cyromazine (Larvadex,Trigard) Pesticide Petition Filing 7/02
ENVIRONMENTAL PROTECTION AGENCY
Notice of Filing a Pesticide Petition To Establish a Tolerance
for a Certain Pesticide Chemical in or on Food
AGENCY: Environmental Protection Agency (EPA).
SUMMARY: This notice announces the initial filing of a pesticide
petition proposing the establishment of regulations for residues of a
certain pesticide chemical in or on various food commodities.
DATES: Comments, identified by docket ID number OPP-2002-0130; must be
received on or before August 16, 2002.
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. To ensure
proper receipt by EPA, it is imperative that you identify docket ID
number OPP-2002-0130; in the subject line on the first page of your
FOR FURTHER INFORMATION CONTACT: By mail: Shaja R. Brothers,
Registration Support Branch, Registration Division (7505C), Office of
Pesticide Programs, Environmental Protection Agency, 1200 Pennsylvania
Ave., NW., Washington, DC 20460; telephone number: (703) 308-3194; e-
mail address: firstname.lastname@example.org.
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 codes 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 under 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,'' ``Regulations and Proposed Rules,'' 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
2. In person. The Agency has established an official record for
this action under docket ID number OPP-2002-0130. 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 ID number OPP-2002-0130 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 (OPP), Environmental Protection
Agency, 1200 Pennsylvania Ave., NW., 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 ID number OPP-2002-0130. 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 under 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
ID 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 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 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
Dated: July 2, 2002.
Director, Registration Division, Office of Pesticide Programs.
Summary of Petition
The petitioner summary of the pesticide petition is printed below
as required by section 408(d)(3) of the FFDCA. The summary of the
petition was prepared by the IR-4 Project, Centre for Minor Crop Pest
Management and represents the view of the Centre for Minor Crop Pest
Management. EPA is publishing the petition summary verbatim without
editing it 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.
Interregional Research Project Number 4
EPA has received a pesticide petition 0E6219 from the IR-4 Project,
Centre for Minor Crop Pest Management, Rutgers, The State University of
New Jersey, 681 U.S. Highway 1 South, North Brunswick, NJ
8920-3390 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
180.414 by establishing a tolerance for residues of the insecticide,
cyromazine, (N-cyclopropyl-1,3,5-triazine-2,4,6-triamine) in or on the
raw agricultural commodity dry bean at 3.0 parts per million (ppm).
This notice includes a summary of the petition prepared by Novartis
Crop Protection Inc., Greensboro, NC 27419. 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
support granting of the petition. Additional data may be needed before
EPA rules on the petition.
A. Residue Chemistry
1. Plant metabolism. The metabolism of cyromazine in plants is
adequately understood for the purposes of these tolerances.
2. Analytical method. Methods AG-408 and AG-417 as listed in the
Food and Drug Administration's Pesticide Analytical Manual (PAM), Vol-
II are adequate to enforce the proposed tolerance.
3. Magnitude of residues. A total of nine residue field tests were
conducted in typical growing regions for dry beans. The data collected
support the proposed tolerance of 3.0 ppm.
B. Toxicological Profile
1. Acute toxicity. A rat acute oral toxicity study with a lethal
dose (LD)50 of approximately 3,387 milligrams/kilogram (mg/
kg) (toxicity category III; moderately toxic). A rat acute dermal
toxicity study with a LD50 greater than 3,100 mg/kg
(toxicity category III; moderately toxic). A rat acute inhalation study
with a lethal concentration (LC)50 greater than 2.9 mg/kg
(toxicity category IV; slightly toxic). A primary eye irritation study
in the rabbit that showed no eye irritation. A primary dermal
irritation study in the rabbit that showed mild irritation (toxicity
category; IV). A dermal sensitization study in the guinea pig that
showed no sensitization.
2. Genotoxicity. Studies on gene mutation and other genotoxic
effects showed no evidence of point mutation in an Ames test; no
indication of mutagenic effects in a dominant lethal test; and no
evidence of mutagenic effects in a nucleus anomaly test in Chinese
3. Reproductive and developmental toxicity. In a rat developmental
toxicity study, the maternal NOAEL was 100 mg/kg/day. The maternal
LOAEL was 300 mg/kg based on decreased body weight gain and clinical
observations. The developmental NOAEL was 300 ppm. The developmental
LOAEL was 600 mg/kg based upon an increase of minor skeletal
In a rabbit developmental toxicity study, the maternal NOAEL was
10 mg/kg. The maternal LOAEL was 30 mg/kg based upon decreased body
weight gain and food consumption. The developmental NOAEL/LOAEL was
greater than or equal to 60 mg/kg.
In a multi-generation study in rats, the systemic NOAEL was 30 ppm
(1.5 mg/kg). The systemic LOAEL was 1,000 ppm (50 mg/kg) based upon
decreased body weights associated with decreased food consumption. The
developmental/offspring systemic NOAEL was 1,000 ppm. The
developmental/offspring systemic LOAEL was 3,000 ppm (150 mg/kg) based
upon decreased body weight at birth through weaning. There were no
effects on reproductive parameters at the highest dose tested (3,000
4. Subchronic toxicity. In a 6-month feeding study in dogs, the
NOAEL was 30 ppm (0.75 mg/kg). The LOAEL was 300 ppm (7.5 mg/kg) based
upon decreased hematocrit and decreased hemoglobin. Groups of male and
female beagle dogs (4/sex/dose) were fed diets containing cyromazine at
0, 30, 300, or 3,000 ppm (0, 0.75, 7.5, or 75 mg/kg/day, respectively)
for 6-months. No treatment-related effects were observed in survival,
clinical signs or body weight parameters. Pronounced effects on
hematologic parameters, were manifested as decreases in hematocrit and
hemoglobin levels at 300 and 3,000 ppm.
5. Chronic toxicity. In a 24-month feeding study in rats the NOAEL
for the study was 30 ppm (1.5 mg/kg/day). The LOAEL was 300 ppm (15.0
mg/kg) based on decreased body weight. In a 24-month mouse chronic
feeding carcinogenicity study the NOAEL was 50 ppm (7.5 mg/kg/day). The
LOAEL was 1,000 ppm (150.0 mg/kg) based upon decreased body weight.
There was no evidence of carcinogenicity at 3,000 ppm (450 mg/kg). In a
24-month rat chronic feeding carcinogenicity study the NOAEL was
greater than 3,000 ppm (150 mg/kg) (highest dose tested). There was no
evidence of carcinogenicity at 3,000 ppm.
6. Animal metabolism. The metabolism of cyromazine has been
adequately characterized in the rat, goat and chicken.
7. Metabolite toxicology. EPA has removed melamine, a metabolite of
cyromazine, from the tolerance expression as a residue of toxicological
concern. For more information on melamine, see the Federal Register of
September 15, 1999 (64 FR 50043) (FRL-6098-7).
8. Endocrine disruption. Cyromazine does not belong to a class of
chemicals proven to have adverse effects on the endocrine system. There
is no evidence that cyromazine has any effect on endocrine function in
developmental or reproduction studies.
C. Aggregate Exposure
1. Dietary exposure. EPA has conducted risk assessments to assess
dietary exposures from cyromazine. Details of these assessments are in
the Federal Register of September 15, 1999 (64 FR 50043).
i. Food--a. Acute risk. A food-use pesticide is presumed to pose an
acute risk if a toxicological study has indicated the possibility of an
effect of concern occurring as a result of a 1-day or single exposure.
There were no toxicological effects attributed to a single exposure
(dose) observed in oral toxicity studies including the developmental
toxicity studies in rats and rabbits. Therefore, there is a reasonable
certainty of no harm from acute dietary exposure.
b. Chronic. The chronic reference dose (RfD) used for the chronic
dietary analysis is 0.0075 milligram/kilogram body weight/day (mg/kg bwt/day).
The following assumptions were used in the dietary risk assessment: (i)
PCT estimates were utilized for cucurbit vegetables, leafy vegetables
(except Brassica), onions, peppers and tomatoes. All other crops 100%
crop-treated was assumed; (ii) anticipated residue estimates were used
for milk, meat, fat, and meat byproducts of cattle, goats, hogs,
horses, and sheep; and (iii) all other commodities tolerance level
residues were assumed.
ii. Drinking water exposure--a. Acute. Because no acute dietary
endpoint was determined, cyromazine does not pose an acute risk through
b. Chronic. EPA has calculated drinking water level of concern
(DWLOC) values for chronic (non-cancer) exposure to cyromazine in
surface water and ground water. A human health DWLOC is the
concentration of a pesticide in drinking water that would result in an
acceptable aggregate risk after having factored in all food exposures
and other non-occupational exposures for which EPA has reliable data.
To calculate the DWLOCs for chronic (non-cancer) exposure relative to a
chronic toxicity endpoint, the chronic dietary food exposure was
subtracted from the RfD to obtain the acceptable chronic (non-cancer)
exposure to cyromazine in drinking water. DWLOCs were then calculated
using default body weights and drinking water consumption figures. The
modeling conducted was based on the environmental profile and the
maximum seasonal application rate proposed for cyromazine (6
applications at 0.125 lb/acre).
2. Non-dietary exposure. Cyromazine is currently registered for
commercial outdoor use on landscape ornamentals and commercial
interiorscapes. There are no lawn or indoor residential uses and
significant residential exposure is not expected.
D. Cumulative Effects
Novartis does not have, at this time, available data to determine
whether cyromazine has a common mechanism 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,
cyromazine does not appear to produce a toxic metabolite produced by
E. Safety Determination
1. U.S. population. The aggregate exposure to cyromazine from food
will utilize 17% of the chronic population dose (cPAD) for the U.S.
population. The major identifiable subgroup with the highest aggregate
exposure is 34% for children (1-6 years old). Other subgroups include
non-nursing infants, (1 year old) utilizing 13% of cPAD, and children
(7-12 years old) utilizing 26% of the cPAD. EPA generally 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.
Based on the chronic dietary (food only) exposures and using
default body weights and water consumption figures, chronic DWLOCs for
drinking water were calculated. For chronic exposure, based on an adult
body weight of 70 kg and 2 liter (2L) consumption of water per day, the
DWLOC from chronic dietary exposure in drinking water is 220 ppb. For
children (10 kg and consuming 1 liter water/day) the DWLOC is 50 parts
per billion (ppb). The estimated chronic drinking water exposure for
cyromazine is 28.9 ppb (surface water) and 1.6 ppb (ground water).
Thus, the potential residues in drinking water are not greater than the
DWLOCs. Therefore, the combined exposure of chronic dietary food and
drinking water exposure to cyromazine would be no greater than 100% of
the cPAD for children or the general U.S. population.
Due to the nature of the non-dietary use, the commercial use of
cyromazine on landscape ornamentals will not result in any significant
residential exposure. Therefore, the chronic risk is the sum of food
and water and there is reasonable certainty that no harm will result
from aggregate exposure to cyromazine residues.
The Cancer Peer Review Committee determined that there is no
evidence of carcinogenicity in studies in either the mouse or rat.
Based upon this determination it can be concluded that cyromazine does
not pose a cancer risk.
Therefore, based on these risk assessments there is a reasonable
certainty that no harm will result from aggregate exposure to
2. Infants and children. The safety factor for infants and children
under FFDCA section 408 provides that EPA shall apply an additional
ten-fold margin of safety for infants and children in the case of
threshold effects to account for prenatal and postnatal toxicity and
the completeness of the data base unless EPA determines that a
different margin of safety will be safe for infants and children. EPA
determined that reliable data support using the standard MOE and
uncertainty factor (100 for combined interspecies and intraspecies
variability) and that an additional safety factor of 10 is not
necessary to be protective of infants and children.
Using the conservative exposure assumptions described above, the
aggregate exposure to cyromazine from food will utilize a maximum 34%
of the cPAD for children 1-6 years old. EPA generally 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. As noted
above, potential exposure from drinking water is at a level below the
DWLOCs. Therefore, based on these risk assessments there is a
reasonable certainty that no harm will result to infants and children
from aggregate exposure to cyromazine residues.
F. International Tolerances
There are currently no codex, Canadian or Mexican limits for
residues of cyromazine on dry beans.
[FR Doc. 02-17688 Filed 7-16-02; 8:45 am]