[Federal Register Volume 66, Number 57 (Friday, March 23, 2001)]
[Notices]
[Pages 16226-16232]
From the Federal Register Online via the Government Publishing Office [www.gpo.gov]
[FR Doc No: 01-7287]


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ENVIRONMENTAL PROTECTION AGENCY

[PF-1000; FRL-6767-3]


Notice of Filing Pesticide Petitions to Establish Tolerances 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 pesticide 
petitions 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-1000, must be 
received on or before April 23, 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-1000 in the subject line on the first page of your 
response.

FOR FURTHER INFORMATION CONTACT: By mail: Cynthia Giles-Parker, 
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:

[[Page 16227]]



------------------------------------------------------------------------
                                                          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'' 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-1000. 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-1000 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-1000. 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 pesticide petitions 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 petitions. Additional data 
may be needed before EPA rules on the petitions.

List of Subjects

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

    Dated: March 12, 2001.
  James Jones,
Director, Registration Division, Office of Pesticide Programs.

Summaries of Petitions

    The petitioner summaries of the pesticide petitions are printed 
below as required by section 408(d)(3) of the FFDCA. The summaries of 
the petitions

[[Page 16228]]

were prepared by the petitioner and represents the view of the 
petitioner. EPA is publishing the petition summaries verbatim without 
editing them in any way. The petitioner's summaries 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.

Rohm and Haas Company

PP 1F3989, 1F3995, and 2F4154

    EPA has received amended pesticide petitions (PP 1F3989, 1F3995, 
and 2F4154) from Rohm and Haas Company, 100 Independence Mall West, 
Philadelphia, PA 19106-2399, proposing pursuant to section 408(d) of 
the FFDCA, 21 U.S.C. 346a(d), to amend 40 CFR part 180 by making 
permanent the time-limited tolerances for the combined residues of 
fenbuconazole (alpha-(2-(4-chlorophenyl)-ethyl)-alpha-phenyl-3-(1H-
1,2,4-triazole)-1-propanenitrile) and its metabolites cis- and trans-5-
(4-chlorophenyl)-dihydro-3-phenyl-3-(1H-1,2,4-triazole-1-ylmethyl)-2-
3H-furanone in or on the raw agricultural commodities (RACs) stone 
fruits (except plums and prunes) at 2.0 parts per million (ppm), pecans 
at 0.1 ppm, and bananas at (0.3 ppm). EPA has determined that the 
request 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 petitions. Additional data may be needed before 
EPA rules on the petition.

Background

    The tolerances that are the subject of this notice will, under 
current regulations, expire on December 31, 2001. The notices of filing 
concerning receipt of PP 3989 (fenbuconazole (only) tolerances in or on 
stone fruits and dried prunes at 2.0 ppm) and PP 3995 (fenbuconazole 
(only) tolerances in or on pecans at 0.1 ppm) were published in the 
Federal Register, at 56 FR 65080 and 65081 (December 13, 1991) (FRL-
4004-1). In the Federal Register, at 59 FR 9985 (March 2, 1994) (FRL-
4760-1), the Agency announced that Rohm and Haas had amended PP 3989 
and PP 3995 by proposing to amend 40 CFR part 180 by establishing 
tolerances for fenbuconazole (alpha-(2-(4-chlorophenyl)-ethyl)-alpha-
phenyl-3-(1H-1,2,4-triazole)-1-propanenitrile) and its metabolites cis- 
and trans-5-(4-chlorophenyl)-dihydro-3-phenyl-3-(1H-1,2,4-triazole-1-
ylmethyl)-2-3H-furanone in or on stone fruits at 2.0 ppm and pecans at 
0.1 ppm. Rohm and Haas subsequently amended PP 3989 to limit the crop 
group to stone fruits (except plums and prunes). There were no comments 
received on any of these notices. The final rule that established the 
tolerances for stone fruits (except plums and prunes) was published in 
the Federal Register, at 60 FR 11029 (March 1, 1995) (FRL-4938-3). The 
tolerances were established as time-limited tolerances because of the 
existence of a data gap for storage stability of fenbuconazole residues 
in other RACs. The notice of filing concerning receipt of PP 2F4154 
(tolerances of fenbuconazole and its metabolite 5-(4-chlorophenyl)-
dihydro-3-phenyl-3-(methyl-1H-1,2,4-triazole-1-yl)-2-3H-furanone in or 
on banana (pulp) at 0.05 ppm and banana (peel) at 0.3 ppm) was 
published in the Federal Register, at 57 FR 62334 (December 30, 1992) 
(FRL-4177-7). In the Federal Register, at 59 FR 33503 (June 29, 1994) 
(FRL-4866-3) the Agency announced that Rohm and Haas had amended PP 
4154 by proposing to amend 40 CFR part 180 by establishing tolerances 
for fenbuconazole (alpha-(2-(4-chlorophenyl)-ethyl)-alpha-phenyl-3-(1H-
1,2,4-triazole)-1-propanenitrile) and its metabolites cis- and trans-5-
(4-chlorophenyl)-dihydro-3-phenyl-3-(1H-1,2,4-triazole-1-ylmethyl)-2-
3H-furanone in or on banana (whole fruit) at 0.3 ppm, of which no more 
than 0.05 ppm can be contained in the banana pulp. No comments were 
received concerning these notices. The final rule that established the 
banana tolerances was published in the Federal Register, at 60 FR 27419 
(May 24, 1995) (FRL-4955-3). These tolerances were also time-limited, 
based on a data gap for residues of fenbuconazole in or on unbagged 
bananas in field trials. The expiration date of each of the above 
tolerances was December 31, 1998. In the Federal Register, at 63 FR 
67476 (December 7, 1998) (FRL-5791-5), the Agency published a notice of 
filing concerning the receipt of amended PP 1989, PP 3995, and PP 4154 
that proposed to amend 40 CFR part 180 by extending the expiration date 
of the tolerances for fenbuconazole and its metabolites (as appropriate 
to each commodity) in or on stone fruits (except plums and prunes) at 
2.0 ppm, pecans at 0.1 ppm, and banana (whole fruit) at 0.3 ppm (of 
which the pulp can contain no more than 0.05 ppm) until December 31, 
2001. Data to fill the data gaps that had caused the tolerances to be 
established as time-limited tolerances had since been received from the 
company. No comments concerning this notice of filing were received. In 
the Federal Register, at 64 FR 7794 (February 17, 1999) (FRL-6059-7), 
the final rule that extended the subject tolerances until December 31, 
2001, was published. The reason for extension of the time-limits on 
these tolerances (instead of making the tolerances permanent at that 
time) was that there was felt to still be a data gap for storage 
stability of fenbuconazole residues in other RACs.

A. Residue Chemistry

    1. Plant metabolism. The metabolism of fenbuconazole in plants 
(peanuts, wheat, peaches, and sugar beets) is adequately understood for 
the purpose of these tolerances. It was qualitatively similar in all 
crops investigated. Metabolism of the test compound proceeded via three 
pathways. Oxidation at the benzylic carbon (pathway 1) led to the 
ketone and the lactone as metabolites. Oxidation or nucleophilic 
substitution on the carbon next to the triazole ring (pathway 2) led to 
triazole alanine (TA) and triazole acetic acid (TAA) presumably through 
free triazole. Metabolic pathway 3 presumably produced the phenolic 
metabolite RH-4911, and led to the glucose conjugates found in all 
crops.
    2. Analytical method. An adequate enforcement method is available 
for the established and proposed tolerances. Quantitation of 
fenbuconazole residues (and lactones RH-9129 and RH-9130) at an 
analytical sensitivity of 0.01 milligrams/kilogram (mg/kg) is 
accomplished by soxhlet extraction of samples in methanol, partitioning 
into methylene chloride, redissolving in toluene, cleanup on silica 
gel, and gas liquid chromatography using nitrogen specific thermionic 
detection.
    3. Magnitude of residues. i. Stone fruit--peaches. Ten field trials 
were conducted on peaches. Seven to 10 applications were made at the 
maximum use rate of 0.1 pounds of active ingredient per acre (lb ai/
acre), and fruit was harvested on the last day of application. The 
highest field residue value was 0.51 ppm, and the average field residue 
value was 0.36 ppm.
    ii. Stone fruit--cherries. Eleven field trials were conducted on 
cherries. Five to 6 applications were made at the maximum use rate of 
0.1 lb ai/acre, and fruit was harvested on the last day of application. 
The highest field residue value was 0.64 ppm, and the average field 
residue value was 0.44 ppm.
    iii. Stone fruit--apricots. Two field trials were conducted on 
apricots. Six applications were made at the maximum use rate of 0.125 
lb ai/acre, and fruit was harvested on the last day

[[Page 16229]]

of application. The field residue values in four samples measured were 
0.17, 0.23, 0.27, and 0.28 ppm.
    iv. Pecans. Four field trials were conducted in pecans. Eight to 10 
applications were made at the maximum use rate of 0.125 lb ai/acre, and 
nuts were harvested 28 days after the last application. Field residue 
values in nutmeat for the four trials were 0.004, 0.004, <0.01, and 
<0.01 ppm.
    v. Bananas. Eighteen field trials were conducted on bagged bananas, 
which are typically used in commerce. Eight applications (five and 
seven applications in two trials) were made at the maximum use rate of 
0.09 lb ai/acre and bananas were harvested on the last day of 
application. The highest field residue value in whole fruit or in pulp 
and peel combined was 0.062 ppm. The average field residue value in 
whole fruit or in pulp and peel combined was 0.03 ppm.
    The results of these studies support the proposed permanent 
tolerances for fenbuconazole on stone fruit, pecans, and bananas.

B. Toxicological Profile

    1. Acute toxicity. Fenbuconazole is practically non-toxic after 
administration by the oral and dermal routes, and was not significantly 
toxic to rats after a 4 hour inhalation exposure. Fenbuconazole is 
classified as not irritating to skin and inconsequentially irritating 
to the eyes. It is not a skin sensitizer.
    2. Genotoxicity. Fenbuconazole was negative (non-mutagenic) in an 
Ames assay with and without hepatic enzyme activation. Fenbuconazole 
was negative in a hypoxanthine guanine phosphoribosyl transferase 
(HGPRT) gene mutation assay using chinese hamster ovary (CHO) cells in 
culture when tested with and without hepatic enzyme activation. In 
isolated rat hepatocytes, fenbuconazole did not induce unscheduled DNA 
synthesis (UDS) or repair. Fenbuconazole did not produce chromosome 
effects in rats in vivo. On the basis of the results from this battery 
of tests, it is concluded that fenbuconazole is not mutagenic or 
genotoxic.
    3. Reproductive and developmental toxicity-- i. Developmental 
toxicity in the rat. In the developmental study in rats, the maternal 
(systemic) no observed adverse effect level (NOAEL) was 30 (mg/kg/day) 
based on decreases in body weight and body weight gain at the lowest 
observed adverse effect level (LOAEL) of 75 mg/kg/day. The 
developmental (fetal) NOAEL was 30 mg/kg/day based on an increase in 
post implantation loss and a significant decrease in the number of live 
fetuses per dam at the LOAEL of 75 mg/kg/day.
    ii. Developmental toxicity in the rabbit. In the developmental 
study in rabbits, the maternal (systemic) NOAEL was 10 mg/kg/day based 
on decreased body weight gain at the LOAEL of 30 mg/kg/day. The 
developmental (fetal) NOAEL was 30 mg/kg/day based on increased 
resorptions at the LOAEL of 60 mg/kg/day.
    iii. Reproductive toxicity. In the 2-generation reproduction 
toxicity study in rats, the maternal (systemic) NOAEL was 4 mg/kg/day 
based on decreased body weight and food consumption, increased number 
of dams delivering nonviable offspring, and increases in adrenal and 
thyroid weights at the LOAEL of 40 mg/kg/day. The reproductive (pup) 
NOAEL was 40 mg/kg/day, the highest dose tested.
    4. Subchronic toxicity--i. Rat 90-day oral study. A subchronic 
feeding study in rats conducted for 13 weeks resulted in a NOAEL of 20 
ppm (1.3 and 1.5 mg/kg/day in males and females, respectively). Minimal 
liver hypertrophy was observed in males at the LOAEL of 80 ppm. 
Increased liver weight, hepatic hypertrophy, thyroid hypertrophy, and 
decreased body weight were observed at the higher doses of 400 and 
1,600 ppm.
    ii. Mouse 90-day oral study. A subchronic feeding study in mice 
conducted for 13 weeks resulted in a NOAEL of 60 ppm (11.1 and 17.6 mg/
kg/day in males and females, respectively). Increased liver weight, 
hypertrophy in the liver (males), and increases in clinical chemistry 
parameters (males) were observed at the LOAEL of 180 ppm. These effects 
were all observed in females at 540 ppm, in addition to males.
    iii. Dog 90-day oral study. A subchronic feeding study in dogs 
conducted for 13 weeks resulted in a NOAEL of 100 ppm (3.3 and 3.5 mg/
kg/day in males and females, respectively). At the LOAEL of 400 ppm, 
increased liver weight, clinical chemistry parameters, and liver 
hypertrophy (males) were observed.
    iv. Rat 4-week dermal study. In a 21-day dermal toxicity in the rat 
study, the NOAEL was greater than 1,000 mg/kg/day, with no effects seen 
at this limit dose.
    5. Chronic toxicity--i. Dog. A one-year feeding study in dogs 
resulted in a NOAEL of 15 ppm (0.62 mg/kg/day) for females and 150 ppm 
(5.2 mg/kg/day) for males. Decreased body weight, increased liver 
weight, liver hypertrophy, and pigment in the liver were observed at 
the LOAEL of 150 and 1,200 ppm in females and males, respectively.
    ii. Mouse. A 78-week chronic/oncogenicity study was conducted in 
male and female mice at 0, 10, 200 (males only), 650, and 1,300 ppm 
(females only). The NOAEL was 10 ppm (1.4 mg/kg/day), and the LOAEL was 
200 ppm (26.3 mg/kg/day) for males and 650 ppm (104.6 mg/kg/day) for 
females based on increased liver weight and histopathological effects 
on the liver, which were consistent with chronic enzyme induction. 
There was no statistically significant increase of any tumor type in 
males. However, there was a statistically significant increase in 
combined liver adenomas and carcinomas in females at the high dose only 
(1,300 ppm; 208.8 mg/kg/day). There were no liver tumors in the control 
females, and liver tumor incidences in the high-dose females just 
exceeded the historical control range. In ancillary mode-of-action 
studies in female mice, the increased tumor incidence was associated 
with changes in several parameters in mouse liver following high doses 
of fenbuconazole, including an increase in P450 enzymes (predominately 
of the CYP 2B type), an increase in cell proliferation, an increase in 
hepatocyte hypertrophy, and an increase in liver weight. Changes in 
these liver parameters, as well as the occurrence of the low incidence 
of liver tumors, were non-linear with respect to dose (i.e., effects 
were observed only at high dietary doses of fenbuconazole). Similar 
findings have been shown with several pharmaceuticals, including 
phenobarbital, which is not carcinogenic in humans. The non-linear dose 
response relationship observed with respect to liver changes (including 
the low incidence of tumors) in the mouse indicates that these findings 
should be carefully considered in deciding the relevance of high-dose 
animal tumors to human dietary exposure.
    iii. Rat. A 24-month chronic/oncogenicity study in male and female 
rats was conducted at 0, 8, 80, and 800 ppm fenbuconazole, and a second 
24-month chronic/oncogenicity study was conducted in male rats at 0, 
800, and 1,600 ppm. The NOAEL was 80 ppm (3 and 4 mg/kg/day in males 
and females, respectively), and the LOAEL was 800 ppm (31 and 43 mg/kg/
day in males and females, respectively) based on decreased body weight, 
increased liver and thyroid weights, and liver and thyroid hypertrophy. 
Fenbuconazole produced a minimal but statistically significant increase 
in the incidence of combined thyroid follicular cell benign and 
malignant tumors. These findings

[[Page 16230]]

occurred only in male rats following life-time ingestion of very high 
levels (800 and 1,600 ppm in the diet) of fenbuconazole.
    6. Animal metabolism. The absorption, distribution, excretion, and 
metabolism of fenbuconazole in rats, goats, and hens were investigated. 
Following oral administration, fenbuconazole was completely and rapidly 
absorbed, extensively metabolized by oxidation/hydroxylation and 
conjugation, and rapidly and essentially completely excreted, 
predominately in the feces. Fenbuconazole did not accumulate in 
tissues.
    7. Metabolite toxicology. Common metabolic pathways for 
fenbuconazole have been identified in both plants (wheat, peaches, and 
sugar beets) and animals (rat, goat, and hen). The metabolic pathway 
common to both plants and animals involves oxidation of the benzylic 
position alpha to the chlorophenyl ring. The metabolites which result 
from this path are the benzylic alcohols and their conjugates, 
including sulfates and glucuronides, the iminolactones, the lactones, 
and the ketoacid, all resulting from intramolecular cyclization. A 
second pathway is oxidation of the unchlorinated ring to produce the 3- 
and 4-phenols and their conjugates. Combinations of the above two 
pathways produce phenol-lactones and their conjugates. A third pathway 
is cleavage of the triazole moiety, which produces free triazole and 
its conjugates. Extensive degradation and elimination of polar 
metabolites occurs in animals such that residues are unlikely to 
accumulate in humans or animals exposed to these residues through the 
diet.
    8. Endocrine disruption. The mammalian endocrine system includes 
estrogen and androgens as well as other hormonal systems. Fenbuconazole 
is not known to interfere with reproductive hormones; thus, 
fenbuconazole should not be considered to be estrogenic or androgenic. 
There are no known instances of proven or alleged adverse reproductive 
or developmental effects to people, domestic animals, or wildlife as a 
result of exposure to fenbuconazole or its residues.

C. Aggregate Exposure

    1. Dietary exposure. Time-limited tolerances have been established 
(40 CFR part 180) for the residues of fenbuconazole in the RACs stone 
fruits (except plum and prune) at 2.0 ppm, pecan at 0.1 ppm, and banana 
(whole fruit) at 0.3 ppm. Risk assessments were conducted by Rohm and 
Haas to assess dietary exposures and risks from fenbuconazole as 
follows.
    i. Food--Acute exposure and risk. No acute endpoint was identified 
for fenbuconazole, and no acute risk assessment is required.
    ii. Chronic exposure and risk. Risk associated with chronic dietary 
exposure from fenbuconazole was assessed on four levels. In the first 
assessment, tolerance level residues and 100% crop treated were 
assumed. In the second assessment, tolerance level residues and Rohm 
and Haas Company's conservative estimates of the highest achievable 
percent crop treated refinements were assumed. Rohm and Haas Company's 
percent of crop treated estimates used in the assessments are stone 
fruit = 30%, bananas = 20%, and pecans = 11%. In the third assessment, 
average field trial (anticipated) residues and 100% crop treated were 
assumed. In the fourth assessment, average field trial residues and 
Rohm and Haas Company's conservative percent of crop treated estimates 
indicated above were assumed. The anticipated residue contribution 
(ARC) from stone fruit (except plums and prunes), pecans, and bananas 
was assessed.
    The reference dose (RfD) used for the chronic dietary analysis is 
0.03 mg/kg/day. Potential chronic exposures were estimated using 
NOVIGEN'S dietary exposure evaluation model (DEEM~ version 7.075), 
which uses United States Department of Agriculture (USDA) food 
consumption data from the 1994-1996 survey. The existing and proposed 
fenbuconazole tolerances, and average fenbuconazole residues, result in 
ARCs that are equivalent to the following percentages of the RfD.

----------------------------------------------------------------------------------------------------------------
       Population Subgroup            DEEM1 %RfD          DEEM2 %RfD          DEEM3 %RfD          DEEM4 %RfD
----------------------------------------------------------------------------------------------------------------
U.S. population (48 states)       1.5                 0.4                 0.2                 0.1
Nursing infants (<1-year old)     5.1                 1.4                 0.8                 0.2
Non-nursing infants (<1-year      10.8                3.1                 1.7                 0.5
 old)
Children (1 to 6 years old)       4.3                 1.2                 0.7                 0.2
Children (7 to 12 years old)      2.0                 0.6                 0.3                 0.1
Females (13+ and nursing)         1.9                 0.5                 0.3                 0.1
----------------------------------------------------------------------------------------------------------------
1Assumes residues are present at tolerance levels and 100% crop treated.
2Assumes residues are present at tolerance levels and includes percent crop treated refinements.
3Assumes residues are present at their average field trial residue levels and 100% crop treated.
4Assumes residues are present at their average field trial residue levels and includes percent crop treated
  refinements.

    iii. Drinking water. Fenbuconazole has minimal tendency to 
contaminate ground water or drinking water because of its adsorptive 
properties on soil, solubility in water, and degradation rate. USDA 
PRZM/GLEAMS computer modeling of laboratory and field dissipation data 
predict that fenbuconazole will not leach into ground water, even if 
heavy rainfall is simulated. The modeling predictions are consistent 
with the data from environmental studies in the laboratory and the 
results of actual field dissipation studies. There is no established 
maximum concentration level (MCL) for residues of fenbuconazole in 
drinking water. No drinking water health advisory levels have been 
established for fenbuconazole. There is no entry for fenbuconazole in 
the ``Pesticides in Ground Water Data Base'' (EPA 734-12-92-001; 
September 1992).
    2. Non-dietary exposure. Fenbuconazole is not currently registered 
for any indoor or outdoor residential uses; therefore, no non-dietary 
residential exposure is anticipated.
    3.Aggregate cancer risk for U.S. population. Fenbuconazole has been 
classified as a group C carcinogen with a Q1* 
value of 0.00359 mg/kg/day-1. Cancer risk assessments for 
fenbuconazole use on stone fruit (except plums/prunes), pecans, and 
bananas for the U.S. population are as follow.

[[Page 16231]]



------------------------------------------------------------------------
                                              Stone fruits (except plums
         Assumptions/ Refinements             and prunes),  pecans, and
                                                       bananas
------------------------------------------------------------------------
Tolerance residue levels and 100% crop      1.67  x  10-6
 treated assumed
Tolerance residue levels and percent crop   4.62  x  10-7
 treated refinements assumed
Anticipated residue levels and 100% crop    2.68  x  10-7
 treated assumed
Anticipated residue levels and percent      7.64  x  10-8
 treated refinements assumed
------------------------------------------------------------------------

D. Cumulative Effects

    The potential for cumulative effects of fenbuconazole with other 
substances that have a common mechanism of toxicity was considered. 
Fenbuconazole belongs to the class of fungicide chemicals known as 
triazoles having demethylase inhibition capability. The toxicological 
effects of fenbuconazole are related to its effects on rodent thyroid 
and liver. Extensive data that are available on the biochemical mode of 
action by which fenbuconazole produces animal tumors in rats and mice 
indicate that the initiating events do not occur below a given dose, 
and that the processes are reversible. There are no data which suggest 
that the mode of action by which fenbuconazole produces these animal 
tumors or any other toxicological effect is common to all fungicides of 
this class. In fact, the closest structural analog to fenbuconazole 
among registered fungicides of this class is not tumorigenic in 
animals, even at maximally tolerated doses, and has a different 
spectrum of toxicological effects.

E. Safety Determination

    1. U.S. population--i. Acute exposure and risk. Since no acute 
endpoint was identified for fenbuconazole, no acute risk assessment is 
required.
    ii. Chronic exposure and risk. Using the conservative exposure 
assumptions described above and taking into account the completeness 
and reliability of the toxicity data, the percentage of the RfD that 
will be utilized by dietary (food only) exposure to residues of 
fenbuconazole from the proposed permanent tolerances is 1.5% for the 
U.S. population, assuming residues are present at their tolerance 
levels and 100% crop treated. The percentage of the RfD that will be 
utilized by dietary (food only) exposure to residues of fenbuconazole 
from the proposed permanent tolerances is 0.1% for the U.S. population, 
assuming residues are present at their average field trial residue 
levels, and conservative percent crop treated refinements. Aggregate 
exposure is not expected to exceed 100%. 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. Rohm and Haas 
concludes that there is a reasonable certainty that no harm will result 
to the U.S. population from aggregate exposure to fenbuconazole 
residues.
    2. Infants and children--i. General. In assessing the potential for 
additional sensitivity of infants and children to residues of 
fenbuconazole, data from developmental toxicity studies in the rat and 
rabbit, and 2-generation reproduction studies in the rat are 
considered. The developmental toxicity studies are designed to evaluate 
adverse effects on the developing organism resulting from maternal 
pesticide exposure during gestation. Reproduction studies provide 
information relating to effects from exposure to the pesticide on the 
reproductive capability of mating animals and data on systemic 
toxicity.
    ii. Developmental toxicity studies--a. Rat. In the developmental 
study in rats, the maternal (systemic) NOAEL was 30 mg/kg/day based on 
decreases in body weight and body weight gain at the LOAEL of 75 mg/kg/
day. The developmental (fetal) NOAEL was 30 mg/kg/day based on an 
increase in post implantation loss and a significant decrease in the 
number of live fetuses per dam at the LOAEL of 75 mg/kg/day.
    b. Rabbit. In the developmental study in rabbits, the maternal 
(systemic) NOAEL was 10 mg/kg/day based on decreased body weight gain 
at the LOAEL of 30 mg/kg/day. The developmental (fetal) NOAEL was 30 
mg/kg/day based on increased resorptions at the LOAEL of 60 mg/kg/day.
    c. Reproductive toxicity study. In the 2-generation reproduction 
toxicity study in rats, the maternal (systemic) NOAEL was 4 mg/kg/day 
based on decreased body weight and food consumption, increased number 
of dams delivering nonviable offspring, and increases in adrenal and 
thyroid weights at the LOAEL of 40 mg/kg/day. The reproductive (pup) 
NOAEL was 40 mg/kg/day, the highest dose tested.
    d. Prenatal and postnatal sensitivity. The prenatal and postnatal 
toxicology data base for fenbuconazole is complete with respect to 
current toxicological data requirements. There is a 10-fold difference 
between the developmental NOAEL of 30 mg/kg/day from the rat and rabbit 
developmental toxicity studies and the NOAEL of 3 mg/kg/day from the 
chronic rat feeding study which is the basis of the RfD. It is further 
noted that in the rabbit and rat developmental toxicity studies, the 
developmental NOAELs are similar to or greater than the respective 
maternal NOAELs. In the rat reproduction study, the maternal NOAEL (4 
mg/kg/day) was 10 times lower than the developmental (pup) and 
reproductive NOAEL (40 mg/kg/day, the highest dose tested). These 
studies indicate that there is no additional sensitivity for infants 
and children in the absence of maternal toxicity for fenbuconazole.
    e. Acute risk. No acute dietary risk has been identified for 
fenbuconazole.
    f. Chronic risk. Using the exposure assumptions described above, 
exposure to fenbuconazole from food will utilize 10.8% of the RfD for 
non-nursing infants <1 year old and 5.1% for nursing infants <1 year 
old assuming residues are present at tolerance levels and 100% crop 
treated. Exposure to fenbuconazole will utilize only 0.5% of the RfD 
for non-nursing infants <1 year old and 0.2% for nursing infants <1 
year old assuming residues are present at their average field trial 
residue levels and conservative percent crop treated refinements. The 
exposure to fenbuconazole from food will utilize 4.3% of the RfD for 
children 1 to 6 years old and 2.0% for children 7 to 12 years old 
assuming residues are present at tolerance levels and 100% crop 
treated, and will utilize only 0.2% of the RfD for children 1 to 6 
years old and 0.1% for children 7 to 12 years old assuming residues are 
present at their average field trial residue levels and conservative 
percent crop treated refinements. 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.
    g. Conclusion. It is concluded that reliable and complete data 
support the use of the 100-fold uncertainty factor (UF), and that an 
additional 10-fold factor is not needed to ensure the safety of infants 
and children from dietary exposure. Rohm and Haas concludes that there 
is a reasonable certainty that no harm will result from aggregate 
exposure of infants and children to fenbuconazole residues.

[[Page 16232]]

F. International Tolerances

    There are currently no Codex maximum residue limits (MRLs) for 
fenbuconazole, but the fenbuconazole data base was evaluated by the 
world health organization (WHO) and the food and agriculture 
organization (FAO) expert panels at the joint meeting on pesticide 
residues (JMPR) in September 1997. An allowable daily intake (ADI; also 
called RfD) of 0.03 mg/kg/day and a total of 32 Codex MRLs were 
proposed in the JMPR report.
[FR Doc. 01-7287 Filed 3-22-01; 8:45 am]
BILLING CODE 6560-50-S