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Diquat Dibromide - Pesticide Petition Filing 11/97

[Federal Register: December 3, 1997 (Volume 62, Number 232)]
[Notices]
[Page 63942-63951]
From the Federal Register Online via GPO Access [wais.access.gpo.gov]
[DOCID:fr03de97-74]

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ENVIRONMENTAL PROTECTION AGENCY

[PF-780; FRL-5756-1]

Notice of Filing of Pesticide Petitions

AGENCY: Environmental Protection Agency (EPA).

ACTION: Notice.

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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-780, must
be received on or before January 2, 1998.
ADDRESSES: By mail submit written comments to: Public Information and
Records Integrity Branch, Information Resources and Services Division
(7502C), Office of Pesticides Programs, Environmental Protection
Agency, 401 M St., SW., Washington, DC 20460. In person bring comments
to: Rm. 1132, CM #2, 1921 Jefferson Davis Highway, Arlington, VA.
    Comments and data may also be submitted electronically to: opp-
docket@epamail.epa.gov. Follow 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 through e-mail. Information marked as CBI will not be
disclosed except in accordance with procedures set forth in 40 CFR part
2. A copy of the comment that does not contain CBI must be submitted
for inclusion in the public record. Information not marked confidential
may be disclosed publicly by EPA without prior notice. All written
comments will be available for public inspection in Rm. 1132 at the
address given above, from 8:30 a.m. to 4 p.m., Monday through Friday,
excluding legal holidays.

FOR FURTHER INFORMATION CONTACT: The product manager listed in the
table below:

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                                   Office location/
        Product Manager            telephone number          Address
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Joanne Miller (PM 23).........  Rm. 237, CM #2, 703-    1921 Jefferson
                                 305-6224, e-            Davis Hwy,
                                 mail:miller.joanne@ep   Arlington, VA
                                 amail.epa.gov.
James Tompkins (PM 25)........  Rm. 239, CM #2, 703-    1921 Jefferson
                                 305-5697, e-mail:       Davis Hwy,
                                 tompkins.james@epamai   Arlington, VA.
                                 l.epa.gov.
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SUPPLEMENTARY INFORMATION: EPA has received pesticide petitions as
follows proposing the establishment and/or amendment of regulations for
residues of certain pesticide chemicals 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 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 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-780] (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 file format or ASCII
file format. All comments and data in electronic form must be
identified by the docket number (insert docket number) and appropriate
petition number. Electronic comments on notice may be filed online at
many Federal Depository Libraries.

List of Subjects

    Environmental protection, Agricultural commodities, Feed additives,
Food additives, Pesticides and pests, Reporting and recordkeeping
requirements.

    Dated: November 21, 1997

Peter Caulkins,
Acting Director, Registration Division, Office of Pesticide Programs.

Summaries of Petitions

    Petitioner summaries of the pesticide petitions are printed below
as required by section 408(d)(3) of the FFDCA. The summaries of the
petitions were prepared by the petitioners and represent the views of
the petitioners. 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.

2. Zeneca Ag Products

PP 6F4609

    EPA has received a pesticide petition (PP 6F4609) from Zeneca Ag
Products, 1800 Concord Pike, P.O. Box 15458, Wilmington, DE 19850.
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 residues of diquat dibromide in or on the
raw agricultural commodity dried shelled pea and bean (except soybean)
subgroup (seed) at 0.80 ppm. The proposed analytical method is a
spectrophotometric method measuring absorption following derivitisation
of the diquat with alkaline sodium dithionite. 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 petition.

A. Residue Chemistry

    1. Plant metabolism. The metabolism of diquat in plants is
adequately understood. The residue of concern in plants is diquat per
se. No further plant metabolism data are necessary for this proposed
use.
    2. Analytical method. The method of analysis is a spectrophotometic
method measuring absorption following derivitisation of the diquat with
alkaline sodium dithinoite.
    3. Magnitude of residues. Dry Pea - Six residue field trials were
conducted during 1994 in California, Idaho, Oregon, Texas, and
Washington. The seed samples were analyzed for the active ingredient
diquat. Diquat residues in dry pea seed ranged from 0.05 to 0.56 ppm.
    Lentil - Five residue field trials were conducted during 1994 in
Idaho, North Dakota, and Washington. The seed samples were analyzed for
the active ingredient diquat. Diquat residues in lentil seed ranged
from < 0.05 to 0.54 ppm.
     Dry Bean - Eight residue field trials were conducted during 1994
in California, Colorado, Idaho, Michigan, Minnesota, North Dakota,
Nebraska, and New York. The bean seed were analyzed for the active
ingredient diquat. Diquat residues were less than the limit of
quantitation (<0.05 ppm) in all the bean seed samples.

B. Toxicological Profile

    1. Acute toxicity. In studies using laboratory animals, diquat
dibromide has been shown generally to be of moderate toxicity. It can
cause slight to severe eye irritation and has been placed in Toxicity
Category II for acute dermal eye irritation effects. It is slightly
acutely toxic by the oral and inhalation routes and has been placed in
Toxicity Category III for these effects. Diquat dibromide causes slight
dermal irritation and has been placed in Toxicity Category IV for this
effect. It is not a skin sensitizer.
    2. Genotoxicty. Diquat dibromide was negative for mutagenicity in
the following test: 1 gene mutation (Ames), 2 structural chromosome
aberration (mouse micronucleus and dominant lethal in mice) and 1 other
genotoxic effects (unscheduled DNA synthesis in rat hepatocytes in
vitro). Diquat was positive in 1 gene mutation test (mouse lymphoma
cell assay) and in 1 chromosome aberration test (human blood
lymphocytes, depending on the concentration of diquat dibromide and the
presence or absence of the metabolic activation system). EPA has
concluded that Diquat does not appear to present a mutagenicity concern
in (in vivo) studies and for heritable risk considerations based on
available information.
    3. Reproductive and developmental toxicity. In a rat
multigeneration study, diquat was fed at dose levels equivalent to 0,
16, 80 or 400/240 ppm of diquat cation. There was evidence of toxicity
in both adults and offspring at 400/240 ppm diquat. A low incidence of
toxicity was seen at 80 ppm in the adult rats only. Based on the
findings, the NOEL and LOEL for systemic toxicity are 16 ppm (0.8 mg/
kg/day) and 80 ppm (4 mg/kg/day), respectively, expressed as diquat
cation. The NOEL and LOEL for reproductive toxicity are 80 ppm (4 mg/
kg/day) and 400/240 ppm (20/12 mg/kg/day) respectively, expressed as
diquat cation.
    In a developmental toxicity study in rabbits, diquat dibromide was
administered by gavage at dose levels of 0, 1, 3, or 10 mg/kg/day.
There was no evidence to suggest that diquat was teratogenic to the
rabbit at any dose level tested. Based on the findings, the NOEL and
LOEL for maternal toxicity are 1 mg/kg/day and 3 mg/kg/day,
respectively, expressed as diquat cation. The developmental toxicity
NOEL and LOEL are, respectively, 3 mg/kg/day and 10 mg/kg/day,
expressed as diquat cation.
    In a developmental toxicity study in the rat, diquat dibromide was
administered by oral gauge dose levels of 0, 4, 12 or 40 mg/kg/day.
Diquat was not a rat teratogen at any of the dose levels tested.
Maternal toxicity and foetotoxicity were in evidence at 40 mg/kg/day
with mild and transient maternal toxicity persisting to the lowest dose
level tested (4 mg/kg/day). The developmental toxicity NOEL and LOEL
are, respectively, 12 mg/kg/day and 40 mg/kg/day expressed as diquat
cation.
    4. Subchronic toxicity. A supplemental subchronic dermal toxicity
study using rabbits exposed to technical diquat dibromide at doses of
0, 20, 40, 80, or 160 mg/kg/day with a toxicological NOEL and LOEL for
systemic toxicity, for both sexes, of 20 mg/kg/day and 40 mg/kg/day,
respectively.
    A repeated dermal toxicity study using rats exposed to technical
diquat dibromide at doses of 0, 5, 20, 40 or 80 mg/kg of body weight/
day with a toxicological NOEL and LOEL for systemic toxicity, for both
sexes, of 5 mg/kg/day and 20 mg/kg/day, respectively.
    An inhalation study using rats resulted in increase in lung weight,
lung/body weight and lung/brain weight, lung lesions, and mottling and
reddening of the lungs in females; however, all effects except the
latter were reversible. A second inhalation study using rats showed no
effects on any of the parameters examined at a dose of 0.1 μg/
l. Based on both studies the NOEL and LOEL on inhalation exposure are
0.1μg/L and 0.49 μg/L, respectively.
    5. Chronic toxicity.-- i. 2-Year rat study. - A chronic feeding
carcinogenicity study was conducted on rats which were fed diets
containing 0, 5, 15, 75 or 375 ppm of diquat cation. The systemic NOEL
for both sexes was 15 ppm (0.58 mg/kg/day for males and

[[Page 63947]]

0.72 mg/kg/day for females, expressed as diquat cation); and the
systemic LOEL was 75 ppm (2.91 mg/kg/day for males and 3.64 mg/kg/day
for females, expressed as diquat cation).
    ii. 1-Year dog study. - A chronic dog study was conducted on
beagles which were fed diets containing 0, 0.5, 2.5, or 12.5 mg/kg/day,
expressed as diquat cation. The systemic NOEL for both sexes was 0.5
mg/kg/day and systemic LOEL was 2.5 mg/kg/day.
    iii. 2-Year mice study. - A chronic feeding/carcinogenicity study
was conducted on mice which were fed diets containing 0,30,100 or 300
ppm, expressed as diquat cation. The systemic NOEL for both sexes was
30 ppm. The systemic LOEL was 100 ppm. Zeneca believes that diquat was
not carcinogenic in this study.
    The carcinogenic potential of diquat dibromide was evaluated by the
Health Effects Division Reference Dose (RfD)/Peer Review Committee on
March 31, 1994. The Committee classified diquat dibromide into Group E
(evidence of noncarcinogenicity for humans, based on a lack of evidence
of carcinogenicity in acceptable studies with two animal species, rat
and mouse.
    6. Animal metabolism. The reregistration requirements for animal
metabolism are fulfilled. The qualitative nature of the residue in
animals is adequately understood based on acceptable poultry, ruminant,
and fish metabolism studies. There are no animal feed items associated
with this proposed use. The diquat metabolism and magnitude of residue
in animals is not germane to this petition.
    7. Metabolite toxicology. The qualitative nature of the residue in
plants is adequately understood based on an acceptable potato
metabolism study and rat bioavailabilty study. The terminal residue of
concern in plants is diquat per se. The qualitative nature of the
residue in animals is adequately understood.

C. Aggregate Exposure

    Diquat is a non-selective, contact herbicide with both food and
non-food uses. As such, aggregate non-occupational exposure would
include exposures resulting from consumption of potential residues in
food and water, as well as from residue exposure resulting from non-
crop use around trees, shrubs, lawns, walks, driveways, etc. Thus, the
possible human exposure from food, drinking water and residential uses
has been assessed below.
    1. Dietary exposure-- i. Food. Acute dietary - The EPA did not
identify an acute toxicity endpoint of concern for diquat in the
Reregistration Eligibility Decision (RED) document, and determined that
an acute dietary risk assessment is not required for this chemical.
    ii. Chronic dietary. For purposes of assessing the potential
chronic dietary exposure, Zeneca has estimated the aggregate exposure
based on Theoretical Maximum Residue Contribution (TMRC) for all
existing tolerances and the proposed tolerances of diquat on dry beans
and dry peas at 0.8 ppm. 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 this exposure assessment:
100% of the crops were treated, the RAC residues would be at the level
of the tolerance, and certain processed food residues would be at
anticipated (average) levels based on processing studies. In addition,
residues of diquat in tap water at the Maximum Contaminant Level (MCL)
of 0.02 ppm was included in the dietary assessment. These conservative
assumptions result in a "worst-case" risk assessment and a
significant overestimate of actual human exposure. An assessment was
also performed using Anticipated Residues Contributions (ARC) derived
from field trial data for sorghum, soybeans, potatoes, dry beans and
peas. The ARC assessment also included percent crop treated data as
cited in the July 1995 Diquat RED, as well as market projections for
dry beans and peas. The resulting TMRC for the US population is
0.002946 mg/kg body weight/day (58.9% of the RfD). For this same group,
the Anticipated Residue Contribution (ARC) is 0.000711 mg/kg body
weight/day (14.2% RfD). For children ages 1 to 6 and non-nursing
infants the TMRC was 0.004571 mg/kg body-weight/day (91.4% RfD) and
0.003620 mg/kg body-weight/day (72.4% RfD), respectively. For these
same groups the ARC was 0.001513 mg/kg body-weight/day (30.3% RfD) for
children ages 1 to 6, and 0.002795 mg/kg body-weight/day (55.9% RfD)
for non-nursing infants. None of the subgroups assessed exceeded 100%
of the RfD.
    iii. Drinking water. In examining aggregate exposure, FQPA directs
EPA to consider available information concerning exposures from the
pesticide residue in food and all other non-occupational exposures. The
primary non-food sources of exposure the Agency looks at, include
drinking water (whether from groundwater or surface water), is exposure
through pesticide use in gardens, lawns, etc (residential uses).
    The lifetime health advisory and maximum contaminant level (MCL)
set by EPA for diquat are the same and given as 0.02 parts per million
(ppm) as required under the Drinking Water Regulations under the Safe
Drinking Water Act. Drinking water which meets the EPA standard is
associated with little to no risk and should be considered safe.
Inclusion of MCL level residues of diquat in water in the dietary
assessment demonstrated a safe exposure level to all subgroups in the
US population. The Agency no longer establishes tolerances for residues
in potable water; the tolerance for diquat dibromide has been replaced
with a designated maximum contaminant level goal (MCLG) of 0.02 ppm for
residues of diquat in potable water.
    The primary route of environmental dissipation of diquat is strong
adsorption to soil particles. Diquat does not hydrolyse or photodegrade
and is resistant to microbial degradation under aerobic and anaerobic
conditions. There were no major degradates isolated from any of the
environmental fate studies. When used as an aquatic herbicide, diquat
is removed from the water column by adsorption to soil sediments,
aquatic vegetation, and organic matter. Adsorbed diquat is persistent
and immobile, and is not expected to be a ground-water contaminant. The
environmental fate data base for diquat is complete for reregistration
of diquat dibromide.
    2. Non-dietary exposure. As a non-selective, contact herbicide,
homeowner use of diquat will consist primarily of spot spraying of
weeds around trees, shrubs, walks, driveways, flower beds, fence lines,
etc. The potential for exposure following application as a spot
treatment in residential gardens, driveway edges, patios, etc. is low
due to the limited frequency and duration of exposure. The exposures
which would result from the use of diquat are determined to be of an
intermittent nature. Any exposures to diquat would result from dermal
exposure. These exposures are not expected to pose any acute toxicity
concerns. Based on the US EPA National Home and Garden Pesticide Use
Survey (RTI/5100/17-01F, March 1992), the average homeowner is expected
to use non-selective herbicides only about four times a year. Thus,
these exposure have not been factored into a chronic exposure
assessment. Also, diquat has extremely low skin permeation, is not
volatile, presenting

[[Page 63948]]

no inhalation risk, and has rapid and strong binding characteristics to
leaf surfaces and soil. The Agency concludes that non-occupational and
non-dietary exposure to diquat will not be significant and has not been
aggregated with dietary exposures in estimating chronic risk.

D. Cumulative Effects

    The only other compound in the bipyridilium chemical family is
paraquat dichloride. Since diquat dibromide and paraquat dichloride
have different toxicological endpoints and therefore do not have a
common mode of action, there is no need for an assessment of cumulative
effects.

E. Safety Determination

    1. U.S. population. The proposed uses utilize 58.9% of the RfD for
the general U.S. population, based on the assumptions of 100% crop
treated, MCL level residues in tap water and all residues at tolerance
levels; 72.4% of the RfD for non-nursing infants under 1-year old,
19.6% of the RfD for nursing infants under 1-year old; 91.4% of the RfD
for children 1-6 years old; and 71.5% of the RfD for children 7-12
years old. An additional risk assessment for residential uses is
unnecessary because there is no evidence for toxicological concern via
the dermal or inhalation routes of exposure. Given diquat's strong
binding characteristics, exposure via drinking water is highly
unlikely. Zeneca concludes that there is reasonable certainty that no
harm will occur from aggregate exposure to diquat.
    2. Infants and children. FFCDA section 408 provides that EPA shall
apply an additional ten fold margin of exposure for infants and
children in the case of threshold effects to account for pre- and post-
natal toxicity and the completeness of the database unless EPA
determines that a different margin of exposure will be safe for infants
and children. EPA believes that reliable data support using the
standard margin of exposure (usually 100 x for combined inter- and
intra-species variability) and not the additional tenfold margin of
exposure when EPA has a complete data base under existing guidelines
and when the severity of the potential effect in infants and children
or the potency or unusual toxic properties of a compound do not raise
concerns regarding the adequacy of the standard margin of exposure.
    Risk to infants and children was determined by the use of a rat
multigeneration reproduction study and developmental toxicity studies
in rabbits and rats. The reproduction study provides information on
potential effects from exposure on the reproductive capability of
mating parents and on systemic toxicity. The developmental studies
provide information on the potential for adverse effects from exposure
on the developing organism during prenatal development.
    The toxicological data base for evaluating pre- and post-natal
toxicity for diquat is considered to be complete. In the rat
reproduction study, systemic toxicity to the mating parents was
observed at 4 and 20/12 mg diquat cation/kg body weight/day, and
reproductive effects in the form of decreased pups per litter and
decreased body weight gain were seen at 20/12 mg/kg/day. Given that the
effects seen in the pups and litters were at doses that clearly
affected the parents at this dose level and below, diquat is considered
not to affect reproductive performance without significantly
compromising the health of the parental animals.
    Developmental effects in the rat and rabbit studies, including
decreased body weights, kidney and liver effects, and delayed
ossification, were only observed at the highest doses tested and are
considered to be related to the significant maternal toxicity exhibited
at these dose levels. There was no evidence in these studies that
diquat caused teratogenic effects.
    Furthermore, the RfD is currently based on effects seen at 0.5 mg/
kg/day in the dog. Effects seen at maternally toxic doses in the rat
developmental study were 80 times higher, and in the rabbit study were
20 times higher than the level on which the RfD is based. Thus, Zeneca
does not believe the effects seen in these studies are of such a
concern to require an additional safety factor. Accordingly, Zeneca
concludes that the RfD has an adequate margin of protection for infants
and children and there is reasonable certainty that no harm will occur
to infants and children from aggregate exposure to diquat.

F. International Tolerances

    Codex lists diquat cation in dry beans and peas at 0.2 ppm. Diquat
is listed in Canada in beans and peas at 0.1 ppm. There are no Mexican
maximum residue limits for diquat on dry beans or peas.

[FR Doc. 97-31542 Filed 12-2-97; 8:45 am]
BILLING CODE 6560-50-F