access to all of the
publicly available docket materials through EPA's electronic public
docket.
For public commenters, it is important to note that EPA's policy is
that public comments, whether submitted electronically or in paper,
will be made available for public viewing in EPA's electronic public
docket as EPA receives them and without change, unless the comment
contains copyrighted material, CBI, or other information whose
disclosure is restricted by statute. When EPA identifies a comment
containing copyrighted material, EPA will provide a reference to that
material in the version of the comment that is placed in EPA's
electronic public docket. The entire printed comment, including the
copyrighted material, will be available in the public docket.
Public comments submitted on computer disks that are mailed or
delivered to the docket will be transferred to EPA's electronic public
docket. Public comments that are mailed or delivered to the docket will
be scanned and placed in EPA's electronic public docket. Where
practical, physical objects will be photographed, and the photograph
will be placed in EPA's electronic public docket along with a brief
description written by the docket staff.
C. How and To Whom Do I Submit Comments?
You may submit comments electronically, by mail, or through hand
delivery/courier. To ensure proper receipt by EPA, identify the
appropriate docket ID number in the subject line on the first page of
your comment. Please ensure that your comments are submitted within the
specified comment period. Comments received after the close of the
comment period will be marked ``late.'' EPA is not required to consider
these late comments. If you wish to submit CBI or information that is
otherwise protected by statute, please follow the instructions in Unit
I.D. Do not use EPA Dockets or e-mail to submit CBI or information
protected by statute.
1. Electronically. If you submit an electronic comment as
prescribed in this unit, EPA recommends that you include your name,
mailing address, and an e-mail address or other contact information in
the body of your comment. Also include this contact information on the
outside of any disk or CD ROM you submit, and in any cover letter
accompanying the disk or CD ROM. This ensures that you can be
identified as the submitter of the comment and allows EPA to contact
you in case EPA cannot read your comment due to technical difficulties
or needs further information on the substance of your comment. EPA's
policy is that EPA will not edit your comment, and any identifying or
contact information provided in the body of a comment will be included
as part of the comment that is placed in the official public docket,
and made available in EPA's electronic public docket. If EPA cannot
read your comment due to technical difficulties and cannot contact you
for clarification, EPA may not be able to consider your comment.
i. EPA Dockets. Your use of EPA's electronic public docket to
submit comments to EPA electronically is EPA's preferred method for
receiving comments. Go directly to EPA Dockets at http://www.epa.gov/edocket/
, and follow the online instructions for submitting comments.
Once in the system, select ``search,'' and then key in docket ID number
OPP-2005-0141. The system is an ``anonymous access'' system, which
means EPA will not know your identity, e-mail address, or other contact
information unless you provide it in the body of your comment.
ii. E-mail. Comments may be sent by e-mail to opp-docket@epa.gov,
Attention: Docket ID Number OPP-2005-0141. In contrast to EPA's
electronic public docket, EPA's e-mail system is not an ``anonymous
access'' system. If you send an e-mail comment directly to the docket
without going through EPA's electronic public docket, EPA's e-mail
system automatically captures your e-mail address. E-mail addresses
that are automatically captured by EPA's e-mail system are included as
part of the comment that is placed in the official public docket, and
made available in EPA's electronic public docket.
iii. Disk or CD ROM. You may submit comments on a disk or CD ROM
that you mail to the mailing address identified in Unit I.C.2. These
electronic submissions will be accepted in WordPerfect or ASCII file
format. Avoid the use of special characters and any form of encryption.
2. By mail. Send your comments to: Public Information and Records
Integrity Branch (PIRIB) (7502C), Office of Pesticide Programs (OPP),
Environmental Protection Agency, 1200 Pennsylvania Ave., NW.,
Washington, DC 20460-0001, Attention: Docket ID Number OPP-2005-0141.
3. By hand delivery or courier. Deliver your comments to: Public
Information and Records Integrity Branch (PIRIB), Office of Pesticide
Programs (OPP), Environmental Protection Agency, Rm. 119, Crystal Mall
2, 1801 S. Bell St., Arlington, VA, Attention: Docket ID
Number OPP-2005-0141. Such deliveries are only accepted during the
docket's normal hours of operation as identified in Unit I.B.1.
D. How Should I Submit CBI to the Agency?
Do not submit information that you consider to be CBI
electronically through EPA's electronic public docket or by e-mail. You
may claim information that you submit to EPA as CBI by marking any part
or all of that information as CBI (if you submit CBI on disk or CD ROM,
mark the outside of the disk or CD ROM as CBI and then identify
electronically within the disk or CD ROM the specific information that
is 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 docket and EPA's electronic public docket. If you submit
the copy that does not contain CBI on disk or CD ROM, mark the outside
of the disk or CD ROM clearly that it does not contain CBI. Information
not marked as CBI will be included in the public docket and EPA's
electronic public docket without prior notice. If you have any
questions about CBI or the procedures for claiming CBI, please consult
the person listed under FOR FURTHER INFORMATION CONTACT.
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.
[[Page 37849]]
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
ID number assignedto this action in the subject line on the first page
of your response. You may also provide thename, date, and Federal
Register citation.
II. What Action is the Agency Taking?
EPA has received a pesticide petition as follows proposing the
establishment and/or amendment of regulations for residues of a certain
pesticide chemical in or on various food commodities under section 408
of the Federal Food, Drug, and Cosmetic Act (FFDCA), 21 U.S.C. 346a.
EPA has determined that this petition contains data or information
regarding the elements set forth in FFDCA section 408(d)(2); however,
EPA has not fully evaluated the sufficiency of the submitted data at
this time or whether the data support 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: June 22, 2005.
Lois Rossi,
Director, Registration Division, Office of Pesticide Programs.
Summary of Petition
The petitioner summary of the pesticide petition is printed below
as required by FFDCA section 408(d)(3). The summary of the petition was
prepared by the petitioner and represents the view of the petitioner.
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.
Syngenta Crop Protection, Inc.
PP 5E6929
EPA has received a pesticide petition (5E6929) from Syngenta Crop
Protection, P.O Box 18300, Greensboro, NC 27419-8300 proposing,
pursuant to section 408 of the Federal Food, Drug, and Cosmetic Act
(FFDCA), 21 U.S.C. 346a, to amend the established exemption from the
requirement of a tolerance under 40 CFR 180.1065 for 2-amino-4,5-
dihydro-6-methyl-4-propyl-s-triazolo(1,5-alpha)pyrimidin-5-one (CAS No.
27277-00-5). 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. 2-amino-4,5-dihydro-6-methyl-4-propyl-s-triazolo(1,5-
alpha)pyrimidin-5-one is also known as ``PP796,'' and shall be referred
to as such in this document for ease of reading.
A. Residue Chemistry
1. Plant metabolism. Plant metabolism studies are generally not
required for exemption from tolerance of an inert ingredient. The plant
metabolism of PP796 has not been investigated. Since this inert is only
utilized as an emetic in paraquat dichloride end use products that are
utilized for non-selective weed control, plant residues of PP796 are
expected to be non-detectable.
2. Analytical method. Analytical methods are generally not required
for exemption from a tolerance of an inert ingredient. Methods have
been developed and could be provided if requested. The requested use is
not expected to result in detectable residues.
3. Magnitude of residues. Potential residues of PP796 in raw and or
processed agricultural commodities as a result of the use of paraquat
dichloride formulations containing up to 0.3 % w/w of this substance
are expected to be minimal. The maximum concentration of PP796 (0.3% w/
w) in paraquat dichloride formulations is much lower than the
concentration of the co-formulated active ingredient (paraquat
dichloride). Based on data presented in the Reregistration Eligibility
Decision (RED) on paraquat dichloride, and on the expected relative
concentrations of paraquat and PP796 on agricultural commodities would
be approximately 110 times lower than paraquat dichloride (assuming the
maximum of 0.3% w/w emetic in a technical containing 33.0% paraquat
ion).
B. Toxicological Profile
1. Acute toxicity. Acute oral toxicity has been evaluated in rats.
Groups of 5 male and 5 female rats received single oral doses of 100,
150 and 200 mg/kg/body weight of PP796. Moderate signs of toxicity were
seen at 100 mg/kg, but all animals recovered by day 7. Marked signs of
toxicity were seen at both 150 and 200 mg/kg, with 9/10 animals dosed
with 150 mg/kg, and 8/10 animals dosed with 200 mg/kg, being found dead
or killed in extremis at day 2. All surviving animals had recovered by
day 10. Clinical sign of toxicity included decreased activity,
salivation, upward curvature of the spine, increased breathing rate,
ptosis and stains around the mouth and nose. With no significant
findings at post mortem, the median lethal dose is estimated as being
between 100 and 150 mg/kg/body weight.
Acute dermal toxicity has been evaluated in rats. 2,000 mg/kg body
weight of PP796 was applied to the skin of 5 male and 5 female rats for
24 hours, washed off, and the animals observed for signs of toxicity
for 14 days. Other than an observation of slight erythema seen in one
male rat on day 2, no signs of dermal irritation were noted. There were
no mortalities, and with no macroscopic effects at post mortem, the
acute dermal median lethal dose is considered to be > 2,000 mg/kg/day.
Skin irritation was evaluated in rats. PP796 caused slight
irritation to rat skin and some evidence of dermal toxicity following
repeated occluded application. Signs of irritation were evident after
the 4\th\ application when all animals developed erythema. In addition,
all animals looked thin after the 5\th\ application, one was subdued
and another was hunched. One animal was found dead on the last day of
the study (after a total dose of 0.6 mg/kg). Histopathological
examination of the skin and selected major organs confirmed the
irritant effect. With no obvious signs of chemical toxicity, the only
systemic effects were severe involution of the thymus and spleen.
Eye irritation was evaluated on rabbits. Instillation of PP796 into
the eyes of rabbits caused moderate initial pain and slight irritation.
Treated eyes were examined at 1-2 hours and at 1-,2-,3-,4-, and 7- days
post instillation. Although no corneal damage was noted, transient
iridial and conjuctival reations were observed. With all signs of
irritation clearing by day 2, PP796 is considered a slight eye
irritant.
Skin sensitization potential was evaluated in guinea pigs. It has
tested negative in a Stevens Ear/Flank test in guinea pigs and as such
is not considered to be a strong skin sensitizer.
2. Genotoxicity. PP796 is non-mutagenic. It has tested negative in
Salmonella Ames tests, both in the presence and absence of metabolic
activation (Arochlor induced liver S9 fraction) with each of 5 tester
strains (TA98, TA100, TA1535 and TA1538).
3.Reproductive and developmental toxicity. Developmental toxicity
was evaluated in rabbits and rats. Tests on pregnant animals during
organogenesis
[[Page 37850]]
showed no deformities in either rat or rabbit offspring, but at high
doses in rabbit, PP796 was toxic to the dam resulting in spontaneous
abortions.
i. Rabbits. Groups of 12 female rabbits were orally dosed days 6-18
of pregnancy with 0, 0.25, 0.75 and 1.25 mg/kg PP796. Half of the
animals in each group were killed by day 28 and the fetuses removed.
The dams were examined for signs of toxicity and macroscopic
abnormalities. The fetuses were examined for soft tissue abnormalities
before subsequent processing for skeletal examination. The remaining
rabbits were allowed to litter and rear their offspring to 4 weeks post
partum.
Dosing with 1.25 and 0.75 mg/kg caused an increase in the number of
reabsorptions. No reabsorptions were seen at the 0.25 mg/kg level. Two
rabbits receiving 1.25 mg/kg aborted day 20, and another one when
killed day 29, had 6 reabsorptions and no viable fetuses. Of those
receiving 0.75 mg/kg, one died day 18 (having 8 fetuses in utero) and
another littered. The two higher dose levels also produced anorexia.
Fewer offspring survived to 28 days of rabbits treated with 0.75 mg/kg.
Only a small number of deformities were detected, including the
presence of extra ribs, a common finding in this strain of rabbit.
PP796 induces vomiting in dogs at high doses. Although rabbits can
not vomit, the high doses in this study resulted in poor appetite/
anorexia.
In conclusion, PP796, is not teratogenic to rabbits, producing
maternal toxicity at 1.25 and 0.75 mg/kg and only minimal fetal
toxicity. The No Observable Effect Level (NOEL) = 0.25 mg/kg/day.
ii. Rats. Groups of 20 female rats were orally dosed days 6-15 of
pregnancy with 0, 0.25 and 1.25 mg/kg of PP796. Half the rats were
killed one day prior to parturition and the fetuses examined for soft
tissue changes before being processed for skeletal examination. The
remaining rats were allowed to litter and rear their offspring to
weaning.
PP796 had no significant effect on stillbirths, reabsorption rates,
litter size or mean offspring weight. There was however evidence of
anorexia and a reduction in body weight gain in top dose females.
Skeletal and soft tissue changes were within normal limits for the
strain of rat. In conclusion, PP796 was not teratogenic to the rat and
had little effect on pregnancy, littering or weaning. The NOEL = 0.25
mg/kg/day.
4. Subchronic toxicity.Subchronic toxicity was evaluated on rats
and dogs.
i. Rats. 10 male and 10 female rats were orally dosed with 0, 0.25,
or 1.25 mg/kg PP796 daily for 3 months. In this study 15 male and 15
female rats were similarly exposed to 5 mg/kg. At the end of the 3-
month dosing period, 5 male and 5 female rats previously exposed to 5
mg/kg PP796 were maintained without treatment for a further 12 weeks to
assess reversibility. There was a slight reduction in body weight gain
in top dose male rats. Many top dose and a few mid dose rats salivated
after dosing the first few weeks of treatment, but thereafter salivated
before dosing. There were no treatment related effects on haematology
(haemoglobin, packed cell volume, total white cell count, differential
white cell count, platelets and mean cell haemoglobin) or on urine
analysis. In terms of clinical chemistry, no treatment related effects
were observed in AST, ICD or total protein. Slightly elevated levels of
alkaline phosphatase were seen in male and female rats treated with 5
mg/kg PP796 on day 22. By day 36, the levels were statistically
significantly different from the controls (Males P< 0.05; females
P< 0.001), but by day 85, had returned to normal. Significantly
increased serum urea levels were noted in female rats exposed to 5 mg/
kg PP796 day 36 (P< 0.001) and day 85 (P< 0.01). Slightly increased
serum urea levels were noted in male rats day 3 only (P< 0.05). At
study termination (and termination of the recovery animals) there were
no effects on organ weights and no histological changes attributable to
treatment.
ii. Dogs. In this study 4 male and 4 female beagles were orally
dosed with capsules containing 0, 0.15, 0.5, or 1.5 mg/kg PP796 daily
for 3 months. From these animals 1 male and 1 female top dose animals
were maintained on study for a further 6 weeks after dosing to assess
recovery.
After the 5\th\ week of treatment, many top dose animals salivated
profusely before dosing. One male from the same group refused to eat
days 9 and 10 of treatment. Vomiting occurred sporadically in 6 top
dose and 3 mid-dose animals from day 9 onwards. One female top dose dog
that was sick on several occasions and passed blood in its feces was
found to have an ileo-caecal intussusception at post-mortem - a
relatively common abnormality in this strain of dog. Examination of
this animal's bone marrow smear showed megaloblastic hyperplasia - a
finding consistent with poor intestinal absorption due to the ileo-
caecal ulceration. Weight gains were similar in both control and
treated males, while top dose females lost weight sporadically. There
were no treatment related effects on haematology, urine analysis,
clinical chemistry or clinical pharmacology. Analysis of serum level
concentrations showed PP796 to be well absorbed via the oral route.
At study termination (and termination of the recovery animals)
there were no effects on organ weights. Macroscopically, many of the
animals (both control and treated) were observed to have reddish areas
in the lungs. These patches of pneumonia or nodules of inflammatory
cells were attributed to the presence of nematodes caused by the
animals not having been treated with anti-helminthics prior to the
start of dosing. One additional top-dose female had a small cystadenoma
in the thyroid.
Other than a similar nematode-related bronchopneumonia, no
pathological changes attributable to PP796 were noted in the recovery
animals.
In conclusion, PP796, when administered to rats and dogs at high
doses produced no pathological changes, which could be attributed to
treatment. The only effects being vomiting in dogs and elevated serum
urea levels in female rats.
5.Chronic toxicity. Chronic toxicity was evaluated in mice. In this
study 25 male and 25 female mice per group and controls were exposed to
5 and 20 ppm (1.25 and 5 mg/kg/day) PP796 in the diet for approximately
78 weeks. Although survival was good, statistically significant dose
related reductions in body weight were evident at the high dose level.
With no significant difference in the tumor incidence between control
and treated animals, it may be concluded that PP796 is not carcinogenic
to mice. The NOEL = 1.25 mg/kg/day.
6. Animal metabolism. PP796 is well absorbed following oral
administration in the mouse, rat, guinea pig, and dog. With the
exception of the rat, at least 70% of the administered dose was passed
in the urine by 48 hours. The rat differs from the other species in
passing a large proportion (43%) of the oral dose in the feces. It has
been shown that biliary excretion is the major route in the rat and
whole body autoradiography indicates that biliary excretion and
reabsorption occurs in mice.
PP796 is extensively metabolized in all the above species, with the
urine containing a metabolite in which the methyl group has been
hydroxylated. In guinea pigs, it has been shown that serum and tissue
levels of total radioactivity are steady over the period 0.25 to 4
hours after oral administration, with maximum levels at about 1 hour.
The maximum serum level of PP796 is higher in guinea pigs (0.87 ug/ml)
than in rats (0.17 ug/ml) or mice (0.06 ug/ml)
[[Page 37851]]
after an oral dose of 1 mg/kg. The mentioned metabolite is a minor
component in the serum of all 3 species with 5, 4, and 7% of the total
radioactivity in serum in the guinea pig, rat and mouse respectively.
Measurement of the concentration of PP796 in the serum of rats and
dogs after prolonged dosing showed:
i. No difference in the levels between sexes.
ii. A linear dose - peak serum level response and a linear dose -
area under the curve response in dogs throughout the range of doses
tested (i.e. 0.15-1.5 mg/kg/day) with slopes of 0.26 ug/ml per 1 mg/kg
dose and 1.18 ug.hr/ml per 1 mg/kg dose, respectively. Similar effects
were noted in rats in the dose range up to 1.25 mg/kg with slopes of
0.11 ug/ml and 0.52 ug.hr/ml per 1 mg/kg dose, i.e. about half the
response seen in dogs.
iii. A biological half-life of < 3 hours in the dog.
There was no evidence to suggest that serum concentration significantly
increased or decreased after prolonged administration, hence PP796 is
unlikely to be cumulative.
7. Metabolite toxicology. The toxicity of metabolites of PP796 has
not been studied. Given the level of anticipated exposure and the
available animal metabolism data, it is unlikely metabolites of this
inert will be of concern.
8. Endocrine disruption. There is no evidence that PP796 has
hormone disrupting activity.
C. Aggregate Exposure
1. Dietary exposure. The residues of PP796 on raw agricultural
commodities, due to application in paraquat dichloride formulations,
are expected to be negligible. This is due to the low concentration in
end use formulations (< 0.2% w/w) and the use pattern for paraquat
dichloride, a nonselective herbicide. In the 1997 RED for paraquat
dichloride the Theoretical Maximum Residue Concentrations (TMRC) were
calculated for the then existing tolerances for paraquat dichloride.
Based on the conservative approach (Tier 1), the chronic exposure of
the U.S. population, and of the most highly exposed population subgroup
(non-nursing infants less than 1-year old), to paraquat was calculated
to be 0.000442 and 0.001398 mg/kg body weight/day, respectively (pg. 55
of RED Paraquat Dichloride).
A formulation that contained the maximum proposed amount of PP796
(0.3% w/w) would contain 110 times more paraquat ion than PP796
(assuming a technical containing 33.0% w/w paraquat ion). Therefore,
the theoretical chronic exposure can be estimated by dividing the
paraquat exposure numbers by 110, resulting in 0.00000402 mg/kg body
weight/day for the U.S. population and 0.0000127 mg/kg body weight/day
for the most exposed population (non-nursing infants (< 1 years old).
i. Food. Exposures to PP796 from food are expected to be
negligible.
ii. Drinking water. Exposures to PP796 from drinking water are
expected to be negligible due to the low concentration in the end-use
products. There are no aquatic uses of products containing paraquat
dichloride.
2. Non-dietary exposure. End use products containing paraquat
dichloride are restricted use pesticides. There are no residential or
homeowner uses. Non-dietary exposure is expected to be negligible.
D. Cumulative Effects
PP796 is only approved for use in paraquat dichloride formulations.
There is no evidence for a common mechanism of toxicity with other
substances. Therefore, there is no expectation that the use of PP796 as
an inert ingredient in paraquat formulations (up to 0.3 % w/w) would
contribute to any cumulative toxicity arising from exposure to other
substances having a common mechanism of toxicity.
E. Safety Determination
1. U.S. population. Based on the toxicity data presented and the
very low level of exposure, Syngenta Crop Protection, Inc. believes
that there is reasonable certainty that no harm will result to the
general U.S. population by increasing the emetic level in paraquat
dichloride formulations. PP796 is included in paraquat dichloride
formulations as an added safety factor as required by USEPA. The 1987
Guidance for the Reregistration of Pesticide Products Containing
Paraquat Dichloride as the Active Ingredient states on page 27 that
``The Agency is continuing to require that an emetic cleared under 40
CFR 180.1001(b) and (c) be incorporated into all manufacturing use and
end use products containing paraquat. Rationale: Based on the history
of poisoning by accidental ingestion of paraquat and partial
effectiveness of therapeutic treatment after exposure, the Agency
determined that an emetic is needed in formulations to induce rapid
vomiting thereby reducing absorption of paraquat.'' Syngenta Crop
Protection, Inc. has developed a novel formulation which significantly
improves acute oral toxicity of paraquat dichloride formulations in
vomiting species. This novel formulation improvement is largely
accomplished by adding a gelling agent which slows the movement of
paraquat into the intestine where most absorption occurs. Improving
human safety is the primary reason for this request, as the emetic
level is being increased to ensure adequate absorption from the gel in
the stomach.
2. Infants and children. Based on the toxicity data presented and
the very low level of exposure, Syngenta Crop Protection, Inc. believes
that there is reasonable certainty that no harm will result to infants
and children by increasing the emetic level in paraquat formulations.
PP796 is included in paraquat dichloride formulations as an added
safety factor as required by U.S. EPA.
F. International Tolerances
Import tolerances are not required for this inert ingredient. It is
listed as a requirement in FAO Specification 56.302/TK (2003). The FAO
specification requires that ``An effective emetic, having the following
characteristics, be incorporated into the technical. It must be rapidly
absorbed (more rapidly than paraquat) and be quick acting. Emesis must
occur in about half an hour in at least 50% of cases. It must be an
effective (strong) stimulant of the emetic center of the brain, to
produce effective emesis. The emetic effect should have a limited
`action period', of about two to three hours, to allow effective
treatment of poisoning. It must act centrally on the emetic center in
the brain. It must not be a gastric irritant because, as paraquat
itself is an irritant, this could potentiate the toxicity of paraquat.
It must be toxicologically acceptable. It must have a short half-life
in the body (to comply with the need for a limited action period). It
must be compatible with, and stable in, the paraquat formulation and
not affect the herbicidal efficacy or occupational use of the product.
To date, the only compound found to meet these requirements is 2-amino-
4,5-dihydro-6-methyl-4-propyl-s-triazole-(1,5a)pyrimidin-5-one (PP796).
PP796 must be present in the technical at not less than 0.8 g/l. The
method for determination of PP796 content is available from the Plant
Protection Officer, FAO Plant Production and Protection Division.''
[FR Doc. 05-12922 Filed 6-29-05; 8:45 am]
BILLING CODE 6560-50-S