[Federal Register Volume 64, Number 178 (Wednesday, September 15, 1999)]
[Proposed Rules]
[Pages 50043-50050]
From the Federal Register Online via the Government Publishing Office [www.gpo.gov]
[FR Doc No: 99-24047]
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ENVIRONMENTAL PROTECTION AGENCY
40 CFR Part 180
[OPP-300913; FRL-6098-7]
RIN 2070-AB78
Cyromazine; Pesticide Tolerance
AGENCY: Environmental Protection Agency (EPA).
ACTION: Proposed rule.
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SUMMARY: EPA proposes to establish tolerances for residues of
cyromazine (CAS No. 66215-27-8) in or on mango at 0.3 parts per million
(ppm); onion, green at 2.0 ppm; onion, dry bulb at 0.1 ppm; potato at
0.8 ppm; corn, sweet, (kernels plus cob with husks removed) at 0.5 ppm;
corn, sweet, forage at 0.5 ppm; corn, sweet, stover at 0.5 ppm; radish,
roots at 0.5 ppm; radish, tops at 0.5 ppm; lima beans at 1.0 ppm;
cotton, undelinted seed at 0.1 ppm; milk at 0.05 ppm; and meat, fat and
meat byproducts (of cattle, goats, hogs, horses and sheep) at 0.05 ppm.
EPA also proposes to remove melamine, a metabolite of cyromazine from
the tolerance expression since it is no longer considered a residue of
concern. The Interregional Research Project (IR-4) and Novartis Crop
Protection, Inc., requested these tolerances under the Federal Food,
Drug, and Cosmetic Act, as amended by the Food Quality Protection Act
of 1996.
DATES: Comments, identified by the docket control number ``OPP-
300913,'' must be received by EPA on or before November 15, 1999.
ADDRESSES: Written objections and hearing requests, identified by the
docket control number, [OPP-300913], must be submitted to: Hearing
Clerk (1900), Environmental Protection Agency, Rm. M3708, 401 M St.,
SW., Washington, DC 20460. In person, bring comments to Rm. 100, CM #2,
1921 Jefferson Davis Hwy., Arlington, VA 22202.
A copy of objections and hearing requests filed with the Hearing
Clerk may be submitted electronically by sending electronic mail (e-
mail) to: opp-docket@epa.gov. Copies of objections and hearing requests
must be submitted as an ASCII file avoiding the use of special
characters and any form of encryption. Copies of objections and hearing
requests will also be accepted on disks in WordPerfect 5.1/6.1 or ASCII
file format. All copies of objections and hearing requests in
electronic form must be identified by the docket control number [OPP-
300913]. No Confidential Business Information (CBI) should be submitted
through e-mail. Electronic copies of objections and hearing requests on
this rule may be filed online at many Federal Depository Libraries.
FOR FURTHER INFORMATION CONTACT: By mail: Linda DeLuise, Registration
Division (7505C), Office of Pesticide Programs, Environmental
Protection Agency, 401 M St., SW., Washington, DC 20460. Office
location, telephone number, and e-mail address: Rm. 202, Crystal Mall
#2, 1921 Jefferson Davis Hwy., Arlington, VA, 703-305-5428; e-mail:
deluise.linda@epa.gov.
SUPPLEMENTARY INFORMATION: In the Federal Register of July 11, 1997 (62
FR 37246) (FRL-5723-1), EPA issued a notice pursuant to section 408 of
the Federal Food, Drug, and Cosmetic Act (FFDCA), 21 U.S.C. 346a as
amended by the Food Quality Protection Act of 1996 (FQPA) (Public Law
104-170) announcing the filing of pesticide petitions (PP) for
tolerances by Novartis Crop Protection, Inc., 410 Swing Road,
Greensboro, NC 27419. The notice included summaries of the petitions
prepared by Novartis Crop Protection, Inc., the registrant. There were
no comments received in response to the notice of filing.
The petition requested that 40 CFR 180.414 be amended by
establishing tolerances for residues of the insecticide cyromazine and
its metabolite melamine, in or on various food commodities as follows:
1. Novartis Corporation PP5E4450 proposes the establishment of a
tolerance for mangoes at 0.3 ppm.
2. Norvartis Corporation PP5F4576 proposes the establishment of a
tolerance for onion, green at 3.0 ppm and onion, dry bulb at 0.3 ppm.
3. Novartis Corporation PP6F4613 proposes the establishment of a
tolerance for potato at 1.5 ppm.
4. Novartis Corporation PP5F4546 proposes establishment of a
tolerance for cotton, undelinted seed at 0.2 ppm.
5. Novartis Corporation PP6F3332 proposes establishment of
tolerances for sweet corn, (kernels plus cob with husks removed),
forage and stover at 0.5 ppm; radish roots, and tops at 0.5 ppm; and
milk at 0.04 ppm for cyromazine and 0.02 ppm melamine.
6. Novartis Corporation PP6F3332 proposes establishment of a
tolerance for meat, fat and meat byproducts (of cattle, goats, hogs,
horses and sheep) at 0.05 ppm.
[[Page 50044]]
7. IR-4 PP7E4905 proposes the establishment of a tolerance for lima
beans at 3.0 ppm.
The tolerance requests for cotton, corn and radish are for indirect
or inadvertent residues when these commodities are planted as
rotational crops. The tolerance request for mangoes is for a tolerance
to enable the importation of mangoes treated in Mexico with cyromazine.
There are no U.S. registrations for use of cyromazine on mangoes as of
the date of this publication.
There currently exists separate tolerances in 40 CFR 180.414(a) for
cyromazine on celery at 10.0 ppm and lettuce, head at 5.0 ppm. Since
the crop group leafy vegetables (except Brassica) includes celery and
lettuce, (head) these individual tolerances under 40 CFR 180.414(a) are
being removed.
EPA has concluded that only residues of the parent compound
cyromazine need to be regulated and used for risk assessment and is
proposing that melamine, a metabolite of cyromazine, be removed from
the tolerance expression as a residue of toxicological concern.
Melamine was initially included in the tolerance expression for
cyromazine because of limited evidence of its carcinogenic potential in
laboratory animals. At that time EPA agreed with FDA's Cancer
Assessment Committee that melamine was not a carcinogen, per se, but
was indirectly responsible for the induction of urinary bladder
neoplasia through production of stones in the bladder. A detailed
discussion of the initial risk of melamine can be found in the Federal
Register of April 27, 1984 (49 FR 18120). Since then EPA has reassessed
the weight-of-the evidence for both cyromazine and melamine with
particular reference to their carcinogenic potential. Cyromazine is
classified as a group ``E'' carcinogen (no evidence of carcinogenicity)
with an chronic RfD of 0.0075 milligram/kilogram/day (mg/kg/day) with
an uncertainty factor (UF) of 100 using a no observed adverse effect
level (NOAEL) of 0.75 mg/kg/day and a lowest observed adverse effect
level (LOAEL) of 7.5 mg/kg/day.
Melamine is a chemical intermediate in the manufacture of amino
resins and plastics as well as a contaminate and/or a metabolite of
several pesticides including cyromazine. Melamine produced bladder
tumors only in the male rat urinary bladder at very high doses i.e., at
a threshold effect > 10,000 ppm in the diet. These tumors were due to
the accumulation of stones (hard crystalline solids) which caused
irritation and secondarily resulted in the formation of tumors;
therefore melamine is not considered to be a direct carcinogen by the
Agency.
In addition, only about 10% of cyromazine is converted to melamine
in vivo. Anticipated human dietary and occupational exposure to the
parent compound cyromazine from its current pesticide usage is
estimated to result in melamine concentrations far below the NOAEL in
rats (500 mg/kg/day) that led to formation of stones in rats. Thus, EPA
does not have any toxicological concerns for the minimal amount of
melamine residues that could result from the use of the pesticide
cyromazine. Also, melamine has been removed from the World Health
Organization as a residue of concern for cyromazine, and Codex limits
are established for the parent cyromazine only.
EPA determined that the requested tolerances for potatoes at 0.8
ppm, green onions at 2.0 ppm, onion, dry bulb at 0.1 ppm, cotton,
undelinted seed at 0.1 ppm, and lima beans at 1.0 ppm are too high
based upon the magnitude of the residue studies and removal of the
metabolite melamine from consideration. Therefore, EPA is proposing
that the tolerance be set at 0.8 ppm, 2.0 ppm, 0.1 ppm, 0.1 ppm, and
1.0 ppm respectively. As a result of the animal feed items, processed
potato waste, potato culls and sweet corn forage and stover being added
to the animal diet at this time, EPA concluded that the requested milk
tolerance of 0.04 ppm was too low and is proposing it be increased to
0.05 ppm. Likewise, as a result of the animal feed items, EPA is
proposing establishment of tolerances in meat, fat and meat byproducts
of cattle, goats, hogs, horses and sheep at 0.05 ppm.
EPA has reassessed the established cyromazine tolerances in order
to determine the tolerance levels without melamine residues. As a
result, EPA is proposing the tolerances be adjusted as follows:
cucurbit vegetables from 2.0 to 1.0 ppm; leafy vegetables (except
Brassica) from 10.0 to 7.0 ppm; mushrooms from 10.0 to 1.0 ppm; pepper
from 4.0 to 1.0 ppm and tomato from 1.0 to 0.5 ppm. The tolerances for
Chinese cabbage and Chinese mustard should remain at 3.0 ppm since the
available field trial data do not support a lowering of the established
tolerances. Since melamine is being removed from the tolerance
expression EPA is proposing to remove 40 CFR 180.414(a)(2) because it
is for melamine only on chicken byproducts.
Cyromazine is an insect growth regulator currently proposed for
control of leafminers on lima beans, Colorado potato beetle and
leafminers on potatoes and seed treatment for control of onion maggots
on onions.
EPA is issuing this action as a proposal (rather than a final)
because after review of the initial petitions and Notices of Filing the
Agency has determined that:
1. The metabolite melamine should be removed from the tolerance
expression.
2. The proposed tolerance in milk needs to be raised.
3. Additional tolerances on animal commodities (meat, fat and milk
byproducts of cattle, goats, hogs, horses and sheep) are needed.
4. A notice of filing was not initially published after receipt of
the petition for lima beans.
Interested persons are invited to submit comments on the proposed
regulation. Comments must bear a notation indicating the docket control
number ``OPP-300913.''
I. Background and Statutory Findings
Section 408(b)(2)(A)(i) of the FFDCA allows EPA to establish a
tolerance (the legal limit for a pesticide chemical residue in or on a
food) only if EPA determines that the tolerance is ``safe.'' Section
408(b)(2)(A)(ii) defines ``safe'' to mean that ``there is a reasonable
certainty that no harm will result from aggregate exposure to the
pesticide chemical residue, including all anticipated dietary exposures
and all other exposures for which there is reliable information.'' This
includes exposure through drinking water and in residential settings,
but does not include occupational exposure. Section 408(b)(2)(C)
requires EPA to give special consideration to exposure of infants and
children to the pesticide chemical residue in establishing a tolerance
and to ``ensure that there is a reasonable certainty that no harm will
result to infants and children from aggregate exposure to the pesticide
chemical residue....''
EPA performs a number of analyses to determine the risks from
aggregate exposure to pesticide residues. For further discussion of the
regulatory requirements of section 408 and a complete description of
the risk assessment process, see the final rule on Bifenthrin Pesticide
Tolerances (62 FR 62961, November 26, 1997) (FRL-5754-7).
II. Aggregate Risk Assessment and Determination of Safety
Consistent with section 408(b)(2)(D), EPA has reviewed the
available scientific data and other relevant information in support of
this action, EPA has sufficient data to assess the
[[Page 50045]]
hazards of cyromazine and to make a determination on aggregate
exposure, consistent with section 408(b)(2), for tolerances for
residues of cyromazine in or on mangoes at 0.3 ppm; onion, green at 2.0
ppm; onion, dry bulb at 0.1 ppm; potato at 0.8 ppm; corn, sweet
(kernels plus cob with husks removed) at 0.5 ppm; corn, sweet, forage
at 0.5 ppm; corn, sweet, stover at 0.05 ppm; radish, root at 0.5 ppm;
radish, tops at 0.05 ppm; lima beans at 1.0 ppm; cotton, undelinated
seed at 0.1 ppm; milk at 0.05 ppm; and meat, fat and meat byproducts
(of beef, goat, hogs, horses and sheep) at 0.05 ppm. EPA's assessment
of the dietary exposures and risks associated with establishing the
tolerance follows.
A. Toxicological Profile
EPA has evaluated the available toxicity data and considered its
validity, completeness, and reliability as well as the relationship of
the results of the studies to human risk. EPA has also considered
available information concerning the variability of the sensitivities
of major identifiable subgroups of consumers, including infants and
children. The nature of the toxic effects caused by technical
cyromazine are discussed in this unit.
A rat acute oral toxicity study with a LD50 of
approximately 3,387 milligrams/kilogram (mg/kg). Toxicity Category III
(Moderately Toxic).
A rat acute dermal toxicity study with an LD50 greater
than 3,100 mg/kg. Toxicity Category III (Moderately Toxic).
A rat acute inhalation study with an LC50 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.
In a 6-month feeding study in dogs the NOAEL was 30 ppm (0.75 mg/
kg). The LOAEL was 300.0 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.
In a 24-month feeding study in rats the NOAEL for the study was 30
ppm (1.5 mg/kg/day). The LOAEL was 300.0 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 1,000.0 ppm (150.0 mg/kg)
based upon decreased body weight. There was no evidence of
carcinogenicity at 3,000.0 ppm (450.0 mg/kg).
In a 24-month rat chronic feeding carcinogenicity study the NOAEL
was greater than 3,000.0 ppm (150.0 mg/kg), highest dose tested. There
was no evidence of carcinogenicity at 3,000 ppm.
In a rat developmental toxicity study the maternal NOAEL was 100
mg/kg/day. The maternal LOAEL was 300.0 mg/kg based on decreased body
weight gain and clinical observations. The developmental NOAEL was
300.0 ppm. The developmental LOAEL was 600.0 mg/kg based upon an
increase of minor skeletal variations.
In a rabbit developmental toxicity study the maternal NOAEL was
10.0 mg/kg. The maternal LOAEL was 30.0 mg/kg based upon decreased body
weight gain and food consumption. The developmental NOAEL/LOAEL was
greater than or equal to 60.0 mg/kg.
In a multi-generation study in rats the systemic NOAEL was 30.0 ppm
(1.5 mg/kg). The systemic LOAEL was 1,000.0 ppm (50.0 mg/kg) based upon
decreased body weights associated with decreased food consumption. The
developmental/offspring systemic NOAEL was 1,000.0 ppm. The
developmental/offspring systemic LOAEL was 3,000.0 ppm (150.0 mg/kg)
based upon decreased body weight at birth thru weaning. There were no
effects on reproductive parameters at the highest dose tested (3,000
ppm).
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 hamsters.
In a dermal absorption study, rats received dermal application of
14C cyromazine (75W, formulation) in an aqueous solution at
0.10, 1.0 or 10 mg/rat. Absorption was measured at 10 and 24 hours post
treatment. Cyromazine was rapidly absorbed into the skin (no peak
discernible) in an inverse dose-related manner. The absorption into the
skin was followed by a slower release into the body. There was no
evidence that the compound was sequestered in the skin permanently. The
main route of excretion was via the urine. At 10 hours post treatment,
the absorption was 7.57, 5.06 and 1.84% for the low, mid and high
doses, respectively. At 24 hours post exposure, the absorption was
6.87, 2.78 and 2.63% for the low, mid and high doses, respectively. For
the 24-hour animals with 48-hour depletion period, the absorption was
16.07, 12.45 and 9.10% for the low, mid and high doses, respectively.
B. Toxicological Endpoints
1. Acute toxicity. (1-day) There was no toxicological effects
attributable to a single exposure (dose) observed in oral toxicity
studies including the developmental toxicity studies in rats or
rabbits. Therefore, a dose and an endpoint was not selected for this
acute dietary risk assessment.
2. Short- and intermediate-term toxicity. The Agency selected
short- and intermediate-term dermal and inhalation endpoints from the
6-month oral toxicity study in dogs, in which pronounced effects on
hematological parameters were manifested as decreases in hematocrit and
hemoglin levels at 7.5 (LOAEL) and 75 mg/kg/day. The hematological
effects began during the first week of the study and continued
throughout the study. The NOAEL is 0.75 mg/kg/day. A margin of exposure
(MOE) of 100 or greater is adequate. For dermal inhalation exposure
adsorption rates of 8% for dermal and 100% for inhalation are
appropriate.
3. Chronic toxicity. The Agency selected a chronic RfD for
cyromazine of 0.0075 mg/kg/day (NOAEL = 0.75 mg/kg/day; UF = 100). This
RfD is based on a 6-month oral toxicity in dogs, in which pronounced
effects on hematological parameters were manifested as decreases in
hematocrit and hemoglobin levels at 7.5 (LOAEL) and 75 mg/kg/day.
4. Carcinogenicity. Cyromazine has been classified a Group E
(evidence of non-carcinogenicity for humans) chemical by the Cancer
Peer Review Committee.
C. Exposures and Risks
1. From food and feed uses. Tolerances have been established (40
CFR 180.414) for the residues of cyromazine, in or on a variety of raw
agricultural commodities at levels ranging from 1.0 ppm in tomatoes to
10 ppm in leafy vegetables and including poultry feed. In addition, EPA
proposes to establish tolerances for mangoes at 0.3 ppm; onion, green
at 2.0 ppm; onion, dry bulb at 0.1 ppm; potato at 0.8 ppm; cotton,
undelinted seed at 0.1 ppm; corn, sweet, (kernels plus cob with husks
removed) at 0.5 ppm; corn, sweet, forage at 0.5 ppm; corn, sweet,
stover at 0.5 ppm; radish, root at 0.5 ppm; radish,
[[Page 50046]]
tops at 0.5 ppm; lima beans at 1.0 ppm; milk at 0.05 ppm and meat, fat
and meat byproducts (of cattle, goat, hogs, horses and sheep) at 0.05
ppm. Risk assessments were conducted by EPA to assess dietary exposures
from cyromazine as follows:
The Agency used Dietary Exposure Evaluation Model
(DEEM) software for conducting a Tier 3 chronic (non-
cancer) dietary (food only) exposure analysis. The following
assumptions were used in the assessment: (i) Percent crop-treated (PCT)
estimates were utilized for cucurbit vegetables, leafy vegetables
(except Brassica), onions, peppers and tomatoes; (ii) all other crops
100% crop-treated was assumed; (iii) anticipated residue estimates were
used for milk, meat, fat, and meat byproducts of cattle, goats, hogs,
horses, and sheep; and (iv) all other commodities tolerance level
residues were assumed. This assessment is considered to be somewhat
refined. The chronic DEEM analysis indicates that the
most highly exposed population subgroup is children (1 to 6 years old),
which occupies 34% of the chronic RfD or chronic population adjusted
dose (PAD)
Section 408(b)(2)(E) authorizes EPA to use available data and
information on the anticipated residue levels of pesticide residues in
food and the actual levels of pesticide chemicals that have been
measured in food. If EPA relies on such information, EPA must require
that data be provided 5 years after the tolerance is established,
modified, or left in effect, demonstrating that the levels in food are
not above the levels anticipated. Following the initial data
submission, EPA is authorized to require similar data on a time frame
it deems appropriate. As required by section 408(b)(2)(E), EPA will
issue a data call-in for information relating to anticipated residues
to be submitted no later than 5 years from the date of issuance of this
tolerance.
Section 408(b)(2)(F) states that the Agency may use data on the
actual PCT for assessing chronic dietary risk only if the Agency can
make the following findings: That the data used are reliable and
provide a valid basis to show what percentage of the food derived from
such crop is likely to contain such pesticide residue; that the
exposure estimate does not underestimate exposure for any significant
subpopulation group; and if data are available on pesticide use and
food consumption in a particular area, the exposure estimate does not
understate exposure for the population in such area. In addition, the
Agency must provide for periodic evaluation of any estimates used. To
provide for the periodic evaluation of the estimate of PCT as required
by section 408(b)(2)(F), EPA may require registrants to submit data on
PCT.
The Agency believes that the three conditions, discussed in section
408(b)(2)(F) in this unit concerning the Agency's responsibilities in
assessing chronic dietary risk findings, have been met. With respect to
PCT, estimates are derived from Federal and private market survey data,
which are reliable and have a valid basis. Typically, a range of
estimates are supplied and the upper end of this range is assumed for
the exposure assessment. By using this upper end estimate of the crop
treated, the Agency is reasonably certain that the percentage of the
food treated is not likely to be underestimated. As to regional
consumption information and consumption information for significant
subpopulations is taken into account through EPA's computer-based model
for evaluating the exposure of significant subpopulations including
several regional groups. Use of this consumption information in EPA's
risk assessment process ensure's that EPA's exposure estimate does not
understate exposure for any significant subpopulation group and allows
the Agency to be reasonably certain that no regional population is
exposed to residue levels higher than those estimated by the Agency.
Other than the data available through national food consumption
surveys, EPA does not have available information on the regional
consumption of food to which cyromazine may be applied in a particular
area.
a. Acute exposure and 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, the
Agency concludes that there is a reasonable certainty of no harm from
acute dietary exposure.
b. Chronic exposure and risk. The chronic and/or chronic PAD 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. The proposed
and established cyromazine tolerances result in an exposure estimate
that is equivalent to the following percents of the RfD: U.S.
population (17% of RfD), non-nursing infants, (1 year old) (13% of
RfD), children (1-6 years old) (34%), and children (7-12 years old)
26%. EPA is generally concerned with chronic exposures that exceed 100%
of the RfD or PAD.
This chronic analysis for cyromazine is an over-estimate of dietary
exposure from food due to the use of tolerance level residues for some
commodities and the assumption that 100% of the crop would be treated
for some of the commodities in this dietary exposure analysis. Thus in
making a safety determination for these tolerances, EPA is taking into
account this conservative exposure assessment.
2. From drinking water. The Agency has calculated drinking water
levels of comparison (DWLOCs) for chronic (non-cancer exposure) to
cyromazine in surface and ground water.
i. Acute exposure and risk. Because no acute dietary endpoint was
determined, EPA does not expect exposure to cyromazine through drinking
water to pose an acute risk.
ii. Chronic exposure and risk. EPA has calculated DWLOCs for
chronic (non-cancer) exposure to cyromazine in surface and ground
water. A human health DWLOC is the concentration of a pesticide in
drinking water which 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. The DWLOCs are 220, 190, 50,
and 210 parts per billion (ppb) for the U.S. population, females 13+,
children, and others respectively. To calculate the DWLOCs for chronic
(non-cancer) exposure relative to a chronic toxicity endpoint, the
chronic dietary food exposure from DEEM 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.
Although cyromazine may be commercially applied to landscape
ornamentals and around residences, EPA believes these uses will not
result in any exposure through the oral route; therefore, aggregate
exposure is limited only to food plus water.
Estimated maximum concentrations of cyromazine in surface and
ground
[[Page 50047]]
water are 28.9 and 1.6 ppb, respectively. The modeling conducted was
based on the environmental profile and the maximum seasonal application
rate proposed for cyromazine (6 applications at 0.125 lbs/A). The
estimated average concentrations of cyromazine in surface and ground
water are less than the Agency's levels of comparison for cyromazine in
drinking water as a contribution to chronic aggregate exposure. Thus,
the Agency concludes that there is reasonable certainity of no harm
from chronic exposure from drinking water.
The Agency bases this determination on a comparison of estimated
concentrations of cyromazine in surface waters and ground waters to
back-calculated ``levels of comparison'' for cyromazine in drinking
water. These levels of comparison in drinking water were determined
after the Agency has considered all other non-occupational human
exposures for which it has reliable data, including all current uses,
and uses considered in this action. The estimates of cyromazine in
surface and ground waters are derived from water quality models that
use conservative assumptions (health-protective) regarding the
pesticide transport from the point of application to surface and ground
water. Because the Agency considers the aggregate risk resulting from
multiple exposure pathways associated with a pesticide's uses, levels
of comparison in drinking water may vary as those uses change. If new
uses (including crop or residential) are added in the future, the
Agency will reassess the potential impacts of cyromazine on drinking
water as a part of the aggregate risk assessment process.
3. From 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. Although
cyromazine could be commercially applied to ornamentals around
residences based upon the large MOE's calculated for occupational use
(i.e. > 1,900) and minimal contact anticipated with the active
ingredient after application, significant residential exposure is not
expected.
4. Cumulative exposure to substances with a common mechanism of
toxicity. Cyromazine is a member of the triazine class of pesticides.
Other members of this class include atrazine, simizine, cyanazine,
prometin, propazine, metribuzin, prometryn, and ametryn.
EPA 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
other substances. For the purposes of this tolerance action, therefore,
EPA has not assumed that cyromazine has a common mechanism of toxicity
with other substances.
D. Aggregate Risks and Determination of Safety for U.S. Population
1. Acute risk. There were no toxicological effects attributable to
a single exposure (dose) observed in oral toxicity studies including
the developmental toxicity studies in rats or rabbits.
2. Chronic risk (food + water). Using the exposure assumptions
described above, EPA has concluded that aggregate exposure to
cyromazine from food will utilize 17% of the chronic RfD for the U.S.
population. The major identifiable subgroup with the highest aggregate
exposure is 34% for children (1-6 years old). EPA generally has no
concern for exposures below 100% of the RfD because the RfD represents
the level at or below which daily aggregate dietary exposure over a
lifetime will not pose appreciable risks to human health. 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 2L consumption of water per day, EPA's level of comparison from
chronic dietary exposure in drinking water is 220 g/L. For
children (10 kg and consuming 1 liter water/day) the level of
comparison for drinking water is 50 g/L. The estimated chronic
drinking water exposure for cyromazine is 28.9 g/L. Thus the
potential residues in drinking water are not greater the EPA's level of
comparison. Therefore, the combined exposure of chronic dietary food
and drinking water exposure to cyromazine would be no greater than 100%
of the RfD for children or the general U.S. population. Due to the
nature of the non- dietary use, EPA believes that 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. The Agency concludes that there is reasonable certainty that no
harm will result from aggregate exposure to cyromazine residues.
3. Short- and intermediate-term risk. These aggregate risk
assessments take into account chronic dietary exposure from food and
water (considered to be a background exposure level) plus (acute,
intermediate, or chronic, as applicable) indoor and outdoor residential
exposure. The Agency selected a dose and toxicological endpoint for
assessments of short- and intermediate-term dermal and inhalation risk.
However, since there are no significant residential uses for cyromazine
(either established or pending) at this time, these risk assessments
are not currently required.
4. Aggregate cancer risk for U.S. population. 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.
5. Determination of safety. Based on these risk assessments, EPA
concludes that there is a reasonable certainty that no harm will result
from aggregate exposure to cyromazine residues.
E. Aggregate Risks and Determination of Safety for Infants and Children
1. Safety factor for infants and children-- i. In general. In
assessing the potential for additional sensitivity of infants and
children to residues of cyromazine, EPA considered data from
developmental toxicity studies in the rat and rabbit and a 2-generation
reproduction study in the rat. The developmental toxicity studies are
designed to evaluate adverse effects on the developing organism
resulting from pesticide exposure during prenatal development to one or
both parents. Reproduction studies provide information relating to
effects from exposure to the pesticide on the reproductive capability
of mating animals and data on systemic toxicity.
FFDCA section 408 provides that EPA shall apply an additional
tenfold margin of safety for infants and children in the case of
threshold effects to account for 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.
Margins of safety are incorporated into EPA risk assessments either
directly through use of a MOE analysis or through using uncertainty
(safety) factors in calculating a dose level that poses no appreciable
risk to humans. EPA believes that reliable data support using the
standard MOE and uncertainty factor (usually 100 for combined
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
[[Page 50048]]
children or the potency or unusual toxic properties of a compound do
not raise concerns regarding the adequacy of the standard MOE/safety
factor.
ii. Developmental toxicity studies. In the rabbit developmental
study, the maternal (systemic) NOAEL was 10 mg/kg/day, the highest dose
tested. In the rat developmental study, the developmental NOAEL was
identified at 300 mg/kg/day, while the maternal NOAEL was 100 mg/kg/
day. Although there were developmental findings at 600 mg/kg/day in rat
fetuses, these findings were not severe effects and only occurred in
the presence of maternal toxicity.
iii. Reproductive toxicity study. In the multi-generation study in
rats the systemic NOAEL was 30.0 ppm (1.5 mg/kg). The systemic LOAEL
was 1,000.0 ppm (50.0 mg/kg) based upon decreased body weights
associated with deceased food consumption. The developmental/offspring
systemic NOAEL was 1,000.0 ppm. The developmental/offspring systemic
LOAEL was 3,000.0 ppm (150.0 mg/kg) based upon decreased body weight at
birth thru weaning. There were no effect on reproductive parameters at
the highest dose tested (3,000 ppm).
iv. Prenatal and postnatal sensitivity. The results of the rat and
rabbit developmental studies did not demonstrate any potential for
additional prenatal sensitivity. In the rat reproduction study, the
parental and reproductive/developmental NOAELs were established at 1.5
and 50 mg/kg/day respectively which suggests that there is no special
postnatal sensitivity to cyromazine.
v. Conclusion. Based on the completeness and reliability of the
toxicity data and the conservative exposure assessment, the Agency
concludes that an additional safety factor of 10 is not necessary to be
protective of infants and children.
2. Acute risk. There were no toxicological effects attributable to
a single exposure (dose) observed in oral toxicity studies including
the developmental toxicity studies in rats or rabbits.
3. Chronic risk. Using the conservative exposure assumptions
described above, EPA has concluded that aggregate exposure to
cyromazine from food will utilize a maximum 34% of the RfD for children
1-6 years old. EPA generally has no concern for exposures below 100% of
the RfD because the RfD represents the level at or below which daily
aggregate dietary exposure over a lifetime will not pose appreciable
risks to human health. As noted above potential exposure from drinking
water is at a level below EPA's level of comparisons. EPA concludes
that there is a reasonable certainty that no harm will result to
infants and children from aggregate exposure to cyromazine residues.
4. Short- and intermediate-term risk. These aggregate risk
assessments take into account chronic dietary exposure from food and
water (considered to be a background exposure level) plus (acute,
intermediate, or chronic, as applicable) indoor and outdoor residential
exposure. The Agency selected a dose and toxicological endpoint for
assessments of short- and intermediate-term dermal and inhalation risk.
However, since there are no significant residential uses for cyromazine
(either established or pending) at this time, these risk assessments
are not currently required.
5. Determination of safety. Based on these risk assessments, EPA
concludes that there is a reasonable certainty that no harm will result
to infants and children from aggregate exposure to cyromazine residues.
III. Other Considerations
A. Metabolism in Plants and Animals
EPA has reviewed the results of plant metabolism studies (celery,
lettuce and tomato) and livestock metabolism studies (goat and hen).
The metabolism of cyromazine in plants and animals is adequately
understood for the purposes of these tolerances. The major residues in
plants, milk, meat and meat byproducts (except liver and kidney) are
cyromazine and melamine. The major residues in liver and kidney are
cyromazine, melamine and 1-methylcyromazine. EPA concluded (see
background) that the metabolite melamine was no longer a residue of
concern and the metabolite 1-methhylcyromazine was only found in
ruminants. Provided the dietary burden to animals remains low only the
parent compound cyromazine needs to be included in the tolerance
expression and used for dietary risk assessment.
B. Analytical Enforcement Methodology
Methods AG-408 and AG-417A are the tolerance enforcement methods as
published in PAM, Vol II. These methods combined, and with minor
modifications is Method AG-621. The residue data on the treated crops
was analyzed by these methods. The limit of quantitation is 0.05 ppm
for cyromazine and 0.05 ppm for melamine expressed as cyromazine
equivalents. These extraction and cleanup procedures are similar to the
Methods AG-408 and AG-417, but AG-621 uses a gas chromatography for
analysis, while the other methods use high pressure liquid
chromatography for determination of cyromazine and melamine levels in
the crop matrix.
Methods AG-408 and AG-417 as listed in FDA's Pesticide Analytical
Manual (PAM), Vol-II are adequate to enforce the proposed tolerance.
AG-621 is acceptable to support the crop field trial residue data for
cyromazine on RAC's.
The PAM II enforcement method for the determination of cyromazine
residues limit of quantitation (LOQ) is 0.05 ppm in meat, fat, and meat
byproducts.
C. Magnitude of Residues
Adequate residue data were provided to support permament tolerances
of mangoes at 0.3 ppm; onion, green at 2.0 ppm; onion, dry blub at 0.1
ppm; potato at 0.8 ppm; corn, sweet (kernels plus cob with husks
removed) at 0.5 ppm; corn, sweet, forage at 0.5 ppm; corn, sweet,
stover at 0.5 ppm; radish, root at 0.5 ppm; radish, tops at 0.5 ppm;
lima beans at 1.0 ppm; milk at 0.05 ppm; meat, fat and meat byproducts
(of beef, goat, hogs, horses and sheep) at 0.05 ppm and in cotton,
undelinted seed at 0.1 ppm. There were no data available for cotton gin
products (commonly called cotton gin trash). The petitioner has
committed to conduct the additional residue trials and obtain data for
cotton gin byproducts. Although residue data for lima beans were
conducted per the EPA guidance that was in effect at the time of the
field trials, EPA now requires residue data for the succulent beans
without the pods. EPA will issue a conditional registration for these
uses while the petitioner generates the additional data.
Processing data provided for potatoes did not show any
concentration of residues for potato chips above the tolerance level.
For potato granules the concentration factor is below 1.5x value that
is generally used for setting tolerances for processed commodities.
Thus no tolerances are required for processed potato commodities.
The only significant animal feed items from either published or
proposed tolerances are potato culls, processed potato waste and sweet
corn forage and stover. Since none of these items are fed to poultry
the established poultry tolerances are adequate.
A ruminant feeding study was submitted. Based upon the results of
this study the data support permanent tolerances in milk at 0.05 ppm
and meat, fat and meat byproducts (of cattle, goat, hogs, horses and
sheep) at 0.05
[[Page 50049]]
ppm resulting from the feeding of animal commodities indicated above.
D. International Residue Limits
With deletion of the metabolite melamine there are no longer any
compatibility problems between Codex limits, Mexican limits and
proposed U.S. tolerances. There are currently no Codex, Canadian or
Mexican limits for residues of cyromazine on potatoes and lima beans.
There is a Codex limit of 0.01 ppm in milk which is less than the
proposed tolerance of 0.05 ppm. Although residues in milk would most
likely be below 0.05 ppm, this level is the limit of quatitation (LOQ)
used for enforcement purposes for determination of cyromazine residues.
E. Rotational Crop Restrictions
Rotational crop tolerances are being requested for cotton,
undelinated seed, sweet corn (kernels plus cob with husks removed),
sweet corn forage and stover as well as radish, roots and tops
(leaves). When these crops are planted as rotational crops, cyromazine
is persistent in soils and residues can be present in crops that are
rotated to treated crops. For those crops with no tolerances
established, a 1 year plant back interval is specified on the label.
IV. Conclusion
Tolerances are being proposed for residues of cyromazine in mangos
at 0.3 ppm; onion, green at 2.0 ppm; onion, dry bulb at 0.1 ppm; potato
at 0.8 ppm; corn, sweet, (kernels plus cob with husks removed) at 0.5
ppm; corn, sweet, forage at 0.5 ppm; corn, sweet, stover at 0.5 ppm;
radish, root at 0.5 ppm; radish, tops at 0.5 ppm; lima beans at 1.0
ppm; cotton, undelinted seed at 0.1 ppm; milk at 0.05 ppm; and meat,
fat and meat byproducts (of cattle, goat, hogs, horses and sheep) at
0.05 ppm. Conditional Registration for use of cyromazine on succulent
lima beans and cotton are being proposed to allow for development and
review of additional residue field studies. The analysis for cyromazine
using tolerance level residues shows that the proposed uses will not
cause exposure to exceed levels at which EPA believes there is an
appreciable risk. All population subgroups examined by EPA are exposed
to cyromazine residues at levels below 100% of the RfD for chronic
effects. Based on the information and data considered, EPA concludes
that the proposed tolerances will be safe. Therefore, these tolerances
are being proposed as set forth below.
V. Public Comment Procedures
EPA invites interested persons to submit written comments,
information, or data in response to this proposed rule. After
consideration of comments, EPA will issue a final rule. Such rule will
be subject to objections. Failure to file an objection within the
appointed period will constitute waiver of the right to raise in future
proceedings issues resolved in the final.
VI. Public Record and Electronic Submissions
EPA has established a record for this regulation under docket
control number [OPP-300913] (including any comments and data submitted
electronically). A public version of this record, including printed,
paper versions of electronic comments, which does not include any
information claimed as CBI, is available for inspection from 8:30 a.m.
to 4 p.m., Monday through Friday, excluding legal holidays. The public
record is located in Room 119 of the Public Information and Records
Integrity Branch, Information Resources and Services Division (7502C),
Office of Pesticide Programs, Environmental Protection Agency, Crystal
Mall #2, 1921 Jefferson Davis Hwy., Arlington, VA.
The official record for this regulation, as well as the public
version, as described in this unit will be kept in paper form.
Accordingly, EPA will transfer any copies of comments received
electronically into printed, paper form as they are received and will
place the paper copies in the official record. The official record is
the paper record maintained at the Virginia address in ``ADDRESSES'' at
the beginning of this document.
VII. Regulatory Assessment Requirements
This action proposes to establish tolerance under FFDCA section
408(e). The Office of Management and Budget (OMB) has exempted these
types of actions from review under Executive Order 12866, entitled
Regulatory Planning and Review (58 FR 51735, October 4, 1993). In
addition this proposed rule does not contain any information
collections subject to OMB approval under the Paperwork Reduction Act
(PRA), 44 U.S.C. 3501 et seq., or impose any enforceable duty or
contain any unfunded mandate as described under Title II of the
Unfunded Mandates Reform Act of 1995 (UMRA) (Public Law 104-4). Nor
does it require any prior consultation as specficed by Executive Order
12875, entitled Enhancing the Intergovernmental Partnership (58 FR
58093, October 28, 1993), or special considerations as required by
Executive Order 12898, entitled Federal Actions to Address
Environmental Justice in Minority Populations and Low-Income
Populations (59 FR 7629, February 16, 1994), or require OMB review in
accordance with Executive Order 13045, entitled Protection of Children
from Environmental Health Risks and Safety Risks (62 FR 19885, April
23, 1997).
In addition, under the Regulatory Flexibility Act (RFA) (5 U.S.C.
601 et seq.), the Agency previously assessed whether establishing
tolerances, exemptions from tolerances, raising tolerance levels or
expanding exemptions might adversely impact small entities and
concluded, as a generic matter, that there is no adverse economic
impact. The factual basis for the Agency's generic certification for
tolerance actions published on May 4, 1981 (46 FR 24950), and was
provided to the Chief Counsel for Advocacy of the Small Business
Administration.
List of Subjects in 40 CFR Part 180
Environmental protection, Administrative practice and procedure,
Agricultural commodities, Pesticides and pests, Reporting and
recordkeeping requirements.
Dated: August 26, 1999.
James Jones,
Director, Registration Division, Office of Pesticide Programs.
Therefore, it is proposed that 40 CFR part 180 be amended as
follows:
PART 180 [AMENDED]
1. The authority citation for part 180 continues to read as
follows:
Authority: 21 U.S.C. 321(q), 346a and 371.
2. Section 180.414, is revised to read as follows:
Sec. 180.414 Cyromazine; tolerances for residues.
(a) General. (1) Tolerances are established for residues of the
insecticide cyromazine (N-cyclopropyl-1,3,5-triazine-2,4,6 triamine) in
or on the following raw agricultural commodities:
------------------------------------------------------------------------
Parts per
Commodity million
------------------------------------------------------------------------
Cattle, fat.................................................. 0.05
Cattle, meat................................................. 0.05
Cattle, meat byproduct....................................... 0.05
Cucurbit vegetables.......................................... 1.0
Eggs......................................................... 0.25
[[Page 50050]]
Goats, fat................................................... 0.05
Goats, meat.................................................. 0.05
Goats, meat byproduct........................................ 0.05
Hogs, fat.................................................... 0.05
Hogs, meat................................................... 0.05
Hogs, meat byproduct......................................... 0.05
Horses, fat.................................................. 0.05
Horses, meat................................................. 0.05
Horses, meat byproduct....................................... 0.05
Leafy vegetables (except Brassica)........................... 7.0
Lima beans................................................... 1.0
Mango1....................................................... 0.3
Milk......................................................... 0.05
Mushrooms.................................................... 1.0
Onion, dry bulb.............................................. 2.0
Onion, green................................................. 0.1
Peppers...................................................... 1.0
Potato....................................................... 0.8
Poultry, fat (from chicken layer hens and chicken breeder 0.05
hens only)..................................................
Poultry, meat byproduct (from chicken layer hens and chicken 0.05
breeder hens only)..........................................
Poultry, meat (from chicken layer hens and chicken breeder 0.05
hens only)..................................................
Sheep, fat................................................... 0.05
Sheep, meat.................................................. 0.05
Sheep, meat byproduct........................................ 0.05
Tomato....................................................... 0.5
------------------------------------------------------------------------
1There are no U.S. registrations on mango as of (inset date of
publication).
(2) The additive cyromazine (N-cyclopropyl-1,3,5-triazine-2,4,6-
triamine) may be safely used in accordance with the following
prescribed conditions:
(i) It is used as a feed additive only in the feed for chicken
layer hens and chicken breeder hens at the rate of not more than 0.01
pound of cyromazine per ton of poultry feed.
(ii) It is used for control of flies in manure of treated chicken
layer hens and chicken breeder hens.
(iii) Feeding of cyromazine-treated feed must stop at least 3 days
(72 hours) before slaughter. If the feed is formulated by any person
other than the end user, the formulator must inform the end user, in
writing, of the 3-day (72 hours) preslaughter interval.
(iv) To ensure safe use of the additive, the labeling of the
pesticide formulation containing the feed additive shall conform to the
labeling which is registered by the U.S. Environmental Protection
Agency, and the additive shall be used in accordance with this
registered labeling.
(v) Residues of cyromazine are not to exceed 5.0 parts per million
(ppm) in poultry feed.
(b) Section 18 emergency exemptions. Time-limited tolerances are
established for the combined residues of the insecticide cyromazine (N-
cyclopropyl-1,3,5-triazine-2,4,6-triamine) and its metabolite, melamine
(1,3,5-triazine-2,4,6-triamine), in connection with use of the
pestiicde under section 18 emergency exemption granted by EPA. The
tolerances are specified in the following table. These tolerances
expire and are revoked on the date specified in the table.
------------------------------------------------------------------------
Expiration/
Commodity Parts per revocation
million date
------------------------------------------------------------------------
Turkey, fat................................... 0.05 4/1/00
Turkey, meat.................................. 0.05 4/1/00
Turkey, meat byproduct........................ 0.05 4/1/00
------------------------------------------------------------------------
(c) Tolerances with regional registrations. As defined in 180.1(n),
are established for the residues of cyromazine (N-cyclopropyl-1,3,5-
triazine-2,4,6-triamine) in or on the following raw agricultural
commodities:
------------------------------------------------------------------------
Parts per
Commodity million
------------------------------------------------------------------------
Cabbage, Chinese............................................. 3.0
Mustard, Chinese............................................. 3.0
------------------------------------------------------------------------
(d) Indirect or inadvertent residues. Tolerances are established
for the indirect or inadvertent residues of cyromazine (N-cyclopropyl-
1,3,5-triazine-2,4,6-triamine), in or on the raw agricultural
commodities when present therein as a result of the application of
cyromazine to growing crops listed in paragraphs (a)(1) of this
section.
------------------------------------------------------------------------
Parts per
Commodity million
------------------------------------------------------------------------
Cotton, undelinted seed...................................... 0.1
Corn, sweet, (kernels plus cob with husks removed)........... 0.5
Corn, sweet, forage.......................................... 0.5
Corn, sweet, stover.......................................... 0.5
Radish, root................................................. 0.5
Radish, tops (leaves)........................................ 0.5
------------------------------------------------------------------------
[FR Doc. 99-24047 Filed 9-14-99; 8:45 am]
BILLING CODE 6560-50-F
