[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: [email protected].
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:
    [email protected]


    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
------------------------------------------------------------------------
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 x10-7 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