[Federal Register Volume 61, Number 239 (Wednesday, December 11, 1996)]
[Notices]
[Pages 65221-65223]
From the Federal Register Online via the Government Publishing Office [www.gpo.gov]
[FR Doc No: 96-31345]
[[Page 65221]]
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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: [email protected]. 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: [email protected].
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 2000 mg/kg and the rat inhalation LC50 is
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/
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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
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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=D[email protected]
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]
BILLING CODE 6560-50-F