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Clopyralid - Pesticide Petition Filing 1/99

[Federal Register: February 9, 1999 (Volume 64, Number 26)]
[Notices]
[Page 6351-6357]
From the Federal Register Online via GPO Access [wais.access.gpo.gov]
[DOCID:fr09fe99-75]

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ENVIRONMENTAL PROTECTION AGENCY

[PF-856; FRL-6058-3]

Notice of Filing of Pesticide Petitions

AGENCY: Environmental Protection Agency (EPA).

ACTION: Notice.

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

DATES: Comments, identified by the docket control number PF-856, must
be received on or before March 11, 1999.

ADDRESSES: By mail submit written comments to: Public Information and
Records Integrity Branch, Information Resources and Services Division
(7502C), Office of Pesticides Programs, Environmental Protection
Agency, 401 M St., SW., Washington, DC 20460. In person bring comments
to: Rm. 119, CM #2, 1921 Jefferson Davis Highway, Arlington, VA.
    Comments and data may also be submitted electronically to: opp-
docket@epamail.epa.gov. Follow the instructions under "SUPPLEMENTARY
INFORMATION." No confidential business information should be submitted
through e-mail.
    Information submitted as a comment concerning this document may be
claimed confidential by marking any part or all of that information as
"Confidential Business Information" (CBI). CBI should not be
submitted through e-mail. Information marked as CBI will not be
disclosed except in accordance with procedures set forth in 40 CFR part
2. A copy of the comment that does not contain CBI must be submitted
for inclusion in the public record. Information not marked confidential
may be disclosed publicly by EPA without prior notice. All written
comments will be available for public inspection in Rm. 1132 at the
address given above, from 8:30 a.m. to 4 p.m., Monday through Friday,
excluding legal holidays.

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

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                                   Office location/
        Product Manager            telephone number          Address
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Joanne I. Miller (PM 23)......  Rm. 237, CM #2, 703-    1921 Jefferson
                                 305-6224, e-            Davis Hwy,
                                 mail:miller.joanne@ep   Arlington, VA
                                 amail.epa.gov.
Sidney Jackson (PM 23)........  Rm. 233, CM #2, 703-    Do.
                                 305-7610, e-mail:
                                 jackson.sidney@epamai
                                 l.epa.gov.
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SUPPLEMENTARY INFORMATION: EPA has received pesticide petitions as
follows proposing the establishment and/or amendment of regulations for
residues of certain pesticide chemicals in or on various food
commodities under section 408 of the Federal Food, Drug, and Comestic
Act (FFDCA), 21 U.S.C. 346a. EPA has determined that these petitions
contain data or information regarding the elements set forth in section
408(d)(2); however, EPA has not fully evaluated the sufficiency of the
submitted data at this time or whether the data supports granting of
the petition. Additional data may be needed before EPA rules on the
petition.
    The official record for this notice of filing, as well as the
public version, has been established for this notice of filing under
docket control number [PF-856] (including comments and data submitted
electronically as described below). 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 official record is located at the address in
"ADDRESSES" at the beginning of this document.
    Electronic comments can be sent directly to EPA at:
    opp-docket@epamail.epa.gov

    Electronic comments must be submitted as an ASCII file avoiding the
use of special characters and any form of encryption. Comments and data
will also be accepted on disks in Wordperfect 5.1 file format or ASCII
file format. All comments and data in electronic form must be
identified by the docket number (insert docket number) and appropriate
petition number. Electronic comments on notice may be filed online at
many Federal Depository Libraries.

List of Subjects

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

    Dated: January 29, 1999.

James Jones,

Director, Registration Division, Office of Pesticide Programs.

Summaries of Petitions

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

1. Dow AgroSciences LLC

 PP 8F 3600

    EPA has received a pesticide petition (8F 3600) from Dow
AgroSciences LLC, 9330 Zionsville Road, Indianapolis, IN 46268,
proposing pursuant to section 408(d) of the Federal Food, Drug, and
Cosmetic Act (FFDCA), 21 U.S.C. 346a(d), to amend 40 CFR part 180 by
establishing a tolerance for residues of the herbicide clopyralid in or
on the raw agricultural commodity sugar beet, roots at 2.0 parts per
million (ppm) and sugar beet, tops at 3.0 ppm and on the processed
agricultural commodity (PAC) sugar beet, molasses at 16.0 ppm. at sugar
beet, roots at 2.0 ppm and sugar beet, tops at 3.0 ppm and on the
processed agricultural commodity (PAC) sugar beet, molasses at 16.0
ppm. EPA has determined that the petition contains data or information
regarding the elements set forth in section 408(d)(2) of the FFDCA;
however, EPA has not fully evaluated the sufficiency

[[Page 6352]]

of the submitted data at this time or whether the data supports
granting of the petition. Additional data may be needed before EPA
rules on the petition.

A. Residue Chemistry

    1. Plant metabolism. The metabolism in plants is adequately
understood. No metabolites of significance were detected in plant
metabolism studies.
    2. Analytical method. There is a practical analytical method for
detecting and measuring levels of clopyralid in or on food with a limit
of quantitation (LOQ) of 0.05 ppm that allows monitoring of food with
residues at or above the levels set in these tolerances. EPA has
provided information on this method to FDA. The method is available to
anyone who is interested in pesticide residue enforcement.
    3. Magnitude of residues. Tolerances for residues of the herbicide
clopyralid in or on the following raw agricultural commodities, sugar
beet roots and tops and the processed agricultural commodity molasses,
were established on August 12, 1988 (53 FR 33488, 33489) at 0.5, 0.5,
and 7.0 ppm, respectively, based upon residue data generated by Craven
Laboratories. The validity of these data were in question and Dow
AgroSciences repeated the residue studies. The last of the required
residue data using a 105 day pre-harvest interval (PHI) were submitted
to the Agency in June 1994. This pesticide petition proposes increased
tolerances based upon data using a 45 day PHI. Residues of clopyralid
were determined in roots and tops from several varieties of sugar
beets, which were harvested from plots treated at the currently labeled
season-maximum rate of 0.25 lb ae/acre in one application. Field test
plots were located at thirteen sites representing the major U.S.
production areas. Highest residues at the 45 day PHI for roots averaged
0.91 μg/g with the highest individual value of 1.47 μg/
g, and for tops averaged 1.52 μg/g with the highest individual
value of 2.48 μg/g. Based on the data, it is expected that
residues of clopyralid in or on sugar beets as a raw agricultural
commodity will not exceed proposed revised tolerances of 2 μg/g
in roots and 3 μg/g in tops when the PHI is 45 days or longer.
With a concentration factor of 8, the proposed tolerance for sugar beet
molasses is 16 μg/g. The proposed revised tolerances would
adequately cover these anticipated residues.

B. Toxicological Profile

    1. Acute toxicity. Clopyralid has low acute toxicity. The rat oral
LD50 is 5,000 milligram/kilograms (mg/kg) or greater for
males, and females. The rabbit dermal LD50 is greater than
2,000 mg/kg and the rat inhalation LC50 is greater than 1.0
mg/L air (the highest attainable concentration). In addition,
clopyralid is not a skin sensitizer in guinea pigs and is not a dermal
irritant. Technical clopyralid is an ocular irritant but ocular
exposure to the technical material would not normally be expected to
occur to infants or children or the general public. End use
formulations of clopyralid have similar low acute toxicity profiles and
most have low ocular toxicity as well. Therefore, based on the
available acute toxicity data, clopyralid does not pose any acute
dietary risks.

    2. Genotoxicty. Clopyralid is not genotoxic. The following studies
have been conducted and all were negative for genotoxic responses. Ames
bacterial mutagenicity assay (with and without exogenous metabolic
activation); Host-Mediated assay In vivo cytogenetic test, rat; In vivo
cytogenetic test, mouse; In vivo dominant lethal test, rat; In vitro
unscheduled DNA synthesis assay in primary rat hepatocyte cultures; In
vitro mammalian cell gene mutations assay in Chinese hamster ovary cell
cultures (with and without exogenous metabolic activation).
    3. Reproductive and developmental toxicity. Developmental toxicity
was studied using rats and rabbits. The developmental study in rats
resulted in a developmental no-observed adverse effect level (NOAEL) of
> 250 milligram/kilograms/day (mg/kg/day) (a maternally toxic dose) and
a maternal toxicity NOAEL of 75 mg/kg/day. A 1974 study in rabbits
revealed no evidence of developmental or maternal toxicity at 250 mg/
kg/day; thus the developmental and maternal NOAEL was > 250 mg/kg/day.
A more recent study in rabbits (1990) resulted in developmental and
maternal NOAELs of 110 mg/kg/day based on maternal toxicity at 250 mg/
kg/day. Based on all of the data for clopyralid, there is no evidence
of developmental toxicity at dose levels that do not result in maternal
toxicity. In a 2-generation reproduction study in rats, pups from the
high dose group which were fed diets containing clopyralid had a slight
reduction in body weight during lactation and an increase in liver
weights in F1a and F1b weanlings. The NOAEL for parental systemic
toxicity was 500 mg/kg/day. There was no effect on reproductive
parameters at > 1,500 mg/kg/day nor was there an adverse effect on the
morphology, growth or viability of the offspring; thus, the
reproductive NOAEL is > 1,500 mg/kg/day.
    4. Subchronic toxicity. The following studies have been conducted
using clopyralid. In a rat 90 day feeding study, Fischer 344 rats were
fed diets containing clopyralid at doses of 5, 15, 50 or 150 mg/kg/day
with no adverse effects attributed to treatment. In a second study,
Fischer 344 rats were fed diets containing clopyralid at doses of 300,
1,500 and 2,500 mg/kg/day. Effects at the highest doses were decreased
food consumption accompanied by decreased body weights and weight gains
in both males and females. Slightly increased mean relative liver and
kidney weights were noted in males of all doses, and in females at the
top 2 doses. Because there were no other effects, the kidney and liver
weight effects were judged as being adaptive rather than directly
toxic. The no-observed adverse effect level (NOAEL) was 1,500 mg/kg/day
for males and females. The NOAEL was 300 mg/kg/day for females. In a
mouse 90 day feeding study, B6C3F1 mice were fed diets containing
clopyralid at doses of 200, 750, 2,000 or 5,000 mg/kg/day. A slight
decrease in body weight occurred at the top dose in both sexes. The
liver was identified as the target organ based on slight increases in
liver weights and minimal microscopic alterations at the higher dose
levels. The liver changes were considered to be reversible and
adaptive. The NOAEL for males was 2,000 mg/kg/day, and for females was
750 mg/kg/day. In a 180 day feeding study, beagle dogs were fed diets
containing clopyralid at doses of 15, 50 or 150 mg/kg/day; there were
no adverse effects. In a second dietary study, dogs also were fed diets
containing clopyralid at doses of 15, 50 or 150 mg/kg/day; the only
effect was an increase in the mean relative liver weight in females at
the 150 mg/kg/day. In a 21 day dermal study, clopyralid was applied by
repeated dermal application to New Zealand White rabbits at dose levels
up to 1,000 mg/kg/day. Treatment produced no systemic effects.
    5. Chronic toxicity. In a chronic toxicity and oncogenicity study,
Sprague-Dawley rats were fed diets containing clopyralid at doses of 5,
15, 50 or 150 mg/kg/day. The only effect was a trend toward a decreased
body weight of female rats receiving the 150 mg/kg/day dose with a
NOAEL of 50 mg/kg/day. In a second study clopyralid was fed to Fischer
344 rats in the diet at doses of 15, 150 or 1,500 mg/kg/day. The
effects were confined almost entirely to the 1,500 mg/kg/day dose
groups and included slightly decreased food consumption and body
weights, slightly increased liver and kidney

[[Page 6353]]

weights and macroscopic and microscopic changes in the stomach. No
tumorigenic response was present. The NOAEL for this study was 150 mg/
kg/day. B6C3F1 mice were maintained for 2 years on diets formulated to
provide targeted dose levels of 10, 500 or 2,000 mg/kg/day. The only
evidence of toxicity was body weight depression in males dosed at 2,000
mg/kg/day. There was no evidence of tumorigenic response at any dose
level. Based on the chronic toxicity data, EPA has established the RfD
for clopyralid at 0.5 mg/kg/day. The RfD for clopyralid is based on a 2
year chronic oncogenicity study in rats with a no-observed-effect level
(NOAEL) of 50 mg/kg/day and an uncertainty (or safety) factor of 100.
Thus, it would not be necessary to require the application of an
additional uncertainty factor above the 100-fold factor already applied
to the NOAEL. Using its Guidelines for Carcinogen Risk Assessment
published September 24, 1986 (51 FR 33992), clopyralid would be
classified as Group E for carcinogenicity (no evidence of
carcinogenicity) based on the results of the carcinogenicity studies.
There was no evidence of carcinogenicity in 2 year feeding studies in
mice and rats at the dosage levels tested. The doses tested are
adequate for identifying a cancer risk. Thus, a cancer risk assessment
would not be appropriate.
    6. Animal metabolism. Disposition and metabolism of clopyralid were
tested in male and female rats at a dose of 5 mg/kg (oral). The
majority of a radioactive dose was excreted in 24 hours of all dose
groups. Fecal elimination was minor. Detectable levels of residual
radioactivity were observed in the carcass and stomach at 72 hours
post-dose. HPLC and TLC analysis of urine and fecal extracts showed no
apparent metabolism of clopyralid.

    7. Metabolite toxicology. There are no clopyralid metabolites of
toxicological significance.
    8. Endocrine disruption. There is no evidence to suggest that
clopyralid is neurotoxic.

C. Aggregate Exposure

    1. Dietary exposure. For purposes of assessing the potential
dietary exposure under these tolerances, exposure is estimated based on
the theoretical maximum residue contribution (TMRC) from the existing
and this proposed amended tolerance for clopyralid on food crops. The
TMRC is obtained by multiplying the tolerance level residues by the
consumption data which estimates the amount of those food products
eaten by various population subgroups. Exposure of humans to residues
could also result if such residues are transferred to meat, milk,
poultry or eggs. The following assumptions were used in conducting this
exposure assessment. 100% of the crops were treated, the raw
agricultural commodities (RAC) residues would be at the level of the
tolerance, certain processed food residues would be at anticipated
(average) levels based on processing studies and all current and
pending tolerances were included. This results in an over estimate of
human exposure and a conservative assessment of risk. Based on a NOAEL
of 50 mg/kg/day in a 2 year chronic feeding/oncogenicity study in the
rat and a hundredfold safety factor, the RfD would be 0.5 mg/kg/day.
Consequently, these tolerances have a TMRC of 0.010277 mg/kg/day and
would utilize approximately 2.1% of the RfD for the general U.S.
population.
    i. Food. The Toxicology database indicates there is no concern
regarding acute and chronic dietary risk since the available data do
not indicate any evidence of significant toxicity from exposure by the
oral route.
    ii. Drinking water. Another potential source of dietary exposure to
residues of pesticides are residues in drinking water. There is no
established maximum concentration level (MCL) for residues of
clopyralid in drinking water. Although there has been limited
detections at parts per billion (ppb) levels in some of the specially
designed studies under highly vulnerable test conditions, no ongoing
monitoring studies (U.S. Geological Survey, Selected Water Resources
Abstracts; Pesticides in Ground WaterDatabase - A Compilation of
Monitoring Studies: 1971-1991 National Summary; U.S. Department of
Agriculture, AGRICOLA database; and, U.S. Department of Commerce,
National Technical Information Service) have reported residues of
clopyralid in ground or surface waters.
    Based on the physical and chemical characteristics of clopyralid,
such as water solubility and its stability under hydrolysis and
photolysis, it has potential for downward movement through the soil
profile. However, the behavior of the compound under field conditions
demonstrates fairly rapid degradation and limited downward movement.
Degradation based on 20 field dissipation sites indicated an average
half-life of 25 days. Degradation is driven primarily by microbial
processes. Downward movement through the soil profile was generally
confined to the upper 18 inches of the soil profile. Validated computer
modeling also predicted the maximum depth of residues to be 18-inches,
with no detections predicted at 6 months after application.
    Because the laboratory derived physical/chemical properties of
clopyralid indicate a potential for downward movement, lysimeter
studies were conducted. In a U.S. study, undisturbed soil columns
(lysimeters), 8 inches in diameter, and 3 feet deep, were treated with
950 g ae/ha (about 5 x labeled use rates) in actual field conditions.
Residues of clopyralid in soil as well as soil-solution (leachate) were
collected in the closed system. The average depth of movement for the
majority of clopyralid (center of mass) was 11 inches, and no
detectable residues were observed in the leachate. In a European study,
lysimeters 1-3 ft. diameter, and 3 ft. deep, were treated with 120 and
240 g ae/ha in actual field conditions. The average center of mass was
12 inches. No detectable residues were observed in the lysimeters. The
amount of 14C in leachate accumulated over 2 years in the
degraded loess and silty sand lysimeters, was only 0.6% and 0.3% of
applied, respectively. The leachate concentrations of 14C-
labeled clopyralid in degraded loess and silty sand throughout the
first 10-16 months of the study ranged from 0.002-0.14 μg/l ppb
and 0.003-0.02 ppb, respectively. A second European lysimeter study
with silty sand lysimeters treated with 120 g ae/ha revealed a 2 year
cumulative clopyralid leachate of only 0.1% of applied (0.04 ppb).
These studies demonstrate that in lysimeter test systems, under field
environmental conditions, clopyralid rapidly dissipates through
mineralization to carbon dioxide. Also the very low levels observed in
leachate demonstrate that there is very little potential for clopyralid
to leach through soil and contaminate ground water.
    In summary, these data on potential water exposure indicate
insignificant additional dietary intake of clopyralid and any exposure
is more than compensated for in the conservative dietary risk
evaluation. Therefore, it is concluded that there is a reasonable
certainty of no harm even at potential upper limit exposures to
clopyralid from drinking water.
    2. Non-dietary exposure. There is a non-dietary use registered
under the Federal Insecticide, Fungicide and Rodenticide Act. The use
is for weed control in residential turf and ornamentals. Potential
exposures for children from non-occupational uses is therefore limited
to turf and ornamental re-entry and this exposure is low.

[[Page 6354]]

    3. Short-term or intermediate-term. The data for clopyralid does
not indicate any evidence of significant toxicity by the dermal and
inhalation routes. Consequently, there is no concern for short-term or
intermediate-term residential risk. Therefore, a short-term or
intermediate-term residential risk assessment would not be required.
    4. Chronic. As part of a hazard assessment process an endpoint of
concern is determined for the chronic occupational or residential risk
assessment. However, as indicated, the exposures that would result from
the use of clopyralid are of an intermittent nature. The frequency and
duration of these exposures do not exhibit a chronic exposure pattern.
The exposure does not occur often enough to be considered a chronic
exposure; i.e., a continuous exposure that occurs for at least several
months. Therefore, it would not be appropriate to aggregate exposure
from the residential use with exposure from food and drinking water.
    5. Acute. No concern would exist for an acute dietary assessment
for clopyralid because the available data indicates no evidence of
significant toxicity from a 1 day or single event exposure by the oral
route. Therefore, an acute dietary risk assessment would not be
required.

D. Cumulative Effects

    The potential for cumulative effects of clopyralid and other
substances that have a common mechanism of toxicity was considered. The
mammalian toxicity of clopyralid is well defined. However, no reliable
information exists to indicate that toxic effects produced by
clopyralid would be cumulative with those of any other chemical
compound. Additionally, clopyralid does not appear to produce a toxic
metabolite produced by other substances. Therefore, consideration of a
common mechanism of toxicity with other compounds is not appropriate at
this time. Thus, only the potential exposures to clopyralid were
considered in the aggregate exposure assessment.

E. Safety Determination

    1. U.S. population. Based on a NOAEL of 50.80 milligram/kilogram/
body weight/day (mg/kg/bwt/day) from a 2 year rat feeding study with a
decreased mean bwt gain effect, and using an uncertainty factor of 100
to account for the interspecies extrapolation and intraspecies
variability, a RfD of 0.5 mg/kg/bwt/day was used for this assessment of
chronic risk. As indicated, there is no endpoint of concern identified
with acute and short- or intermediate-term exposures. Based on the
known toxicity and exposure data, the proposed and existing tolerances
would utilize approximately 2.1% of the RfD for the U.S. population.
And, as indicated previously, whatever upper limit might be used for
drinking water exposure, the exposure estimate for clopyralid would not
exceed the RfD. Generally, exposures below 100% of the RfD are of no
concern because the RfD represents the level at or below which daily
aggregate dietary exposure over a lifetime will not pose appreciable
risk to human health. Thus, there is a reasonable certainty that no
harm will result from aggregate exposure to clopyralid residues.
    2. Infants and children. In assessing the potential for additional
sensitivity of infants and children to residues of clopyralid, data
from developmental toxicity studies in the rat and rabbit and a 2-
generation reproduction study in the rat were considered. The
developmental toxicity studies are designed to evaluate adverse effects
on the developing organism during prenatal development resulting from
pesticide exposure to one or both parents. Reproduction studies provide
(i) information relating to effects from exposure to the pesticide on
the reproductive capability of mating animals and (ii) data on systemic
toxicity.
    Developmental toxicity was studied using rats and rabbits. The
developmental study in rats resulted in a developmental NOAEL of > 250
mg/kg/day (a maternally toxic dose), and a maternal toxicity NOAEL of
75 mg/kg/day. A 1974 study in rabbits revealed no evidence of
developmental or maternal toxicity at 250 mg/kg/day; thus the
developmental andmaternal NOAEL was > 250 mg/kg/day. A more recent
study in rabbits (1990) resulted in developmental and maternal NOAEL's
of 110 mg/kg/day based on severe maternal toxicity at 250 mg/kg/day.
Based on all of the data for clopyralid, there is no evidence of
developmental toxicity at dose levels that do not result in maternal
toxicity.
    In a 2-generation reproduction study in rats, pups from the high
dose group which were fed diets containing clopyralid had a slight
reduction in bwt during lactation and an increase in liver weights in
F1a and F1b weanlings. The NOAEL for parental systemic toxicity was 500
mg/kg/day. There was no effect on reproductive parameters at > 1,500
mg/kg/day nor was there an adverse effect on the morphology, growth or
viability of the offspring; thus, the reproductive NOAEL is > 1,500 mg/
kg/day.
    FFDCA section 408 provides that EPA may apply an additional safety
factor for infants and children in the case of threshold effects to
account for pre- and post-natal toxicity and the completeness of the
database. Based on the current toxicological data requirements, the
database relative to pre- and post-natal effects for children is
complete. These data suggest minimal concern for developmental or
reproductive toxicity and do not indicate any increased pre- or post-
natal sensitivity. Therefore, an additional uncertainty factor is not
necessary to protect the safety of infants and children and that the
RfD at 0.5 mg/kg/day is appropriate for assessing aggregate risk to
infants and children.
    The percent of the RfD that will be utilized by the aggregate
exposure from all tolerances to clopyralid will be much less than 10%
for non-nursing infants and for children (1-6 years of age). Therefore,
based on the completeness and reliability of the toxicity data and the
conservative exposure assessment, it is concluded that there is a
reasonable certainty that no harm will result to infants and children
from aggregate exposure to clopyralid residues.

F. International Tolerances

    There are no Codex maximum residue levels established for
clopyralid.

[FR Doc. 99-3146 Filed 2-8-99; 8:45 am]
BILLING CODE 6560-50-F