paraquat Pesticide Petition Filing 9/98
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ENVIRONMENTAL PROTECTION AGENCY
Notice of Filing of Pesticide Tolerance Petitions
AGENCY: Environmental Protection Agency (EPA).
SUMMARY: This notice announces the initial filing of pesticide
petitions proposing the establishment of regulations for residues of
certain pesticide chemicals in or on various food commodities.
DATES: Comments, identified by the docket control number PF-831, must
be received on or before November 6, 1998.
ADDRESSES: By mail submit written comments to: Public Information and
Records Integrity Branch, Information Resources 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, Crystal Mall (CM) #2, 1921 Jefferson Davis Highway,
Comments and data may also be submitted electronically by following
the instructions under ``SUPPLEMENTARY INFORMATION.'' No Confidential
Business Information (CBI) 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
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. 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: The product manager listed in the
Product Manager telephone number Address
Leonard Cole.................. Rm. 209, CM #2, 703- 1921 Jefferson
305-5412; e-mail: Davis Hwy,
cole.leonard@epamail. Arlington, VA
Mark Dow...................... Rm. 214, CM #2, 703- Do.
James Tompkins................ Rm. 239, CM #2, 703 Do.
SUPPLEMENTARY INFORMATION: EPA has received pesticide petitions as
follows proposing the establishment of regulations for residues of
certain pesticide chemicals in or on various raw food commodities under
section 408 of the Federal Food, Drug, and Comestic Act (FFDCA), 21
U.S.C. 346a. EPA has determined that these petitions contain data or
information regarding the elements set forth in section 408(d)(2);
however, EPA has not fully evaluated the sufficiency of the submitted
data at this time or whether the data supports grantinig of the
petition. Additional data may be needed before EPA rules on the
The official record for this notice, as well as the public version,
has been established for this notice of filing under document control
number PF-831 (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''.
Electronic comments can be sent directly to EPA at:
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 document control number (PF-831) and appropriate
petition number. Electronic comments on this notice may be filed online
at many Federal Depository Libraries.
Authority: 21 U.S.C. 346a.
List of Subjects
Environmental protection, Agricultural commodities, Food additives,
Feed additives, Pesticides and pests, Reporting and recordkeeping
Dated: September 29, 1998.
Director, Registration Division, Office of Pesticide Programs.
Summaries of Petitions
Below summaries of the pesticide petitions are printed. The
summaries of the petitions were prepared by the petitioners. 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.
3. Zeneca Ag. Products
EPA has received pesticide petitions PP 5F1625 and 5H5088 from
Zeneca Ag Products, 1800 Concord Pike, P.O. Box 15458, Wilmington,
Delaware 19850-5458, proposing pursuant to section 408(d) of the
Federal Food, Drug, and Cosmetic Act, (FFDCA) 21 U.S.C. 346a(d), to
amend 40 CFR part 180 by establishing a tolerance for residues of the
herbicide paraquat (1,1-dimethyl-4,4'-bypyridinium) derived from the
corn harvest-aid application of the dichloride salt (calculated as the
cation) in or on the raw agricultural commodities corn, pop, grain at
0.05 part per million (ppm); corn, field, grain at 0.05 ppm; corn,
field, forage at 3.0 ppm; corn, pop, forage at 3.0 ppm; corn, field,
stover at 10.0 ppm; corn, pop, stover at 10 ppm; and corn, flour at 0.1
An adequate analytical method (spectrophotometric method) has been
accepted and published in the Pesticide Analytical Manual (PAM Vol. II)
for the enforcement of tolerances in plant
commodities. EPA has determined that the petition contains data or
information regarding the elements set forth in section 408(d)(2) of
the FFDCA; however, EPA has not fully evaluated the sufficiency 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
A. Residue Chemistry
1. Plant metabolism. The qualitative nature of the residue in
plants is adequately understood based on studies depicting the
metabolism of paraquat in carrots and lettuce following pre-emergence
treatments and in potatoes and soybeans following desiccant treatment.
The residue of concern in plants is the parent, paraquat; the current
tolerance expression for plant commodities, as defined in 40 CFR
180.205(a) and (b).
2. Analytical method. An adequate analytical method (spectrometric
method) has been accepted and published in the The Pesticide Analytical
Manual (PAM Vol. II) for the enforcement of tolerances in plant
3. Magnitude of residues. Paraquat residues on corn forage ranged
from <0.025 to 3 ppm and on corn fodder ranged from 0.025 to 6 ppm
following preemergence and post-directed applications as described for
MRID 41151523 and 41151506. Residue data submitted in tolerance
petition PP 5F1625 (MRID 00114426) for corn harvest-aid use of paraquat
indicate that corn grain residues would not exceed the established
tolerance of 0.05 ppm when applied broadcast postemergence at 0.5 lbs
ai/A with a 7-day pre-harvest interval. Residue data submitted in
tolerance petition PP 5F1625 (MRID 00114426) for corn harvest-aid use
of paraquat indicate that corn fodder (stover) residues range from 1.3
to 10.0 ppm when applied broadcast postemergence at 0.5 lbs ai/A with a
7-day pre-harvest interval. These data support a corn forage tolerance
of 3 ppm and a corn stover tolerance of 10 ppm.
B. Toxicological Profile
1. Acute Toxicity. Acute toxicity studies conducted with the 45.6%
paraquat dichloride technical concentrate give the following results:
oral LD<INF>50</INF> in the rat of 344 mg/kg (males) and 283 mg/kg
(females) (Category II); dermal LD<INF>50</INF> in the rat of
<ls-thn-eq> 2,000 mg/kg for males and females (Category III); the
primary eye irritation study showed corneal involvement with clearing
within 17 days (Category II); and dermal irritation of slight erythema
and edema at 72 hours (Category IV). Paraquat is not a dermal
sensitizer. Acute inhalation studies conducted to EPA guideline with
aerosolized sprays result in LD<INF>50</INF> of 0.6 to 1.4 <greek-m>g
paraquat cation/Liter (L) (Category I). However, since paraquat
dichloride has no measurable vapor pressure; and hydraulic spray
droplets are too large to be respirable, inhalation exposure is not a
concern in practice.
2. Genotoxicity. Paraquat dichloride was not mutagenic in the Ames
test using Salmonella typhinurium strains TA1535, TA1538, TA98, and
TA100; the chromosomal aberrations in the bone marrow test system; or
in the dominant lethal mutagenicity study with CD-1 mice. Additionally,
paraquat dichloride was negative for unscheduled DNA synthesis in rat
hepatocytes in in vitro and in vivo. Paraquat was weakly positive in
the mouse lymphoma cell assay only in the presence of metabolic
activation. Paraquat dichloride was weakly positive in mammalian cells
(lymphocytes) and positive in the sister chromatid exchange (SCE) assay
in Chinese hamster lung fibroblasts. Paraquat is non-mutagenic.
3. Reproductive and developmental toxicity. A 3-generation
reproduction study in rats fed diets containing 0, 25, 75, and 150 ppm
which correspond to 0, 1.25, 3.75 or 7.5 mg of paraquat cation/kg/day,
respectively. Paraquat, at all levels tested, had no effect on body
weight gain, food consumption and utilization, fertility and length of
gestation of the F<INF>0</INF> F<INF>1</INF> and F<INF>2</INF> parents.
The NOAEL and LOEL for systemic toxicity are 25 ppm (1.25 mg/kg/day)
and 75 ppm (3.75 mg/kg/day), respectively, expressed as paraquat
cation. The NOAEL for reproductive toxicity is <gr-thn-eq>150 ppm (7.5
mg/kg/day; HDT) expressed as paraquat cation, as there were no
reproductive effects observed.
Two developmental toxicity studies were conducted in rats given
gavage doses of 0, 1, 5, and 10 mg/kg/day and 0, 1, 3, and 8 mg/kg/day,
respectively, expressed as paraquat cation. In the first study, the
NOAEL for maternal toxicity was 1 mg/kg/day based on clinincal signs of
toxicity and decreased body weight gain at 5 mg/kg/day (the LOEL). The
NOAEL for developmental toxicity was set at 5 mg/kg/day based on
delayed ossification of the forelimb and hindlimb digits. In the
second, study, the maternal and developmental NOAEL is 8 mg/kg/day
(HDT) as there were no effects observed at any dose level even though
the animals were examined more carefully in the manus and pes
assessment. Based on both studies the overall NOAEL for maternal and
developmental toxicity is at least 3 mg/kg/day.
Two developmental toxicity studies were conducted in mice given
gavage doses of 0, 1, 5, and 10 mg/kg/day and 0, 7.5, 15, or 25 mg/kg/
day paraquat ion, respectively. Both the maternal and developmental
NOAEL's are at 15 mg/kg/day in the second study. The maternal LOEL of
25 mg paraquat cation/kg/day is based on death, decreases in body
weight and body weight gain, and other clinical signs. The
developmental LOEL is 25 mg/kg/day. In the first study there was a
statistically significant effect on ``partial ossification'' of the 4th
sternebra at 10 mg/kg/day (HDT). However, it is not believed the
ossification pattern of the 4th sternebra was affected by paraquat as
evidenced by the lack of increase in ``4th sternebra - not ossified.''
Additionally there were no statistically significant skeletal
abnormalities seen in the second study. The developmental/maternal
NOAEL should be based on the second study and is 15 mg/kg/day. Paraquat
dichloride is not a developmental toxin.
4. Subchronic toxicity. A 90 day feeding study in dogs fed doses of
0, 7, 20, 60 or 120 ppm with a NOAEL of 20 ppm based on long effects
such as alveolitis and alveolar collapse seen at the LOEL of 60 ppm.
A 21 day dermal toxicity study in rabbits exposed dermally to doses
of 0, 1.5, 3.4, 7.8 or 17.9 mg/kg/day with a NOAEL of 1.15 mg/kg/day
and a LOEL of 2.6 mg/kg/day based on dermal irritation.
A 21 day inhalation toxicity study in rats were exposed to
respirable aerosols of paraquat at doses of 0, 0.01, 0.1, 0.5 and 1.0
<greek-m>g/L with a NOAEL of 0.01 <greek-m>g/L and a LOEL of 0.10
<greek-m>g/L based on histopathological changes to the epithelium of
the larynx and nasal discharge.
5. Chronic toxicity. In a 12-month feeding study in dogs fed dose
levels of 0, 15, 30, or 50 ppm, expressed as paraquat cation. These
levels corresponded to 0, 0.45, 0.93 or 1.51 mg of paraquat cation/kg/
day, respectively, in male dogs or 0, 0.48, 1.00 or 1.58 mg of paraquat
cation/kg/day, respectively for female dogs. There was a dose-related
increase in the severity and extent of chronic pneumonitis in the mid-
dose and high-dose male and female dogs. This effect was also noted in
the low-dose male group, but was minimal when compared with the male
controls. The systemic NOAEL is 15 ppm (0.45 mg/kg/day for males and
0.48 mg/kg/day for females, expressed as paraquat cation). The systemic
LOEL is 30 ppm (0.93 mg/kg/day for males and
1.00 mg/kg/day for females, expressed as paraquat cation).
In a 2-year chronic feeding/carcinogenicity study, rats were fed
doses of paraquat dichloride at 0, 25, 75, or 150 ppm which
corresponded to 0, 1.25, 3.75, or 7.5 mg of paraquat cation/kg/day.
Paraquat enhanced the development of ocular lesions in all of the
treated groups. The predominant lesions detected opthalmoscopically
were lenticular opacities and cataracts. At test week 103, dose-related
statistically significant (P<0.001) increases in the incidence of
ocular lesions were observed only in the mid-dose and high-dose male
and female groups. Based on these findings, the NOAEL (approximate) and
the LOEL for systemic toxicity, for both sexes, are 25 ppm (1.25 mg/kg/
day) and 75 ppm (3.75 mg/kg/day), respectively.
In another 2-year chronic feeding/carcinogenicity study, rats were
dosed at 0, 6, 30, 100 or 300 ppm, expressed as paraquat dichloride
(nominal concentrations), equivalent to 0, 0.25, 1.26, 4.15, or 12.25
mg/kg/day, respectively (males) and 0, 0.30, 1.5, 5.12 or 15.29 mg/kg/
day respectively (females), expressed as paraquat dichloride. The
incidence of ocular changes were low and not caused by paraquat in this
study. The systemic NOAEL is 100 ppm of paraquat dichloride (4.15 and
5.12 mg/kg/day, for males and females, respectively); or 3.0 mg/kg/day
(males) and 3.7 mg/kg/day (females), expressed as paraquat cation. The
systemic LOEL is 300 ppm of paraquat dichloride (12.25 and 15.29 mg/kg/
day, for males and females, respectively); or 9.0 mg/kg/day (males) and
11.2 mg/kg/day (females), expressed as paraquat cation.
A chronic feeding/carcinogenicity study in rats fed dose levels of
0, 25, 75 or 150 ppm, expressed as paraquat cation (nominal
concentrations). These doses corresponded to 0, 1.25, 3.75, or 7.5 mg
paraquat cation/kg/day, respectively. There was uncertain evidence of
carcinogenicity (squamous cell carcinomas in the head region; ears,
nasal cavity, oral cavity and skin) in males at 7.5 mg/kg/day (HDT)
with a systemic NOAEL of 1.25 mg/kg/day. Upon submission of additional
data to EPA, the incidence of pulmonary adenomas and carcinomas was
well within historical ranges and it was determined that paraquat was
not carcinogenic in the lungs and the head region of the rat.
In another chronic feeding/carcinogenicity study, rats were fed
dose levels of 0, 6, 30, 100 or 300 ppm, expressed as paraquat
dichloride. There were no carcinogenic findings in this study at the
highest dose tested. In a two year chronic feeding/oncogenicity study,
SPF Swiss derived mice were fed paraquat dichloride at dose levels of
0, 12.5, 37.5, or 100/125 ppm, expressed as paraquat cation. These
rates correspond to 0, 1.87, 5.62, and 15 mg/kg/day as cation. Because
no toxic signs appeared after 35 weeks of dosing, the 100 ppm level was
increased to 125 ppm at week 36. There were no carcinogenic effects
observed in this study.
The systemic NOAEL for both sexes is 12.5 ppm (1.87 mg/kg/day) and
the systemic LOEL is 37.5 ppm (5.6 mg/kg/day), each expressed as
paraquat cation based on renal tubular degeneration in males and weight
loss and decreased food intake in females.
Paraquat is classified Category E for carcinogenicity (no evidence
of carcinogenicity in animal studies).
6. Animal metabolism. The qualitative nature of the residue in
animals is adequately understood based on the combined studies
conducted with ruminants (goats and cows), swine, and poultry. The
residue of concern in eggs, milk, and poultry and livestock tissues is
the parent, paraquat.
7. Metabolite toxicology. The nature of residues in plants and
animals is adequately understood. The residue of concern in eggs, milk,
poultry, livestock, and in crops is the parent paraquat. There are no
8. Endocrine disruption. EPA is required to develop a screening
program to determine whether certain substances (including all
pesticides and inerts) ``may have an effect produced by a naturally
occurring estrogen, or such other endocrine effect .'' The Agency is
currently working with interested stakeholders, including other
government agencies, public interest groups, industry and research
scientist in developing a screening and testing program and a priority
setting scheme to implement this program. Congress has allowed 3 years
from passage of FQPA (August 3, 1999) to implement this program. At
that time, EPA may require further testing of this active ingredient
and end use products for endocrine disrupter effects.
C. Aggregate Exposure
In examining aggregate exposure, FQPA directs EPA to take into
account available information concerning exposures from the pesticide
residue in food and all other exposures for which there is reliable
information. These other sources of exposure including drinking water,
and non-occupational exposures, e.g., to pesticides used in and around
the home. For estimating acute and chronic risks the Agency considers
aggregate exposures from the diet and from drinking water. Exposures
from uses in and around the home that may be short term, intermediate
or other duration may also be aggregated as appropriate for specific
1. Dietary exposure. The Residue Chemistry data base for paraquat
is substantially complete, and the nature of the residues in plants and
animals is adequately understood. The residue of concern is the parent,
paraquat; the current tolerance expression for plants and animal
commodities, as defined in 40 CFR 180.205(a) and (b), is adequate. The
Reference Dose (RfD) for chronic dietary assessments is 0.0045 mg/kg/
day, based on a NOAEL of 0.45 mg/kg/day from a 1 year dog study and the
addition of a standard uncertainty factor of 100.
2. Food. --i. Chronic dietary assessment. A chronic dietary
exposure analysis was performed using current and reassessed tolerance
level residues, contributions from the proposed use as a corn harvest
aid, and 100% crop treated information to estimate the Theoretical
Maximum Residue Contribution (TMRC) for the general population and 22
subgroups. The resulting TMRC for the general U.S. population from all
established uses is 0.001669 mg/kg/day (37% of the RfD). For children
ages 1-6, the most highly exposed subgroup, the resulting TMRC is
0.003679 mg/kg/day (82% of the RfD). A refined chronic dietary
assessment using percent crop treated data provided a more accurate
estimate of exposure, called the Anticipated Residue Contribution
(ARC). The resulting ARC for the general population is 0.00037 mg/kg/
day (8.0% of the RfD), and 0.001 mg/kg/day (22% of the RfD) for
children ages one to six.
ii. Acute dietary assessment. EPA has determined that current data
on paraquat shows no acutedietary endpoint of concern. Therefore, an
acute dietary risk assessment is not required for paraquat.
3. Drinking water. Paraquat is not expected to be a contaminant of
groundwater. Paraquat dichloride binds strongly to soil clay particles
and it did not leach from the surface in terrestrial field dissipation
studies. There were, however, detections of paraquat in drinking water
wells from 2 states cited in the Pesticides in Ground Water Database
(1991). These detections are not considered to be representative of
normal paraquat use. Therefore, paraquat is not expected to be a
groundwater contaminant or concern based on normal use patterns.
Due to its persistent nature, paraquat could potentially be found
water systems associated with soil particles carried by erosion,
however, paraquat is immobile in most soils, and at very high
application rates (50-1,000X), there was no desorption of paraquat from
soils. Therefore, based on paraquat's normal use patterns and unique
environmental fate characteristics, exposures to paraquat in drinking
water are not expected to be obtained from surface water sources.
4. Non-dietary exposure. Paraquat dichloride has no residential or
other non-occupational uses that might result in non-occupational, non-
dietary exposure for the general population. Paraquat products are
Restricted Use, for use by Certified Applicators only, which means the
general public cannot buy or use paraquat products.
D. Cumulative Effects
In assessing the potential risk from cumulative effects of paraquat
and other chemical substances, the Agency has considered structural
similarities that exist between paraquat and other bipyridylium
compounds such as diquat dibromide. Examination of the toxicology
databases of paraquat and diquat dibromide, indicates that the two
compounds have clearly different target organs. Based on available
data, the Agency does not believe that the toxic effects produced by
paraquat would be cumulative with those of diquat dibromide.
E. Safety Determination
1. U.S. population. Based on the information provided in this
notice, EPA has determined that for the aggregate exposure assessment
the only exposure route of concern for paraquat is chronic dietary. The
toxicology database for paraquat is considered by EPA to be complete
and reliable. Using the conservative assumptions presented earlier, EPA
has established an RfD of 0.0045 mg/kg/day. This was based on the NOAEL
for the 1-year dog study of 0.45 mg/kg/day and employed a 100-fold
uncertainty factor. Results of this aggregate exposure assessment,
which includes EPA's reassessment of tolerances for existing crops and
the addition of corn harvest aid, utilize a maximum of 22% of the RfD.
Generally, exposures below 100% of the RfD are of no concern because it
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 reasonable certainty that no harm will result from aggregate
exposures to paraquat residues.
2. Infants and children. EPA has determined that the established
tolerances for paraquat, with amendments and changes as specified in
this notice, meet the safety standards under the FQPA amendments to
section 408(b)(2)(C) for infants and children. The safety determination
for infants and children considers the factors noted above for the
general population, but also takes into account the possibility of
increased dietary exposure due to specific consumption patterns of
infants and children, as well as the possibility of increased
susceptibility to the toxic effects of paraquat residues in this
In determining whether or not infants and children are particularly
susceptible to toxic effects from paraquat residues, EPA considered the
completeness of the database for developmental and reproductive
effects, the nature and severity of the effects observed, and other
Based on the current data requirements, paraquat has a complete
database for developmental and reproductive toxicity. In the
developmental studies effects were seen (delayed ossification in the
forelimb and hindlimb digits) in the fetuses only at the same or higher
dose levels than effects in the mother. In the reproduction study, no
effects on reproductive performance were seen. Also because the NOAELs
from the developmental and reproduction studies were equal to or
greater than the NOAEL used for establishing the reference dose, EPA
concludes that it is unlikely that there is additional risk concern for
immature or developing organisms. Finally, the Agency has no
epidemiological information suggesting special sensitivity of infants
and children to paraquat. Therefore, the Agency finds that the
uncertainty factor (100X) routinely used in RfD calculations is
adequately protective of infants and children, and an additional
uncertainty factor is not warranted for paraquat.
Zeneca estimates that paraquat residues in the diet of non-nursing
infants (less than 1 year) account for 18% of the RfD and 22% of the
RfD for children aged 1-6 years. Further, residues in drinking water
are not expected. Therefore, the Zeneca has determined that there is
reasonable certainty that dietary exposure to paraquat will not cause
harm to infants and children.
F. International Tolerances
Codex maximum residue levels (MRL) are established for residues of
paraquat for corn grain at 0.1 ppm. The proposed tolerances for corn
grain at 0.05 ppm differ from the Codex MRL's based on field residue
data generated in the United States for this use (Pesticide Petitions
5F1625 and 5H5088 for corn grain. Differences in use patterns and pre-
harvest intervals may account for the differences between the Codex
MRLs and the tolerance values generated from the pesticide residue
trials in the United States. (Jim Tompkins)
[FR Doc. 98-26783 Filed 10-6-98; 8:45 am]
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