[Federal Register Volume 65, Number 12 (Wednesday, January 19, 2000)]
[Notices]
[Pages 2949-2953]
From the Federal Register Online via the Government Publishing Office [www.gpo.gov]
[FR Doc No: 00-1214]


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ENVIRONMENTAL PROTECTION AGENCY

[PF-912; FRL-6485-8]


Notice of Filing a Pesticide Petition to Establish a Tolerance 
for Certain Pesticide Chemicals in or on Food

AGENCY:  Environmental Protection Agency (EPA).

ACTION:  Notice.

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SUMMARY:  This notice announces the initial filing of pesticide 
petitions proposing the establishment of regulations for residues of 
certain pesticide chemicals in or on various food commodities.

DATES:  Comments, identified by docket control number PF-912, must be 
received on or before February 18, 2000.

ADDRESSES:  Comments may be submitted by mail, electronically, or in 
person. Please follow the detailed instructions for each method as 
provided in Unit I.C. of the ``SUPPLEMENTARY INFORMATION.'' To ensure 
proper receipt by EPA, it is imperative that you identify docket 
control number PF-912 in the subject line on the first page of your 
response.

FOR FURTHER INFORMATION CONTACT:  By mail: Cynthia Giles-Parker, 
Registration Support Branch, Registration Division (7505C), Office of 
Pesticide Programs, Environmental Protection Agency, 401 M St., SW., 
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            potentially
                                                       affected entities
------------------------------------------------------------------------
Industry                          111                 Crop production
 
                                  112                 Animal production
 
                                  311                 Food manufacturing

[[Page 2950]]

 
                                  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-912. 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 (CM 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-912 in the subject line on the 
first page of your response.
    1. By mail. Submit your comments to: Public Information and Records 
Integrity Branch (PIRIB), Information Resources and Services Division 
(7502C), Office of Pesticide Programs (OPP), Environmental Protection 
Agency, 401 M St., SW., Washington, DC 20460.
    2. In person or by courier. Deliver your comments to: Public 
Information and Records Integrity Branch (PIRIB), Information Resources 
and Services Division (7502C), Office of Pesticide Programs (OPP), 
Environmental Protection Agency, Rm. 119, CM 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-912. Electronic comments may 
also be filed online at many Federal Depository Libraries.

D. How Should I Handle CBI That I Want to Submit to the Agency?

    Do not submit any information electronically that you consider to 
be CBI. You may claim information that you submit to EPA in response to 
this document as CBI by marking any part or all of that information as 
CBI. Information so marked will not be disclosed except in accordance 
with procedures set forth in 40 CFR part 2. In addition to one complete 
version of the comment that includes any information claimed as CBI, a 
copy of the comment that does not contain the information claimed as 
CBI must be submitted for inclusion in the public version of the 
official record. Information not marked confidential will be included 
in the public version of the official record without prior notice. If 
you have any questions about CBI or the procedures for claiming CBI, 
please consult the person identified under ``FOR FURTHER INFORMATION 
CONTACT.''

E. What Should I Consider as I Prepare My Comments for EPA?

    You may find the following suggestions helpful for preparing your 
comments:
    1. Explain your views as clearly as possible.
    2. Describe any assumptions that you used.
    3. Provide copies of any technical information and/or data you used 
that support your views.
    4. If you estimate potential burden or costs, explain how you 
arrived at the estimate that you provide.
    5. Provide specific examples to illustrate your concerns.
    6. Make sure to submit your comments by the deadline in this 
notice.
    7. To ensure proper receipt by EPA, be sure to identify the docket 
control number assigned to this action in the subject line on the first 
page of your response. You may also provide the name, date, and Federal 
Register citation.

II. What Action is the Agency Taking?

     EPA has received a pesticide petition as follows proposing the 
establishment and/or amendment of regulations for residues of certain 
pesticide chemical in or on various food commodities under section 408 
of the Federal Food, Drug, and Comestic Act (FFDCA), 21 U.S.C. 346a. 
EPA has determined that this petition contains data or information 
regarding the elements set forth in section 408(d)(2); however, EPA has 
not fully evaluated the sufficiency of the submitted data at this time 
or whether the data supports granting of the petition. Additional data 
may be needed before EPA rules on the petition.

List of Subjects

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

    Dated: January 11, 2000
James Jones,
Director, Registration Division, Office of Pesticide Programs.

Summaries 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.

[[Page 2951]]

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.

 1. Novartis Crop Protection, Inc.

 PP 9F05070

     EPA has received a pesticide petition (PP 9F05070) from Novartis 
Crop Protection, Inc., PO Box 18300, Greensboro, NC 27419, 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 a 
tolerance for residues of Trifloxystrobin in or on the raw agricultural 
commodities almond nutmeats at 0.02 parts per million (ppm), almond 
hulls at 1.5 ppm, fruiting vegetables crop group at 0.7 ppm, hops - 
dried cones at 11 ppm, potato tubers at 0.02 ppm, sugarbeet roots at 
0.05 ppm, sugarbeet tops at 2.5 ppm, sugarbeet dried pulp at 0.25 ppm, 
wheat grain at 0.05 ppm, wheat forage at 0.03 ppm, wheat hay at 0.2 
ppm, wheat straw at 0.05 ppm, and wheat aspirated grain fractions at 
0.5 ppm. EPA has determined that the petition contains data or 
information regarding the elements set forth in section 408(d)(2) of 
the FFDCA; however, EPA has not fully evaluated the sufficiency of the 
submitted data at this time or whether the data supports granting of 
the petition. Additional data may be needed before EPA rules on the 
petition.

 A. Residue Chemistry

     1.  Plant metabolism. The metabolism of trifloxystrobin in plants 
(cucumbers, apples, wheat and peanuts) is well understood. Identified 
metabolic pathways are substantially similar in plants and animals 
(goat, rat and hen). Novartis proposes trifloxystrobin, per se, as the 
residue of concern for tolerance setting purposes.
     2.  Analytical method. Novartis Crop Protection Inc. has submitted 
practical analytical methodology for detecting and measuring levels of 
trifloxystrobin in or on raw agricultural commodities. The limit of 
detection (LOD) for each analyte of this method is 0.08 ng injected, 
and the limit of quantitation (LOQ) is 0.02 ppm. The method is based on 
crop specific cleanup procedures and determination by gas 
chromatography with nitrogen-phosphorus detection.
     3.  Magnitude of residues -- residue trials. A residue program was 
performed for trifloxystrobin on a full geography of tomatoes and 
peppers as representative fruiting vegetable crops, potatoes as a 
representative crop of tuberous and corm vegetables, almonds, hops, 
wheat, and sugarbeets. A study was conducted on indicator crops to 
assay for secondary residues in rotational crops. Novartis also 
completed a three-level poultry study to determine the rate of transfer 
of residues of trifloxystrobin from residues in animal feed to poultry 
commodities.
    i. Acute toxicity. Studies conducted with the technical material of 
trifloxystrobin:
     Rat acute oral toxicity study with a LD50 
>5,000 mg/kg
     Mouse acute oral toxicity study with a LD50 
>5,000 mg/kg
     Rabbit acute dermal toxicity study with a LD50 
>2,000 mg/kg
     Rat acute dermal toxicity study with a LD50 
>2,000 mg/kg
     Rat acute inhalation toxicity study with a LC50 
>4.65 mg/L
     Rabbit eye irritation study showing slight irritation 
(Category III)
     Rabbit dermal irritation study showing slight irritation 
(Category IV)
     Guinea pig dermal sensitization study with the Buehler's 
method showing negative findings
     Guinea pig clem sal sensitization study with the 
Maximization method showing some positive findings
    ii. Genotoxicty. No genotoxic activity is expected of 
trifloxystrobin under in-vivo or physiological conditions. The compound 
has been tested for its potential to induce gene mutation and 
chromosomal changes in five different test systems. The only positive 
finding was seen in the in vitro test system (Chinese hamster V79 
cells) as a slight increase in mutant frequency at a very narrow range 
(250 - 278 g/ml) of cytotoxic and precipitating concentrations 
(compound solubility in water was reported to be 0.61 g/ml; 
precipitate was visually noted in culture medium at 150 g/ml). 
The chemical was found to be non-mutagenic in the in vivo system or all 
other in vitro systems. Consequently, the limited gene mutation 
activity in the V79 cell line is considered a nonspecific effect under 
non-physiological in vitro conditions and not indicative of a real 
mutagenic hazard.
    iii. Reproductive and developmental toxicity. FFDCA section 408 
provides that EPA may apply an additional safety factor for infants and 
children in the case of threshold effects to account for pre- and post-
natal toxicity and the completeness of the database. Based on the 
current toxicological data requirements, the database on 
trifloxystrobin relative to pre- and post-natal effects for children is 
complete.
    In assessing the potential for additional sensitivity of infants 
and children to residues of trifloxystrobin, Novartis considered data 
from teratogenicity studies in the rat and the rabbit and a 2-
generation reproduction study in the rat. The teratogenicity studies 
are designed to evaluate adverse effects on the developing embryo as a 
result of chemical exposure during the period of organogenesis. 
Reproduction studies provide information on effects from chemical 
exposure on the reproductive capability of mating animals and systemic 
and developmental toxicity from in utero exposure.
    In the rat teratology study, reductions in body weight gain and 
food consumption were observed in the dam at  100 mg/kg. No 
teratoganic effects or any other effects were seen on pregnancy or 
fetal parameters except for the increased incidence of enlarged thymus, 
which is a type of variation, at 1,000 mg/kg. The developmental no 
observed-adverse-effect level (NOAEL) was 100 mg/kg.
    In the rabbit teratology study, body weight loss and dramatically 
reduced food consumption were observed in the dam at  250 
mg/kg. No teratogenic effects or any other effects were seen on 
pregnancy or fetal parameters except for the increase in skeletal 
anomaly of fused sternebrae-3 and -4 at the top dose level of 500 mg/
kg. This finding is regarded as a marginal effect on skeletal 
development that could have resulted from the 40- to 65% lower food 
intake during treatment at this dose level. The developmental NOAEL was 
250 mg/kg.
    In the 2-generation rat reproduction study, body weight gain and 
food consumption were decreased at > 750 ppm, especially in females 
during lactation. Consequently, the reduced pup weight gain during 
lactation (> 750 ppm) and the slight delay in eye opening (1,500 ppm) 
are judged to be a secondary effect of maternal toxicity. No other 
fetal effects or any reproductive changes were noted. The low 
developmental NOAEL, 50 ppm (5 mg/kg), seen in this study was probably 
due to the lack of intermediate dose levels between 50 and 750 ppm. 
Based on an evaluation of the dose-response relationship for pup weight 
at 750 ppm and 1,500 ppm, the NOAEL should have been nearly ten-fold 
higher if such a dose was available.
    Based on all these teratology and reproduction studies, the lowest 
NOAEL for developmental toxicity is 5 mg/kg while the lowest NOAEL in 
the subchronic and chronic studies is 2.5

[[Page 2952]]

mg/kg/day (from the rat chronic study). Therefore, no additional 
sensitivity for infants and children to trifloxystrobin is suggested by 
the data base.
    iv. Subchronic toxicity. In subchronic studies, several mortality 
related changes were reported for the top dose in dogs (500 mg/kg) and 
rats (800 mg/kg). At these dose levels, excessive toxicity has resulted 
in body weight loss and mortality with the associated and nonspecific 
changes in several organs (such as atrophy in the thymus, pancreas, 
bone marrow, lymph node, and spleen) which are not considered specific 
target organs for the test compound. In the dog, specific effects were 
limited to hepatocellular hypertrophy at 150 mg/kg and hyperplasia of 
the epithelium of the gall bladder at 500 mg/kg. Target organ effects 
in the rat were noted as hepatocellular hypertrophy ( 200 
mg/kg) and the related liver weight increase ( 50 mg/kg). In 
the mouse, target organ effects included single cell necrosis (300 mg/
kg) and hypertrophy (1,050 mg/kg) in the liver and extramedullary 
hematopoiesis ( 300 mg/kg) and hemosiderosis in the spleen 
(1,050 mg/kg).
    In general, definitive target organ toxicity, mostly in the liver, 
was seen at high feeding levels of over 100 mg/kg for an extended 
treatment period. At the lowest observed adverse effect level, no 
serious toxicity was observed other than mostly non-specific effects 
including a reduction in body weight and food consumption or liver 
hypertrophy.
    5. Chronic toxicity. The liver appears to be the major primary 
target organ based on the chronic studies conducted in mice, rats, and 
dogs. It was identified as a target organ in both the mouse and the dog 
studies with trifloxystrobin. However, no liver effect was seen in the 
chronic rat study which produced the lowest NOAEL of 2.5 mg/kg based on 
reduced body weight gain and food consumption seen at higher dose 
levels.
    The compound did not cause any treatment-related increase in 
general tumor incidence, any elevated incidence of rare tumors, or 
shortened time to the development of palpable or rapidly lethal tumors 
in the 18-month mouse and the 24-month rat studies. Dosages in both 
studies were sufficient for identifying a cancer risk. In the absence 
of carcinogenicity, Novartis believes that a Reference Dose (RfD) 
approach is appropriate for quantitation of human risks.
    6. Animal metabolism. Trifloxystrobin is moderately absorbed from 
the gastrointestinal tract of rats and is rapidly distributed. 
Subsequent to a single oral dose, the half life of elimination is about 
2 days and excretion is primarily via bile. Trifloxystrobin is 
extensively metabolized by the rat into about 35 metabolites, but the 
primary actions are on the methyl ester (hydrolysis into an acid), the 
methoxyimino group (O-demethylation), and the methyl side chain 
(oxidation to a primary alcohol). Metabolism is dose dependent as it 
was almost complete at low doses but only about 60% complete at high 
doses.
    In the goat, elimination of orally administered trifloxystrobin is 
primarily via the feces. The major residues were the parent compound 
and the acid metabolite (CGA-321113) plus its conjugates. In the hen, 
trifloxystrobin is found as the major compound in tissues and in the 
excreta, but hydroxylation of the trifluormethyl-phenyl moiety and 
other transformations, including methyl ester hydrolysis and 
demethylation of the methoxyimino group, are also seen. In conclusion, 
the major pathways of metabolism in the rat, goat, and hen are the 
same.
    7. Metabolite toxicology. Metabolism of trifloxystrobin has been 
well characterized in plants, soil, and animals. In plants and soil, 
photolytically induced isomerization results in a few minor metabolites 
not seen in the rat; however, most of the applied materials remained as 
parent compound as shown in the apple and cucumber studies. All 
quantitatively major plant and/or soil metabolites were also seen in 
the rat. The toxicity of the major acid metabolite, CGA-321113 (formed 
by hydrolysis of the methyl ester), has been evaluated in cultured rat 
hepatocytes and found to be 20-times less cytotoxic than the parent 
compound. Additional toxicity studies were conducted for several minor 
metabolites seen uniquely in plants and/or soil. The studies indicate 
that these metabolites, including CGA-357261, CGA-373466, and NOA-
414412, are not mutagenic to bacteria and are of low acute toxicity 
(LD50 > 2,000 mg/kg). In conclusion, the metabolism and 
toxicity profiles support the use of an analytical enforcement method 
that accounts for parent trifloxystrobin.
    8. Endocrine effects. Trifloxystrobin does not belong to a class of 
chemicals known for having adverse effects on the endocrine system. 
Developmental toxicity studies in rats and rabbits and reproduction 
study in rats gave no indication that trifloxystrobin might have any 
effects on endocrine function related to development and reprodufftion. 
The subchronic and chronic studies also showed no evidence of a long-
term effect related to the endocrine system.
    9. Endocrine disruption. CGA-279202 does not belong to a class of 
chemicals known for having adverse effects on the endocrine system. 
Developmental toxicity studies in rats and rabbits and reproduction 
study in rats gave no indication that CGA-279202 might have any effects 
on endocrine function related to development and reproduction. The 
subchronic and chronic studies also showed no evidence of a long-term 
effect related to the endocrine system.

C. Aggregate Exposure

    1. Dietary Exposure-- i. Food. Dietary exposure was calculated 
using field trial residues generated at the maximum label rate and 
minimum preharvest interval. Chronic exposure was calculated by taking 
the mean value of the field trial values, and acute exposure was 
calculated by using the entire residue distribution in a Monte Carlo 
analysis. The resulting acute and chronic exposure estimates 
demonstrated negligible exposure. Using the chronic toxicological 
endpoint (rat feeding study), the sub-population with the highest 
predicted exposure was non-nursing infants ( 1 year old) with 1.3% of 
the reference dose. Acute exposure for the most exposed sub-population, 
non-nursing infants ( 1 year old), was 2.1% of the acute reference dose 
at the 99.9th pecentile. These results demonstrate a very large margin 
of safety for the use of trifloxystrobin on crops.
    ii. Drinking water exposure-- a. estimated surface drinking water 
concentration. The generic expected environmental concentration 
(GENEEC) estimated surface water concentrations for the proposed Flint 
and Compass uses contributed little to the overall exposure. These 
estimated concentrations were not adjusted for the estimated market 
share or percentage of use area. The two highest day-56 estimated 
environmetal concentration (EEC) values were 0.06 parts per billion 
(ppb) and 0.05 ppb provided by the Compass turf and ornamental uses, 
respectively. According to the EPA ``OPP's Interim Approach for 
Addressing Drinking Water Exposure,'' the average day-56 value is 
divided by three when correcting for overestimation of the GENEEC 
model. This was applied to the ornamental use and the resulting 
potential exposure via surface water was 0.05 ppb / 3 = 0.017 ppb. The 
EPA has accepted that the average day-56 EEC value is divided by six in 
the case when the product is applied to turf and accounts for the

[[Page 2953]]

effects of grass/turf in decreasing runoff (EPA, 1998, EPA-730-F-97-
002, PB97-137806, page 15). This division by six was used to calculate 
the potential exposure via surface water from the Compass turf 
application, 0.06 ppb / 6 = 0.010 ppb. Therefore, the highest potential 
exposure to trifloxystrobin from surface water is from the Compass 
ornamental use, 0.017 ppb.
    b. Estimated ground water concentrations. The screening 
concentration in ground water (SCI-GROW) estimated ground water 
concentrations for the proposed Flint and Compass uses also contributed 
little to the overall exposure. The estimated concentrations were not 
adjusted for the estimated market share or percentage of use area. In 
each use scenario, the concentration of trifloxystrobin in ground water 
was predicted to be below 1 part per trillion. The highest estimated 
concentration of trifloxystrobin in the ground water was 0.000587 ppb 
provided by the Compass turf use.
    c. Drinking water levels of concern-- acute exposure. The estimated 
maximum concentrations of trifloxystrobin in surface water at Peak Day-
0 was 2.48 ppb (GENEEC) and 0.000587 ppb in ground water (SCI-GROW). 
The acute drinking water level of concentration (DWLOC) values were 
calculated and compared to these estimated water concentrations. Per 
EPA preference, the 10-day multiple dosing rat teratology study defined 
the acute NOAEL at 10 mg/kg/day.
    From the acute dietary exposure analysis, the lowest Margin of 
Exposure (MOE) from the use of trifloxystrobin was 1,960 at the 
99.9th percentile for the U.S. population and all population 
subgroups. This indicates a food exposure of less than 0.0051 mg/kg/day 
for all populations. Based on the EPA's ``Interim Guidance for 
Conducting Drinking Water Exposure and Risk Assessments'' document 
(draft 12/2/97), acute drinking water levels of concern 
(DWLOCacute) were calculated for trifloxystrobin. The lowest 
acceptable Margin of Exposure (MOE) for any pesticide is 100. This 
value was used in the DWLOC calculations as a conservative approach. 
Based on this analysis, trifloxystrobin estimated surface water (2.48 
ppb) and ground water concentrations (0.000587 ppb) do not exceed the 
calculated acute DWLOC values (3,497, 3,496, 2,997, 997). Therefore, 
trifloxystrobin exposures would not exceed the exposure allowable by 
the risk cup.
    d. Chronic exposure. The estimated maximum concentrations of 
trifloxystrobin in surface water at Day-56/3 was 0.017 ppb (GENEEC) and 
0.000587 ppb in ground water (SCI-GROW). The chronic DWLOC values were 
calculated and compared to these estimated water concentrations. The 
chronic reference dose for trifloxystrobin is 0.025 mg/kg body wt/day, 
based upon the findings in the rat chronic toxicity study. From the 
chronic dietary exposure analysis, an exposure estimate of 0.000140 mg/
kg body wt/day was determined for the U.S. population and > 0.00032 for 
all subgroups. Using this information, chronic drinking water levels of 
concern (DWLOCchronic) were calculated for trifloxystrobin. 
The trifloxystrobin estimated ground water (0.000587 ppb) and surface 
water (0.017 ppb) concentrations do not exceed the calculated chronic 
DWLOC values (872, 870, 746, 247). Therefore, trifloxystrobin exposures 
would not exceed the exposure allowable by the risk cup.
    2. Non-dietary exposure. Non-dietary exposure to trifloxystrobin is 
considered negligible as the chemical is intended primarily for 
commercial and agricultural use. Post-application re-entry exposure to 
homeowners from professional use on residential ornamentals is 
considered negligible. For workers handling this chemical, acceptable 
margins of exposure (in the range of thousands) have been obtained for 
both acute and chronic scenarios.

D. Cumulative Risk

    Consideration of a common mechanism of toxicity is not appropriate 
at this time since there is no information to indicate that toxic 
effects produced by trifloxystrobin would be cumulative with those of 
any other types of chemicals. Furthermore, the oximinoacetate is a new 
type of fungicide and no compound in this general chemical class 
currently has a significant market share. Consequently, Novartis is 
considering only the potential exposure to trifloxystrobin in its 
aggregate risk assessment.

E. Safety Determination

    1. U.S. population. Using the conservative exposure assumptions 
described above and based on the completeness and reliability of the 
toxicity data base for trifloxystrobin, Novartis has calculated 
aggregate exposure levels for this chemical. The calculation shows that 
only 0.5% of the RfD will be utilized for the U.S. population based on 
chronic toxicity endpoints. EPA generally has no concern for exposures 
below 100 percent 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. Novartis concludes that there 
is a reasonable certainty that no harm will result from aggregate 
exposure to trifloxystrobin residue.
    2. Infants and children. Developmental toxicity, manifested as 
reduced weaning pup weight, enlarged thymus, or fused sternabrae, was 
observed in the teratology study and 2-generation rat reproduction 
studies at maternally toxic doses. All of these findings are judged to 
be non-specific, secondary effects of maternal toxicity. The lowest 
NOAEL for developmental toxicity was established in the rat 
reproduction study at 5 mg/kg, a level that is likely to be an overly 
low estimate (as a result of dose gap) but is still higher than the 
chronic NOAEL of 2.5 mg/kg on which the RfD is based.
    Using the same conservative exposure assumptions as employed for 
the determination in the general population, Novartis has calculated 
that the percent of the RfD that will be utilized by aggregate exposure 
to residues of trifloxystrobin is only 2.1% for non-nursing infants (> 
l year old) (the most impacted sub-population). Therefore, based on the 
completeness and reliability of the toxicity data base and the 
conservative exposure assessment, Novartis concludes that there is a 
reasonable certainty that no harm will result to infants and children 
from aggregate exposure to trifloxystrobin residues.

F. International Tolerances

     No Codex MRL's have been established for residues of 
trifloxystrobin. Flint has been registered on pome fruit in 
Switzerland, and Stratego (trifloxystrobin + propiconazole) has been 
registered on cereals in Switzerland.
[FR Doc. 00-1214 Filed 1-18-00; 8:45 am]
BILLING CODE 6560-50-F