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Clopyralid - Pesticide Tolerance Petition 12/96

[Federal Register: December 11, 1996 (Volume 61, Number 239)] [Notices]
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ENVIRONMENTAL PROTECTION AGENCY
[PF-675; FRL-5574-4]
Pesticide Tolerance Petition; Notice of Filing
AGENCY: Environmental Protection Agency (EPA).
ACTION: Notice of filing.
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SUMMARY: This notice is a summary of a pesticide petition proposing the
establishment of a regulation for residues of clopyralid in or on field corn.
This summary was prepared by the petitioner.
DATES: Comments, identified by the docket number [PF-675], must be received on
or before, January 10, 1997.
ADDRESSES: By mail, submit written comments to: Public Response and Program
Resources Branch Field Operations Division (7506C), Office of Pesticide
Programs, Environmental Protection Agency, 401 M St., SW., Washington, DC
20460. In person, bring comments to: Rm. 1132, CM #2, 1921 Jefferson Davis
Highway, Arlington, VA 22202.
Comments and data may also be submitted electronically by sending electronic
mail (E-mail) to: 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 docket number [PF-675]. Electronic comments on this
notice may be filed online at many Federal Depository Libraries. Additional
information on electronic submissions can be found below in this document.
Information submitted as comments 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 a.m. to 4:30 p.m., Monday through Friday,
excluding legal holidays.
FOR FURTHER INFORMATION CONTACT: Joanne Miller, PM-23, (7505C) Rm. 237,
Crystal Mall #2, 1921 Jefferson Davis Highway, Arlington, VA 22202, (703) 305-
6224; e-mail: miller.joanne@epamail.epa.gov.
SUPPLEMENTARY INFORMATION: EPA has received a pesticide petition (PP) 8F3622
from DowElanco, 9330 Zionsville Road Indianapolis, IN 46268- 1054, proposing
pursuant to section 408(d) of the Federal Food, Drug and Cosmetic Act, 21
U.S.C. section 346a(d), to amend 40 CFR Part 180 by establishing a tolerance
for residues of the herbicide clopyralid in or on the raw agricultural
commodities (RACs) field corn, fodder at 10.0 ppm; field corn, forage at 3.0
ppm; field corn, grain at 1.0 ppm and on processed agricultural commodity
(PAC) field corn, milling fractions at 1.5 ppm. The proposed analytical method
is available for enforcement purposes.
Pursuant to the section 408(d)(2)(A)(i) of the FFDCA, as amended, DowElanco
has submitted the following summary of information, data and arguments in
support of their pesticide petition. This summary was prepared by DowElanco
and EPA has not fully evaluated the merits of the petition. EPA edited the
summary to clarify that the conclusions and arguments were the petitioners and
not necessarily EPAs and to remove certain extraneous material.
I. DOWELANCO Petition Summary:
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 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. Time limited tolerances were established on April
25, 1994 (59 FR 19639) for residues of the herbicide clopyralid in or on the
following raw agricultural commodities which are to expire December 31, 1996:
field corn, grain at 1.0 parts per million (ppm), field corn, fodder at 10.0
ppm, field corn, forage at 3.0 ppm, and for corn processed milling fractions
at 1.5 ppm. Adequate residue data supporting these tolerances were submitted
to the Agency in mid year 1994.
4. Residues of Clopyralid Found in Field Corn - Clopyralid was applied at the
maximum label rate and residues were detected at the following ppm ranges;
Grain 0.01 - 0.8, Fodder 0.02 - 8.8, and Silage 0.04 - 2.7. The proposed
tolerances would adequately cover these anticipated residues.
5. Residues of Clopyralid Found in Processed Field Corn - Clopyralid was
applied to corn at approximately 1X and 5X the label rate. The 5X treatment
was used for the processing residue study. At the 5X rate, the corn grain RAC
(raw agricultural commodity) sample was found to contain 4.3 ppm clopyralid.
Starch and refined oil samples obtained from the wet milling of corn contained
no residues above the LOQ (0.05 ppm) of the method, while crude oil was found
to contain 0.063 ppm. The dry milling fractions contained 4.9 ppm in flour,
2.7 ppm in meal, with no residues above the LOQ found in crude and refined
oil. Grain dust contained 4.8 ppm clopyralid, similar to levels found in the
RAC. The proposed milling fractions tolerance would cover these residue levels
when adjusted from the 5X treatment rate.
B. Toxicological Profile
1. Acute Toxicity. Clopyralid has low acute toxicity. The rat oral LD50 is
5000 mg/kg or greater for males and females. The rabbit dermal LD50 is less
than or equal to 2000 mg/kg and the rat inhalation LC50 is less than or equal
to 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. Genotoxicity. 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 NOEL of >250 mg/kg/day (a maternally toxic dose) and a maternal
toxicity NOEL 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 NOEL was >250 mg/kg/day. A more recent study in rabbits (1990)
resulted in developmental and maternal NOELs 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 fla and flb
weanlings. The NOEL for parental systemic toxicity was 500 mg/kg/day. There
was no effect on reproductive parameters at >1500 mg/kg/day nor was there an
adverse effect on the morphology, growth or viability of the offspring; thus,
the reproductive NOEL is >1500 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, 1500 and 2500 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 3 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 1500 mg/kg/day for
males and females. The no-observed-effect level (NOEL) 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, 2000 or 5000 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 NOEL for males was 2000
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 1000 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 NOEL 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 1500 mg/kg/day. The effects were confined almost entirely to the
1500 mg/kg/day dose groups and included slightly decreased food consumption
and body weights, slightly increased liver and kidney weights and macroscopic
and microscopic changes in the stomach. No tumorigenic response was present.
The NOEL for this study was 15 mg/kg/day.
B6C3F1 mice were maintained for 2 years on diets formulated to provide
targeted dose levels of 10, 500 or 2000 mg/kg/day. The only evidence of
toxicity was body weight depression in males dosed at 2000 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 milligrams (mg)/kilogram (kg)/day. The RfD for clopyralid is based on a
2-year chronic oncogenicity study in rats with a no-observed-effect level
(NOEL) 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 NOEL.
6. Carcinogenicity. 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.
7. 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 pooled urine and fecal extracts showed no apparent metabolism of
clopyralid.
8. Metabolite Toxicity. There are no clopyralid metabolites of toxicological
significance.
9. Endocrine Effects. There is no evidence to suggest that clopyralid has an
effect on any endocrine system.
C. Aggregate Exposure
1. Dietary Exposure - Food. For purposes of assessing the potential dietary
exposure under these tolerances, exposure is estimated based on the TMRC from
the existing and pending tolerances 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 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 overestimate of human exposure and a conservative assessment of risk.
Based on a NOEL of 50 mg/kg/day in a 2-year chronic feeding/ oncogenicity
study in the rat and a hundredfold safety factor, the reference dose (RfD)
would be 0.5 mg/kg/day. Consequently, all existing and pending tolerances have
a theoretical maximum residue contribution of 0.001535 mg/kgBW/day and would
utilize less than 2.3 percent of the RfD.
2. Dietary Exposure - Drinking Water. Another potential source of dietary
exposure to residues of pesticides are residues in drinking water. There is no
established Maximum Concentration Level for residues of clopyralid in drinking
water. Although there has been limited detections at 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, and Pesticides in Ground Water Database - A Compilation of
Monitoring Studies: 1971 - 1991 National Summary; U.S. Department of
Agriculture, AGRICOLA database; U.S. Department of Commerce, National
Technical Information Service) have reported residues of clopyralid in ground
or surface waters.
Consequently, 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.
3. Non-Dietary Exposure. Non-occupational exposure to clopyralid is limited to
re-entry to treated turf grass sites. Estimated exposures for children is less
than 0.05 mg/kg/day or 10% of the reference dose.
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. Therefore, consideration of a common
mechanism of toxicity with other compounds is not appropriate. Thus only the
potential exposures to clopyralid were considered in the aggregate exposure
assessment.
E. Safety Determinations
1. U.S. Population in General. Using the conservative exposure assumptions
described above and based on the completeness and reliability of the toxicity
data, it is concluded that aggregate exposure to clopyralid will utilize
approximately 7 percent of the RfD for the U.S. population. Generally,
exposures below 100 percent 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 the previously
discussed 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 (1) information relating to
effects from exposure to the pesticide on the reproductive capability of
mating animals and (2) data on systemic toxicity. These studies indicate no
evidence of developmental toxicity at dose levels below those that cause
maternal toxicity.
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. Therefore, it is concluded that an
additional uncertainty factor is not warranted and that the RfD at 0.5
mg/kg/day is appropriate for assessing aggregate risk to infants and children.
Using the conservative exposure assumptions, it is concluded that the percent
of the RfD that will be utilized by aggregate exposure to residues of
clopyralid will be less than 12 percent of the RfD for all populations and
subgroups. This estimate represents the "worst case" exposure for a given
population (i.e. children ages 1-6), exposure is less for any other sub-
population e.g. infants. 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 exposures to clopyralid residues.
F. International Tolerances
There are no Codex maximum residue levels established for clopyralid.
II. Administrative Matters
Interested persons are invited to submit comments on this notice of filing.
Comments must bear a notation indicating the document control number, [PF-
675]. All written comments filed in response to this petition will be
available in the Public Response and Program Resources Branch, at the address
given above from 8:30 a.m. to 4 p.m., Monday through Friday, except legal
holidays.
A record has be established for this notice under docket number [PF-675]
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 public record is located in: Public Response and Program Resources Branch,
Field Operations Division (7506C), Office of Pesticide Programs, Environmental
Protection Agency, Crystal Mall #2, Rm. 1132, 1921 Jefferson Davis Highway,
Arlington, VA 22202.
Electronic comments can be sent directly to EPA at: opp=Docket@epamail.epa.gov
Electronic comments must be submitted as ASCII file avoiding the use of
special characters and any form of encryption.
The official record for this rulemaking, as well as the public version, as
described above will be kept in paper form. Accordingly, EPA will transfer all
comments received electronically into printed, paper form as they are received
and will place the paper copies in the official rulemaking record which will
also include all comments submitted directly in writing. The official
rulemaking record is the paper record maintained at the address in ADDRESSES
at the beginning of this document.
List of Subjects
Environmental Protection Agency, Administrative practice and procedure,
Agricultural commodities, Pesticides and pests, Reporting and recordkeeping
requirements.
Dated: November 27, 1996.
Stephen L. Johnson,
Director, Registration Division, Office of Pesticide Programs.
[FR Doc. 96-31345 Filed 12-10-96; 8:45 am]