[Federal Register Volume 64, Number 195 (Friday, October 8, 1999)]
[Notices]
[Pages 54885-54889]
From the Federal Register Online via the Government Publishing Office [www.gpo.gov]
[FR Doc No: 99-26335]
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ENVIRONMENTAL PROTECTION AGENCY
[PF-894; FRL-6384-2]
Notice of Filing a Pesticide Petition to Establish a Tolerance
for Certain Pesticide Chemicals in or on Food
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
certain pesticide chemicals in or on various food commodities.
DATES: Comments, identified by docket control number PF-894, must be
received on or before November 8, 1999.
ADDRESSES: Comments may be submitted by mail, electronically, or in
person. Please follow the detailed instructions for each method as
provided in Unit I.C. of the ``SUPPLEMENTARY INFORMATION'' section. To
ensure proper receipt by EPA, it is imperative that you identify docket
control number PF-894 in the subject line on the first page of your
response.
FOR FURTHER INFORMATION CONTACT: By mail: Susan Stanton, Registration
Support Branch, Registration Division (7505C), Office of Pesticide
Programs, Environmental Protection Agency, 401 M St., SW., Washington,
DC 20460; telephone number: (703) 305-5218; and e-mail address:
[email protected].
SUPPLEMENTARY INFORMATION:
I. General Information
A. Does this Action Apply to Me?
You may be affected by this action if you are an agricultural
producer, food manufacturer or pesticide manufacturer. Potentially
affected categories and entities may include, but are not limited to:
------------------------------------------------------------------------
Examples of
Categories NAICS potentially
affected entities
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Industry 111 Crop production
112 Animal production
311 Food manufacturing
32532 Pesticide
manufacturing
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This listing is not intended to be exhaustive, but rather provides
a guide for readers regarding entities likely to be affected by this
action. Other types of entities not listed in the table could also be
affected. The North American Industrial Classification System (NAICS)
codes have been provided to assist you and others in determining
whether or not this action might apply to certain entities. If you have
questions regarding the applicability of this action to a particular
entity, consult the person listed in the FOR FURTHER INFORMATION
CONTACT section.
B. How Can I Get Additional Information, Including Copies of this
Document and Other Related Documents?
1. Electronically. You may obtain electronic copies of this
document, and certain other related documents that might be available
electronically, from the EPA Internet Home Page at http://www.epa.gov/.
To access this document, on the Home Page select ``Laws and
Regulations'' and then look up the entry for this document under the
``Federal Register--Environmental Documents.'' You can also go directly
to the Federal Register listings at http://www.epa.gov/fedrgstr/.
2. In person. The Agency has established an official record for
this action under docket control number PF-894. The official record
consists of the documents specifically referenced in this action, any
public comments received during an applicable comment period, and other
information related to this action, including any information claimed
as confidential business information (CBI). This official record
includes the documents that are physically located in the docket, as
well as the documents that are referenced in those documents. The
public version of the official record does not include any information
claimed as CBI. The public version of the official record, which
includes printed, paper versions of any electronic comments submitted
during an applicable comment period, is available for inspection in the
Public Information and Records Integrity Branch (PIRIB), Rm. 119,
Crystal Mall #2, 1921 Jefferson Davis Highway, Arlington, VA, from 8:30
a.m. to 4 p.m., Monday through Friday, excluding legal holidays. The
PIRIB telephone number is (703) 305-5805.
C. How and to Whom Do I Submit Comments?
You may submit comments through the mail, in person, or
electronically. To ensure proper receipt by EPA, it is imperative that
you identify docket control number PF-894 in the subject line on the
first page of your response.
1. By mail. Submit your comments to: Public Information and Records
Integrity Branch (PIRIB), Information Resources and Services Division
(7502C), Office of Pesticide Programs (OPP), Environmental Protection
Agency, 401 M St., SW., Washington, DC 20460.
2. In person or by courier. Deliver your comments to: Public
Information and Records Integrity Branch (PIRIB), Information Resources
and Services Division (7502C), Office of Pesticide Programs (OPP),
Environmental Protection Agency, Rm. 119, Crystal Mall #2, 1921
Jefferson Davis Highway, Arlington, VA. The PIRIB is open from 8:30
a.m. to 4 p.m., Monday through Friday, excluding legal holidays. The
PIRIB telephone number is (703) 305-5805.
3. Electronically. You may submit your comments electronically by
E-mail to: ``[email protected],'' or you can submit a computer disk as
described above. Do not submit any information electronically that you
consider to be CBI. Avoid the use of special characters and any form of
encryption. Electronic submissions will be accepted in Wordperfect 5.1/
6.1 or ASCII file format. All comments in electronic form must be
identified by docket control number PF-894. Electronic comments may
also be filed online at many Federal Depository Libraries.
D. How Should I Handle CBI That I Want to Submit to the Agency?
Do not submit any information electronically that you consider to
be CBI. You may claim information that you submit to EPA in response to
this document as CBI by marking any part or all of that information as
CBI. Information so marked will not be
[[Page 54886]]
disclosed except in accordance with procedures set forth in 40 CFR part
2. In addition to one complete version of the comment that includes any
information claimed as CBI, a copy of the comment that does not contain
the information claimed as CBI must be submitted for inclusion in the
public version of the official record. Information not marked
confidential will be included in the public version of the official
record without prior notice. If you have any questions about CBI or the
procedures for claiming CBI, please consult the person identified in
the ``FOR FURTHER INFORMATION CONTACT'' section.
E. What Should I Consider as I Prepare My Comments for EPA?
You may find the following suggestions helpful for preparing your
comments:
1. Explain your views as clearly as possible.
2. Describe any assumptions that you used.
3. Provide copies of any technical information and/or data you used
that support your views.
4. If you estimate potential burden or costs, explain how you
arrived at the estimate that you provide.
5. Provide specific examples to illustrate your concerns.
6. Make sure to submit your comments by the deadline in this
notice.
7. To ensure proper receipt by EPA, be sure to identify the docket
control number assigned to this action in the subject line on the first
page of your response. You may also provide the name, date, and Federal
Register citation.
II. What Action is the Agency Taking?
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.
List of Subjects
Environmental protection, Agricultural commodities, Feed additives,
Food additives, Pesticides and pests, Reporting and recordkeeping
requirements.
Dated: September 24, 1999.
Peter Caulkins,
Acting 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 summary verbatim without
editing it 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.
Bayer Corporation
PP 9F6011
EPA has received a pesticide petition (9F6011) from Bayer
Corporation, 8400 Hawthorne Road, Kansas City, Missouri 64120-0013
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 tolerances for residues of flucarbazone sodium: 4,5-
dihydro-3-methoxy-4-methyl-5-oxo-N-[[2-
(trifluoromethoxy)phenyl]sulfonyl]-1H-1,2,4-triazole-1-carboxamide,
sodium salt; and its N-desmethyl degradate, 4,5-dihydro-3-methoxy-5-
oxo-N-[[2-( trifluoromethoxy)phenyl]sulfonyl]-1H-1,2,4-triazole-1-
carboxamidein in or on the raw agricultural commodities (RACs):
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Commodity Parts per million
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Wheat Forage.............................. 0.30
Wheat Hay................................. 0.10
Wheat Straw............................... 0.05
Wheat Grain............................... 0.01
Milk...................................... 0.005
Meat (cattle, goats, sheep, horses, hogs). 0.01
Liver (cattle, goats, sheep, horses, hogs) 0.60
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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 flucarbazone-sodium in wheat
was rapid and extensive. Little or no parent flucarbazone-sodium was
found in the RACs. A primary metabolic pathway in wheat involved the N-
demethylation of flucarbazone-sodium to give N-desmethyl flucarbazone-
sodium. N-desmethyl flucarbazone-sodium was found in all of the wheat
RACs. The N-desmethyl flucarbazone-sodium was then either hydrolyzed or
conjugated with glucose. Another primary metabolic pathway was
hydrolysis of flucarbazone-sodium yielding sulfonic acid and
sulfonamide which were isolated, and N,O-dimethyl triazolinone which
was not isolated. Other metabolites were then subsequently formed by
oxidative reactions, hydrolytic reactions, and conjugation.
2. Analytical method--Plants. The proposed tolerance expression is
parent flucarbazone-sodium and N-desmethyl flucarbazone-sodium. An
analytical method was developed to measure these two analytes in plant
matrices. This method was validated in wheat tissues. The flucarbazone-
sodium and N-desmethyl flucarbazone-sodium residues are extracted from
the wheat samples with 0.05 M NH4 OH by accelerated solvent extraction
(ASE). The extracts are purified by a combination of C-18 solid phase
extraction (spe) and ethylene diamine-N-propyl (PSA) spe. The resultant
analytes are detected by liquid chromatography/tandem mass spectroscopy
(lc/ms/ms) and quantified against known amounts of deuterated internal
standards. The method limit of quantitation (LOQ) is 0.01 milligram/
kilogram (mg/kg) of either analyte in all wheat matrices. The method
limit of detection (LOD) is 0.005 mg/kg of either analyte in all wheat
matrices.
3. Animals. An analytical method was developed to measure the
residues of flucarbazone-sodium in animal tissues and milk. Since the
flucarbazone-sodium-related residues were present in ruminant tissues
as a mixture of bound, conjugated, and unconjugated residues, a method
was developed that simultaneously extracted and hydrolyzed the majority
of the flucarbazone-sodium-related residues to flucarbazone-sodium
sulfonamide. The flucarbazone-sodium residues are simultaneously
hydrolyzed to flucarbazone-sodium sulfonamide and extracted from the
animal tissues and milk by heating with 8% trifluoroacetic acid (TFA)
in water. The analysis of fat was complicated by the large quantities
of lipids that were released during
[[Page 54887]]
hydrolysis and extraction. Therefore, the flucarbazone-sodium residues
are extracted into acetonitrile/water (9:1) before they are hydrolyzed
to flucarbazone-sodium sulfonamide. After conversion to flucarbazone-
sodium sulfonamide, the residues are purified and partitioned. The
residues are detected by lc/ms/ms and quantified against known amounts
of deuterated internal standards. The LOQ in the tissues and milk is
0.020 and 0.005 mg/kg, respectively. The estimated LOD (3x highest
background response) in the liver, muscle, and milk is 0.014 0.002 and
0.004 mg/kg, respectively. The recoveries of flucarbazone-sodium were
determined in all tissues and milk after fortification with
flucarbazone-sodium. The average recoveries of flucarbazone-sodium from
liver fortified at 0.020 and 0.100 mg/kg were 104% and 100%,
respectively. The average recoveries of flucarbazone-sodium from muscle
fortified at 0.020 and 0.100 mg/kg were 97% and 102%, respectively. In
milk the average recoveries of flucarbazone-sodium at fortifications of
0.005, 0.010, and 0.050 mg/kg were 111% (after correction for
background in the control samples, the average recovery was 92%), 97%
and 91%, respectively. An independent laboratory validation of the
analytical method was performed. The method was successfully validated
indicating that the method could be satisfactorily run by following the
written procedure.
3. Magnitude of residues. Field trials were conducted with wheat at
36 locations to evaluate the quantity of flucarbazone-sodium residues
in wheat forage, hay, straw, and grain following treatment with
flucarbazone-sodium 70WG at a rate of 30 grams active ingredient/
hectacre (g ai/ha). The highest average field trial (HAFT) residue
detected in forage, hay, and straw were 0.27, 0.08, and 0.04 mg/kg,
respectively. Residues of flucarbazone-sodium were < 0.01 mg/kg in
wheat grain.
B. Toxicological Profile
1. Acute toxicity--i. Flucarbazone-sodium is not toxic to fasted
rats following a single oral administration. The oral lethal dose
(LD50) is > 5,000 mg/kg body weight (bwt) for males and
females.
ii. Flucarbazone-sodium is not toxic to rats following a single
dermal application. The dermal LD50 is > 5,000 mg/kg bwt for
males and females.
iii. An acute inhalation study with rats showed low toxicity with a
4-hour dust aerosol lethal concentration (LC50) > 5,130 mg/
m3 air for males and females.
iv. An eye irritation study in rabbits showed only very slight,
reversible irritation.
v. A dermal irritation study in rabbits showed flucarbazone-sodium
is not irritating to skin.
vi. Flucarbazone-sodium has no skin sensitizing potential under the
conditions of the maximization test in guinea pigs.
2. Genotoxicity. The genotoxic action of flucarbazone-sodium was
studied in bacteria and mammalian cells with the aid of various in
vitro test systems (Salmonella microsome test, hypoxanthine guanine
phophoribosyl transferase (HGPRT) test with Chinese hamster V79 cells,
cytogenetic study with Chinese hamster V79 cells and unscheduled DNA
synthesis test) and in one in vivo test (micronucleus test). None of
the tests revealed any evidence of a mutagenic or genotoxic potential
of flucarbazone-sodium. The compound did not induce point mutation, DNA
damage, or chromosome aberration.
3. Reproductive and developmental toxicity. In a 2-generation
reproduction study, Wistar rats were administered dietary levels of
flucarbazone-sodium at levels of 0, 50, 4,000, and 20,000/12,000 (dose
reduction week 6). The no observed adverse effect levels (NOAELs) for
reproductive parameters was established at 4,000 ppm, based on slight
reduction in pup weight development at 12,000 ppm. The NOAELs
established for parental males and females were 4,000 ppm and 50 ppm,
respectively.
i. A developmental toxicity study was conducted with Sprague-Dawley
rats via oral gavage of flucarbazone-sodium at levels of 0, 100, 300,
and 1,000 mg/kg bwt/day on days 6 through 19 of gestation. There were
no signs of maternal toxicity, embryotoxicity, fetotoxicity, or
teratogenicity at the level of 1,000 mg/kg bwt/day. Therefore, the
maternal and developmental NOAELs for rats were established at 1,000
mg/kg bwt/day, the limit dose for this study type.
ii. Himalayan rabbits were administered flucarbazone-sodium at
levels of 0, 100, 300, 500, or 1,000 mg/kg bwt by oral gavage days 6
through 28 post coitum in a test for developmental toxicity. A maternal
NOAEL of 100 mg/kg bwt/day was established based on clinical findings,
bwt loss, decreased feed consumption, gastrointestinal changes,
increased liver weights and fatty liver changes at 300 mg/kg bwt/day.
The gestation rate NOAEL of 100 mg/kg bwt/day was based on one abortion
(assessed as secondary due to maternal toxicity) at 300 mg/kg bwt/day.
The NOAEL for fetal parameters of 300 mg/kg bwt/day was based on
decreased fetal weights and delayed ossification at 500 mg/kg bwt/day.
No teratogenic potential of flucarbazone-sodium was evident in rabbits.
iii. A 90-day feeding study with male and female B6C3F1 mice
established a NOAEL of 7,000 (equivalent to 2,083 and 3,051 mg/kg bwt/
day for males and females, respectively). The dose of 7,000 ppm was the
highest dose tested (HDT).
4. Subchronic toxicity--i. A 28-day dermal rat study established a
systemic NOAEL of 1,000 mg/kg bwt/day (the dermal limit dose) for males
and females. The local dermal effects, skin thickening, seen at 1,000
mg/kg were regarded as a result of mechanical friction and of no
toxicological relevance.
ii. A 90-day rat feeding study defined a NOAEL at 250 ppm (17.6 mg/
kg bwt/day) for males and 1,000 ppm (101.7 mg/kg bwt/day) for females
based on a decreased spleen weight in males at 1,000 ppm and on
immunologic changes at 4,000 ppm in females.
iii. A 90-day feeding study with male and female B6C3F1 mice
established a NOAEL of 7,000 ppm (equivalent to 2,083, and 3,051 mg/kg
bwt/day for males and females, respectively). The dose of 7,000 ppm was
the HDT.
iv. A 90-day dog feeding study at levels of 0, 1,000, 5,000, and
50,000 ppm established a NOAEL of 1,000 ppm (equivalent to 33.8 mg/kg
bwt/day in males and 35.2 mg/kg bwt/day in females) based on decreased
thyroxine levels and increased thyroxine-binding capacity, macroscopic
and microscopic effects on the gastric mucosa and an eosinophilic
hepatocellular cytoplasm occurring at 5,000 ppm and above. The liver
enzyme induction at 1,000 ppm was assessed as a slight adaptive
response in the detoxification process of flucarbazone-sodium but not
as an adverse effect, due to the absence of clinical chemical changes
that would indicate liver damage and due to the absence of any
histopathologic liver changes at this dietary level.
5. Chronic toxicity--i. A 2-year chronic toxicity/oncogenicity
study was conducted with male and female Wistar rats at dietary levels
of 0, 2.5, 7.5, 125, and 1,000 mg/kg bwt. A NOAEL of 125 mg/kg was
established based on increased food consumption (both sexes) and lower
bwts (females) at 1,000 mg/kg. No carcinogenic potential was indicated.
ii. B6C3F1 mice were administered flucarbazone-sodium via the diet
at levels of 0, 50, 1,000, and 7,000 ppm in a 2-year carcinogenicity
study. The NOAEL was established in males and females at 1,000 ppm
(equivalent to
[[Page 54888]]
274.5 and 458.9 mg/kg bwt/day, respectively) based on reduced bwt gain
in both sexes and on increased feed consumption in males at the 7,000
ppm level. No carcinogenic potential was indicated.
iii. A 1-year feeding study in dogs at levels of 0, 200, 1,000, and
5,000 ppm established a NOAEL of 1,000 ppm for males (equal to 35.87
mg/kg bwt/day) based on decreased bwt development, increased ALAT- and
ASAT-levels and slightly increased N-demethylase levels. The NOAEL of
200 ppm for females (equal to 7.43 mg/kg bwt/day) was based on elevated
ALAT-, ASAT-, and GLDH-levels at 1,000 ppm in one female.
Histopathology revealed no treatment-related effects.
6. Animal metabolism. Flucarbazone-sodium was metabolized via two
pathways. The major pathway involved the hydrolysis of the urea linkage
forming sulfonamide and N,O-dimethyltriazolinone. The sulfonamide was
shown to be the major metabolite in the blood, fat, liver, and muscle
at 4 to 6 hours following oral administration of [phenyl-UL-
14C] flucarbazone-sodium. The sulfonamide was conjugated
with glucuronic acid or acetate [sulfonamide N-glucuronide or N-acetyl
sulfonamide] or hydroxylated and then conjugated with glucuronic acid
to form hydroxysulfonamide-O-glucuronide prior to elimination in the
urine. A minor pathway involved N-demethylation of flucarbazone-sodium
to form N-desmethyl flucarbazone-sodium followed by hydrolysis to form
the sulfonamide and O-methyltriazolinone. Demethylation of N,O-
dimethyltriazolinone led to the formation of N-methyltriazolinone, O-
methyltriazolinone, and ultimately, urazole; methyl urethane was
probably formed from the cleavage of O-methyltriazolinone.
7. Metabolite toxicology--i. The animal and plant metabolite
flucarbazone-sodium sulfonamide (trifluoromethoxysulfonamide) has a low
acute oral toxicity (LD50 > 2,000 mg/kg bwt) in fasted rats.
ii. The plant metabolite flucarbazone-sodium sulfonamide lactate
conjugate has no acute oral toxicity (NOAEL: 5,000 mg/kg bwt) in fasted
rats.
iii. The plant metabolite flucarbazone-sodium sulfonamide alanine
has no acute oral toxicity (NOAEL: 5,000 mg/kg bwt) in fasted rats.
iv. The soil metabolite O-desmethyl flucarbazone-sodium has an
acute oral LD50 value in fasted male and female rats of >
2,500 - < 5,000 mg/kg bwt.
v. The plant, animal, and soil metabolite, MKH 10868 (flucarbazone-
sodium sulfonic acid Na-salt), has no acute oral toxicity
(LD50 > 5,000 mg/kg bwt) in fasted male and female rats.
vi. MKH 10868 was considered non-mutagenic with and without S9 mix
in the plate incorporation as well as in the preincubation modification
of the Salmonella/microsome test.
8. Endocrine disruption. There is no evidence to suggest that
flucarbazone-sodium has an effect on the endocrine system. Studies in
this data base include evaluation of the potential effects on
reproduction and development, and an evaluation of the pathology of the
endocrine organs following short- and long-term exposure. These studies
revealed no endocrine effects due to flucarbazone-sodium.
9. Other studies--i. An acute neurotoxicity screening study in rats
established an overall NOAEL for males and females of 500 mg/kg based
on transient neurobehavioral effects. Evidence of toxicity was only
slight at a limit dose of 2,000 mg/kg and complete recovery occurred
within 7 days following treatment.
ii. A subchronic neurotoxicity screening study in rats established
an overall NOAEL of 2,000 ppm for males (equal to 147 mg/kg bwt/day)
and 20,000 ppm (equal to 1,730 mg/kg bwt/day) for females based on a
slight decrease in bwt and food consumption. The NOAEL for microscopic
lesions was 20,000 ppm for males and females, the highest dose tested
(HDT). There was no evidence of neurotoxicity at any dietary level.
iii. A plaque-forming-cell assay (to investigate
immunotoxicological potential) was performed on rats after a 4-week
dietary exposure. The NOAEL of 20,000 ppm (equivalent to 2,205, or
2,556 mg/kg bwt/day in males or females, respectively) was based on the
lack of specific effects in the HGT.
iv. The immunotoxicity potential of flucarbazone-sodium was
additionally investigated in antibody plaque-cell forming assays and in
assays examining splenic T-cells, B-cells, and NK-cells after 4-week
dietary administrations in male and female rats at levels up to and
including 1,000 mg/kg bwt/day. There was no statistically significant
effect on the humoral immune system and no effects on splenic cell
populations, cell-mediated immune response or the innate immune
response in males or females. The NOAEL for immunotoxicity from these
studies was 1,000 mg/kg bwt/day, the immunotoxicity limit dose.
C. Aggregate Exposure
1. Dietary exposure--i. Food. Estimates of chronic dietary exposure
to residues of flucarbazone-sodium utilized the proposed tolerance-
level residues for wheat forage, wheat hay, wheat straw, wheat grain,
meat, liver, and milk of 0.30, 0.10, 0.05, 0.01, 0.01, 0.60, and 0.005
ppm, respectively. Other assumptions were that 100% of the target crop
would be treated with flucarbazone-sodium and that no loss of residue
would occur due to processing and or cooking. A reference dose (RfD) of
0.04 mg/kg/day was assumed based on the NOAEL of 4 mg/kg/day from the
2-generation study in Wistar rats. A safety factor of 100 was used
based on interspecies extrapolation (10x) and intraspecies variability
(10x). Using these conservative assumptions, dietary residues of
flucarbazone-sodium contribute 0.0002 mg/kg/day (0.5% of the RfD) for
children 1-6 years, the most sensitive sub-population. For the U.S.
population the exposure was 0.00008 mg/kg/day (0.2% of the RfD). For
acute dietary exposure, the same conservative assumptions were made.
Based on the NOAEL of 500 mg/kg/day from the acute neurotoxicity study,
the calculated MOE's for acute risk from flucarbazone-sodium and its
degradates for the general U.S. population was 386,108 and for the most
exposed subgroup, children 1-6 years the margin of exposure (MOE) was
141,262. These figures are well above 100 which is the level of concern
based on interspecies extrapolation (10x) and intraspecies variability
(10x).
ii. Drinking water. Given the post-emergence application pattern,
low use rates and rapid soil degradation of flucarbazone-sodium, the
risk of ground and surface water contamination and exposure via
drinking water is negligible. The surface water model generic expected
environment concentration (GENEEC) and the ground water model SCI-GROW
were used to determine whether drinking water from surface or ground
water sources represented a worst-case exposure scenario. These models
predict residues of flucarbazone-sodium would be higher in surface
water. Assuming a worst-case GENEEC scenario where residues of
flucarbazone-sodium occur in surface water used for drinking water at
the highest predicted acute and chronic concentrations, the risk from
exposure to residues of flucarbazone-sodium are well within EPA's
acceptable limits.
The GENEEC model predicted an acute surface water concentration of
flucarbazone-sodium of 1.22 g/L. Assuming a 70 kg adult drinks
2 liters/day containing 1.22 g/L, the acute exposure would be
0.0000349 mg/kg/day for adults. Assuming a 10 kg child drinks 1 liter/
day containing 1.22 g/L, the exposure would be 0.000122 mg/kg/
[[Page 54889]]
day. Based on the the NOAEL of 500 mg/kg/day from the acute oral
neurotoxicity screening study in rats and assuming a safety of 100 (10x
for interaspecies variability and 10x for interspecies extrapolation),
the MOE for adults of 143,000 and for children of 41,000 do not exceed
EPA's level of concern for adults or children. This assessment is based
on the GENEEC highest predicted acute concentration of flucarbazone-
sodium in drinking water using worst-case assumptions.
Using GENEEC, the highest predicted chronic concentration of
flucarbazone-sodium was 1.14 g/L. Assuming a 70 kg adult
consumes 2 L of water per day containing 1.14 g/L of
flucarbazone-sodium residues for a period of 70 years, less than 0.04%
of the RfD was consumed from residues of flucarbazone-sodium in surface
water used for drinking water (worst-case scenario). For a 10 kg child
drinking 1 L of water per day containing 1.14 g/L of
flucarbazone-sodium residues only 0.15% of the RfD was consumed by
drinking water.
2. Non-dietary exposure. There are no current non-food uses for
flucarbazone-sodium registered under the Federal Insecticide,
Fungicide, and Rodenticide Act (FIFRA), as amended. No non-food uses
are proposed for flucarbazone-sodium. No non-dietary exposures are
expected for the general population.
D. Cumulative Effects
Flucarbazone-sodium falls into the category of sulfonamide
herbicides. There is no information to suggest that any of this class
of herbicides has a common mechanism of mammalian toxicity or even
produce similar effects so it is not appropriate to combine exposures
of flucarbazone-sodium with other herbicides. Bayer Corporation is
considering only the potential risk of flucarbazone-sodium.
E. Safety Determination
1. U.S. population. As presented previously, the exposure of the
U.S. general population to flucarbazone-sodium is low, and the risks,
based on comparisons to the reference dose, are minimal. The margins of
safety from the use of flucarbazone-sodium are well within EPA's
acceptable limits. Bayer Corporation concludes that there is a
reasonable certainty that no harm will result to the U.S. population
from aggregate exposure to flucarbazone-sodium residues.
2. Infants and children. The complete toxicological data base
including the developmental toxicity and 2-generation reproduction
studies were considered in assessing the potential for additional
sensitivity of infants and children to residues of flucarbazone-sodium.
The developmental toxicity studies in rats and rabbits revealed no
increased sensitivity of rats or rabbits to in-utero exposure to
flucarbazone-sodium. The 2-generation reproduction study did not reveal
any increased sensitivity of rats to in-utero or postnatal exposure to
flucarbazone-sodium. Furthermore, none of the other toxicology studies
revealed any data demonstrating that young animals were more sensitive
to flucarbazone-sodium than adult animals. The data taken collectively
clearly demonstrate that application of a Food Quality Protection Act
(FQPA) uncertainty factor for increased sensitivity of infants and
children is not necessary for flucarbazone-sodium.
F. International Tolerances
There are currently no international (Codex) tolerances established
for flucarbazone-sodium. It is not currently registered in any other
countries. There are no harmonized Maximum Residue Levels (MRLs) at the
European Union level at present. Petitions for MRLs for flucarbazone-
sodium in/on wheat, meat, milk, and liver have been submitted to the
Pesticide Management Regulatory Agency in Canada.
[FR Doc. 99-26335 Filed 10-7-99; 8:45 am]
BILLING CODE 6560-50-F