[Federal Register Volume 66, Number 100 (Wednesday, May 23, 2001)]
[Notices]
[Pages 28470-28478]
From the Federal Register Online via the Government Publishing Office [www.gpo.gov]
[FR Doc No: 01-12907]


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ENVIRONMENTAL PROTECTION AGENCY

[PF-1020; FRL-6780-7]


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.

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

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.

[[Page 28471]]


DATES: Comments, identified by docket control number PF-1020, must be 
received on or before June 22, 2001.

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-1020 in the subject line on the first page of your 
response.

FOR FURTHER INFORMATION CONTACT: By mail: Cynthia Giles-Parker, 
Fungicide Branch, Registration Division (7505C), Office of Pesticide 
Programs, Environmental Protection Agency, 1200 Pennsylvania Ave., NW., 
Washington, DC 20460; telephone number: (703) 305-7740; 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 codes         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,'' ``Regulation 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-1020. 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-1020 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-1020. 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

[[Page 28472]]

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 Cosmetic 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.


    Dated: May 3, 2001.
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.

BASF Corporation, Agricultural Products

PP 0F6139

    EPA has received pesticide petition number 0F6139 from BASF 
Corporation, Agricultural Products, P.O. Box 13528, Research Triangle 
Park, NC 27709-3528 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 combined residues 
of BAS 500 F or pyraclostrobin (methyl-N-(((1-(4-chlorophenyl)pyrazol-
3-yl)oxy, o-tolyl)N-methoxycarbamate) and its metabolite BF 500-3 
(methyl-N-(((1-(4-chlorophenyl pyrazol-3-yl)oxy)o-tolyl)carbamate); 
expressed as parent compound in or on the raw agricultural commodities 
almond hulls at 1.6 ppm, banana at 0.04 parts per million (ppm), barley 
(grain) at 0.4 ppm, barley (hay) at 25 ppm, barley (straw) at 6.0 ppm, 
berries (crop group) at 1.0 ppm, bulb vegetables (crop group) at 0.7 
ppm, citrus fruits (crop group) at 0.7 ppm, cucurbits (crop group) at 
0.5 ppm, fruiting vegetables (crop group) at 1.0 ppm, grape at 2.0 ppm, 
grass seed (seed screenings) at 27 ppm, grass seed (straw) at 14.0 ppm, 
grass seed (forage) at 10.0 ppm, grass seed (hay) at 4.5 ppm, lentil at 
0.5 ppm, orange oil at 4.2 ppm, orange pulp (dry) at 6.3 ppm, peanut at 
0.05 ppm, peanut oil at 0.1 ppm, pea (dry, seed ) at 0.4 ppm, radish 
tops at 16.0 ppm, raisin at 6.0 ppm, root vegetables (crop subgroup 1-
B) at 0.4 ppm, rye (grain) at 0.04 ppm, rye (straw) at 0.5 ppm), stone 
fruits (crop group) at 0.7 ppm, strawberry at 0.4 ppm, sugar beet (dry 
pulp) at 1.6 ppm, sugar beet (root) at 0.2 ppm, sugar beet (top) at 8.0 
ppm, tomato paste at 2.0 ppm, tree nuts (crop group) at 0.04 ppm, 
tuberous and corm vegetables (crop subgroup 1-C) at 0.04 ppm, wheat 
(grain) at 0.2 ppm, wheat (hay) at 6.0 ppm, wheat (straw) at 6.0 ppm, 
cattle (fat) at 0.1 ppm, cattle (kidney) at 0.1 ppm, cattle (liver) at 
0.6 ppm, cattle (milk) at 0.03 ppm, cattle (muscle) at 0.1 ppm, poultry 
(egg) at 0.1 ppm, poultry (muscle) at 0.1 ppm, poultry (liver) at 0.1 
ppm, poultry (fat) at 0.1 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 sufficency 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

    1. Plant and animal metabolism. Nature of the residue studies 
(OPPTS 860.1300) were conducted in grape, potato and wheat as 
representative crops in order to characterize the fate of BAS 500 F in 
all crop matrices. BAS 500 F demonstrated a similar pathway and fate in 
all three crops. In all three crops the BAS 500 F residues of concern 
were characterized as parent (BAS 500 F) and BAS 500-3.
    2. Analytical method. In plants the method of analysis is aqueous 
organic solvent extraction, column clean up and quantitation by LC/MS/
MS. In animals the method of analysis involves base hydrolysis, organic 
extraction, column clean up and quantitation by LC/MS/MS or 
derivatization (methylation) followed by quantitation by GC/MS.
    3. Magnitude of residues. Field trials were carried out in order to 
determine the magnitude of the residue in the following crops: almond, 
banana, barley, carrot, citrus, cucurbits (crop group), peas (dry, 
field), grape, grass grown for seed, lentil, onions (dry bulb and 
green), peanut, pecan, peppers (bell and chili), pistachio, potato, 
radish, berries (crop group), rye, stone fruits, strawberry, sugar 
beet, tomato and wheat. The residue trials in bananas were carried out 
in Latin America. Field trials for the rest of the crops were conducted 
in the United States and Canada. Field trials were carried out using 
the maximum label rate, the maximum number of applications, and the 
minimum preharvest interval for each crop or crop group. In addition, 
processing studies were conducted on the following crops to determine 
concentration factors during normal processing of the raw agricultural 
commodity into the processed commodities: citrus, grape, peanut, 
potato, stone fruits, sugar beet, tomato, and wheat. Magnitude of the 
residue trials were also carried out in cow and poultry.

B. Toxicological Profile

    1. Acute toxicity. Based on available acute toxicity data BAS 500 F 
and its formulated products do not pose acute toxicity risks. The acute 
toxicity studies place technical BAS 500 F in toxicity category IV for 
acute oral, category III for acute dermal, and category II for acute 
inhalation. BAS 500 F is category III for both eye and skin irritation 
and is not a dermal sensitizer. Two formulated end use products are 
proposed, an Emulsifiable Concentrate (EC) and an Extruded Granule 
(EG). The EC has an acute oral toxicity category of II, acute dermal of 
III, acute inhalation of IV, eye and skin irritation categories of III, 
and is not a dermal sensitizer. The WG has acute oral and dermal 
toxicity categories of III, acute inhalation of IV, eye irritation of 
III, skin irritation of IV, and is not a dermal sensitizer.

                                 Table 1.--Acute Toxicity of Technical BAS 500 F
----------------------------------------------------------------------------------------------------------------
              Study Type                       Species                  Results             Toxicity Category
----------------------------------------------------------------------------------------------------------------
Oral LD50                              Rat                      LD50*> 5,000 mg/kg bwt   IV

[[Page 28473]]

 
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Dermal LD50                            Rat                      LD50 > 2,000 mg/kg bwt   III
----------------------------------------------------------------------------------------------------------------
Inhalation LC50                        Rat                      0.31 < LC50**< 1.07 mg/  II
                                                                 L
----------------------------------------------------------------------------------------------------------------
Eye irritation                         Rabbit                   Slight irritation        III
----------------------------------------------------------------------------------------------------------------
Skin irritation                        Rabbit                   Moderate irritation      III
----------------------------------------------------------------------------------------------------------------
Skin sensitization                     Guinea pig               Non-sensitizing
----------------------------------------------------------------------------------------------------------------
Acute oral neurotoxicity (0, 100,      Rat                      No neurotoxic effects
 300, and 1,000 mg/kg bwt)                                       at doses up to 1,000
                                                                 mg/kg
----------------------------------------------------------------------------------------------------------------
*Lethal Dose 50%
**Lethal Concentration 50%


           Table 2.--Acute Toxicity of Formulated End-Use Product, BAS 500 00F (Headline EC Fungicide)
----------------------------------------------------------------------------------------------------------------
              Study Type                       Species                  Results             Toxicity Category
----------------------------------------------------------------------------------------------------------------
Oral LD50                              Rat                      LD50 > 500 mg/kg bwt     II
                                                                 (males); 260 mg/kg
                                                                 (200-500 mg/kg) bwt
                                                                 (females)
----------------------------------------------------------------------------------------------------------------
Dermal LD50                            Rat                      LD50 > 4,000 mg/kg bwt   III
----------------------------------------------------------------------------------------------------------------
Inhalation LC50                        Rat                      LC50 = 3.51 mg/L         IV
----------------------------------------------------------------------------------------------------------------
Eye irritation                         Rabbit                   Moderate irritation      III
----------------------------------------------------------------------------------------------------------------
Skin irritation                        Rabbit                   Moderate irritation      III
----------------------------------------------------------------------------------------------------------------
Skin sensitization                     Guinea pig               Non-sensitizing
----------------------------------------------------------------------------------------------------------------


     Table 3.--Acute Toxicity of Formulated End-Use Product, BAS 500 02F (Cabrio EG and Insignia Fungicides)
----------------------------------------------------------------------------------------------------------------
              Study Type                       Species                  Results             Toxicity Category
----------------------------------------------------------------------------------------------------------------
Oral LD50                              Rat                      LD50 > 2,000 mg/kg bwt   III
----------------------------------------------------------------------------------------------------------------
Dermal LD50                            Rat                      LD50 > 2,000 mg/kg bwt   III
----------------------------------------------------------------------------------------------------------------
Inhalation LC50                        Rat                      LC50 = 4.7 mg/L          IV
----------------------------------------------------------------------------------------------------------------
Eye irritation                         Rabbit                   Slight irritation        III
----------------------------------------------------------------------------------------------------------------
Skin irritation                        Rabbit                   Slight irritation        IV
----------------------------------------------------------------------------------------------------------------
Skin sensitization                     Guinea pig               Non-sensitizing
----------------------------------------------------------------------------------------------------------------

    2. Genotoxicity. Ames Test (one study; point mutation): Negative; 
in vitro CHO/HGPRT Locus Mammalian Cell Mutation Assay (one study; 
point mutation): Negative; in vitro V79 Cells CHO Cytogenetic Assay 
(one study; chromosome damage): Negative; in vivo Mouse Micronucleus 
(one study; chromosome damage): Negative; in vitro Rat Hepatocyte (one 
study; DNA damage and repair): Negative.
    BAS 500 F has been tested in a total of five genetic toxicology 
assays consisting of in vitro and in vivo studies. It can be stated 
that BAS 500 F did not show any mutagenic, clastogenic or other 
genotoxic activity when tested under the conditions of the studies 
mentioned above. Therefore, BAS 500 F does not pose a genotoxic hazard 
to humans.

                             Table 4.--Summary of Genotoxicity Studies on BAS 500 F
----------------------------------------------------------------------------------------------------------------
                Study                       Test Organism         Concentration Range            Results
----------------------------------------------------------------------------------------------------------------
Gene mutation: Ames reverse mutation   S. typhimurium strains   20 to 5,000 g   Negative with and
 assay                                  TA 1535, TA 100, TA      per plate                without metabolic
                                        1537 and TA 98; E.                                activation
                                        Coli strain WP2 uvrA;
                                        with and without
                                        metabolic activation.
----------------------------------------------------------------------------------------------------------------
Gene mutation: in vitro Chinese        HGPRT locus of Chinese   0.625 to 20 g/  Negative with and
 Hamster Ovaryin vitro cell study       Hamster Ovary cells,     mL*                      without activation
 (HGPRT locus)                          with and without
                                        metabolic activation
----------------------------------------------------------------------------------------------------------------
Chromosomal aberration:in vitro        Chinese hamster V79      0.005 to 25 g/  Negative with and
 cytogenicity                           cells, with and          mL                       without metabolic
                                        without metabolic                                 activation
                                        activation
----------------------------------------------------------------------------------------------------------------
Unscheduled DNA synthesis:in vitro     Primary hepatocytes      0.004 to 1.0 g/ Negative
 assay with primary rat hepatocytes     from Wistar rats         mL

[[Page 28474]]

 
----------------------------------------------------------------------------------------------------------------
Cytogenetic study in vivo:             NMRI mice                0, 75, 150 and 300 mg/    Negative
 mousemicronucleus test                                          kg bwt
----------------------------------------------------------------------------------------------------------------
*micrograms per milliliter

    3. Reproductive and developmental toxicity. The reproductive and 
developmental toxicity of BAS 500 F was investigated in a 2-generation 
rat reproduction study as well as in rat and rabbit teratology studies. 
There were no adverse effects on reproduction in the 2-generation study 
so the no observed adverse effect level (NOAEL) is the highest dose 
tested of 300 parts per million (ppm) (32.6 milligrams per kilogram 
body weight per day (mg/kg bwt/day)). Parental toxicity in the form of 
reduced body weight gain and pup effects were observed at the highest 
dose tested only. Pup effects consisted primarily of reduced body 
weight gain. Most likely due to the small pup size, reduced organ 
weights were observed in the thymus, spleen and brain of F2 pups, and a 
slight delay in vaginal opening time was observed in some F1 female 
pups. Therefore, the parental systemic and developmental toxicity 
NOAELs are the same at 75 ppm (8.2 mg/kg bwt).
    No teratogenic effects were noted in either the rat or rabbit 
developmental studies. In the rat study, maternal toxicity observed at 
the mid and high dose consisted of decreased food consumption and body 
weight gain. There were no treatment-related developmental effects. The 
maternal NOAEL was 10 mg/kg bwt and the developmental NOAEL was the 
highest dose tested of 50 mg/kg bwt.
    In the rabbit teratology study, maternal toxicity observed at the 
mid and high doses consisted of decreased food consumption and body 
weight gain (severe at the high dose). An increased postimplantation 
loss was also observed at the mid and high doses due to an increase in 
early resorptions. In rabbits, these types of effects are often 
observed with significant stress on the mothers (as seen by the body 
weight gain decrease in this study) and not indicative of frank 
developmental toxicity. The NOAEL for both maternal and developmental 
toxicity was 5 mg/kg bwt.

                    Table 5.--Summary of Reproductive and Developmental Studies on BAS 500 F
----------------------------------------------------------------------------------------------------------------
                                                                                           Effects at LOAEL or
                Study                           NOAEL                   LOAEL *                   Higher
----------------------------------------------------------------------------------------------------------------
Multigeneration rat reproduction: 0,   Reproductive function:   Reproductive function:   No impairment of
 25, 75, and 300 ppm (0, 2.7, 8.2,      32.6 mg/kg bwt (300      >32.6 mg/kg bwt (> 300   reproductive function
 and 32.6 mg/kg bwt)                    ppm); systemic           ppm); systemic           at any of the dose
                                        toxicity: 8.2 mg/kg      toxicity: 32.6 mg/kg     levels tested. 300
                                        bwt (75 ppm);            bwt (> 300 ppm);         ppm: parental -
                                        developmental            developmental            reduced body weight
                                        toxicity: 8.2 mg/kg      toxicity: 32.6 mg/kg     and food consumption;
                                        bwt (75 ppm)             bwt (> 300 ppm)          pups - reduced body
                                                                                          weight during
                                                                                          lactation with
                                                                                          corresponding organ
                                                                                          weight changes (F2)
                                                                                          and slightly delayed
                                                                                          vaginal opening (F1
                                                                                          only)
----------------------------------------------------------------------------------------------------------------
Rat teratology: 0, 10, 25, and 50 mg/  Maternal toxicity: 10    Maternal toxicity: 25    No teratogenic effects.
 kg bwt                                 mg/kg bwt;               mg/kg bwt;               25 mg/kg bwt: maternal
                                        developmental            developmental            effects were decreased
                                        toxicity: 50 mg/kg bwt   toxicity: > 50 mg/kg     body weight gain and
                                                                 bwt                      decreased food
                                                                                          consumption. 50 mg/kg
                                                                                          bwt: maternal effects
                                                                                          were a severe decrease
                                                                                          in body weight gain,
                                                                                          and reduced food
                                                                                          consumption.
----------------------------------------------------------------------------------------------------------------
Rabbit teratology: 0, 5, 10, and 20    Maternal: 5 mg/kg bwt;   Maternal: 10 mg/kg bwt;  No teratogenic effects.
 mg/kg bwt                              developmental            developmental            10 mg/kg bwt: maternal
                                        toxicity: 5 mg/kg bwt    toxicity: 10 mg/kg bwt   effects were decreased
                                                                                          body weight gain and
                                                                                          food consumption, and
                                                                                          decreased mean gravid
                                                                                          uterus weight;
                                                                                          developmental effects
                                                                                          were increased post-
                                                                                          implantation loss due
                                                                                          to early resorptions,
                                                                                          with subsequent
                                                                                          decrease in mean live
                                                                                          fetuses per rabbit. 20
                                                                                          mg/kg bwt: maternal
                                                                                          effects were severely
                                                                                          decreased body weight
                                                                                          gain, decreased food
                                                                                          consumption, and
                                                                                          decreased gravid
                                                                                          uterus weight;
                                                                                          developmental effects
                                                                                          were increased
                                                                                          postimplantation loss
                                                                                          due primarily to early
                                                                                          resorptions.
----------------------------------------------------------------------------------------------------------------
*Lowest observed adverse effect level

    4. Subchronic toxicity. The subchronic toxicity of BAS 500 F was 
investigated in 90-day feeding studies with rats, mice and dogs, and in 
a 28-day dermal administration study in rats. A 90-day neurotoxicity 
study in rats was also performed. Generally, mild toxicity was 
observed. At high dose levels in feeding studies, general findings in 
all three species were decreased food consumption and body weight gain 
and a thickening of the duodenum. Anemia occurred at high dose levels 
in both rats and mice with accompanying extramedullary hematopoiesis of 
the spleen in rats. In rats only, a finding of liver cell hypertrophy 
was indicative of a physiological response to the handling of the 
chemical. Overall, only mild toxicity was observed in oral subchronic 
testing.

[[Page 28475]]

    In the 28-day repeat dose dermal study, no systemic effects were 
noted up to the highest dose tested.
    In a 90-day rat neurotoxicity study, a direct neurotoxic effect was 
not observed. The grip strength of forelimbs was statistically 
significantly decreased in high dose females at the end of the study. 
This was assessed as being related to the significant body weight 
impairment at this dose level. This is confirmed by the fact that 
functional observational batteries and motor activity measurement did 
not reveal any other signs indicative for neurotoxicity. Moreover, 
comprehensive microscopic investigation of the central and peripheral 
nervous system did not reveal any substance-dependent changes. This is 
outlined in the table.

                              Table 6.--Summary of Subchronic Studies for BAS 500 F
----------------------------------------------------------------------------------------------------------------
                                                                                           Effects at LOAEL or
                emsp;                           NOAEL                    LOAEL                    Higher
----------------------------------------------------------------------------------------------------------------
4-Week dermal rat: 0, 40, 100, and      250 mg/kg bwt            > 250 mg/kg bwt          Skin irritation at
 250 mg/kg bwt                          (systemic)                                        application site; no
                                                                                          systemic effects
                                                                                          related to treatment
----------------------------------------------------------------------------------------------------------------
90-Day rat feeding study: 0, 50, 150,  3.5 mg/kg bwt males;     10.7 mg/kg bwt males;    Generally mild toxicity
 500, 1000 and 1,500 ppm (0, 3.5,       4.2 mg/kg bwt females    12.6 mg/kg bwt females   at high doses. 150 ppm
 10.7, 34.7, 68.8 and 105.8 mg/kg bwt   (equivalent to 50 ppm    (equivalent to 150 ppm   (LOAEL): decreased
 for males; 0, 4.2, 12.6, 40.8,         both sexes)              both sexes)              absolute liver weight
 79.7,and 118.9 mg/kg bwt for                                                             males; increased
 females).                                                                                extramedullary
                                                                                          hematopoiesis.  500 ppm: decreased
                                                                                          food consumption and
                                                                                          body weight change;
                                                                                          leukocytosis;
                                                                                          hemolytic anemia
                                                                                          males; mild anemia
                                                                                          females; decreased
                                                                                          serum liver enzymes;
                                                                                          increased relative
                                                                                          weights of spleen and
                                                                                          adrenal gland (both
                                                                                          sexes), kidney,
                                                                                          testes, brain (males),
                                                                                          and liver and ovaries
                                                                                          (females); mucosal
                                                                                          hyperplasia of
                                                                                          duodenum; increased
                                                                                          extramedullary
                                                                                          hematopoiesis of
                                                                                          spleen; hepatocellular
                                                                                          hypertrophy.
----------------------------------------------------------------------------------------------------------------
 90-Day mouse feeding study: 0, 50,    9.2 mg/kg bwt males;     30.4 mg/kg bwt males;    Generally mild toxicity
 150, 500, 1,000, and 1,500 ppm (0,     12.9 mg/kg bwt females   40.4 mg/kg bwt females   at high doses. 150 ppm
 9.2, 30.4, 119.4, 274.4, and 475.5     (equivalent to 50 ppm    (equivalent to 150 ppm   (LOAEL): decreased
 mg/kg bwt for males; 0, 12.9, 40.4,    for both sexes)          both sexes)              body weight gain and
 162, 374.1, and 634.8 mg/kg bwt for                                                      hematocrit (males);
 females)                                                                                 decreased
                                                                                          triglycerides and
                                                                                          thickening of the
                                                                                          duodenum (females).
                                                                                          500 ppm: decreased
                                                                                          body weight change;
                                                                                          mild leukopenia; mild
                                                                                          hypochromic microcytic
                                                                                          anemia; decreased
                                                                                          serum protein,
                                                                                          globulins, and
                                                                                          triglycerides;
                                                                                          thickening of the
                                                                                          duodenal mucosa.
----------------------------------------------------------------------------------------------------------------
90-Day Beagle dog feeding study: 0,    5.8 mg/kg bwt males;      12.9 mg/kg bwt males;    Generally mild
 100, 200 and 450 ppm (0, 2.8, 5.8,     6.2 mg/kg bwt females    13.6 mg/kg bwt females   toxicity at high
 and 12.9 mg/kg bwt males; 0, 3.1,      (equivalent to 200 ppm   (equivalent to 450 ppm   doses. 450 ppm
 6.2, 13.6 mg/kg bwt females)           for both sexes)          both sexes)              (LOAEL): Decreased
                                                                                          food consumption
                                                                                          (females); slight body
                                                                                          weight loss and
                                                                                          diarrhea; decreased
                                                                                          serum protein,
                                                                                          albumin, and
                                                                                          globulins; increased
                                                                                          platelets (females);
                                                                                          hypertrophy in
                                                                                          duodenum.
----------------------------------------------------------------------------------------------------------------
90-Day rat feeding neurotoxicity       Systemic: 3.5 mg/kg bwt  Systemic: 16.9 mg/kg     250 ppm (males):
 study 0, 50, 250, 750 - males, 0,      (50 pm) - males; 20.4    bwt (250 ppm ) -         Reduced food and water
 50, 250 and 1500 ppm - females (0,     mg/kg bwt (250 ppm)-     males; 49.9 mg/kg bwt    consumption.
 3.5, 16.9, 49.9 mg/kg bwt - males;     females                  (750 ppm) - females
 0, 4.0, 20.4, 49.9 and 119.9 mg/kg
 bwt - females)
----------------------------------------------------------------------------------------------------------------

    5. Chronic toxicity. The following are summaries of chronic 
toxicity studies submitted to EPA.
    BAS 500 F was administered to groups of five male and five female 
purebred Beagle dogs in the diet at concentrations of 0, 100, 200 and 
400 ppm over a period of 12 months. Signs of toxicity were observed at 
the high dose. Diarrhea was observed throughout the study period for 
both sexes. High dose males and females initially lost weight and body 
weight gain was decreased for the entire study period for females. 
Hematological changes observed were an increase in white blood cells in 
males, and an increase in platelets in both sexes at the high dose. 
Clinical chemistry demonstrated a

[[Page 28476]]

decrease in serum total protein, albumin, globulins, and cholesterol in 
high dose animals of both sexes, possibly due to the diarrhea and 
reduced nutritional status of the animals. The NOAEL was 200 ppm (ca. 
5.5 mg/kg bwt/day males; 5.4 mg/kg bwt/day females).
    For the chronic toxicity portion of the rat study, BAS 500 F was 
administered to groups of 20 male and 20 female Wistar rats at dietary 
concentrations of 0, 25, 75, and 200 ppm for 24 months. For the 
carcinogenicity portion of the rat study, BAS 500 F was administered to 
groups of 50 male and 50 female Wistar rats at dietary concentrations 
of 0, 25, 75, and 200 ppm for 24 months. The results of a 2-year 
chronic toxicity study and a 2-year carcinogenicity study in rats 
indicate that a maximum tolerated dose was clearly met at the high dose 
of 200 ppm (ca. 9 mg/kg bwt males and 12 mg/kg bwt females). This is 
demonstrated by a body weight gain depression of 10-11% in males and 
14-22% in females. The only other effect observed was a decrease in 
serum alkaline phosphatase in both sexes at the high dose and decreased 
alanine aminotransferase in high dose males. There was no evidence that 
BAS 500 F produced a carcinogenic effect in rats. The NOAEL for the 
chronic rat and the cancer rat study is 75 ppm (ca. 3.4 mg/kg bwt/day 
males; 4.6 mg/kg bwt/day females).
    BAS 500 F was administered to groups of 50 male and 50 female 
B6C3F1 mice at dietary concentrations of 0, 10, 30, 120, and 180 ppm 
(females only) for 18 months. Body weights were reduced at the highest 
doses tested in both males and females. The high dose body weight gain 
decreases of 27% in females and 29% in males exceeded that required for 
a maximum tolerated dose. No other signs of toxicity were noted at any 
dose level. The NOAEL was found to be 120 ppm (ca. 20.5 mg/kg bwt/day) 
for females and 30 ppm (ca. 4.1 mg/kg bwt/day) for males. There was no 
evidence that BAS 500 F produced a carcinogenic effect in mice.
    6. Carcinogenicity. There were no tumors associated with treatment 
observed in either a 2-year rat oncogenicity study or in an 18-month 
mouse oncogenicity study. Based on EPA Proposed Guidelines For 
Carcinogen Risk Assessment, BASF believes that BAS 500 F will be 
classified as ``not likely'' to be carcinogenic to humans. Under the 
current assessment method, BASF believes that EPA will classify BAS 500 
F as Group E `(evidence of noncarcinogenicity to humans).

                     Table 7.--Summary of Chronic Toxicity/Oncogenicity Studies on BAS 500 F
----------------------------------------------------------------------------------------------------------------
                Study                           NOAEL                    LOAEL                   Comments
----------------------------------------------------------------------------------------------------------------
12-Month beagle dog feeding study: 0,  5.5 mg/kg bwt males;     10.8 mg/kg bwt males;    Generally mild
 100, 200 and 400 ppm (0, 2.8, 5.5      5.4 mg/kg bwt females    11.2 mg/kg bwt females   toxicity. 400 ppm:
 and 10.8 mg/kg bwt males; 2.7, 5.4,    (200 ppm both sexes)     (400 ppm both sexes)     decreased body weight
 11.2 mg/kg bwt females)                                                                  gain (initially in
                                                                                          males and throughout
                                                                                          study in females);
                                                                                          decreased food
                                                                                          consumption (females);
                                                                                          diarrhea; decreased
                                                                                          serum total protein,
                                                                                          albumin, globulins,
                                                                                          and cholesterol;
                                                                                          increased platelets;
                                                                                          increased white blood
                                                                                          cells (males).
----------------------------------------------------------------------------------------------------------------
18-Month mouse oncogenicity study: 0,  4.1 mg/kg bwt males (30  17.2 mg/kg bwt males     Generally mild
 10, 30, and 120 ppm males (1.4, 4.1,   ppm); 20.5 mg/kg bwt     (120 ppm); 32.8 mg/kg    toxicity. No treatment-
 and 17.2 mg/kg bwt); 0, 10, 30, 120    females (120 ppm)        bwt females (180 ppm)    related tumors. 120
 and 180 ppm females (1.6, 4.8, 20.5,                                                     ppm: decreased body
 32.8 mg/kg bwt)                                                                          weight and body weight
                                                                                          change (males). 180
                                                                                          ppm (females only):
                                                                                          Decreased body weight
                                                                                          and body weight
                                                                                          change.
----------------------------------------------------------------------------------------------------------------
24-Month chronic toxicity study in     3.4 mg/kg bwt males;     9.0 mg/kg bwt males;     Generally mild
 Rats: 0, 25, 75, and 200 ppm (0,       4.6 mg/kg bw females     12.3 mg/kg bwt females   toxicity. 200 ppm:
 1.1, 3.4, and 9.0 mg/kg bwt males;     (75 ppm both sexes)      (200 ppm both sexes)     decreased body weight
 0, 1.5, .4.6 and 12.3 mg/kg bwt                                                          and body weight
 females)                                                                                 change; decreased
                                                                                          serum alkaline
                                                                                          phosphatase (both
                                                                                          sexes) and alanine
                                                                                          aminotransferase
                                                                                          (males)
----------------------------------------------------------------------------------------------------------------
24-month carcinogenicity study in      3.4 mg/kg bwt males;     9.2 mg/kg bwt males;     Generally mild
 rats: 0, 25, 75 and 200 ppm (0, 1.2,   4.7 mg/kg bwt females    12.6 mg/kg bwt females   toxicity. No treatment-
 3.4, and 9.2 mg/kg bwt males; 0,       (75 ppm both sexes).     (200 ppm both sexes)     related tumors. 200
 1.5, 4.7, and 12.6 mg/kg bw females)                                                     ppm: decreased body
                                                                                          weight gain (both
                                                                                          sexes); decreased food
                                                                                          consumption (males);
                                                                                          increased liver cell
                                                                                          necrosis.
----------------------------------------------------------------------------------------------------------------

    7. Animal metabolism. In hens the residues of concern were 
determined to be parent compound and a hydroxlated metabolite, BAS 500-
16. In goats the residues of concern were determined to be parent and a 
hydroxylated metabolite BAS 500-10.
    8. Metabolite toxicology. A comparison of the rat metabolism 
results with the plant metabolism/residue results indicate that 
toxicology studies performed with the parent compound are sufficient to 
cover dietary exposure. Therefore, no specific toxicity studies were 
conducted on metabolites of this compound.
    9. Endocrine disruption. No specific tests have been conducted with 
BAS 500 F to determine whether the chemical may have an effect in 
humans that is similar to an effect produced by a naturally occurring 
estrogen or other endocrine effects. However, there were no significant 
findings in other relevant toxicity studies (i.e., subchronic and 
chronic toxicity, teratology, and multigeneration reproductive studies) 
which would suggest that BAS 500 F produces endocrine-related effects.
    10. Threshold effects. Based on a review of the available chronic 
toxicity data, BASF believes EPA will establish the Reference Dose 
(RfD) for BAS 500 F at 0.04 mg/kg/day. This RfD for BAS 500 F is based 
on the 2-year chronic and 2-year oncogenicity studies in rats with a 
threshold average NOAEL of 4 mg/kg/day for males and females. Using an 
uncertainty factor of 100, the RfD is calculated to be 0.04 mg/kg/day. 
Based on the acute toxicity data, BASF believes that 500 F does not 
pose any dietary risks.
    11. Non-threshold effects. There were no tumors associated with 
treatment observed in either a 2-year rat oncogenicity study or in an 
18-month mouse oncogenicity study. Based on

[[Page 28477]]

EPA Proposed Guidelines For Carcinogen Risk Assessment, BASF believes 
that BAS 500 F will be classified as ``not likely'' to be carcinogenic 
to humans. Under the current assessment method, BASF believes that EPA 
will classify BAS 500 F as Group E (evidence of noncarcinogenicity to 
humans).

C. Aggregate Exposure

    BASF believes that pyraclostrobin does not pose any acute dietary 
risks, so an acute exposure analysis is not necessary. Based on a 
review of the available chronic toxicity data, BASF believes EPA will 
base the chronic RfD for pyraclostrobin on the 2-year chronic and 2-
year oncogenicity studies in rats, which had an average threshold NOAEL 
of 4 mg/kg/day for males and females. BASF further believes that EPA 
will use an uncertainty factor of 100 and establish the RfD at 0.04 mg/
kg/day. The following table expresses the results of the chronic 
aggregate analysis of exposure to pyraclostrobin. This analysis is 
discussed further below.

      Table 8.--Summary of Chronic Aggregate Exposure to BAS 500 F
------------------------------------------------------------------------
                                  U.S. Population (%  Children 1-6 (% of
                                        of RfD)              RfD)
------------------------------------------------------------------------
Chronic dietary exposure          5%                  10%
------------------------------------------------------------------------
Residential exposure*             2.5%                12.5%
------------------------------------------------------------------------
Total RfD used by diet and        7.5%                22.5%
 residential exposure
------------------------------------------------------------------------
Remainder of RfD available for    92.5%               77.5%
 water (%) (Drinking Water Level
 of Concern)
------------------------------------------------------------------------
SCIGROW modelground water         <1%                 <1%
 estimation**
------------------------------------------------------------------------
GENEEC model (56 d) surface       <1%                 <1%
 water estimation**
------------------------------------------------------------------------
Total of RfD used by diet, water  7.5%                77.5%
 and residential
------------------------------------------------------------------------
*Acute values used as worst case
**Used highest values predicted from the model for all agricultural
  uses; assumes 2 liters/day consumed and 60 kg bwt for adults and 1
  liter/day and 10 kg bwt for children

    1.Dietary exposure-- i. Food. For purposes of assessing the 
potential dietary exposure, BASF has estimated aggregate exposure based 
on the Theoretical Maximum Residue Contribution (TMRC) from the 
proposed tolerances for BAS 500 F.
    A Tier 1 worst case estimate of dietary exposure was conducted 
assuming that 100% of all crops for which tolerances are established 
are treated and that pesticide residues are always found at the 
tolerance levels. The TMRC from the proposed uses of BAS 500 F on all 
crops is 0.002 mg/kg bwt/day and utilizes 5% of the RfD for the overall 
U.S. population. The exposure of the most highly exposed subgroup in 
the population, children (1-6 years old), is 0.004 mg/kg bwt/day and 
utilizes 10% of the RfD.
    The following table summarizes the mean dietary exposures and the 
percents of RfD occupied by these exposures.

    Table 9.--Summary of Chronic Dietary Exposure to BAS 500 F--(DRES
                    (Dietary Risk Evaluation System))
------------------------------------------------------------------------
                                  g/kg body
              Group                   weight/day             %RfD
------------------------------------------------------------------------
U.S. population                   2.004               5
------------------------------------------------------------------------
All infants (<1 year old)         2.260               6
------------------------------------------------------------------------
Children 1-6 years old            4.144               10
------------------------------------------------------------------------
Children 7-12 years old           2.092               5
------------------------------------------------------------------------
Females 13-50 years old           1.338               3
------------------------------------------------------------------------

    ii. Drinking water. Estimates of ground water levels and surface 
water levels were determined using the Screening Concentration in 
Groundwater (SCIGROW) and Generic Estimated Environmental Concentration 
(GENEEC) models, respectively. The drinking water levels of concern 
(DWLOCs) for chronic exposure are obtained by subtracting the chronic 
dietary food exposures and residential exposures from the RfD, as 
outlined in Table 10.

 Table 10.--Percentages of Reference Dose for chronic water exposure to
                                BAS 500 F
------------------------------------------------------------------------
                                  U.S. Population (%  Children 1-6 (% of
                                        of RfD)              RfD)
------------------------------------------------------------------------
Chronic dietary exposure          5%                  10%
------------------------------------------------------------------------
Residential exposure*             2.5%                12.5%
------------------------------------------------------------------------
Total RfD used by diet and        7.5%                22.5%
 residential
------------------------------------------------------------------------
Remainder of RfD available for    92.5%               77.5%
 water (%) (Drinking Water Level
 of Concern)
------------------------------------------------------------------------
SCIGROW ground water              <1%                 <1%
 estimation**
------------------------------------------------------------------------
GENEEC (56 d) surface water       <1%                 <1%
 estimation**

[[Page 28478]]

 
------------------------------------------------------------------------
Total of RfD used by diet, water  7.5%                77.5%
 and residential
------------------------------------------------------------------------
*Acute values used as worst case
** Used highest values predicted from the model for all agricultural
  uses; Assumes 2 liters/day consumed and 60 kg bwt for adult and 1
  liter/day and 10 kg bwt for child

    The SCIGROW and GENEEC estimates of ground and surface water levels 
for BAS 500 F are well below the DWLOC. Overall, using worst-case 
parameters the predicted aggregate exposure by all potential routes for 
both adults and children is less than the chronic referencedose.
    2. Non-dietary exposure. BAS 500 F is planned for use on 
residential lawns. Acute exposure was estimated using data from a BAS 
500 F turf transferable residue (TTR) study, a dermal penetration of 
2.6% and default values from the EPA Standard Operating Procedures for 
residential exposure. For adults, the exposure estimate of 0.001 mg/kg 
bwt/day is equivalent to only 2.5% of the chronic reference dose. 
Estimation of exposure of children includes dermal contact on the lawn 
plus oral ingestion via fingers in the mouth, grass and dirt. Using the 
worst-case EPA defaults, the acute exposure result is estimated to be 
0.005 mg/kg bwt/day which is 12.5% of the chronic Reference Dose.

D. Cumulative Effects

    Section 408(b)(2)(D)(v) requires that, when considering whether to 
establish, modify, or revoke a tolerance, the Agency consider 
``available information'' concerning the cumulative effects of a 
particular pesticide's residues and ``other substances that have a 
common mechanism of toxicity.'' BAS 500 F is a foliar fungicide which 
belongs to the new class of strobilurin chemistry. It is a synthetic 
analog of strobilurin A, a naturally occurring antifungal metabolite of 
the mushroom Strobillurus tenacellus (Anke et. al., 1977). The active 
ingredient acts in the fungal cell through inhibition of electron 
transport in the mitochondrial respiratory chain at the position of the 
cytochrome-bc1 complex. The protective effect is due to the resultant 
death of the fungal cells by disorganization of the fungal membrane 
system. BAS 500 F also acts curatively to prevent the increase and 
spread of fungal infections by inhibiting mycelial growth and 
sporulation on the leaf surface. BAS 500F inhibits spore germination, 
germ tube growth and penetration into the host tissues.
    The EPA is currently developing methodology to perform cumulative 
risk assessments. At this time, there is no available data to determine 
whether BAS 500F has a common mechanism of toxicity with other 
substances or how to include this pesticide in a cumulative risk 
assessment. Unlike other pesticides for which EPA has followed a 
cumulative risk approach based on a common mechanism of toxicity, BAS 
500 F does not appear to produce a toxic metabolite produced by other 
substances

E. Safety Determination

    1. U.S. population. Using the conservative exposure assumptions 
described above and based on the completeness and the reliability of 
the toxicity data, BASF has estimated that aggregate exposure to BAS 
500 F will utilize 5% of the RfD for the U.S. population. BASF 
concludes that there is a reasonable certainty that no harm will result 
from the aggregate exposure to BAS 500 F, including anticipated dietary 
exposure and non-occupational exposures.
    2. Infants and children. A developmental study was conducted via 
oral gavage in rats with dosages of 0, 10, 25, and 50 mg/kg bwt/day 
with a maternal NOAEL of 10 mg/kg bwt/day and a developmental NOAEL of 
50 mg/kg bwt/day. No evidence of developmental toxicity was observed up 
to the highest dose tested. These NOAELs are higher than the NOAEL of 4 
mg/kg bwt/day from the chronic rat study used to establish the RfD.
    A developmental study was conducted via oral gavage in rabbits with 
dosages of 0, 5, 10, and 20 mg/kg bwt/day. The NOAEL for both maternal 
and developmental toxicity was 5 mg/kg bwt/day. No teratogenic effects 
were observed at any dose level, and the only developmental effect 
observed was an increase in postimplantation loss at doses which 
produced maternal toxicity. These NOAELs are higher than the NOAEL of 4 
mg/kg bwt/day from the chronic ratstudy used to establish the RfD.
    A 2-generation reproduction study in rats was conducted with 
dosages of 0, 2.7, 82, and 32.6 mg/kg bwt/day. The NOAELs are 32.6 mg/
kg bwt/day (highest dose tested) for reproductive function and 8.2 mg/
kg bwt/day for parental and developmental toxicity. No impairment of 
reproductive function was noted at any dose level. At the high dose 
reduced parental body weight gains were accompanied by reduced pup 
weights and corresponding reduced pup organ weights (F2 only) and 
slightly delayed vaginal opening (F1 only). The slight delay in vaginal 
opening was most likely due to the smaller pups and corresponding delay 
in physical development. These NOAELs are higher than the NOAEL of 4 
mg/kg bwt/day from the chronic rat study used to establish the RfD.
    Based on these results, no additional safety factors to protect 
children are warranted. Since developmental and reproductive toxicity 
occurs at levels above the levels shown to exhibit parental toxicity 
and since these levels are higher than those used to calculate the RfD, 
BASF believes the RfD of 0.04 mg/kg/day (4 mg/kg/day and an Uncertainty 
Factor of 100) is an appropriate measure of safety for infants and 
children.
    Dietary exposure of the most highly exposed subgroup in the 
population, children (1-6 years old) is 0.004 mg/kg bwt/day. This 
accounts for 10% of the RfD. Worst case default predictions indicate 
that residential uses of BAS 500 F will amount to 12.5% of the RfD and 
that contamination of drinking water is extremely small and amounts to 
1% of the reference dose. Aggregate exposure of children (1-6 years 
old) amounts to 22.5% of the RfD. In addition, there were no 
significant findings in relevant toxicity studies (i.e., subchronic and 
chronic toxicity, teratology, and multi-generation reproductive 
studies) which would suggest that BAS 500 F produces endocrine-related 
effects.
    Therefore, based on the completeness and reliability of the 
toxicity data and the conservative exposure assessment, BASF concludes 
that there is a reasonable certainty that no harm will result to 
infants and children from aggregate exposure to BAS 500 F, including 
all anticipated dietary exposure and all other non-occupational 
exposures.

F. International Tolerances

    A maximum residue level (MRL) has not been established for BAS 500 
F in any crop by the Codex Alimentarius Commission.
[FR Doc. 01-12907 Filed 5-22-01; 8:45 am]
BILLING CODE 6560-50-S