[Federal Register Volume 65, Number 183 (Wednesday, September 20, 2000)]
[Notices]
[Pages 56901-56908]
From the Federal Register Online via the Government Publishing Office [www.gpo.gov]
[FR Doc No: 00-24212]


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ENVIRONMENTAL PROTECTION AGENCY

[PF-974; FRL-6742-7]


Notice of Filing a Pesticide Petition to Establish a Tolerance 
for a Certain Pesticide Chemical 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 a 
certain pesticide chemical in or on various food commodities.

DATES: Comments, identified by docket control number PF-974, must be 
received on or before October 20, 2000.

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. To ensure 
proper receipt by EPA, it is imperative that you identify docket 
control number PF-974 in the subject line on the first page of your 
response.

FOR FURTHER INFORMATION CONTACT: By mail: James Tompkins, Herbicide 
Branch, Registration Division (7505W), Office of Pesticide Programs, 
Environmental Protection Agency, 1200 Pennsylvania Ave., NW., 
Washington, DC 20460; telephone number: (703) 305-5697; 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

[[Page 56902]]

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 under FOR FURTHER INFORMATION 
CONTACT.

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,'' ``Regulations and Proposed Rules,'' 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-974. 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-974 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, 1200 Pennsylvania Ave., NW., 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 6.1/
8.0 or ASCII file format. All comments in electronic form must be 
identified by docket control number PF-974. 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 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 under FOR FURTHER INFORMATION 
CONTACT.

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 a 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 support 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.



[[Page 56903]]


    Dated: September 11, 2000.

  James Jones,

Director, Registration Division, Office of Pesticide Programs.

Summary of Petition

    The petitioner summary of the pesticide petition is printed below 
as required by section 408(d)(3) of the FFDCA. The summary of the 
petition was prepared by the petitioner and represents the view of the 
petitioners. 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.

Valent U.S.A. Corporation

PP 9F6044

    EPA has received a pesticide petition (PP 9F6044) from Valent 
U.S.A. Corporation at 1333 North California Boulevard, Suite 600, 
Walnut Creek, CA 94596-8025 as agent for K-I Chemical U.S.A. Inc. 
proposing, pursuant to section 408(d) of the FFDCA, 21 U.S.C. 346a(d), 
to amend 40 CFR part 180 by establishing a tolerance for residues of 
bispyribac-sodium, sodium 2,6-bis [(4,6-dimethoxypyrimidin-
2yl)oxy]benzoate in or on the raw agricultural commodities (RAC) rice 
grain, and rice straw at 0.02 parts per million (ppm). 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 support granting of the petition. Additional data 
may be needed before EPA rules on the petition.

A. Residue Chemistry

    Summary. Radiocarbon plant and animal metabolism studies have 
demonstrated that the residue of concern is best defined as parent, 
bispyribac-sodium. Practical, validated enforcement residue methodology 
is available to analyze all appropriate matrices for bispyribac-sodium 
residue with limit of quantitation (LOQ) of 0.02 ppm, adequate to 
enforce all proposed tolerances. The magnitude of residues of 
bispyribac-sodium has been evaluated in rice grain, rice straw, and in 
the appropriate processed products. Finite residues in fed ruminants, 
and poultry are not expected. These studies are adequate to support 
appropriate tolerances and dietary risk analyses.
    1. Plant and animal metabolism. Rice plants extensively metabolize 
bispyribac-sodium and the terminal residues in the RAC are low. 
Application of radio labeled bispyribac-sodium to 5-6 leaf rice 
resulted in total radiocarbon residues (TRR) of 0.007 and 0.021 ppm 
(bispyribac-sodium equivalents) in mature rice grain and 0.116 and 
0.274 ppm in mature rice straw in the [pyrimidine-2-14C] and 
[U-14C-benzene] metabolism studies, respectively.
    No parent or parent related metabolites were detected in grain with 
much of the grain radioactivity incorporated into starch. Bispyribac-
sodium was detected in straw at 0.010 and 0.042 ppm in the [pyrimidine-
2-14C] and [U-14C-benzene] metabolism studies, 
respectively. The maximum residue values for the metabolites that were 
found in straw are:
    BX-180 (0.024 ppm)
    Me2BA (0.006 ppm)
    DesMe-180 (0.002 ppm)
    DesMe-2023 (0.001 ppm)
    No single metabolite in rice straw was greater than 10% of the 
total radiocarbon residues, and all of the aglycones identified in rice 
straw were also identified in the rat metabolism study.
    Bispyribac-sodium is extensively metabolized and rapidly excreted 
by lactating goats. Treatment was at highly exaggerated feeding levels 
(11 ppm) relative to the proposed 0.02 ppm rice grain and straw 
tolerances. These study feeding levels correspond to more than 650 
times the tolerance level dietary burden for goats (using cattle diet 
values). Even at this exaggerated treatment level the total radioactive 
residue TRR concentrations in milk were extremely low (0.002 ppm, 
bispyribac-sodium equivalents).
    The edible tissue concentrations (bispyribac-sodium equivalents) 
indicate the very low bioaccumulation potential of bispyribac-sodium 
residues:
    Muscle (0.002 ppm)
    Fat (<0.003 ppm)
    Kidney (<0.041 ppm)
    Liver (<0.204 ppm)
    The metabolites identified in goat liver and kidney were:
    Glucuronide conjugates of bispyribac-sodium
    Me2BA
    BX-180
    2,6-DBA
    Me2BA
    DesMe-180
    All the metabolites are polar and easily excreted. Based on the low 
concentrations of metabolites in goat milk and tissues from the 
exaggerated doses used in the ruminant metabolism study, residues 
expected in milk and edible tissue from a tolerance level (1X) feed 
intake of bispyribac-sodium are extremely low (<<0.02 ppm). Thus, there 
is no reasonable expectation of finite secondary residues in meat, meat 
by-products, or milk, and tolerances are not necessary.
    Laying hens were treated with radiocarbon labeled bispyribac-sodium 
in their diets at 12 ppm. This high feeding level represents 600 times 
the maximum theoretical dietary burden. The TRR concentrations in 
radiocarbon bispyribac-sodium equivalents in most tissues and eggs were 
very low--0.009 ppm in muscle, 0.016 ppm in fat and eggs. TRR 
concentration in hen liver was much higher, 4.98 ppm, virtually all of 
which was unconjugated bispyribac (4.82 ppm). Based on the low 
concentrations of metabolites in eggs and most tissues from the 
exaggerated doses used in the hen metabolism study, residues 
anticipated in eggs, and edible tissue from a tolerance level (1X) feed 
intake of bispyribac-sodium are extremely low (<<0.005 ppm). In chicken 
liver, the tissue with the highest radiocarbon content, maximum 
theoretical residues are still well below the enforcement LOQ of 0.02 
ppm. Finite residues were not detected in rice grain samples from any 
of the field residue trials. The limit of detection (LOD) of the method 
was determined by statistical analysis of instrument responses in 
untreated versus treated field samples. The LOD for rice grain and bran 
is 0.001 ppm with 0.005 ppm for hulls. Even at 2X application rates, 
residues in rice grain were not detected. Assuming anticipated residues 
in rice derived poultry feed at half the LOD from the field residue 
samples, gives a maximum anticipated dietary burden for poultry of 
0.0008 ppm, and maximum residues in poultry liver of 0.0003 ppm. Thus, 
there is no reasonable expectation of finite secondary residues in 
meat, meat by-products or eggs, and tolerances are not necessary.
    2. Analytical method. Practical analytical methods for detecting 
and measuring levels of bispyribac-sodium have been developed and 
validated in/on the RAC, rice grain, and rice straw; processing 
fractions polished rice, rice hulls, and rice bran; and environmental 
samples. The extraction methodology has been validated using aged radio 
chemical residue samples from 14C-metabolism studies. 
Bispyribac-sodium is a benzoic acid salt. To allow gas/liquid 
chromatography, the residues are methylated and measured as the methyl

[[Page 56904]]

ester of the benzoic acid. The analytical methods have been validated 
in rice, rice straw, and environmental matrices at an independent 
laboratory. The LOQ of bispyribac-sodium in the enforcement method is 
0.02 ppm which will allow monitoring of food with residues at the 
levels proposed for the tolerances. Because the enforcement methodology 
uses a different methylating agent, the methodology used for analysis 
of the field residue trials had a LOQ of 0.01 ppm, a defined LOD of 
0.005 ppm, and a statistical LOD of 0.001 ppm in rice grain.
    3. Magnitude of residues--i. Crop. Data from sixteen (16) field 
trials in rice conducted in 1996 and 1997 in six (6) states throughout 
the rice growing regions of the U.S. show that at the proposed maximum 
total seasonal application rate (24 g active ingredient/Acre (ai/a), 
0.053 lb ai/a) all measured residue values in rice grain were less than 
0.005 ppm (n = 32). Data from three trials at a 2X rate (48 g ai/a) 
also all showed measured residue in the six samples of rice grain to be 
less than 0.005 ppm (n = 6). Nine (9) out of thirty-two (32) samples of 
rice straw from the sixteen 1X field sites showed finite residues of 
bispyribac-sodium. The average of the nine finite residues in rice 
straw is 0.007 ppm (n = 9, n-1 = 0.003 ppm) with a 
maximum value of 0.013 ppm. There were no finite residues (<0.005 ppm) 
observed in the six samples of rice straw from the 2X treatment rates. 
The processing study in rice using grain from a plot treated at 2X 
demonstrated that bispyribac-sodium was not detectable (<0.005 ppm) in 
rice grain, and did not concentrate (<0.005 ppm) in polished rice, rice 
hulls, or rice bran. No separate tolerances are necessary for processed 
rice products. The actual limit of detection of the analytical 
methodology used for all these studies was 0.001 ppm in rice grain and 
bran and 0.005 ppm in rice hulls. Finite residues were not detected in 
any treated rice grain sample even at exaggerated (2X) rates, or in any 
processed fraction. Because of the reduced sensitivity of the 
enforcement methodology, tolerances are proposed in rice grain and 
straw at 0.02 ppm. The field residue data indicate that the proposed 
tolerances are more than adequate to support bispyribac-sodium use on 
rice.
    ii. Secondary residues. Using proposed tolerances to calculate the 
maximum feed exposure to fed animals, and using the generally very low 
potential for residue transfer demonstrated in the milk goat and laying 
hen metabolism studies, quantifiable secondary residues (>0.02 ppm) of 
bispyribac-sodium in animal tissues, milk, and eggs are not expected. 
Poultry liver is the tissue with the highest treatment to residue 
ratio. Using anticipated residues in poultry feed from rice, and rice 
products derived from the limit of detection of the field residue 
methodology, the potential residues in poultry liver would be a maximum 
of 0.0003 ppm. This is 60-fold below the RAC enforcement LOQ. The 
refore, tolerances are not proposed for secondary residues in any fed 
animal commodity.
    iii. Rotational crops. Rotational crops planted 28 and 48 days 
after soil treatment with the 1X rate of bispyribac-sodium all showed 
radiocarbon equivalent residues of less than 0.01 ppm at normal 
harvest. This study demonstrates that bispyribac-sodium is not adsorbed 
by following crops, and that no rotational tolerances or labeling 
restrictions are necessary.
    iv. Irrigated crops. Tomatoes, table beets, and bok choy were 
sprinkler irrigated with water containing 0.07 ppm bispyribac-sodium. 
No residues were detected in any sample of tomato fruit or table beet 
roots. Immature whole beet plants, mature beet tops, and bok choy 
leaves contained 0.015 to 0.025 ppm. Bispyribac-sodium in the soil from 
treated plots did not exceed 0.012 ppm. Sprinkler application of water 
containing high concentrations of bispyribac-sodium (the highest time 
zero concentration in paddy water from the aquatic field dissipation 
studies) led to low residues in leafy crops. This study demonstrates 
that bispyribac-sodium is not adsorbed by irrigated crops and thus 
tolerances or use restrictions are not necessary.

B. Toxicological Profile

    Summary. A full battery of toxicology testing including studies of 
acute, chronic, oncogenicity, developmental, mutagenicity, and 
reproductive effects has been completed for bispyribac-sodium. The 
acute toxicity of bispyribac-sodium is low by all routes. Bispyribac-
sodium is not a developmental or reproductive toxicant, and is not 
mutagenic or oncogenic. The toxicology reports for bispyribac-sodium 
have not yet been reviewed by EPA and thus, the Agency has not yet 
established toxic endpoints of concern, specifically chronic and acute 
oral toxicity endpoints for the compound. For the purpose of chronic 
dietary risk analysis, Valent proposes 0.017 milligrams/kilograms (mg/
kg) body weight (bwt/day) as a chronic reference dose (RfD). This 
proposed RfD is based on a chronic endpoint of 1.7 mg/kg bwt/day no 
observed adverse effect level (NOAEL) for females from the two year 
oncogenicity feeding study in mice, and an uncertainty factor of one 
hundred. Bispyribac-sodium is of very low toxicity in all short-term 
evaluations, however, for the purposes of discussion, Valent proposes 
to use the NOAEL for maternal toxicity from the rabbit developmental 
toxicity study of 100 mg/kg bwt/day as an acute oral toxic endpoint. 
Valent is unable to identify toxicity endpoints of concern for acute, 
short term or chronic human exposures by any route other than oral.
    1. Acute toxicity. Bispyribac-sodium technical produces very low to 
slight toxicity following oral, dermal or inhalation acute exposures. 
Bispyribac-sodium is slightly irritating to the eye, is not irritating 
to the skin and does not cause dermal sensitization in guinea pigs. 
Technical bispyribac-sodium and its formulated product should be 
classified in toxicity category III.
    2. Genotoxicty. Bispyribac-sodium does not present a genetic 
hazard. Bispyribac-sodium technical was negative in the following 
genotoxicity assays:
    Reverse mutation (Ames).
    Chinese hampster ovary (CHO), chromosomal aberration (in 
vitro).
    Unscheduled DNA synthesis.
    Micronucleus in mice (in vivo).
    In a bacterial DNA repair assay with Bacillus subtilis, bispyribac-
sodium was potentially damaging to DNA. Overall, however, it is 
unlikely that bispyribac-sodium presents a genetic hazard.
    3. Reproductive and developmental toxicity. Bispyribac-sodium is 
not a developmental or reproductive toxicant. Developmental toxicity 
studies have been performed in rats and rabbits, and multi-generational 
effects on reproduction were tested in rats.
    In the developmental toxicity study conducted with rats, 
bispyribac-sodium. technical was administered by gavage at levels of 0, 
100, 300, and 1,000 mg/kg bwt/day during gestation days 6-15. All 
animals were necropsied on gestation day 20 followed by a teratologic 
examination of the fetuses. One-half of the fetuses were examined for 
skeletal malformations and one-half for visceral malformations. There 
were no deaths in any of the groups. There were no treatment-related 
observations at necropsy. No other biologically relevant differences 
were noted. The incidence of fetal malformations and developmental 
variations was comparable with the controls. The maternal toxicity 
observed at 1,000 mg/kg bwt/day consisted of ano-genital staining. The 
maternal NOAEL was 300 mg/kg bwt/day and the developmental NOAEL was 
1,000 mg/kg bwt/day.

[[Page 56905]]

    In the developmental toxicity study conducted with rabbits, 
technical bispyribac-sodium was administered by gavage at levels of 0, 
30, 100, and 300 mg/kg bwt/day during gestation days 6-18. Does were 
sacrificed on day 28. An external, visceral and skeletal examination 
was performed on all fetuses. Maternal toxicity included one death, two 
premature deliveries, and slight depression of body weight gain and 
food consumption in the high dose group. There were no specific changes 
noted at necropsy and no effects on fetal mortality, number of live 
fetuses or fetal weights. The NOAEL for maternal toxicity was 100 mg/kg 
bwt/day, and for developmental toxicity the NOAEL was 300 mg/kg bwt/
day.
    A two-generation reproduction study in rats was conducted with 
bispyribac- sodium technical at doses of 0, 20, 1,000, and 10,000 ppm. 
Systemic adult toxicity included decreased bwt gain and food 
consumption; increased liver weight; and histopathological changes in 
the liver and bile duct. The growth of the F1 and F2 offspring was 
inhibited at 10,000 ppm. The NOAELs for systemic adult toxicity and 
offspring developmental parameters were 20 and 1,000 ppm, respectively. 
No effects on reproduction were produced at 10,000 ppm, the highest 
dose tested.
    4. Subchronic toxicity. Subchronic oral toxicity studies conducted 
with bispyribac-sodium technical in the rat and dog indicate a low 
level of toxicity.
    Bispyribac-sodium technical was tested in rats at dose levels of 0, 
100, 1,000, 10,000, and 20,000 ppm in the diet for 13 weeks. Effects 
observed at higher doses included organ weight changes; 
histopathological changes in the liver, and the bile duct; increased 
serum GOT, GPT, ALP, and BUN; various alterations in hematology 
parameters; and reduced food consumption, food efficiency and bwt gain. 
The NOAEL was 100 ppm (7.2 mg/kg bwt/day) in males and 1,000 ppm (79.9 
mg/kg bwt/day) in female rats.
    Bispyribac-sodium technical was also tested in dogs for 13 weeks at 
doses of 0, 30, 100, and 600 mg/kg bwt/day. Vomiting, salivation, and 
loose stools were observed in animals exposed to 600 mg/kg bwt/day. 
Histopathological changes in the liver and bile ducts were also noted 
in males at 600 mg/kg bwt/day. The NOAEL was 100 mg/kg bwt/day.
    In a 21-day dermal toxicity study in rats, there was essentially no 
significant indication of toxicity. The NOAEL for this study was the 
highest dose tested (HDT) of 1,000 mg/kg bwt/day (the limit dose).
    5. Chronic toxicity. Bispyribac-sodium technical has been tested in 
chronic studies with dogs, rats, and mice.
    Bispyribac-sodium technical is not a carcinogen. Studies with 
bispyribac-sodium technical in rats and mice have shown that repeated 
high dose exposures produced decreased bwt gain, changes in 
hematological, blood biochemistry values, and histopathological lesions 
of the liver, and bile duct in rats; and reduced bwt gain, decreased 
liver weight, increased kidney weight, and histopathological changes in 
the liver in mice; but did not produce cancer in test animals. No 
oncogenic response was observed in a rat 2-year chronic feeding/
oncogenicity study or in the two-year feeding oncogenicity study in 
mice.
    Bispyribac-sodium technical was tested in rats for 2 years at doses 
of 0, 20, 200, 3,500, and 7,000 ppm in males and 0, 20, 200, 5,000, and 
10,000 ppm in females. Effects observed at higher doses included 
decreased bwt gain, changes in hematological and blood biochemistry 
values, and histopathological lesions of the liver, and bile duct. No 
neoplastic lesions were observed. The NOAEL was 200 ppm (male 10.9 mg/
kg b.w./day, female 13.9 mg/kg bwt/day).
    Bispyribac-sodium technical was tested in mice for 2 years at doses 
of 0, 10, 100, 2,500, and 5,000 ppm. Effects observed at higher doses 
included reduced bwt gain, decreased liver weight, increased kidney 
weight, and histopathological changes in the liver. No neoplastic 
lesions were observed. The NOAEL was 100 ppm (14.1 mg/kg bwt/day) in 
males and 10 ppm (1.7 mg/kg bwt/day) in females based on organ weight 
changes.
    A 52-week chronic toxicity study of bispyribac-sodium technical was 
conducted in dogs at doses of 0, 10, 100, and 750 mg/kg bwt/day. 
Effects observed at higher doses included salivation, vomiting, and 
loose stools; increased liver weight; and histopathological changes in 
the bile duct. The NOAEL was 10 mg/kg bwt/day.
    6. Mechanistic studies. Mechanistic studies were undertaken to 
investigate the histopathological effects on the common and, 
intralobular bile duct observed in the long-term rat studies. Similar 
histopathological effects were not noted in the chronic studies with 
the mouse or the dog, which, like the human, have an intact gall 
bladder. The results suggest that an increased production and flow of 
bile acids in the rat may relate to the histopathological changes 
observed.
    7. Animal metabolism. The absorption, tissue distribution, 
metabolism, and excretion of 14C-labeled bispyribac-sodium 
were studied in rats. Following administration to the rodent, the 
majority of bispyribac-sodium is excreted into the feces via the bile. 
The majority of material excreted in the feces is either unchanged 
parent compound or its desmethylated derivative. Approximately half of 
the material excreted into the urine was also unchanged parent 
material. The half-life of bispyribac-sodium in rats is between 28 to 
30 hours. These data show that bispyribac-sodium is readily excreted 
but not extensively metabolized in the rodent. Very low concentrations 
of radiocarbon in tissues over time indicate that the potential for 
bioaccumulation is minimal. There were no significant sex or dose-
related differences in excretion or metabolism. Animal metabolites are 
the same as those detected in rice and in the environment.
    8. Metabolite toxicology. Studies show that bispyribac-sodium is 
extensively metabolized by rice. Therefore, a series of acute oral and 
genetic toxicity tests were performed to investigate the potential 
toxicity of the primary rice plant degradates. None of these tests 
indicates any acute or genetic hazard from these metabolites. Because 
parent and metabolites are not retained in the body, the potential for 
acute toxicity from in situ formed metabolites is low. The potential 
for chronic toxicity is adequately tested by chronic exposure to the 
parent at the maximum tolerance dose (MTD) and consequent chronic 
exposure to the internally formed metabolites.
    9. Endocrine disruption. No special studies to investigate the 
potential for estrogenic or other endocrine effects of bispyribac-
sodium have been performed. However, as summarized above, a large and 
detailed toxicology data base exists for the compound including studies 
in all required categories. These studies include acute, sub-chronic, 
chronic, developmental, and reproductive toxicology studies including 
detailed histology and histopathology of numerous tissues, including 
endocrine organs, following repeated or long term exposure. These 
studies are considered capable of revealing endocrine effects, and the 
results of all of these studies show no evidence of any endocrine-
mediated effects and no pathology of the endocrine organs. 
Consequently, it is concluded that bispyribac-sodium does not possess 
endocrine disrupting properties.

[[Page 56906]]

C. Aggregate Exposure

    1. Dietary exposure. The toxicology data base for bispyribac-sodium 
has not yet been reviewed by EPA and thus, the Agency has not yet 
established toxic endpoints of concern, specifically chronic and acute 
oral toxicity endpoints for the compound. As discussed above, for the 
purpose of chronic dietary risk analysis, Valent proposes 0.017 mg/kg 
bwt/day as a chronic RfD, including an uncertainty factor of one 
hundred. Bispyribac-sodium is of very low toxicity in all short-term 
evaluations. Valent proposes to use 100 mg/kg bwt/day as an acute oral 
toxic endpoint. Valent is unable to identify toxicity endpoints of 
concern for acute, short term or chronic human exposures by any route 
other than oral.
    i. Food-- Chronic. A Tier I chronic dietary exposure and risk 
analysis for bispyribac-sodium residues was calculated using tolerance 
level residues for the U.S. population and 26 population subgroups. The 
results from several representative subgroups are listed below in 
Table. Chronic dietary exposure was at or below 0.16% of the RfD. 
Generally, the Agency has no cause for concern if total residue 
contribution for published and proposed tolerances is less than 100% of 
the RfD.

 Table 1.--Tier I Calculated Chronic Dietary Exposures to the Total U.S.
 Population and Selected Sub-Populations to Tolerance Level Bispyribac-
                         Sodium Residues in Food
------------------------------------------------------------------------
                                    Exposure (mg/kg
       Population subgroup             bwt/day)         Percent of RfD
------------------------------------------------------------------------
Total U.S. population (all        0.000006            0.035
 seasons)
Non-hispanic other than black or  0.000027            0.159
 white
Females (20+ years, not preg. or  0.000004            0.024
 nursing
Children (1-6 Years)              0.000011            0.065
All Infants (<1 Year Old)         0.000016            0.094
Non-Nursing Infants (<1 Year      0.000018            0.106
 Old)
Nursing Infants (<1 Year Old)     0.000009            0.053
------------------------------------------------------------------------

    Acute. A Tier I acute dietary exposure and risk analysis for 
bispyribac-sodium residues was calculated using tolerance level 
residues and 100% of the crop treated for the U.S. population, females 
(13 +), and five infant and child subgroups. The calculated exposures 
and margins of exposure (MOE) for the higher exposed proportions of the 
subgroups are listed below in Table 2. In all cases, margins of 
exposure are very large, and for the 95th percentile, all 
exceed 1-million.

Table 2.--Tier I Calculated Acute Dietary Exposures to the Total U.S. Population and Selected Sub-Populations to
                      Tolerance Level Bispyribac-Sodium Residues in Food (Per-capita Days)
----------------------------------------------------------------------------------------------------------------
                                                        95th Percentile                  99.9th Percentile
                                              ------------------------------------------------------------------
             Population subgroup                Exposure (mg/kg                    Exposure (mg/
                                                    bwt/day)            MOE         kg bwt/day)         MOE
----------------------------------------------------------------------------------------------------------------
U.S. population                                         0.000031      >1,000,000        0.000152         787,000
----------------------------------------------------------------------------------------------------------------
Females (13+)                                           0.000023      >1,000,000        0.000097      >1,000,000
----------------------------------------------------------------------------------------------------------------
Children 1-6                                            0.000061      >1,000,000        0.000249         402,000
----------------------------------------------------------------------------------------------------------------
Children 7-12                                           0.000041      >1,000,000        0.000127         787,000
----------------------------------------------------------------------------------------------------------------
All Infants                                             0.000083      >1,000,000        0.000267         375,000
----------------------------------------------------------------------------------------------------------------
Nursing Infants (<1)                                    0.000044      >1,000,000        0.000235         426,000
----------------------------------------------------------------------------------------------------------------
Non-Nursing Infants (<1)                                0.000087      >1,000,000        0.000268         373,000
----------------------------------------------------------------------------------------------------------------

    ii. Drinking water. Since bispyribac-sodium is applied outdoors to 
rice, the potential exists for bispyribac-sodium or its metabolites to 
reach ground or surface water that may be used for drinking water. 
Bispyribac-sodium will not move to ground water because of the nearly 
complete lack of leaching from rice paddies along with the low use rate 
therefore a SCI-GRO estimation of groundwater contamination was not 
performed. To quantify potential high end bispyribac-sodium exposure 
from drinking water, ``Tier I'' potential surface water concentrations 
were estimated using the rice simulation in generic expected 
environmental concentration (GENEEC) 1.3. The highest average 56-day 
concentration predicted in the simulated paddy water by GENEEC 1.3 was 
15.45 parts per billion (ppb). Reducing this estimate by a factor of 
three gives a high end estimate for drinking water contamination. Using 
standard assumptions about bwt and water consumption, the maximum 
chronic exposure from this drinking water would be 0.00015 and 0.00052 
mg/kg bwt/day for adults and children, respectively; 3.03% of the RfD 
for children. Based on this worse case analysis, the contribution of 
drinking water derived from treated rice paddy water to the dietary 
risk is much greater than that from tolerance level food, but still 
well within the acceptable range.
    2. Non-dietary exposure. Bispyribac-sodium has only proposed 
agricultural use on rice, and no other crop, homeowner, turf, or 
industrial uses. Thus, no non-dietary risk assessment is needed.

D. Cumulative Effects

    Section 408(b)(2)(D)(v) requires that the Agency must consider 
``available information'' concerning the cumulative effects of a 
particular pesticide's residues and ``other substances that have a 
common mechanism of toxicity''. Available information in this context 
include not only toxicity, chemistry, and exposure data, but also 
scientific

[[Page 56907]]

policies and methodologies for understanding common mechanisms of 
toxicity and conducting cumulative risk assessments. For most 
pesticides, although the Agency has some information in its files that 
may turn out to be helpful in eventually determining whether a 
pesticide shares a common mechanism of toxicity with any other 
substances, EPA does not, at this time, have the methodologies to 
resolve the complex scientific issues concerning common mechanism of 
toxicity in a meaningful way.
    There are no other pesticidal compounds that are structurally 
related to bispyribac-sodium and have similar effects on animals. In 
consideration of potential cumulative effects of bispyribac-sodium and 
other substances that may have a common mechanism of toxicity, there 
are currently no available data or other reliable information 
indicating that any toxic effects produced by bispyribac-sodium would 
be cumulative with those of other chemical compounds. Thus, only the 
potential risks of bispyribac-sodium have been considered in this 
assessment of aggregate exposure and effects.
    Valent will submit information for EPA to consider concerning 
potential cumulative effects of bispyribac-sodium consistent with any 
schedule established by EPA pursuant to the Food Quality Protection Act 
(FQPA).

E. Safety Determination

    The Food Quality Protection Act of 1996 introduces a new standard 
of safety, a reasonable certainty of no harm. To make this 
determination, at this time the Agency should consider only the 
incremental risk of bispyribac-sodium in its exposure assessment. Since 
the potential chronic and acute exposures to bispyribac-sodium are 
small even using worse case drinking water and Tier I dietary (food) 
exposures (<<100% of RfD, MOE >>100) the provisions of the FQPA of 1996 
will not be violated.
    1. U.S. population--i. Chronic exposure. Using the Tier I dietary 
exposure assessment procedures described above for bispyribac-sodium, 
calculated chronic dietary exposure resulting from residue exposure 
from the proposed rice use of bispyribac-sodium is minimal. The 
estimated chronic dietary exposure from food for the overall U.S. 
population and many non-child/infant subgroups is 0.159 to 0.018% of 
the RfD (0.000027 to 0.000003 mg/kg bwt/day). Addition of the worse 
case potential chronic exposure from drinking water obtained from 
treated rice paddy water increases exposure by 0.000147 mg/kg bwt/day 
to 0.000174 mg/kg bwt/day for the maximally exposed adult 
subpopulation, non-hispanic other than black or white, and the maximum 
occupancy of the RfD from 0.159% to 1.02 percent. Generally, the Agency 
has no cause for concern if total residue contribution is less than 
100% of the RfD. It can be concluded that there is a reasonable 
certainty that no harm will result to the overall U.S. population and 
many non-child/infant subgroups from aggregate, chronic exposure to 
bispyribac-sodium residues.
    ii. Acute Exposure. Using the Tier I acute dietary exposure 
assessment procedures described above for bispyribac-sodium, calculated 
acute dietary exposure resulting from tolerance level residue exposure 
to the U.S. population from the proposed rice use of bispyribac-sodium 
is minimal. The estimated acute dietary exposure at the 95th 
and 99th percentiles of exposure from food for the overall 
U.S. population is 0.000031 and 0.000152 mg/kg bwt/day, respectively. 
Addition of the worse case potential chronic exposure from drinking 
water increases exposure by 0.000147 mg/kg bwt/day. This addition of 
water exposure reduces the MOE value at the 99.9th 
percentile of exposure for the U.S. population from 658,000 to 334,000. 
Similarly, at the 95th percentile the MOE value is reduced 
from >1,000,000 to 562,000. In a conservative policy, the Agency has no 
cause for concern if total acute exposure in a Tier I calculation for 
the 95th percentile yields a MOE of 100 or larger. It can be 
concluded that there is a reasonable certainty that no harm will result 
to the overall U.S. population and many non-child/infant subgroups from 
aggregate, acute exposure to bispyribac-sodium residues.
    2. Infants and children. Safety factor for infants and children. In 
assessing the potential for additional sensitivity of infants and 
children to residues of bispyribac-sodium, FFDCA section 408 provides 
that EPA shall apply an additional margin of safety, up to ten-fold, 
for added protection for infants and children in the case of threshold 
effects unless EPA determines that a different margin of safety will be 
safe for infants and children.
    The toxicological data base for evaluating prenatal and postnatal 
toxicity for bispyribac-sodium is complete with respect to current data 
requirements. There are no special prenatal or postnatal toxicity 
concerns for infants and children, based on the results of the rat and 
rabbit developmental toxicity studies or the 2-generation reproductive 
toxicity study in rats. Valent concludes that reliable data support use 
of the standard 100-fold uncertainty factor and that an additional 
uncertainty factor is not needed for bispyribac-sodium to be further 
protective of infants and children.
    i. Chronic risk. Using the conservative, Tier I exposure 
assumptions described above, the percentage of the RfD utilized by 
dietary (food only) exposure to residues of bispyribac-sodium is very 
small. Exposures range from 0.000018 mg/kg bwt/day for non-nursing 
infants (<1 year old) to 0.000007 mg/kg bwt/day for children 7-12 --
0.106 to 0.041% of the RfD. Adding the worse case potential incremental 
exposure to infants and children from bispyribac-sodium in drinking 
water obtained from treated rice paddy water (0.000515 mg/kg bwt/day) 
materially increases the aggregate, chronic dietary exposure and 
increases the occupancy of the RfD by 3.03% to 3.14% for non-nursing 
infants (<1-year old). EPA generally has no concern for exposures below 
100% of the RfD because the RfD represents the level at or below which 
daily aggregate dietary exposure over a lifetime will not pose 
appreciable risks to human health. It can be concluded that there is a 
reasonable certainty that no harm will result to infants and children 
from aggregate, chronic exposure to bispyribac-sodium residues.
    ii. Acute Exposure. The potential acute exposure from food to the 
various child and infant population subgroups all provide very large 
MOE values exceeding 370,000. Addition of the worse case ``background'' 
dietary exposure from water (0.000515 mg/kg bwt/day) reduces the MOE 
values at the 99.9th percentile of exposure for non-nursing 
infants (<1 year old) from 373,000 to 128,000. Similarly, at the 
95th percentile the MOE value is reduced from >1,000,000 to 
166,000. In a conservative policy, the Agency has no cause for concern 
if total acute exposure in a Tier I calculation for the 95th 
percentile yields a MOE of 100 or larger. It can be concluded that 
there is a reasonable certainty that no harm will result to infants and 
children from aggregate, acute exposure to bispyribac-sodium residues.
    3. Safety determination summary. Aggregate acute or chronic dietary 
exposure to various sub-populations of children and adults demonstrate 
acceptable risk, even though total calculated dietary exposure is 
dominated by the unrealistic overestimation of potential drinking water 
concentrations. Chronic exposures to bispyribac-sodium occupy 
considerably less than 100% of the RfD,

[[Page 56908]]

and all acute MOE values greatly exceed 100. Chronic and acute dietary 
risk to children from bispyribac-sodium should not be of concern. 
Further, bispyribac-sodium has only agricultural uses and no other 
uses, such as indoor pest control, homeowner or turf, that could lead 
to unique, enhanced exposures to vulnerable sub-groups of the 
population. It can be concluded that there is a reasonable certainty 
that no harm will result to the U.S. population or to any sub-group of 
the U.S. population, including infants and children, from aggregate 
chronic or aggregate acute exposures to bispyribac-sodium residues 
resulting from pending uses.

  Table 3.--Summary of Exposure Values and Corresponding Risk Quotients for Aggregate Exposures to Bispyribac-Sodium by Different Routes and Durations
                                                        (all exposure values are in mg/kg bw/day)
--------------------------------------------------------------------------------------------------------------------------------------------------------
                                      Percentile             Food                Water             Aggregate          Percent RfD             MOE
--------------------------------------------------------------------------------------------------------------------------------------------------------
Chronic dietary (RfD = 0.017 mg/
 kg b.w./day).
  Adult (Non-Hispanic other than  NA*                 0.000027            0.000147            0.000174            1.02                NA
   black or white).
  Infants and children (Non-      NA                  0.0000187           0.000515            0.000533            3.14                NA
   nursing infants (<1 year
   old)).
--------------------------------------------------------------------------------------------------------------------------------------------------------
Acute dietary: Acute endpoint =
 100 mg/kg bw/day.
  Adult (U.S. Population).......  99.9th              0.000152            0.000147            0.000299            NA                  334,000
    ............................  95.5th              0.0000312           0.000147            0.0001782           NA                  561,000
                                 -----------------------------------------------------------------------------------------------------------------------
 
  Infants and children (Non-      99.9th              0.000268            0.000515            0.000783            NA                  128,000
   nursing infants (<1 year
   old)).
                                  95th                0.000087            0.000515            0.000602            NA                  166,000
--------------------------------------------------------------------------------------------------------------------------------------------------------
*Not applicable

F. International Tolerances

    There are presently no Codex maximum residue limits (MRL) 
established for bispyribac-sodium. The compound is presently registered 
for use on rice in several countries in Asia, Southeast Asia, Japan, 
South and Central America, the Dominican Republic, and Turkey. The use 
pattern is very similar to that proposed for the United States. Two 
countries have established tolerances: Japan a minimum MRL of 0.1 ppm 
and Brazil a MRL of 0.01 ppm both bispyribac-sodium in/on brown rice.
[FR Doc. 00-24212 Filed 9-19-00; 8:45 am]
BILLING CODE 6560-50-S