[Federal Register Volume 63, Number 194 (Wednesday, October 7, 1998)]
[Rules and Regulations]
[Pages 53820-53826]
From the Federal Register Online via the Government Publishing Office [www.gpo.gov]
[FR Doc No: 98-26902]


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ENVIRONMENTAL PROTECTION AGENCY

40 CFR Part 180

[OPP-300738; FRL-6036-8]
RIN 2070-AB78


Fludioxonil; Pesticide Tolerance

AGENCY: Environmental Protection Agency (EPA).

ACTION: Final rule.

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SUMMARY: This regulation establishes tolerances for residues of 
fludioxonil (4-(2,2-difluoro 1,3 benzodioxol-4-yl)-1H-pyrrole-3-
carbonitrile) in or on the following raw agricultural commodities 
(RACs): rape seed, rape forage, peanuts, meat (hulls removed), peanut 
hay, sunflower seed, leafy vegetables except brassica, brassica leafy 
vegetables, legume vegetables, foliage of legume vegetables, fruiting 
vegetables except cucurbits, cucurbit vegetables, forage, fodder, and 
straw of cereal grains, grass, forage, fodder, and hay, and non-grass 
animal feeds at 0.01 parts per million (ppm); root and tuber 
vegetables, leaves of root and tuber vegetables, bulb vegetables, 
cereal grains, and herbs and spices at 0.02 ppm; and cotton seed and 
cotton gin byproducts at 0.05 ppm. Novartis Crop Protection, Inc, 
requested this tolerance under the Federal Food, Drug and Cosmetic Act 
(FFDCA), as amended by the Food Quality Protection Act of 1996 (Pub. L. 
104-170).

DATES: This regulation is effective October 7, 1998. Objections and 
requests for hearings must be received by EPA on or before December 7, 
1998.

ADDRESSES: Written objections and hearing requests, identified by the 
docket control number, [OPP-300738], must be submitted to: Hearing 
Clerk (1900), Environmental Protection Agency, Rm. M3708, 401 M St., 
SW., Washington, DC 20460. Fees accompanying objections and hearing 
requests shall be labeled ``Tolerance Petition Fees'' and forwarded to: 
EPA Headquarters Accounting Operations Branch, OPP (Tolerance Fees), 
P.O. Box 360277M, Pittsburgh, PA 15251. A copy of any objections and 
hearing requests filed with the Hearing Clerk identified by the docket 
control number, [OPP-300738], must also be submitted to: Public 
Information and Records Integrity Branch, Information Resources and 
Services Division (7502C), Office of Pesticide Programs, Environmental 
Protection Agency, 401 M St., SW., Washington, DC 20460. In person, 
bring a copy of objections and hearing requests to Rm. 119, Crystal 
Mall #2, 1921 Jefferson Davis Hwy., Arlington, VA.
    A copy of objections and hearing requests filed with the Hearing 
Clerk may also be submitted electronically by sending electronic mail 
(e mail) to: opp [email protected]. Copies of objections and 
hearing requests must be submitted as an ASCII file avoiding the use of 
special characters and any form of encryption. Copies of objections and 
hearing requests will also be accepted on disks in WordPerfect 5.1/6.1 
file format or ASCII file format. All copies of objections and hearing 
requests in electronic form must be identified by the docket control 
number [OPP-300738]. No Confidential Business Information (CBI) should 
be submitted through e mail. Electronic copies of objections and 
hearing requests on this rule may be filed online at many Federal 
Depository Libraries.

FOR FURTHER INFORMATION CONTACT: By mail: Mary Waller, Registration 
Division [7505C], Office of Pesticide Programs, Environmental 
Protection Agency, 401 M St., SW., Washington, DC 20460. Office 
location, telephone number, and e mail address: Crystal Mall #2, 1921 
Jefferson Davis Hwy., Arlington, VA, 703-308-9354, e mail: 
[email protected].

SUPPLEMENTARY INFORMATION: In the Federal Register of August 26, 1998 
63 FR 45497 (FRL-6023-4), EPA issued a notice pursuant to section 408 
of the Federal Food, Drug, and Cosmetic Act (FFDCA), 21 U.S.C. 346a 
announcing the filing of a pesticide petition (PP 8F4978) for 
tolerances by Novartis Crop Protection, Inc., 410 Swing Road, 
Greensboro, NC 27419. This notice included a summary of the petition 
prepared by Novartis Crop Protection Inc., the registrant. There were 
no comments received in response to the Notice of Filing.
    The petition requested that 40 CFR 180.516 be amended by 
establishing tolerances for residues of fludioxonil in or on the 
following RACs: rape seed and rape forage (reported as canola in the 
Notice of Filing), peanuts, meat (hulls removed) and peanut hay 
(reported as peanuts in the Notice of Filing), sunflower seed, leafy 
vegetables except brassica (Crop Group 4); brassica leafy vegetables 
(Crop Group 5); legume vegetables (Crop Group 6); foliage of legume 
vegetables (Crop Group 7); fruiting vegetables except cucurbits (Crop 
Group 8); cucurbit vegetables (Crop Group 9); forage, fodder, and straw 
of cereal grains (Crop Group 16); grass, forage, fodder, and hay (Crop 
Group 17); and non-grass animal feeds (Crop Group 18) at 0.01 ppm; root 
and tuber vegetables (Crop Group 1); leaves of root and tuber 
vegetables (Crop Group 2); bulb vegetables (Crop Group 3); cereal 
grains (Crop Group 15); and herbs and spices (Crop Group 19) at 0.02 
ppm; cotton seed, and cotton gin byproducts at 0.05 ppm.

I. Risk Assessment and Statutory Findings

    Section 408(b)(2)(A)(i) of the FFDCA allows EPA to establish a 
tolerance (the legal limit for a pesticide chemical residue in or on a 
food) only if EPA determines that the tolerance is ``safe.'' Section 
408(b)(2)(A)(ii) defines ``safe'' to

[[Page 53821]]

mean that ``there is a reasonable certainty that no harm will result 
from aggregate exposure to the pesticide chemical residue, including 
all anticipated dietary exposures and all other exposures for which 
there is reliable information.'' This includes exposure through 
drinking water and in residential settings, but does not include 
occupational exposure. Section 408(b)(2)(C) requires EPA to give 
special consideration to exposure of infants and children to the 
pesticide chemical residue in establishing a tolerance and to ``ensure 
that there is a reasonable certainty that no harm will result to 
infants and children from aggregate exposure to the pesticide chemical 
residue.....''
    EPA performs a number of analyses to determine the risks from 
aggregate exposure to pesticide residues. For further discussion of the 
regulatory requirements of section 408 and a complete description of 
the risk assessment process, see the Final Rule on Bifenthrin Pesticide 
Tolerances (62 FR 62961, November 26, 1997) (FRL-5754-7).

II. Aggregate Risk Assessment and Determination of Safety

    Consistent with section 408(b)(2)(D), EPA has reviewed the 
available scientific data and other relevant information in support of 
this action. EPA has sufficient data to assess the hazards of 
fludioxonil and to make a determination on aggregate exposure, 
consistent with section 408(b)(2), for tolerances in or on the 
following raw agricultural commodities (RACs): rape seed, rape forage, 
peanuts, meat (hulls removed), peanut hay, sunflower seed, leafy 
vegetables except brassica, brassica leafy vegetables, legume 
vegetables, foliage of legume vegetables, fruiting vegetables except 
cucurbits, cucurbit vegetables, forage, fodder, and straw of cereal 
grains, grass, forage, fodder, and hay, and non-grass animal feeds at 
0.01 ppm; root and tuber vegetables, leaves of root and tuber 
vegetables, bulb vegetables, cereal grains, and herbs and spices at 
0.02 ppm; and cotton seed and cotton gin byproducts at 0.05 ppm. EPA's 
assessment of the dietary exposures and risks associated with 
establishing the tolerance follows.

A. Toxicological Profile

    EPA has evaluated the available toxicity data and considered its 
validity, completeness, and reliability as well as the relationship of 
the results of the studies to human risk. EPA has also considered 
available information concerning the variability of the sensitivities 
of major identifiable subgroups of consumers, including infants and 
children. The nature of the toxic effects caused by fludioxonil are 
discussed below.
     1. A battery of acute toxicity studies place technical fludioxonil 
in Toxicity Category IV for oral, inhalation, and dermal irritation 
studies, and Category III for dermal and eye irritation studies. 
Fludioxonil is not a skin sensitizer.
     2. A subchronic oral toxicity study in rats dosed orally with 
technical fludioxonil at levels of 0, 0.8, 6.6, 64, 428, and 1,283 mg/
kg/day (males); 0, 1.0, 7.1, 70, 462, and 1,288 mg/kg/day (females) 
resulted in the Lowest-Observed-Adverse-Effect Level (LOAEL) of 428 mg/
kg/day in males and 462 mg/kg/day in females, based on the increased 
incidence of microscopic pathology of the kidney and liver and the 
deceased body weight gain. The No-Observed-Adverse-Effect level (NOAEL) 
is 64 mg/kg/day in males; 70 mg/kg/day in females.
     3. In a subchronic oral toxicity study, fludioxonil technical was 
administered to dogs for 13 weeks at 0, 200, 2,000, and 15,000/10,000 
ppm (15,000 ppm for 17 days and 10,000 ppm from day 18 until study 
termination). These dose levels correspond to nominal doses of 0, 5, 
50, or 375/250 mg/kg/day, as actual intake data were not provided. A 
LOAEL of 2,000 ppm in males and females was determined based on the 
observation of diarrhea. The NOAEL is 5 mg/kg/day in males and females.
     4. In a subchronic oral toxicity study, technical fludioxonil was 
administered to mice at doses of 0, 1.3, 13.9, 144, 445, or 1,052 mg/
kg/day (males); 0, 1.9, 16.8, 178, 559, or 1,307 mg/kg/day (females). 
The LOAEL is 1,052 mg/kg/day in males, and 1,307 mg/kg/day in females, 
based on decreased body weight gain in female mice, changes in serum 
chemistry in male and female mice, increased liver to body weight 
ratio, and the increased incidence of nephropathy and centrilobular 
hypertrophy of the liver in both sexes. The NOAEL is 445 mg/kg/day in 
males and 559 mg/kg/day in females.
     5. In a 28 day repeated dermal toxicity test, rats were dosed with 
technical fludioxonil under occlusive dressing (6 hrs/day, 5 days/week, 
for 4 weeks) at 0, 40, 200, and 1,000 mg/kg/day. The dermal irritation 
LOAEL and NOAEL are both greater than 1,000 mg/kg for males and 
females. The systemic toxicity LOAEL is 1,000 mg/kg for females based 
on increased AST and adrenal weight, and 1,000 mg/kg for males based on 
increased creatinine and adrenal weight and the systemic toxicity NOAEL 
is 200 mg/kg/day for males and females.
     6. In a chronic oral toxicity study, dogs were dosed with 
technical fludioxonil for 52 weeks at 0, 3.1, 33.1, and 297.8 mg/kg/day 
(males); 3.3, 35.5, and 330.7 mg/kg/day (females). The LOAEL for male 
dogs is 297.8 mg/kg/day based on decreased body weight, hematology 
alterations (increased platelets and fibrin), clinical chemistry 
alterations (increased cholesterol and alkaline phosphatase) and 
increased liver weight. The LOAEL for female dogs is 35.5 mg/kg/day 
based on a marked decrease in body weight gain for weeks 1-13 and 1-52 
of the study. The NOAEL is 33.1 mg/kg/day for male dogs and 3.3 mg/kg/
day for female dogs.
     7. In a combined chronic toxicity/carcinogenicity study, rats were 
fed technical fludioxonil at 0, 10, 30, 100, 1,000, and 3,000 ppm 
(males: 0, 0.37, 1.1, 3.7, 37 and 113 mg/kg/day; females: 0, 0.44, 1.3, 
4.4, 44, and 141 mg/kg/day) for either 12 or 24 months. In addition, 
rats from the control and 3,000 ppm groups were fed the test diets for 
12 months and then allowed to recover for 1 month prior to sacrifice. 
There was no treatment related effect on food or water consumption. 
Males dosed at 1,000 and 3,000 ppm and females dosed at 3,000 ppm 
exhibited a number of effects including higher incidence of dark stool 
and urine, staining (mostly blue) around the pelvic region and abdomen, 
higher frequency of diarrhea (males only), and decreased body weight 
gain. Females dosed at 3,000 ppm had some evidence of slight anemia at 
the 12 month evaluation. At necropsy, males at the 3,000 ppm dose level 
exhibited an increased incidence of enlarged livers and kidneys with 
discolored foci or general discoloration and an increased severity of 
progressive nephropathy; kidneys with cysts were reported at both the 
1,000 and 3,000 ppm dose levels. For females in the 1,000 and 3,000 ppm 
dose levels there was an increase incidence of discoloration of the 
kidneys. Males and females in the 3,000 ppm group had an increased 
incidence and more severe grade of histopathological changes in the 
liver. There was an increased incidence of hepatocellular tumors in 
both sexes of the 3,000 ppm group; however, the increase in males was 
not statistically significant. The statistically significant finding in 
females was an increase in combined adenomas and carcinomas (0/70, 1/
60, 0/60, 1/60, 2/60 and 5/70 in the 0, 10, 30, 100, 1,000 and 3,000 
ppm groups, respectively). Males and females in the 3,000 ppm group had 
an increased incidence of basophilic foci in the liver; males also had 
an increase in hepatocellular hypertrophy. The LOAEL

[[Page 53822]]

for males and females was 113 and 141 mg/kg/day, respectively (3,000 
ppm) based on decreased body weight and weight gain, slight anemia in 
females at 12 months, and increased incidence and severity of 
histopathology changes in the liver. The NOAEL for males and females 
was 37 and 44 mg/kg/day, respectively. Fludioxonil technical was not 
carcinogenic in male rats. There was a statistically significant 
increase in the incidence of combined adenomas and adenocarcinomas of 
the liver in female rats in the 3,000 ppm group. The 3,000 ppm level is 
considered adequate for carcinogenicity testing based on decreased body 
weight and weight gain in both sexes, slight anemia in females at 12 
months, and an increased incidence and severity of liver histopathology 
changes in both sexes.
     8. A carcinogenicity study in mice administered technical 
fludioxonil in the diet at 0, 10, 100, 1,000, and 3,000 ppm (0, 1.1, 
11.3, 112, and 360 mg/kg/day for males and 0, 1.4, 13.5, 133, and 417 
mg/kg/day for females). Male mice at 360 mg/kg/day level exhibited 
clinical toxicity in the form of an incidence of ``convulsed'' when 
handled. No significant effects on body weight, weight gain, food 
consumption, hematology, or microscopic non neoplastic pathology were 
reported in either sex. Increased liver weight (9%) and spleen weight 
(34%) were observed in male mice at the 360 mg/kg/day dose level, which 
correlated with the macroscopic observations of enlarged spleen and 
raised foci of liver. Female mice showed a statistically significant 
increase in liver weight at the 417 mg/kg dose level and this is also 
supported by the macroscopic observation of enlarged liver. Other 
macroscopic changes in female mice were an increased incidence of 
enlarged thymus, spleen, mediastinal lymph node, and liver and an 
increased incidence of lymphoma in these organs. The LOAEL is 112 mg/
kg/day for male mice, based on the increased incidence of clinical 
toxicity and 417 mg/kg/day for female mice, based on the increased 
liver weight and the increased incidence of macroscopic pathology. The 
NOAEL is 11.3 mg/kg/day and 133 mg/kg/day in male and female mice, 
respectively. There was evidence of carcinogenicity in female mice 
based on increased incidence of lymphomas, which contributed to death. 
This effect was due to the early onset and high incidence of lymphoma 
at the 3,000 ppm dose relative to the control group. Total incidence of 
lymphoma was 11/59, 10/59, 13/60, 12/60, and 18/60 for the 0, 10, 100, 
1,000, and 3,000 ppm dose levels in female mice, respectively. This 
increase in total lymphoma was significant by a trend test, but not by 
a pair wise comparison. Whether an adequate dose level was used in this 
study to assess the carcinogenic potential of fludioxonil is 
complicated by the observation of an increased lymphoma incidence at 
the 3,000 ppm dose level. This dose level produced some systemic 
effects, such as an increased incidence of male mice which 
``convulsed'' when handled and macroscopic pathology in both sexes. But 
this dose level produced no significant effects on body weight gain, 
food consumption, hematology, or microscopic non neoplastic pathology 
in either sex.
     In a second carcinogenicity study in mice fludioxonil technical 
was administered in the diet at nominal dose levels of 0, 3, 30, 5,000, 
and 7,000 ppm (0, 0.33, 3.3, 590, and 851 mg/kg/ day in males; 0, 0.41, 
4.1, 715, and 1,008 mg/kg/day for females). The 7,000 ppm dose level in 
males and females produced significant systemic effects in addition to 
significant nephropathy, which contributed to death in a majority of 
test animals. Survival in female mice was below 25% and exceeded the 
guideline criteria for survival in a mouse carcinogenicity study. 
Changes in liver weights were observed in both sexes at the 5,000 and 
7,000 ppm dose levels, but could not be related to histological 
alterations in the liver. The LOAEL is estimated at 851 mg/kg/day in 
males, and 1,008 mg/kg/day in females. The NOAEL is 590 mg/kg/day in 
males, and 715 mg/kg/day in females. The 7,000 ppm dose is adequate for 
testing carcinogenic potential in male mice, based on the significant 
systemic effects and nephropathy observed at this dose. For female 
mice, the 7,000 ppm dose level is considered excessive, based on the 
reduction in survival of the test animals. There was no evidence of 
increased incidence of tumors in this study for male or female mice.
     9. In a developmental toxicity (teratology) study, pregnant rats 
(gestation days 6-15 inclusive) were administered technical fludioxonil 
at 0, 10, 100, and 1,000 mg/kg/day by oral gavage. Maternal toxicity 
was evident at 1,000 mg/kg/day with a 16% reduction in corrected body 
weight gain. Developmental toxicity was evident at the 1,000 mg/kg/day 
dose with increased fetal and litter incidence of dilated renal pelvis 
and dilated ureter. Based on these observations, the Maternal LOAEL and 
Developmental toxicity LOAEL are at 1,000 mg/kg/day and the Maternal 
NOAEL and Developmental toxicity NOAEL are at 100 mg/kg/day.
     10. In another developmental toxicity study, rabbits (gestation 
days 6 through 18) were dosed with technical fludioxonil by oral gavage 
at 0, 10, 100, and 300 mg/kg/day. Minimal maternal toxicity was noted 
in the mid and high dose groups as less body weight during the dosing 
period (gestation days 6 through 18) and dosing plus post dosing period 
(gestation days 6 through 28). The high dose group consumed less food 
than the control group during the dosing period, the post dosing period 
(gestation days 19 through 28), the dosing plus post dosing period, and 
for the overall gestation period. However, food efficiency was 
decreased in the mid and high dosed groups during the dosing plus post 
dosing periods, and for the entire gestation period. The Maternal 
Toxicity LOAEL is 100 mg/kg/day and the Maternal Toxicity NOAEL is 10 
mg/kg/day based on decreased body weight gains and decreased food 
efficiency. No developmental toxicity was noted at the dose levels 
tested. The Developmental Toxicity LOAEL is greater than 300 mg/kg/day 
and the Developmental Toxicity NOAEL is equal to or greater than 300 
mg/kg/day.
     11. In a reproductive toxicity study, rats received 0, 2.19, 
22.13, and 221.61 mg/kg/day (males) and 0, 2.45, 24.24, and 249.67 mg/
kg/day (females) fludioxonil technical in the diet for 2 generations. 
The Parental Systemic Toxicity LOAEL is 221.61 mg/kg/day for males and 
249.67 mg/kg/day for females. The Parental Systemic Toxicity NOAEL is 
22.13 mg/kg/day for males, and 24.24 mg/kg/day for females based on 
clinical observations, reduced body weight and weight gains, and 
reduced food consumption. The Reproductive/Developmental Toxicity LOAEL 
is 221.61 mg/kg/day for males and 249.67 mg/kg/day for females. The 
Reproductive/Developmental Toxicity NOAEL is 22.13 mg/kg/day for males 
and 24.24 mg/kg/day for females based on reduced pup body weights.
     12. Gene mutation and other genotoxic effects were studied using 
fludioxonil technical:
    i. Ames Salmonella assay with and without metabolic activation 
provided evidence of cytotoxicity at 1,250 and 5,000 micrograms/plate 
(g/plate) concentrations.
    ii. Unscheduled DNA Synthesis assay (in vitro) indicated 
cytotoxicity at 313 g/ml.
    iii. Chromosome aberrations assay (in vitro) in Chinese hamster 
ovary (CHO) cells with and without S9 activation provided convincing 
evidence that

[[Page 53823]]

fludioxonil is a clastogen and polyploidy inducer.
    iv. Chromosome Aberrations assay (in vitro) in Chinese hamster bone 
marrow cells noted occurrence of hyperploidy in one mid-dose female and 
trisomy in one high dose male.
    v. Micro nucleus assay (in vitro) using rat hepatocytes provided no 
definitive conclusions as to dose related increase in micro nucleate 
hepatocytes and therefore, this study will be repeated.
    vi. Dominant Lethal assay indicated no test material induced 
dominant lethal mutations in male mouse germinal cells sampled over the 
entire period of spermatogenesis.
    vii. Point Mutation test in CHO cells (in vitro) with and without 
S9 activation produced no increase in the number of thioguanine 
resistant colonies, mutant frequency, or mutant factor.
    viii. Mouse Micro nucleus assay using mouse bone morrow Micro 
nucleus test produced no statistically significant increase in number 
of micronucleated polychromatic erythrocytes in male and female mice.

B. Toxicological Endpoints

    1. Acute toxicity. Fludioxonil exhibits very low mammalian toxicity 
when tested by the oral route. There is no concern for an acute dietary 
risk. The available data do not indicate any evidence of significant 
toxicity from 1 day or single event exposure by oral route.
     2. Short and intermediate term toxicity. Subchronic studies 
conducted with fludioxonil contain no end points suggesting the need 
for short term occupational or residential risk assessments for the 
dermal route of exposure. For intermediate term, the recommended LOAEL 
and NOAEL are 50 mg/kg/day and 5 mg/kg/day, respectively from the 13 
week oral toxicity study in dogs. For the intermediate term risk 
assessment, the 50 mg/kg/day is used as the NOAEL, since the effects of 
concern are believed to occur at doses in excess of 50 mg/kg/day.
     3. Chronic toxicity. EPA has established the RfD for fludioxonil 
at 0.03 mg/kg/day. This RfD is based on the 1 year oral toxicity study 
in dogs with a NOAEL of 3.3 mg/kg/day in females and an uncertainly 
factor of 100 to account for both interspecies extrapolation and 
intraspecies variability.
    4. Carcinogenicity. Fludioxonil has been classified as a Group D 
chemical not classifiable as to human carcinogenicity. That is, the 
evidence is inadequate and cannot be interpreted as showing either the 
presence or absence of a carcinogenic effect.

C. Exposures and Risks

    1. From food and feed uses. Tolerances have been established at 40 
CFR 180.516 for residues of fludioxonil in or on potatoes and time 
limited tolerances under the Section 18 program have been established 
for apricot, nectarines, peaches, and plums. Risk assessments were 
conducted by EPA to assess dietary exposures from fludioxonil as 
follows:
    i.  Acute exposure and risk. Acute dietary risk assessments are 
performed for a food use pesticide if a toxicological study has 
indicated the possibility of an effect of concern occurring as a result 
of a 1 day or single exposure. There is no concern for an acute dietary 
exposure to fludioxonil. The available data do not indicate any 
evidence of significant toxicity from 1 day or single event exposure by 
oral route.
    ii. Chronic exposure and risk. Fludioxonil is currently registered 
for seed treatment uses on corn, sorghum, and potatoes and for 
greenhouse uses on non food crops. Section 18 requests have been 
approved for post harvest treatment on apricots, nectarines, peaches, 
and plums. There is no reasonable expectation of residues on corn and 
sorghum as a result of treatment of corn and sorgham seed, therefore, 
these uses did not require tolerances and no exposure was assumed to 
result from these registered uses. Potatoes has a tolerance of 0.02 ppm 
and apricots, nectarines, peaches, plums have a time limited tolerance 
of 5 ppm. There are no residential uses for fludioxonil; therefore no 
chronic residential exposure is expected. Based on a Novigen Dietary 
Exposure Evaluation Model (DEEM) and using conservative assumptions 
(100% of crops treated and tolerance level residues) and a chronic RfD 
of 0.03 mg/kg/day, EPA estimates the chronic exposure to fludioxonil 
from food will utilize 22% of the chronic RfD for the most highly 
exposed population subgroup, (non-nursing infants < 1 year old). All 
other population subgroups have risk estimates below that of the non-
nursing infants.
    2. From drinking water. There are no maximum contaminant levels or 
health advisory levels established for residues of fludioxonil in 
drinking water. In view of the currently registered use patterns and 
the proposed seed treatment of food and feed crops at very low levels 
(1.13 to 2.26 grams of active ingredient (ai) per 100 lbs seed), 
fludioxonil is not expected to impact ground or surface waters. Thus 
the likelihood of residues of fludioxonil entering in drinking water is 
considered negligible.
    3. From non-dietary exposure. Fludioxonil is not currently 
registered for any residential non-food uses. Therefore, oral, dermal, 
and inhalation exposure from residential uses is not expected.
    4. Cumulative exposure to substances with common mechanism of 
toxicity. 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.''
    Fludioxonil is a representative of a new class of plant protection 
agents derived from the structure of a naturally occurring plant 
antibiotic called pyrrolnitrin. EPA does not have, at this time, 
available data to determine whether fludioxonil 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, fludioxonil does not appear to produce a toxic metabolite 
produced by other substances. For the purposes of this tolerance 
action, therefore, EPA has not assumed that fludioxonil has a common 
mechanism of toxicity with other substances. For information regarding 
EPA's efforts to determine which chemicals have a common mechanism of 
toxicity and to evaluate the cumulative effects of such chemicals, see 
the Final Rule for Bifenthrin Pesticide Tolerances (62 FR 62961, 
November 26, 1997).

D. Aggregate Risks and Determination of Safety for U.S. Population

    1. Chronic risk. Using the Theoretical Maximum Residue Contribution 
(TMRC) exposure assumptions described in this preamble, EPA has 
concluded that aggregate exposure to fludioxonil from food will utilize 
22% of the RfD for the most highly exposed population subgroup. The 
major identifiable subgroup with the highest aggregate exposure is the 
non-nursing infants, < 1 year old. EPA generally has no concern for 
exposures below 100% of the RfD because the RfD represents the level at 
or below which daily aggregate dietary exposure over a lifetime will 
not pose appreciable risks to human health.
    2. Short- and intermediate-term risk. Short- and intermediate-term 
aggregate exposure takes into account chronic dietary food and water 
(considered to be

[[Page 53824]]

a background exposure level) plus indoor and outdoor residential 
exposure. Fludioxonil is not registered for indoor uses. Based on 
registered and proposed uses, exposure to fludioxonil from drinking 
water is not expected.
    3. Aggregate cancer risk for U.S. population. Fludioxonil has been 
classified as a Group D chemical not classifiable as to human 
carcinogenicity. The available carcinogenicity studies in the rat and 
mouse show some increase in the combined tumors only in the female rat 
above that in the concurrent controls. However, this statistical 
increase in liver tumors in female rats was only at the high dose. Some 
of this significant increase was due to the lack of any liver tumors in 
the concurrent control, whereas the historical control from the same 
lab indicated a range of 1.4 to 15% for combined liver tumors. 
Therefore, based on available information, EPA believes that this 
pesticide does not pose a significant cancer risk.
    4. Determination of safety. Based on these risk assessments, EPA 
concludes that there is a reasonable certainty that no harm will result 
from aggregate exposure to fludioxonil residues.

E. Aggregate Risks and Determination of Safety for Infants and Children

    1. Safety factor for infants and children-- i. In general. In 
assessing the potential for additional sensitivity of infants and 
children to residues of fludioxonil, EPA considered data from 
developmental toxicity studies in the rat and rabbit and a 2-generation 
reproduction study in the rat. 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.
    FFDCA section 408 provides that EPA shall apply an additional 
tenfold margin of safety for infants and children in the case of 
threshold effects to account for pre and post natal toxicity and the 
completeness of the database unless EPA determines that a different 
margin of safety will be safe for infants and children. Margins of 
safety are incorporated into EPA risk assessments either directly 
through use of a margin of exposure (MOE) analysis or through using 
uncertainty (safety) factors in calculating a dose level that poses no 
appreciable risk to humans. EPA believes that reliable data support 
using the standard uncertainty factor (usually 100 for combined inter 
and intra species variability) and not the additional tenfold MOE/
uncertainty factor when EPA has a complete data base under existing 
guidelines and when the severity of the effect in infants or children 
or the potency or unusual toxic properties of a compound do not raise 
concerns regarding the adequacy of the standard MOE/safety factor.
    ii. Pre- and post-natal sensitivity. The toxicity data base for 
fludioxonil includes acceptable prenatal developmental toxicity studies 
in rats and rabbits and an acceptable 2-generation reproduction study 
in rats. The data did not suggest any additional sensitivity to the 
embryo or neonate following in utero or early postnatal exposure to 
fludioxonil. In the rat developmental study, the Maternal NOAEL and the 
Developmental (fetal and pup) NOAEL were both 100 mg/kg/day. In the 
rabbit developmental study, the Maternal NOAEL was 10 mg/kg/day. No 
developmental toxicity was noted at any dosing level. The Developmental 
NOAEL was set equal to or greater than 300 mg/kg/day, the highest dose 
tested. Results from the 2-generation reproduction study for rats 
indicated a Developmental/Reproduction NOAEL of 22.13 mg/kg/day for 
males and 24.24 mg/kg/day for females. The Developmental/Reproductive 
NOAEL is at least 600 fold higher then the RfD (0.03 mg/kg/day), and 
should be protective for infants and children.
    iii. Conclusion. There is a complete toxicity data base for 
fludioxonil and exposure data is complete or is estimated based on data 
that reasonably accounts for potential exposures.
    2. Chronic risk. Using the exposure assumptions described in Unit 
II.C. of this preaamble, EPA has concluded that aggregate exposure to 
fludioxonil from food will utilize 22% of the RfD for infants and 
children. 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. As exposure from drinking water, non-dietary, or 
non-occupational sources are not anticipated, EPA does not expect 
aggregate exposure to exceed 100% of RfD.
    3. Determination of safety. Based on these risk assessments, EPA 
concludes that there is a reasonable certainty that no harm will result 
to infants and children from aggregate exposure to fludioxonil 
residues.

III. Other Considerations

A. Metabolism In Plants and Animals

    Plant metabolism studies in potatoes, rice, and wheat were 
previously submitted. Additional studies on cotton and soybeans were 
provided in conjunction with the proposed use. There is minimal uptake 
of the active ingredient when applied as a seed treatment. Based on 
these studies, EPA concludes that the nature of fludioxonil residues in 
plants are adequately understood and the residue of concern is the 
parent compound. Two animal metabolism studies conducted in ruminant 
and poultry indicate that there is no reasonable expectation of finite 
residues of fludioxonil in ruminant tissues, milk, poultry tissues, and 
eggs.

B. Analytical Enforcement Methodology

    The Ciba-Geigy Analytical Method AG-597B has been adequately 
validated for use in enforcing the proposed tolerances. The method may 
be requested from: Calvin Furlow, PRRIB, IRSD (7502C), Office of 
Pesticide Programs, Environmental Protection Agency, 401 M St., SW., 
Washington, DC 20460. Office location and telephone number: Rm 101FF, 
Crystal Mall #2, 1921 Jefferson Davis Hwy., Arlington, VA 22202, (703-
305-5229).

C. Magnitude of Residues

    The submitted field trial data on cucumber, leaf lettuce, radish, 
succulent peas, and wheat indicate that residue levels were less than 
the limit of quantitation (LOQ) in each crop. The submitted residue 
data support the following proposed tolerance levels of fludioxonil. 
The RAC and the respective tolerance ppm are: rape seed (0.01 ppm), 
rape forage (0.01 ppm), sunflower seed (0.01 ppm), peanuts, meat (hulls 
removed) (0.01 ppm), peanut hay (0.01 ppm), leafy vegetables except 
brassica (0.01 ppm), brassica (cole) leafy vegetables (0.01 ppm), 
legume vegetables (0.01 ppm), foliage of legume vegetables (0.01 ppm), 
fruiting vegetables except cucurbits (0.01 ppm), cucurbit vegetables 
(0.01 ppm), forage, fodder, and straw of cereal grains (0.01 ppm), 
grass, forage, fodder, and hay (0.01 ppm), non-grass animal feeds (0.01 
ppm), root and tuber vegetables (0.02 ppm), leaves and roots of tuber 
vegetables (0.02 ppm), bulb vegetables, (0.02 ppm), cereal grains (0.02 
ppm), herbs and spices (0.02 ppm), cotton, undelinted seed (0.05 ppm), 
and cotton gin byproducts (0.05 ppm).

D. International Residue Limits

    There are currently no established or proposed maximum residue 
limits

[[Page 53825]]

(MRLs) in Canada, CODEX, or Mexico for fludioxonil residues in/on crops 
and crop groups included in this submission. Therefore, problems with 
compatibility of tolerances/MRLs do not exist.

IV. Conclusion

    Therefore, tolerances are established for residues of fludioxonil 
in the following RACs at (ppm): rape seed (0.01 ppm), rape forage (0.01 
ppm), sunflower seed (0.01 ppm), peanuts, meat (hulls removed) (0.01 
ppm), peanut hay (0.01 ppm), leafy vegetables except brassica (0.01 
ppm), brassica (cole) leafy vegetables (0.01 ppm), legume vegetables 
(0.01 ppm), foliage of legume vegetables (0.01 ppm), fruiting 
vegetables except cucurbits (0.01 ppm), cucurbit vegetables (0.01 ppm), 
forage, fodder, and straw of cereal grains (0.01 ppm), grass, forage, 
fodder, and hay (0.01 ppm), non-grass animal feeds (0.01 ppm), root and 
tuber vegetables (0.02 ppm), leaves and roots of tuber vegetables (0.02 
ppm), bulb vegetables, (0.02 ppm), cereal grains (0.02 ppm), herbs and 
spices (0.02 ppm), cotton, undelinted seed (0.05 ppm), and cotton gin 
byproducts (0.05 ppm)].

V. Objections and Hearing Requests

    The new FFDCA section 408(g) provides essentially the same process 
for persons to ``object'' to a tolerance regulation issued by EPA under 
new section 408(e) and (l)(6) as was provided in the old section 408 
and in section 409. However, the period for filing objections is 60 
days, rather than 30 days. EPA currently has procedural regulations 
which govern the submission of objections and hearing requests. These 
regulations will require some modification to reflect the new law. 
However, until those modifications can be made, EPA will continue to 
use those procedural regulations with appropriate adjustments to 
reflect the new law.
    Any person may, by December 7, 1998, file written objections to any 
aspect of this regulation and may also request a hearing on those 
objections. Objections and hearing requests must be filed with the 
Hearing Clerk, at the address given above (40 CFR 178.20). A copy of 
the objections and/or hearing requests filed with the Hearing Clerk 
should be submitted to the OPP docket for this rulemaking. The 
objections submitted must specify the provisions of the regulation 
deemed objectionable and the grounds for the objections (40 CFR 
178.25). Each objection must be accompanied by the fee prescribed by 40 
CFR 180.33(i). If a hearing is requested, the objections must include a 
statement of the factual issues on which a hearing is requested, the 
requestor's contentions on such issues, and a summary of any evidence 
relied upon by the requestor (40 CFR 178.27). A request for a hearing 
will be granted if the Administrator determines that the material 
submitted shows the following: There is genuine and substantial issue 
of fact; there is a reasonable possibility that available evidence 
identified by the requestor would, if established, resolve one or more 
of such issues in favor of the requestor, taking into account 
uncontested claims or facts to the contrary; and resolution of the 
factual issues in the manner sought by the requestor would be adequate 
to justify the action requested (40 CFR 178.32). Information submitted 
in connection with an objection or hearing request may be claimed 
confidential by marking any part or all of that information as 
Confidential Business Information (CBI). Information so marked will not 
be disclosed except in accordance with procedures set forth in 40 CFR 
part 2. A copy of the information that does not contain CBI must be 
submitted for inclusion in the public record. Information not marked 
confidential may be disclosed publicly by EPA without prior notice.

VI. Public Record and Electronic Submissions

    EPA has established a record for this rulemaking under docket 
control number [OPP-300738] (including any comments and data submitted 
electronically). A public version of this record, including printed, 
paper versions of electronic comments, which does not include any 
information claimed as CBI, is available for inspection from 8:30 a.m. 
to 4 p.m., Monday through Friday, excluding legal holidays. The public 
record is located in Room 119 of the Public Information and Records 
Integrity Branch, Information Resources and Services Division (7502C), 
Office of Pesticide Programs, Environmental Protection Agency, Crystal 
Mall #2, 1921 Jefferson Davis Hwy., Arlington, VA.
    Electronic comments may be sent directly to EPA at:
    [email protected].

    Electronic comments must be submitted as an ASCII file avoiding the 
use of special characters and any form of encryption.
    The official record for this rulemaking, as well as the public 
version, as described above will be kept in paper form. Accordingly, 
EPA will transfer any copies of objections and hearing requests 
received electronically into printed, paper form as they are received 
and will place the paper copies in the official rulemaking record which 
will also include all comments submitted directly in writing. The 
official rulemaking record is the paper record maintained at the 
Virginia address in ``ADDRESSES'' at the beginning of this document.

VII. Regulatory Assessment Requirements

A. Certain Acts and Executive Orders

    This final rule establishes tolerances under FFDCA section 408(d) 
in response to a petition submitted to the Agency. The Office of 
Management and Budget (OMB) has exempted these types of actions from 
review under Executive Order 12866, entitled Regulatory Planning and 
Review (58 FR 51735, October 4, 1993). This final rule does not contain 
any information collections subject to OMB approval under the Paperwork 
Reduction Act (PRA), 44 U.S.C. 3501 et seq., or impose any enforceable 
duty or contain any unfunded mandate as described under Title II of the 
Unfunded Mandates Reform Act of 1995 (UMRA) (Pub. L. 104-4). Nor does 
it require any prior consultation as specified by Executive Order 
12875, entitled Enhancing the Intergovernmental Partnership (58 FR 
58093, October 28, 1993), or special considerations as required by 
Executive Order 12898, entitled Federal Actions to Address 
Environmental Justice in Minority Populations and Low-Income 
Populations (59 FR 7629, February 16, 1994), or require OMB review in 
accordance with Executive Order 13045, entitled Protection of Children 
from Environmental Health Risks and Safety Risks (62 FR 19885, April 
23, 1997).
    In addition, since tolerances and exemptions that are established 
on the basis of a petition under FFDCA section 408(d), such as the 
tolerance in this final rule, do not require the issuance of a proposed 
rule, the requirements of the Regulatory Flexibility Act (RFA) (5 
U.S.C. 601 et seq.) do not apply. Nevertheless, the Agency has 
previously assessed whether establishing tolerances, exemptions from 
tolerances, raising tolerance levels or expanding exemptions might 
adversely impact small entities and concluded, as a generic matter, 
that there is no adverse economic impact. The factual basis for the 
Agency's generic certification for tolerance actions published on May 
4, 1981 (46 FR 24950) and was provided to the Chief Counsel for 
Advocacy of the Small Business Administration.

[[Page 53826]]

B. Executive Order 12875

    Under Executive Order 12875, entitled Enhancing the 
Intergovernmental Partnership (58 FR 58093, October 28, 1993), EPA may 
not issue a regulation that is not required by statute and that creates 
a mandate upon a State, local, or tribal government, unless the Federal 
government provides the funds necessary to pay the direct compliance 
costs incurred by those governments. If the mandate is unfunded, EPA 
must provide to OMB a description of the extent of EPA's prior 
consultation with representatives of affected State, local, and tribal 
governments, the nature of their concerns, copies of any written 
communications from the governments, and a statement supporting the 
need to issue the regulation. In addition, Executive Order 12875 
requires EPA to develop an effective process permitting elected 
officials and other representatives of State, local, and tribal 
governments ``to provide meaningful and timely input in the development 
of regulatory proposals containing significant unfunded mandates.''
    Today's rule does not create an unfunded Federal mandate on State, 
local, or tribal governments. The rule does not impose any enforceable 
duties on these entities. Accordingly, the requirements of section 1(a) 
of Executive Order 12875 do not apply to this rule.

C. Executive Order 13084

    Under Executive Order 13084, entitled Consultation and Coordination 
with Indian Tribal Governments (63 FR 27655, May 19,1998), EPA may not 
issue a regulation that is not required by statute, that significantly 
or uniquely affects the communities of Indian tribal governments, and 
that imposes substantial direct compliance costs on those communities, 
unless the Federal government provides the funds necessary to pay the 
direct compliance costs incurred by the tribal governments. If the 
mandate is unfunded, EPA must provide to OMB, in a separately 
identified section of the preamble to the rule, a description of the 
extent of EPA's prior consultation with representatives of affected 
tribal governments, a summary of the nature of their concerns, and a 
statement supporting the need to issue the regulation. In addition, 
Executive Order 13084 requires EPA to develop an effective process 
permitting elected officials and other representatives of Indian tribal 
governments ``to provide meaningful and timely input in the development 
of regulatory policies on matters that significantly or uniquely affect 
their communities.''
    Today's rule does not significantly or uniquely affect the 
communities of Indian tribal governments. This action does not involve 
or impose any requirements that affect Indian tribes. Accordingly, the 
requirements of section 3(b) of Executive Order 13084 do not apply to 
this rule.

VIII. Submission to Congress and the Comptroller General

    The Congressional Review Act, 5 U.S.C. 801 et seq., as added by the 
Small Business Regulatory Enforcement Fairness Act of 1996, generally 
provides that before a rule may take effect, the agency promulgating 
the rule must submit a rule report, which includes a copy of the rule, 
to each House of the Congress and to the Comptroller General of the 
United States. EPA will submit a report containing this rule and other 
required information to the U.S. Senate, the U.S. House of 
Representatives, and the Comptroller General of the United States prior 
to publication of the rule in the Federal Register. This rule is not a 
``major rule'' as defined by 5 U.S.C. 804(2).

List of Subjects in 40 CFR Part 180

    Environmental protection, Administrative practice and procedure, 
Agricultural commodities, Pesticides and pests, Reporting and 
recordkeeping requirements.

    Dated: September 29, 1998.

James Jones,

Director, Registration Division, Office of Pesticide Programs.
    Therefore, 40 CFR chapter I is amended as follows:

PART 180--[AMENDED]

    1. The authority citation for part 180 continues to read as 
follows:
    Authority: 21 U.S.C. 346a and 371.

    2. In Sec. 180.516 by revising paragraph (a) to read as follows:


Sec. 180.516  Fludioxonil; tolerances for residues.

    (a) General. Tolerances are established for residues of the 
fungicide fludioxonil (4-(2,2-difluoro-1,3-benzodioxol-4-yl)-1H-
pyrrole-3-carbonitrile) in or on the following commodities:

------------------------------------------------------------------------
                                                                  Parts
                           Commodity                               per
                                                                 million
------------------------------------------------------------------------
Bassica (cole) leafy vegetables................................    0.01
Bulb vegetables................................................    0.02
Cereal grains..................................................    0.02
Cotton gin byproducts..........................................    0.05
Cotton, undelinted seed........................................    0.05
Cucurbit vegetables............................................    0.01
Foliage of legume vegetables...................................    0.01
Forage, fodder, and straw of cereal grains.....................    0.01
Fruiting vegetables except cucurbits...........................    0.01
Grass, forage, fodder, and hay.................................    0.01
Herbs and spices...............................................    0.02
Leafy vegetables except Brassica...............................    0.01
Leaves and roots of tuber vegetables...........................    0.02
Legume vegetables..............................................    0.01
Non-grass animal feeds.........................................    0.01
Peanut hay.....................................................    0.01
Peanuts, meat (hulls removed)..................................    0.01
Rape forage....................................................    0.01
Rape seed......................................................    0.01
Root and tuber vegetables......................................    0.02
Sunflower seed.................................................    0.01
------------------------------------------------------------------------

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[FR Doc. 98-26902 Filed 10-6-98; 8:45 am]
BILLING CODE 6560-50-F