[Federal Register Volume 63, Number 224 (Friday, November 20, 1998)]
[Notices]
[Pages 64489-64494]
From the Federal Register Online via the Government Publishing Office [www.gpo.gov]
[FR Doc No: 98-31067]
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ENVIRONMENTAL PROTECTION AGENCY
[PF-840; FRL-6039-6]
Dow AgroSciences LLC; Pesticide Tolerance Petition Filing
AGENCY: Environmental Protection Agency (EPA).
ACTION: Notice.
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SUMMARY: This notice announces the initial filing of a pesticide
petition proposing the establishment of regulations for residues of a
certain pesticide chemical in or on various food commodities.
DATES: Comments, identified by the docket control number PF-840, must
be received on or before December 21, 1998.
ADDRESSES: By mail submit written comments to: Information and Records
Integrity Branch, Public Information and Services Divison (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 by following
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
[[Page 64490]]
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. 119 at the address given above,
from 8:30 a.m. to 4 p.m., Monday through Friday, excluding legal
holidays.
FOR FURTHER INFORMATION CONTACT: James A. Tompkins, Herbicide Branch,
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. 239, Crystal
Mall #2, 1921 Jefferson Davis Highway, Arlington, VA 22202, (703) 305-
5697; e-mail: tompkins.jim@epamail.epa.gov.
SUPPLEMENTARY INFORMATION: EPA has received a pesticide petition as
follows proposing the establishment and/or amendment of regulations for
residues of certain pesticide chemical 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 this petition
contains data or information regarding the elements set forth in
section 408(d)(2); however, EPA has not fully evaluated the sufficiency
of the submitted data at this time or whether the data 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-840] (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. Comment and data
will also be accepted on disks in Wordperfect 5.1/6.1 file format or
ASCII file format. All comments and data in electronic form must be
identified by the docket control number (PF-840) and appropriate
petition number. Electronic comments on this 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: October 22, 1998.
James Jones,
Director, Registration Division, Office of Pesticide Programs.
Summary of Petition
The petitioner summary of the pesticide petition is printed below
as required by section 408(d)(3) of the FFDCA. The summary of the
petition was prepared by the petitioner and represents the views of the
petitioner. 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 4F4412
On May 13, 1997 (62 FR 26305) EPA published a notice that EPA had
received pesticide petition (PP 4F4412) from Dow AgroSciences, 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.
346a(d), to amend 40 CFR part 180 by establishing a tolerance for
inadvertent residues of the herbicide picloram in or on the raw
agricultural commodity grain sorghum grain, forage, and stover at 0.3,
0.2, and 0.5 parts per milliom (ppm), respectively. No comments were
received to the initial notice of filing. This notice announces that
the petition was amended by also proposing to establish a tolerance for
residues of the herbicide picloram in or on the raw agricultural
commodity aspirated grain fractions at 4 ppm. The analytical method is
Method A and III listed in the Pesticide Analytical Manual (PAM), Vol.
II. EPA has determined that the petition contains data or information
regarding the elements set forth in section 408(d)(2); however, EPA has
not fully evaluated the sufficiency of the submitted data at this time
or whether the data supports granting of the petition. Additional data
may be needed before EPA rules on the petition.
A. Residue Chemistry
1. Plant metabolism. The qualitative nature of the residue in
plants is understood based on a wheat metabolism study. The residue of
concern in wheat forage, straw and grain is conjugated picloram, which
is hydrolyzable by acid, base and B-glucosidase. The minor metabolites
that were identified in grain and straw were 4-amino-6-hydroxy-3,5-
dichloropicolinic acid and 4-amino-2,3,5-trichloropyridine.
2. Analytical method. The analytical portions of the magnitude of
residue studies were performed at Dow AgroSciences in Midland, MI. The
analytical method utilized for the determination of picloram residue
levels in the submitted studies was ACR 73.3.S2. There is a practical
analytical method for detecting and measuring levels of picloram 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.
Summary Of Residues Of Picloram (ppm) Found In Grain Sorghum
------------------------------------------------------------------------
Matrix Range
------------------------------------------------------------------------
Grain..................................... NDa-0.23
Forage.................................... ND-0.17
Fodder.................................... ND-0.44
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aND = less than one-half of the validated lower limit of quantitation of
0.05 g/g in grain and 0.1 g/g in forage and fodder.
B. Toxicological Profile
1. Acute toxicity. Studies for acute toxicity indicate that
picloram is classified as category III for acute oral toxicity,
category III for acute dermal toxicity, category I/II (depending on
whether acid or salts) for acute inhalation toxicity, category IV for
skin irritation potential, and category III for eye irritation
potential. The potassium salt is classified as a skin sensitizer. In
addition, picloram has a low vapor pressure.
Picloram potassium salt has low acute toxicity. The rat oral
LD50 is 3,536 milligrams/kilogram (mg/kg) or greater for
males and females. The rabbit dermal LD50 is >2,000 mg/kg
and the rat inhalation LC50 is >1.63 mg/L air (the highest
attainable concentration).
[[Page 64491]]
Picloram potassium salt is a positive skin sensitizer in guinea pigs
but is not a dermal irritant. Technical picloram potassium salt is a
moderate 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 picloram have similar low acute
toxicity profiles plus low ocular toxicity as well. Therefore based on
the available acute toxicity data, picloram does not pose any acute
dietary risks.
2. Genotoxicty. Picloram acid was evaluated in the Ames test using
Salmonella typhimurium. Doses ranged up to 5,000 g/plate, with
and without metabolic activation. The test substance did not produce a
mutagenic response either in the presence or absence of activation.
Picloram acid was evaluated for gene mutation in mammalian cells
(HGPRT/CHO). As evaluated up to toxic levels (1,750 g/ml
without metabolic activation; 4,500 g/ml with metabolic
activation), the compound was found to be negative for inducing forward
mutation in Chinese hamster ovary (CHO) cells.
Picloram acid was evaluated for cytogenetic effects on bone marrow
cells of rats via intra gastric administration at dosage levels of 0
(vehicle), 20, 200 or 2,000 mg/kg. The test material did not produce
cytogenetic effects in the study.
Picloram acid was evaluated for genotoxic potential as administered
to primary rat hepatocyte cultures at concentrations of 0 (vehicle),
10, 33.3, 100, 333.3 or 1,000 g/ml. The test material was
negative for unscheduled DNA synthesis (UDS, a measure of DNA damage/
repair) treated up to cytotoxic levels of (1,000 g/ml).
3. Reproductive and developmental toxicity. The HED reference dose
(RfD) Peer Review Committee concluded that there was no evidence, based
on the available data, that picloram and its salts were associated with
significant reproductive or developmental toxicity under the testing
conditions.
In the following developmental toxicity studies, the dose levels
that appear in parenthesis are picloram acid equivalents where the
conversion factor employed was 0.86 as applied to doses of potassium
salt.
Picloram potassium salt was administered to New Zealand rabbits by
oral gavage at dosage levels of 0, 40, 200 and 400 mg/kg/day (picloram
acid equivalents) during days 6 to 18 of gestation. The maternal no
observed adverse effect level (NOAEL) is 40 (34) mg/kg/day, where the
lowest observed adverse effect level (LOAEL) is 200 (172) mg/kg/day
based on reduced maternal weight gain during gestation. The
developmental NOAEL is 400 (340) mg/kg/day and the LOAEL was not
determined. The potassium salt of picloram was administered to CD rats
by gastric intubation at dosage levels of 0, 35 (30), 174 (150) and 347
(298) mg/kg/day during day 6-15 of gestation: The test vehicle was
distilled water. There was no evidence of developmental toxicity at
doses up to and including the high dose of 347 (298) mg/kg/day. The
maternal LOAEL is 347 (298) mg/kg/day based upon excessive salivation
in the dams of the high dose group. Hence, the developmental toxicity
NOAEL is greater than or equal to 347 (298) mg/kg/day. The maternal
toxicity LOAEL is 347 (298) mg/kg/day and NOAEL is 174 (150) mg/kg/day.
Picloram acid was evaluated in a 2-generation reproduction study in
the CD rat. Dosage levels employed were 0, 20, 200 or 1,000 mg/kg/day.
The parental LOAEL is 1,000 mg/kg/day based on histopathological
lesions in the kidney of males of both generations and some females. In
males of both generations, blood in the urine, decreased urine specific
gravity, increased absolute and relative kidney weight, and increased
body weight gain was observed at the high dose. The parental LOAEL is
1,000 mg/kg/day and the NOAEL is 200 mg/kg/day. The reproductive LOAEL
was not identified and the NOAEL is 1,000 mg/kg/day.
4. Subchronic toxicity. In a 90 day oral toxicity study, picloram
acid was administered via the diet to groups of 15 F344 rats/sex/dose
at dosage levels of 0, 15, 50, 150, 300 or 500 mg/kg/day. Based upon
liver weight changes and minimal microscopic changes in the liver, the
systemic LOAEL is 150 mg/kg/day. The NOAEL is 50 mg/kg/day.
In a 1982 6 month dog dietary study, picloram acid was evaluated at
dosage levels of 0, 7, 35 or 175 mg/kg/day. The systemic NOAEL is 35
mg/kg/day and the LOAEL is 175 mg/kg/day based on decreases in body
weight gain and food consumption and increases in liver weights
(relative), alkaline phosphatase and alanine transaminase. Increased
liver to body weight ratios and absolute liver weights were observed in
only two males at the 35 mg/kg/day dosage level.
In a 21 day dermal toxicity study, the potassium salt of picloram
was administered dermally to groups of five New Zealand white rabbits
of each sex at doses of 0 (vehicle control), 75.3, 251 or 753 mg/kg/day
(0, 65, 217 or 650 mg/kg/day picloram acid equivalents) for a total of
15 applications over the 21 day period. The NOAEL is greater than or
equal to 753 mg/kg/day for both sexes: hence, a LOAEL was not
established for either sex. Although the limit dose of 1,000 mg/kg/day
was not achieved, practical difficulties precluded administering more
test material. The study revealed the non-systemic effects of dermal
irritation and very slight to well defined edema and/or erythema in
both sexes at all dose levels.
5. Chronic toxicity. In a 1988 1 year chronic feeding study in the
dog, picloram acid was administered orally via the diet at dosage
levels of 0, 7, 35 or 175 mg/kg/day The LOAEL is 175 mg/kg/day based on
increased liver weight (absolute and relative). The NOAEL is 35 mg/kg/
day.
In a chronic toxicity/carcinogenicity feeding study conducted in
the F344 rat, picloram acid (technical grade 93 % containing 197 ppm
hexachlorobenzene as an impurity) was evaluated at 0, 20, 60 or 200 mg/
kg/day for 2 years. The chronic toxicity LOAEL was 60 mg/kg/day as
evidenced by altered size, tinctorial properties of centrilobular
hepatocytes, and increased absolute and/or relative liver weights in
both sexes. The NOAEL was 20 mg/kg/day. The study was negative for
carcinogenicity, but due to concerns that a MTD may not have been
achieved and the fact that the test material contained 197 ppm
hexachlorobenzene impurity, the study was not considered to fulfill
adequately the carcinogenicity testing requirement.
In response to the deficiencies cited in the study above, an
additional 2 year dietary chronic/carcinogenicity study was conducted
(in 1992) using F344 rats administered picloram acid at dosage levels
of 0, 250 or 500 mg/kg/day for 104 weeks. Chronic toxicity was observed
at 250 mg/kg/day among males only (increased incidence and severity of
glomerulonephritis, blood in urine, decreased specific gravity of
urine, increased size of hepatocytes that often had altered staining
properties). Among females there were chronic effects only at 500 mg/
kg/day (increased glomerulonephropathy, increased absolute and relative
kidney weight). There was no evidence of carcinogenicity in this study.
It should be noted that use of the Osborne-Mendel rat was waived due to
lack of availability of the strain of rat. In addition, the level of
hexachlorobenzene in the test material employed in this study was 12
ppm. These two studies fulfill the guidelines 83-l(a) and 83-2(a) for
rats.
In a 1992 2 year dietary carcinogenicity study in B6C3F1 mice,
picloram acid was evaluated at doses of 0, 100, 500 or 1,000 mg/kg/day.
The systemic NOAEL in this study is 500
[[Page 64492]]
mg/kg/day based on a significant increase in absolute and relative
kidney weights in males at the high dose level (HDT). No
histopathological lesions were found to corroborate these changes.
There was no evidence of carcinogenicity.
The dose levels tested in the 1992 carcinogenicity studies in rats
and mice were considered adequate for carcinogenicity testing. The
treatment did not alter the spontaneous tumor profile in mice or
different strains of rats tested under the testing conditions. The
chemical was classified as a ``Group E - Evidence of Non-
Carcinogenicity for humans''. This classification applies to the
picloram acid and potassium salt forms for which acceptable
carcinogenicity studies were available for review by the HED
Carcinogenicity Peer Review Committee (May 26, 1988).
Using its Guidelines for Carcinogen Risk Assessment published
September 24, 1986 (51 FR 33992), picloram is classified as Group ``E''
for carcinogenicity (no evidence of carcinogenicity) based on the
results of the carcinogenicity studies. The dose levels tested in the
1992 carcinogenicity studies in rats and mice were considered adequate
for carcinogenicity testing. The treatment did not alter the
spontaneous tumor profile in mice or different strains of rats tested
under the testing conditions. The chemical was classified as a ``Group
E - Evidence of Non-Carcinogenicity for humans''. This classification
applies to the picloram acid and potassium salt forms for which
acceptable carcinogenicity studies were available for review by the HED
Carcinogenicity Peer Review Committee (May 26, 1988). Thus, a cancer
risk assessment would not be appropriate.
Hexachlorobenzene (HCB), a recognized impurity in picloram
compounds, is considered to be an animal carcinogen and probable human
carcinogen as discussed in the 1988 Registration Standard for picloram.
The Q* is 1.02 (mg/kg/day)-1. The maximum level of HCB in picloram is
considered to be 0.005%.
6. Animal metabolism. The absorption, distribution, metabolism and
excretion of picloram acid was evaluated in female rats administered a
single i.v. or oral gavage dose of 10 mg/kg, an oral gavage dose of
1,000 mg/kg 14C-picloram, or 1 mg/kg/day unlabeled picloram
by gavage for 14 days followed by a single oral gavage dose of 10 mg/kg
14C-picloram on day 15. The study demonstrates that
14C-picloram is rapidly absorbed, distributed and excreted
following oral and i.v. administration. This study alone is not
adequate; however, this study is acceptable when considered in
conjunction with a male rat metabolism study which yielded similar
results.
7. Endocrine disruption. An evaluation of the potential effects on
the endocrine systems of mammals has not been determined; However, no
evidence of such effects were reported in the chronic or reproductive
toxicology studies described above. There was no observed pathology of
the endocrine organs in these studies. There is no evidence at this
time that picloram causes endocrine effects.
C. Aggregate Exposure
In examining aggregate exposure, FFDCA section 408 requires that
EPA take into account available and reliable information concerning
exposure from the pesticide residue in the food in question, residues
in other foods for which there are tolerances, residues in groundwater
or surface water that is consumed as drinking water, and other non-
occupational exposures through pesticide use in gardens, lawns, or
buildings (residential and other indoor uses).
1. Dietary exposure--i. Food. For purposes of assessing the
potential dietary exposure under these tolerances, aggregate exposure
is estimated based on the theoretical maximum residue contribution
(TMRC) from the existing and future potential tolerances for picloram
on food crops. The TMRC is obtained by multiplying the tolerance level
residues (existing and proposed) 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 the HED exposure assessment 100% of
the crops were treated, the RAC residues would be at the level of the
tolerance, and some refinements were made based on marketing
information previously supplied to HED by BEAD. This screening level
analysis results in an overestimate of human exposure and a
conservative assessment of risk. .
The chronic dietary exposure/risk estimates for picloram are
extremely low. For the United States population as a whole, the TMRC is
0.0011 milligram kilogram body weight day (mg/kg/bwt/day), <1 of="" the="" rfd.="" the="" subgroup="" with="" the="" greatest="" routine="" chronic="" exposure="" is="" non-="" nursing="" infants="">< 1="" year="" old),="" which="" has="" a="" tmrc="" of="" 0.0042="" mg/kg/bwt/="" day="" (2%="" of="" the="" rfd).="" there="" is="" currently="" no="" form="" of="" sorghum="" observed="" in="" human="" consumption="" surveys="" utilized="" by="" epa="" in="" their="" dietary="" risk="" evaluation="" system="" (dres)="" assessments.="" furthermore,="" residues="" of="" picloram="" in="" sorghum="" do="" not="" increase="" the="" dietary="" burden="" of="" picloram="" in="" animal="" feeds.="" therefore,="" sorghum="" tolerances="" will="" have="" no="" effect="" on="" the="" human="" dietary="" consumption="" of="" picloram,="" and="" the="" proposed="" action,="" as="" well="" as="" existing="" tolerances,="" pose="" no="" concern="" with="" regards="" to="" chronic="" dietary="" exposure="" to="" food="" residues="" of="" picloram.="" the="" estimated="" carcinogenic="" dietary="" risk="" for="" hcb="" as="" an="" impurity="" in="" picloram="" only="" for="" the="" u.s.="" population="" is="" 1.5="">-7 which is
less than the 1.0 x10-6 point below which risk is generally
considered to be negligible.
ii. Drinking water. An additional potential source of dietary
exposure to residues of pesticides are residues in drinking water. The
Maximum Contaminant Level (MCL) for residues of picloram in drinking
water has been established at 500 g/L and a 1-10 day Health
Advisory of 20,000 g/L.
The Agency has published screening methods for estimating chemical
residues in both ground water (SCI-GROW2) and surface water (GENEEC).
Employing these methods yields the following 56 day Expected
Environmental Concentrations (EEC) for a range of application rates:
------------------------------------------------------------------------
Application rate (lb. acid SCI-GROW2 EEC GENEEC EEC (g/L) m>g/L)
------------------------------------------------------------------------
0.023 (wheat, barley, and oats 4.4............... 1.2
use rate).
1 (maximum broadcast rate in 189............... 51.3
label).
2 (maximum spot treatment rate 379............... 103.1
in label).
------------------------------------------------------------------------
The 56 day value is an appropriate endpoint to employ for the
chronic exposure scenario. Default, conservative inputs were used for
the models, as described in July 27, 1998 memorandum from EPA to Dow
AgroSciences. Employing these values, a worst-case drinking water risk
assessment can be performed as summarized below:
[[Page 64493]]
--------------------------------------------------------------------------------------------------------------------------------------------------------
Maximum Water
Population Subgroup\1\ RfD (mg/kg/day) Food Exposure (mg/ Exposure (mg/kg/ DWLOC (g/ SCI-GROW2 EEC GENEEC EEC (g/L) m>g/L)
--------------------------------------------------------------------------------------------------------------------------------------------------------
US Population................... 0.2............... 0.0011............ 0.2............... 7000.............. 379............... 103.1
Females (13-19, not nursing or 0.2............... 0.00090........... 0.2............... 6000.............. 379............... 103.1
pregnant).
Non-Nursing infants (< 1="" yr.="" 0.2...............="" 0.0043............="" 0.2...............="" 2000..............="" 379...............="" 103.1="" old).="" --------------------------------------------------------------------------------------------------------------------------------------------------------="" \1\="" population="" subgroups="" chosen="" in="" epa="" memorandum="" of="" 7/27/98="" \2\="RfD" -="" arc="" from="" dres="" (cited="" above)="" \3\="" drinking="" water="" level="" of="" concern,="" based="" on="" default="" water="" body="" weights="" and="" water="" consumption="" of="" :="" 70="" kg/2l="" (adult="" males),="" 60="" kg/2l="" (adult="" female),="" 10="" kg/1l="" (infant)="" this="" tables="" shows="" that="" for="" even="" the="" most="" highly="" exposed="" population,="" exsure="" from="" water="" is="" below="" hed's="" dwloc="" for="" chronic="" dietary="" exposure.="" further="" refinement="" is="" also="" possible,="" based="" on="" monitoring="" data.="" monitoring="" data="" available="" from="" the="" pesticides="" in="" ground="" water="" database="" indicate="" that="" picloram="" has="" been="" detected="" in="" ground="" water="" at="" concentrations="" ranging="" up="" to="" 30="">g/L. Results reported in this
database typically were focused on highly vulnerable areas and in many
cases, the database reports information from poorly constructed or
damaged wells. These wells are at high risk because of the potential
for surface residues to be carried directly down the casing into the
ground water. Recognizing these high risk situations, an analysis of
this database shows that less than 3% of the wells sampled were found
to contain picloram. No distinction has been made between point and non
point sources of material. Many of the detections are known to be
related to point source contamination including spills at mixing/
loading sites, near wells and back siphoning events. Of the detections
which may have resulted from non-point sources, none are documented to
occur on sites where application would be recommended based on current
labeling. Nearly 99% of the ground water detections are at levels of
less than 1% of the Maximum Contaminant Level ( i.e., > 5 g/L)
established for human consumption by the EPA Office of Drinking Water.
The STORET database maintained by the USEPA Office of Drinking Water
indicates that picloram has been reported in surface water samples
before 1988. Of these detections, 85% were at concentrations 0.13
/L or lower and the maximum was 4.6
/L. The maximum concentration reported was 4.6
/L. Comparing these values to the DWLOC shows an even
greater degree of protection for all of the population subgroups.
HCB contamination of ground water resources is relatively unlikely
due to its high binding potential.
Based on monitoring data and fate properties it is unlikely that
long term HCB concentrations in surface water would exceed 10 parts per
trillion (ppt). Therefore, exposure from water is below EPA's drinking
water level of concern of 34 ppt for chronic dietary exposure to HCB
for the U.S. population.
In summary, these data on potential water exposure indicate
insignificant additional dietary intake and risk for picloram.
2. Non-dietary exposure. This is a restricted use chemical that has
no residential uses at this time; therefore, there are no human risks
associated with residential uses. Entry into a treated area soon after
the application of picloram is expected to be rare given the cultural
practices typically associated with the use-sites (rights-of-way,
forestry, pastures, range lands, and small grains) defined by the
picloram labels at this time. Furthermore, if entry should occur, the
potential exposures are expected to be minimal due to the
characteristics of those use-sites
D. Cumulative Effects
Picloram is a pyridine carboxylic acid herbicide. Other herbicides
in this class include clopyralid, quinclorac and thiazopyr. Section
408(b)(2)(D)(v) of the Food Quality Protection Act (FQPA) requires
that, when considering whether to establish, modify, or revoke a
tolerance, the Agency consider ``available information'' concerning the
cumulative effects of a particular pesticide's residues and ``other
substances that have a common mechanism of toxicity''. The Agency
believes that ``available information'' in this context might include
not only toxicity, chemistry, and exposure data, but also scientific
policies and methodologies for understanding common mechanisms of
toxicity and conducting cumulative risk assessments. For most
pesticides, although the Agency has some information in its files that
may turn out to be helpful in eventually determining whether a
pesticide shares a common mechanism of toxicity with any other
substances, EPA does not at this time have the methodologies to resolve
the complex scientific issues concerning common mechanism of toxicity
in a meaningful way. EPA has begun a pilot process to study this issue
further through the examination of particular classes of pesticides.
The Agency hopes that the results of this pilot process will increase
the Agency's scientific understanding of this question such that EPA
will be able to develop and apply scientific principles for better
determining which chemicals have a common mechanism of toxicity and
evaluating the cumulative effects of such chemicals. The Agency
anticipates, however, that even as its understanding of the science of
common mechanisms increases, decisions on specific classes of chemicals
will be heavily dependent on chemical specific data, much of which may
not be presently available.
Although at present the Agency does not know how to apply the
information in its files concerning common mechanism issues to most
risk assessments, there are pesticides as to which the common mechanism
issues can be resolved. These pesticides include pesticides that are
toxicologically dissimilar to existing chemical substances (in which
case the Agency can conclude that it is unlikely that a pesticide
shares a common mechanism of activity with other substances) and
pesticides that produce a common toxic metabolite (in which case common
mechanism of activity will be assumed).
EPA does not have, at this time, available data to determine
whether picloram has a common mechanism of toxicity with other
substances or how to include this pesticide in a cumulative risk
assessment. For the purposes of these tolerance actions, therefore, EPA
has not assumed that picloram has a
[[Page 64494]]
common mechanism of toxicity with other substances.
E. Safety Determination
1. U.S. population. In the meeting of September 30, 1993, the OPP
RfD Peer Review Committee recommended that the RfD for this chemical be
based on a NOAEL of 20 mg/kg/day for a dose-related increase in size
and altered tinctorial properties of centrilobular hepatocytes in males
and females at 60 and 200 mg/kg/day in a chronic toxicity study in
rats. An uncertainty factor (UF) of 100 was used to account for the
inter-species extrapolation and intra-species variability. On this
basis, the RfD was calculated to be 0.20 mg/kg/day. The TMRC from
existing tolerances is 0.001845 mg/kg/day. Existing tolerances utilize
>1% of the RfD. It should be noted that no regulatory value has been
established for this chemical by the World Health Organization (WHO) up
to this date. The committee classified picloram as a ``Group E''
chemical, no evidence of carcinogenicity for humans.
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 picloram will utilize
approximately 1% of the RfD for the U.S. population. 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 picloram residues.
2. Infants and children. In assessing the potential for additional
sensitivity of infants and children to residues of picloram, 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
(1) information relating to effects from exposure to the pesticide on
the reproductive capability of mating animals and (2) data on systemic
toxicity.
Developmental toxicity was studied using rats and rabbits. The
developmental study in rats resulted in a developmental NOAEL of >298
mg/kg/day and a maternal toxicity NOAEL of 280 mg/kg/day. A study in
rabbits resulted in a maternal NOAEL of 34 mg/kg/day and a
developmental NOAEL of 344 mg/kg/day. Based on all of the data for
picloram, 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, The NOAEL for
parental systemic toxicity is 200 mg/kg/day. There was no effect on
reproductive parameters at 1,000 mg/kg/day nor was there an adverse
effect on the morphology, growth or viability of the offspring; thus,
the reproductive NOAEL is 1,000 mg/kg/day.
FDCA 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 0.2 mg/kg/day is
appropriate for assessing aggregate risk to infants and children.
Using the conservative exposure assumption previously described, it
is concluded that the percent of the RfD that will be utilized by
aggregate exposure to residues of picloram will be less than 4% of the
RfD for all populations and subgroups. Since this estimate represents
the `worst case' exposure for a given population (Non-nursing infants,
>1 year old), exposures will be less for all other sub-populations e.g.
children, 1-6 years. 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
picloram residues.
F. International Tolerances
There are no Codex maximum residue levels established for residues
of picloram.
G. Other Considerations
Data Gaps. Residue data for sorghum aspirated grain fractions is
currently being generated. Based on the toxicological data and the
levels of exposure, EPA has determined that the proposed tolerances
will be safe.
[FR Doc. 98-31067 Filed 11-19-98; 8:45 am]
BILLING CODE 6560-50-F
