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flucarbazone-sodium Pesticide Petition Filing 9/99

  


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.

-----------------------------------------------------------------------

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: 
stanton.susan@epa.gov.

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
------------------------------------------------------------------------
Industry                          111                 Crop production

                                  112                 Animal production

                                  311                 Food manufacturing
                                  32532               Pesticide
                                                       manufacturing
------------------------------------------------------------------------


    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: ``opp-docket@epa.gov,'' 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):

------------------------------------------------------------------------
                 Commodity                        Parts per million
------------------------------------------------------------------------
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
------------------------------------------------------------------------

    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 
(LD<INF>50</INF>) 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 LD<INF>50</INF> 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 (LC<INF>50</INF>) > 5,130 mg/
m<SUP>3</SUP> 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-
<INF>14</INF>C] 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 (LD<INF>50</INF> > 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 LD<INF>50</INF> 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 
(LD<INF>50</INF> > 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 <greek-m>g/L. Assuming a 70 kg adult drinks 
2 liters/day containing 1.22 <greek-m>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 <greek-m>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 <greek-m>g/L. Assuming a 70 kg adult 
consumes 2 L of water per day containing 1.14 <greek-m>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 <greek-m>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