[Federal Register Volume 64, Number 103 (Friday, May 28, 1999)]
[Rules and Regulations]
[Pages 28917-28924]
From the Federal Register Online via the Government Publishing Office [www.gpo.gov]
[FR Doc No: 99-13656]


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ENVIRONMENTAL PROTECTION AGENCY

40 CFR Part 180

[OPP-300866; FRL-6082-7]
RIN 2070-AB78


Fenhexamid; Pesticide Tolerance

AGENCY: Environmental Protection Agency (EPA).

ACTION: Final rule.

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SUMMARY: This regulation establishes tolerances for fenhexamid (N-2,3-
dichloro-4-hydroxyphenyl)-1-methyl cyclohexanecarboxamide) in or on 
grapes at 4.0 parts per million (ppm), strawberries at 3.0 ppm, and 
raisins at 6.0 ppm. The TM-402 Fungicide Task Force comprised of Tomen 
Agro, Inc. and Bayer Corporation requested these tolerances under the 
Federal Food, Drug, and Cosmetic Act, as amended by the Food Quality 
Protection Act of 1996.

DATES: This regulation is effective May 28, 1999. Objections and 
requests for hearings must be received by EPA on or before July 27, 
1999.

ADDRESSES: Written objections and hearing requests, identified by the 
docket control number, [OPP-300866], 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

[[Page 28918]]

by the docket control number, [OPP-300866], 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 (CM #2), 1921 Jefferson Davis Hwy., Arlington, VA.
    A copy of objections and hearing requests filed with the Hearing 
Clerk may be submitted electronically by sending electronic mail (e-
mail) to: [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-300866]. 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 L. Waller, Product 
Manager 21, 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: Rm. 
249, CM #2, 1921 Jefferson Davis Hwy., Arlington, VA, (703) 308-9354, 
[email protected].

SUPPLEMENTARY INFORMATION: In the Federal Register of November 20, 1998 
(63 FR 64498) (FRL-6042-1), EPA issued a notice pursuant to section 408 
of the Federal Food, Drug, and Cosmetic Act (FFDCA), 21 U.S.C. 346a as 
amended by the Food Quality Protection Act of 1996 (FQPA) (Pub. L. 104-
170) announcing the filing of a pesticide petition (PP 7F4890) for 
tolerances by the TM-402 Fungicide Task Force comprised of Tomen Agro, 
Inc. and Bayer Corporation. The notice included a summary of the 
petition prepared by the TM-402 Fungicide Task Force. There were no 
comments received in response to the notice of filing.
    The petition requested that 40 CFR part 180 be amended by 
establishing tolerances for the fungicide, fenhexamid in or on grapes 
at 4.0 ppm, strawberries at 3.0 ppm, and raisins at 6.0 ppm.

I. Background 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 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 
fenhexamid and to make a determination on aggregate exposure, 
consistent with section 408(b)(2), for tolerances in or grapes at 4.0 
ppm, strawberries at 3.0 ppm, and raisins at 6.0 ppm. EPA's assessment 
of the dietary exposures and risks associated with establishing the 
tolerances 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 fenhexamid are 
discussed in this unit.
    1. Acute toxicity--i. The acute oral LD50 and acute 
dermal LD50 for rats was > 5,000 milligrams/kilograms (mg/
kg) for both sexes. The acute LC50 for rats was > 5.06 mg/
liters (L) for both sexes. Fenhexamid was not an eye or skin irritant 
and was not a dermal sensitizer.
    ii. In an acute neurotoxicity study, rats were gavaged with a 
single oral dose of fenhexamid at dose levels of 0, 200, 630, or 2,000 
mg/kg. The rats were observed for 14 days. Functional Observational 
Battery and motor activity testing were performed 7 days prior to 
dosing, approximately 20 minutes to 3 hours post-dosing, and on days 7 
and 14. The no observed adverse effect level (NOAEL) in males was 630 
mg/kg. The NOAEL in females was 2,000 mg/kg. The lowest observed 
adverse effect level (LOAEL) in males was 2,000 mg/kg based on a 
marginally decreased mean body temperature (the only treatment-related 
effect noted in the study). The LOAEL in females was not established.
    2. Subchronic toxicity--i. In an inhalation toxicity range-finding 
study, 10 rats/sex/dose were exposed (head/nose only) to fenhexamid at 
concentrations of 0, 11.8, 97.7 or 1,092.6 mg/m3 in air for 
6 hours per day for 5 days. One-half of the rats were sacrificed 7 days 
after the first exposure and the other one-half were sacrificed 21 days 
after the first exposure. The NOAEL was 0.098 mg/L and the LOAEL was 
1.092 mg/L based on the observations of macroscopic grey coloration of 
the lungs and marginally increased lung weights.
    ii. In a 21-day dermal toxicity study, fenhexamid was applied to 
the shaved skin of 5 male and female rabbits at a dose level of 1,000 
mg/kg/day for 17 days over a 3-week period. There were no compound 
related effects. The NOAEL was 1,000 mg/kg/day and the LOAEL was > 
1,000 mg/kg/day for both systemic and local effects on the skin.
    iii. In a 28-day oral toxicity range finding study, 10 rats/sex/
dose were gavaged at dose levels of 0, 100, 300, or 1,000 mg/kg/day for 
28 days. There were no compound-related effects in mortality, clinical 
signs, body weight, food consumption, hematology, clinical chemistry, 
organ weights, or gross and histologic pathology. The NOAEL was 1,000 
mg/kg/day.
    iv. In a 90-day oral toxicity study, 10 rats/sex/dose were fed 
fenhexamid at dose levels of 0, 2,500, 5,000, 10,000 or 20,000 ppm (0, 
202, 415, 904, and 1,904 mg/kg/day for males and 0, 270, 549, 1,132, 
and 2,824 mg/kg/day for females). No treatment-related changes were 
seen in clinical signs, mortality, opthalmoscopic examinations, 
hematology, urinalyses, or gross pathology. The NOAEL was 5,000 ppm in 
males and 10,000 ppm in females.

[[Page 28919]]

 The LOAEL in males was 10,000 ppm based on decreased terminal body 
weights and body weight gains, increased food consumption, decreased 
food efficiency and increased Alanin amino-transferase (ALAT) levels. 
The LOAEL in females was 20,000 ppm based on increased food 
consumption, decreased food efficiency, decreased liver weights, and 
liver histopathology (Kupffer cell proliferation and altered hepatocyte 
morphology).
    v. In a 90-day oral toxicity study, 4 dogs/sex were fed fenhexamid 
at dose levels of 0, 1,000, 7,000 or 50,000 ppm (0, 33.9, 239.1, or 
1,747.7 mg/kg/day for males and 0, 37, 261, or 1,866.2 mg/kg/day for 
females). The NOAEL in males and females was 1,000 ppm. The LOAEL in 
males and females was 7,000 ppm based on significant increases in Heinz 
bodies in males and females and increased absolute and relative liver 
weights in females.
    vi. In a 90-day oral toxicity study, 10 mice/sex/dose were fed 
fenhexamid at dose levels of 0, 100, 1,000 or 10,000 ppm (0, 26.5, 
266.5 or 3,283.5 mg/kg/day in males and 0, 51.6, 453.9, or 5,151.1 mg/
kg/day in females) for 14 weeks. The NOAEL in males and females was 
1,000 ppm. The LOAEL in males and females was 10,000 ppm based on the 
observation in both sexes of: increased serum cholesterol, bilirubin 
and creatinine, decreased kidney weights, increased water consumption, 
increased food consumption (males), decreased food efficiency (males), 
renal cortical tubular basophilia (both sexes), renal protein casts and 
cellular detritus (males), and marginal alterations of liver function 
(increased serum cholesterol, bilirubin, decreased Aspartate amino-
transferase (ASAT), ALAT), marginal increase in liver weights and 
reduced glycogen content of hepatocytes (males).
    vii. In a 56-day oral toxicity study, 10 rats/sex/dose were fed 
fenhexamid at dose levels of 0, 1,000, 5,000, 10,000, 15,000, or 20,000 
ppm (0, 57.5, 284.7, 575.7, 943.8, or 1,217.1 mg/kg/day for males and 
0, 78, 407.1, 896.5, 1,492.5, or 1,896.7 mg/kg/day for females). At 
20,000 ppm, rats had fenhexamid plasma levels below the level of 
detection. Urine samples showed measurable excretion of conjugated 
fenhexamid indicating intestinal absorption in the dose range examined. 
Males had a maximum excretion rate at 15,000 ppm indicating a 
saturation of intestinal absorption between 15,000 and 20,000 ppm. 
Urine excretion in females was somewhat lower than in males, at 
concentrations of 10,000 ppm and above. The highest value was 
determined at 20,000 ppm suggesting that saturation in intestinal 
absorption was not achieved with this dose level in females.
    3. Developmental toxicity--i. In a developmental toxicity study, 30 
rats/dose were gavaged at dose levels of 0 and 1,000 (1,044 determined 
analytically) mg/kg/day from days 6 through 15 of gestation. At 1,000 
mg/kg/day, there were no treatment-related effects on maternal 
mortality, clinical signs, cesarean parameters, or gross pathology. No 
treatment-related effects were noted in any embryo/fetal parameters. 
Under the conditions of the study, fenhexamid was not embryotoxic, 
fetotoxic, or teratogenic at a dose of 1,044 mg/kg/day. The NOAEL for 
maternal toxicity was < 1,044 mg/kg/day. The developmental NOAEL was 
1,044 mg/kg/day. The LOAEL for maternal toxicity was 1,044 mg/kg/day 
based on the decreased body weight gain (-12% of controls) during 
gestation days 6-16 and a decrease in food consumption (10% of 
controls) during gestation days 6-11.
    ii. In a developmental toxicity study, 16 rabbits were gavaged with 
fenhexamid at dose levels of 0, 100, 300, or 1,000 mg/kg/day from days 
6 through 18 of gestation. No treatment-related effects were seen on 
mortality, general appearance or behavior. The NOAEL for maternal 
toxicity was 100 mg/kg/day. The LOAEL for maternal toxicity was 300 mg/
kg/day based on observations at this dose and above of alterations of 
excretory products (discolored urine, small scybala), decreased body 
weight gain and feed consumption (mainly during the first week of the 
treatment period) and decreased placental weights. One abortion at 300 
mg/kg/day and one abortion and two total litter resorptions at 1,000 
mg/kg/day were not considered to be treatment-related because the 
incidences fell within the ranges of historical control data submitted 
with the study. Reduced and/or light feces were also noted at 1,000 mg/
kg/day. Pale livers were noted in the 2 dams that aborted. The NOAEL 
for developmental toxicity was 300 mg/kg/day. The LOAEL for 
developmental toxicity was 1,000 mg/kg/day based on marginally 
decreased male fetal body weights and evidence of delayed ossification. 
Fenhexamid did not induce any treatment-related fetal malformations or 
deviations at any of the doses tested under the conditions of this 
study. All effects on intrauterine development were correlated with 
maternal toxicity and, therefore, no primary developmental effect was 
evident. Fenhexamid was not teratogenic up to and including 1,000 mg/
kg/day.
    4. Reproductive toxicity. In 2-generation reproduction study, 30 
rats/sex/dose were fed fenhexamid at dose levels of 0, 100, 500, 5,000 
or 20,000 ppm (0, 7.6, 38.2, 406, or 1,814 for males and 0, 9.0, 44.8, 
477, or 2,043 mg/kg/day for females determined for the 10-week 
premating period). There were no compound-related effects on mortality, 
clinical signs, behavior or reproductive parameters for adult animals. 
The NOAEL for reproductive toxicity was 20,000 ppm.
    The neonatal NOAEL was 500 ppm and the neonatal LOAEL was 5,000 ppm 
based on significantly decreased pup body weights on lactation days 14 
and 21 for the F1 (6-11% < controls) and on lactation days 
7, 14, and 21 for F2 pups (9-11% < controls). At 20,000 ppm, 
significantly decreased pup body weights were observed on lactation 
days 7, 14, and 21 for F1 pups (15-30% < controls) and for 
F2 pups (11-19% < controls). Treatment-related decreased pup 
body weights were not observed at birth or on lactation day 4. An 
additional effect observed at 20,000 ppm was an increase in the number 
of pups among the post-weaning F1 pups selected to be 
F1 parents which died viz. 0/66, 2/68, 0/68, 0/68 and 10/78 
for the control, 100, 500, 5,000, and 20,000 ppm dose groups, 
respectively. This effect was attributed to the small size of the pups 
at weaning (30% < controls).
    The parental NOAEL was 500 ppm and the parental LOAEL in males was 
5,000 ppm based on increased creatinine levels in P-generation (but not 
F1 generation) males at premating (20%, p<0.05) and at 
termination (20%, not significant); slightly increased alkaline 
phosphatase levels in P-generation and F1-generation males 
at premating and at termination (20-34%, not significant); decreased 
absolute liver weight in P-generation and F1-generation 
males (11-12%, p<0.05) and decreased liver/body weight ratios in P-
generation and F1-generation males (8-9%, p<0.05 for P-
generation and not significant for F1-generation); decreased 
absolute kidney weights in F1-generation (but not P-
generation) males (12%, p<0.05); and decreased kidney/body weight 
ratios in F1-generation (but not P-generation) males (8%, 
p>0.05). The parental LOAEL in females was based on increased alkaline 
phosphatase levels in F1-generation) (but not P-generation) 
females at premating (43%, p<0.05) and at termination (63%, p<0.05); 
and on very small increases in gamma glutamyl transferase (GGT) (not 
considered to be biologically relevant). Overall, treatment-related 
effects observed at 5,000 ppm in males and females were also observed 
at 20,000

[[Page 28920]]

ppm, but were slightly increased in severity. Toxicologically relevant 
additional toxicological effects observed at 20,000 ppm were decreased 
body weights and increased food consumption in males and increased urea 
nitrogen and creatinine levels, decreased kidney weights, decreased 
body weights, and increased food consumption in females.
    5. Mutagenicity. No mutagenicity was noted in the following assays: 
Reverse gene mutation, S. typhimurium, E. coli; Forward gene mutation - 
Hypoxanthine guanine phophoribosyl transferase (HGPRT) locus; 
Chromosome aberration, Chinese hampster ovary (CHO) cells; Unscheduled 
DNA synthesis, rat hepatocytes; and Micronucleus assay in mice.
    6. Chronic toxicity--i. In a 1-year chronic oral toxicity study, 
dogs were fed dose levels of 0, 500, 3,500, or 25,000 ppm (0, 17.4, 
124.3, or 917.8 mg/kg/day for males and 0, 19.2, 132.7, or 947.1 mg/kg/
day for females). The NOAEL in males and females was 500 ppm. The LOAEL 
was 3,500 ppm in males and females based on decreases in red blood 
cells (RBC), hemoglobin (Hb), and hematocrit (Hct) and on significant 
increases in Heinz bodies in both sexes, increased adrenal weight 
parameters in females, and the presence of intracytoplasmic vacuoles in 
the adrenal cortex of 3/4 females.
    ii. In a combined chronic toxicity/carcinogenicity study, 50 rats/
sex/dose were fed fenhexamid at dose levels of 0, 500, 5,000 or 20,000 
ppm (0, 28, 292, or 1,280 mg/kg/day for males and 0, 40, 415, 2,067 mg/
kg/day for females) for 24 months. The NOAEL in males and females was 
500 ppm. The LOAEL for chronic toxicity in males and females was 5,000 
ppm based on observations of decreased body weight gain (-6.8%) and 
food efficiency (-11.8%) in females, increased incidence of cecal 
mucosal hyperplasia in males, increased cellularity (hyperplasia) of 
the bone marrow in females and the presence of splenic extramedullary 
hematopoiesis in males. At 20,000 ppm, observations were increased food 
consumption, increased numbers of circulating reticulocytes, enlarged 
spleens observed macroscopically, increased splenic weights, and 
thyroid colloid alterations (both sexes). Fenhexamid was non-oncogenic 
at doses up to and including 20,000 ppm in the diet. At doses tested, 
there were no treatment related increases in tumor incidence, tumor 
spectrum, or latency when compared to controls.
    7. Carcinogenicity. In a carcinogenicity study, 50 mice/sex/dose 
were fed fenhexamid at dose levels of 0, 800, 2,400, or 7,000 ppm (0, 
247.4, 807.4, or 2,354.8 mg/kg/day for males and 0, 364.8, 1,054.5, or 
3,178.2 mg/kg/day for females) for 2 years. The NOAEL for males was 800 
ppm and the NOAEL for females was 2,400 ppm. The LOAEL for males was 
2,400 ppm based on the observation of decreased kidney weights and 
decreases in sex-specific vacuolation of the proximal tubules in the 
kidneys in males. A marginal decrease in body weights (up to 8%) and 
body weight gain (17%) was observed in males at 7,000 ppm. The LOAEL 
for females was 7,000 ppm based on significantly increased water 
consumption, decreased kidney weights, and renal histopathology 
(increased incidence of basophilic cortical tubules). Fenhexamid was 
not oncogenic in mice at doses up to and including 7,000 ppm. There 
were no treatment-related increases in tumor incidence, tumor spectrum, 
or latency when compared to controls.
    8. Dermal absorption. In a dermal absorption study, radiolabeled 
fenhexamid (50% formulation) was applied to the shaved skin of male 
rats at dose levels of 0.00138, 0.0147, or 0.148 mg/cm2. A 
volume of 100 L was applied to a skin area of approximately 
12.5 cm2 on each rat. Four rats/dose level were sacrificed 
at 0.5, 1, 2, 4, 10, 24, and 120 hours postdose. Mean total recovery of 
radioactivity ranged from 90.3% to 97.6% of the applied dose. The 
majority of radioactivity was recovered from the skin wash (69.9% to 
96.1%). Radioactivity in the skin test site ranged from 0.44% to 10.2%; 
in the urine from ``not detectable'' to 3.34%; and in the feces from 
``not detectable'' to 11.6% of the applied dose. Radioactivity in blood 
did not exceed 0.03% and in the carcass did not exceed 9.37%. Estimates 
of dermal absorption were based on the sum of radioactivity (as test 
material) in the skin test site, urine, feces, blood and carcass. The 
percentage dermal absorption decreased with increasing dose levels. The 
percentage dermal absorption at 10 hours post-dose was 19.58%, 7.62%, 
and 2.63% and at 120 hours post-dose was 21.0%, 6.91%, and 2.13% for 
the low, mid and high dose levels respectively.
    9. Metabolism. In a metabolism study, rats were administered 
radiolabeled fenhexamid (a single oral low dose of 1 mg/kg, a single 
oral high dose of 100 mg/kg, or 15 repeated low doses of 1 mg/kg/day). 
Radiolabeled fenhexamid was rapidly absorbed from the gastrointestinal 
(GI) tract in all dose groups. After single and repeated administration 
of the low dose, the plasma concentration peaked within 5 to 10 
minutes. After administration of the high dose, the maximum was 
detected 40 to 90 minutes post-dosing. The absorption of the test 
compound was shown to be almost complete in a bile-cannulation 
experiment, as more than 97% of the administered dose was absorbed from 
the GI tract 48 hours after intra-duodenal administration. These 
results are indicative of a pronounced first pass effect and 
enterohepatic circulation. Tissue residues declined rapidly and after 
48 hours the total radioactivity residue in the body excluding the GI 
tract, was < 0.3% of the administered dose in all dose groups. Liver 
and kidney were the organs with the highest concentrations of 
radioactivcity in all dose groups. Excretion was rapid and almost 
complete with feces as the major route of excretion. Approximately 62-
81% of the recovered radioactivity was found in feces, and 15-36% in 
urine within 48 hours post-dosing. More than 90% of the recovered 
radioactivity was eliminated with bile in the bile cannulation 
experiment. Only 0.02% of the administered radioactivity was recovered 
in exhaled air. Radioactive residues in rat bodies (excluding GI tract) 
were significantly lower in females after a single high dose. There was 
significantly higher renal excretion for females in comparison with 
males after 15 repeated low doses. In both sexes renal excretion was 
significantly higher after a single low dose when compared with a 
single high dose. Metabolite characterization studies showed that the 
main component detected in excreta was the unchanged parent compound 
which accounted for 62 to 75% of the dose independent of the dosing 
regime and sex. Metabolite 1, the glucuronic acid conjugate of the 
parent compound, ranged from 4 to 23% of the dose. Metabolite fractions 
2 and 3 accounted for up to 3 and 7% of the dose, respectively. The 
proposed major pathway for biotransformation is via conjugation of the 
aromatic hydroxyl group with glucuronic acid. Prior to fecal excretion, 
hydrolysis in the intestine converts the conjugate back to the parent 
compound giving rise to enterohepatic circulation. Identification of 
radioactive residues ranged from 88% to 99% and was independent of dose 
and sex.

B. Toxicological Endpoints

    1. Acute toxicity. An acute toxicological endpoint was not 
identified resulting from a single oral exposure, and therefore, an 
acute Reference Dose (RfD) was not selected.
    2. Short- and intermediate-term toxicity. A short- and 
intermediate-term

[[Page 28921]]

dermal endpoint of 1,000 mg/kg/day from the 21-day dermal toxicity 
study in rabbits was selected for occupational exposure. No short- and 
intermediate-term endpoint was selected for non-occupational exposure 
as there are no residential uses of fenhexamid.
    3. Chronic toxicity. EPA has established the RfD for fenhexamid at 
0.17 mg/kg/day. This RfD is based on 1-year feeding study in dogs with 
a NOAEL = 17 mg/kg/day. An additional 3x FQPA safety factor was added 
and applies to all population subgroups resulting in a chronic 
population-adjusted dose (chronic PAD) of 0.057 mg/kg/day.
    4. Carcinogenicity. Fenhexamid was classified as a ``not likely'' 
human carcinogen based on the lack of evidence of carcinogenicity in 
mice and rats and the lack of genotoxicity in a battery of mutagenicity 
studies.

C. Exposures and Risks

    1. From food and feed uses. Fenhexamid is a new chemical and no 
tolerances are currently established. In today's action, tolerances are 
being established at 40 CFR 180.553 for grapes at 4.0 ppm, strawberries 
at 3.0 ppm, and raisins at 6.0 ppm. Risk assessments were conducted by 
EPA to assess dietary exposures from fenhexamid 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. No toxicological endpoint attributable 
to a single (acute) dietary exposure was identified.
    ii. Chronic exposure and risk. The chronic risk analysis used the 
chronic PAD of 0.057 mg/kg/day which applies to all populations 
subgroups. The Dietary Exposure Evaluation Model (DEEM) which is a 
exposure analysis system that estimates exposure to a pesticide 
chemical in food comprising the diets of the U.S. population, including 
population subgroups was used to conduct the chronic (food) risk 
analysis. DEEM contains food consumption data as reported by 
respondents in the USDA Continuing Surveys of Food Intake by 
Individuals conducted in 1989-1992. The chronic food exposure was 
calculated assuming theoretical maximum residue contribution (TMRC) 
values and 100% crop treated estimates. The percent of the chronic PAD 
utilized is as follows: 6.6% for nursing infants (< 1 year); 4.8% for 
children (1-6 years); 3.6% for females (13+/nursing) and for all 
infants (< 1 year); 2.7% for the Pacific regions; 2.4% for non-nursing 
infants (< 1 year), Western region, and non-Hispanic other than black 
or white; and 1.8% for the U.S. population (48 states-all seasons).
    2. From drinking water. In soil, fenhexamid is relatively immobile 
(Koc = 446) and non-persistent (t\1/2\ =  1 day). 
Fenhexamid is not expected to be a ground water contaminant, but has 
some potential to reach surface water on eroded soil particles. In 
surface water, fenhexamid would be expected to photodegrade rapidly 
(t\1/2\ =  0.2 days).
    No monitoring data are available to perform a quantitative drinking 
water assessment. The Agency estimated surface water exposure using the 
Generic Expected Environmental Concentration (GENEEC) model, a 
screening level model for determining concentrations of pesticides in 
surface water. GENEEC uses the soil/water partition coefficient, 
hydrolysis half life, and the maximum label rate to estimate surface 
water concentration. GENEEC contains a number of conservative 
underlying assumptions. Therefore, the drinking water concentrations 
derived from GENEEC for surface water are likely to be overestimated. 
The modeling was conducted based on the environmental profile and the 
maximum seasonal application rate proposed for fenhexamid: 0.75 lb. 
active ingredient/acre x 4 applications/acre/year. The estimated 
environmental concentrations (EECs) derived from GENEEC are 17 
g/L (peak value) and 4.8 g/L (56-day average).
    The Agency used the Screening Concentration in Ground Water (SCI-
GROW) model to estimate pesticide levels in ground water. The SCI-GROW 
model is based on actual monitoring data collected for a number of 
pesticides that serve as benchmarks to predict EECs in ground water. 
Using SCI-GROW, the EEC calculated for fenhexamid is 0.0007 g/
L (acute and chronic).
    i. Acute exposure and risk. Drinking water levels of comparison 
(DWLOCs) for acute exposure were not calculated as there was no 
appropriate toxicological endpoint attributable to a single (acute) 
dietary exposure.
    ii. Chronic exposure and risk. Chronic (non-cancer) DWLOCs were 
calculated for the U.S. population and the population subgroups with 
the highest (chronic) food exposure. The DWLOCs are as follows: 530 
g/L for infants/children; 1,700 g/L for females 13+; 
1,900 g/L for the U.S. population - pacific region; and 2,000 
g/L for U.S. population (48 states, all seasons). The EECs 
(0.0007 g/L from SCI-GROW, and 4.8 g/L from GENEEC) 
for fenhexamid are well below the DWLOCs and therefore, are below the 
Agency's level of concern. Therefore, the Agency concludes with 
reasonable certainty that residues of fenhexamid in drinking water do 
not contribute significantly to the aggregate chronic human health 
risk.
    3. From non-dietary exposure. Fenhexamid is not registered for use 
on residential non-food sites. Therefore, no non-occupational, non-
dietary exposure and risk are 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.'
    EPA does not have, at this time, available data to determine 
whether fenhexamid 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, 
fenhexamid 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 fenhexamid 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. Acute risk. Acute aggregate risk is the sum of exposures 
resulting from acute dietary food + acute drinking water. The Agency 
did not identify an appropriate toxicological endpoint attributable to 
a single (acute) dietary exposure.
    2. Chronic risk. Using the TMRC, exposure assumptions described in 
this unit, EPA has concluded that aggregate exposure to fenhexamid from 
food will utilize 1.8% of the chronic PAD for the U.S. population. The 
major identifiable subgroup with the highest aggregate exposure is 
nursing infants (< 1 year) discussed below. EPA generally has no 
concern for exposures below 100% of the chronic PAD because the chronic 
PAD represents the level at or below which daily aggregate dietary 
exposure over a lifetime will not pose appreciable risks to human 
health. Despite the

[[Page 28922]]

potential for exposure to fenhexamid in drinking water, EPA does not 
expect the aggregate exposure to exceed 100% of the chronic PAD. EPA 
concludes that there is a reasonable certainty that no harm will result 
from aggregate exposure to fenhexamid residues.
    3. Short- and intermediate-term risk. Short- and intermediate-term 
aggregate exposure takes into account chronic dietary food and water 
(considered to be a background exposure level) plus indoor and outdoor 
residential exposure. Although short- and intermediate-term endpoints 
were identified, there are no residential uses for fenhexamid.
    4. Aggregate cancer risk for U.S. population. Fenhexamid was 
classified as ``not likely'' to be a human carcinogen.
    5. 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 Fenhexamid 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 fenhexamid, 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 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 postnatal toxicity and the 
completeness of the data base 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 postnatal sensitivity. Qualitatively, there is 
evidence of increased susceptibility in rat pups compared to adults, 
based on the relative severity of effects in the 2-generation 
reproduction study in rats. The effects on pups were of concern 
because: significant pup body weight decreases were observed in both 
the F1 and the F2 generations; the pup body 
weight decreases in the F2 generation were observed during 
early lactation (lactation days 7 through day 21) when the pups are 
exposed to the test material primarily through the mother's milk; the 
pup body weight decreases in the F1 generation were observed 
during late lactation (lactation days 14 through 21) when the pups are 
exposed to the test material through the mother's milk and through the 
feed; and, in the metabolism study on fenhexamid, glucuronidation of 
fenhexamid was clearly demonstrated to be the single major route of 
metabolism, detoxification and excretion of fenhexamid in adult male 
and female rats. The demonstrated poor glucuronidation capacity of rat 
pups between days 7 and 21 indicates a possibly increased sensitivity 
of pups and serves to support a concern for neonatal toxicity.
    iii. Conclusion. There is a complete toxicity data base for 
fenhexamid and exposure data are complete or are estimated based on 
data that reasonably accounts for potential exposures. Although there 
is qualitative evidence of increased susceptibility, the Agency decided 
that an additional safety factor of 3x would be appropriate based on 
the following reasons: the increased susceptibility demonstrated in the 
2-generation reproduction study was only qualitative (not quantitative) 
evidence and was observed only in the presence of parental toxicity; 
the qualitative offspring effect was limited to decreased body weight 
and no other adverse effects (e.g., decreased pup survival, behavioral 
alterations, etc.) were observed; and there is no indication of 
increased susceptibility of rat or rabbit fetuses to in utero exposure 
in the prenatal developmental toxicity studies with fenhexamid.
    2. Acute risk. An acute endpoint was not identified and this risk 
assessment was not required.
    3. Chronic risk. Using the exposure assumptions described in this 
unit, EPA has concluded that highest aggregate exposure to fenhexamid 
from food will utilize 6.6% of the chronic PAD for all infants (< 1 
year). EPA generally has no concern for exposures below 100% of the 
chronic PAD because the chronic PAD represents the level at or below 
which daily aggregate dietary exposure over a lifetime will not pose 
appreciable risks to human health. Despite the potential for exposure 
to fenhexamid in drinking water and from non-dietary, non-occupational 
exposure, EPA does not expect the aggregate exposure to exceed 100% of 
the chronic PAD.
    4. Short- or intermediate-term risk. There are no residential uses 
and thus these risks are not presented.
    5. 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 fenhexamid residues.

III. Other Considerations

A. Metabolism In Plants and Animals

    The parent compound, fenhexamid, is the only compound of concern. 
Radiolabeled fenhexamid plant metabolism studies were conducted on 
grapes, tomatoes, and apples. The qualitative nature of fenhexamid 
residues in plants is adequately understood. The data indicate very 
little translocation of residues, i.e., residues of fenhexamid are non-
systemic and are thus primarily surface residues. There are no animal 
feedstuffs associated with the uses of fenhexamid on grapes, 
strawberries, and ornamentals. Therefore, no animal metabolism data 
were submitted or required.

B. Analytical Enforcement Methodology

    Adequate enforcement methodology (a high performance liquid 
chromotography method with electrochemical detection) is available to 
enforce the tolerance expression. 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, 1921 Jefferson Davis 
Hwy., Arlington, VA, (703) 305-5229.

C. Magnitude of Residues

    An adequate number of geographically representative field trials 
were submitted to support the proposed uses on grapes and strawberries. 
These studies were conducted via use patterns approximating those 
proposed by the petition requesting these tolerances. The data indicate 
that residues of fenhexamid will not exceed the proposed tolerances. 
Residues concentrated an average of 1.9x in raisins. Multiplying 1.9x 
by the highest

[[Page 28923]]

average field trial residue value in grapes (2.3 ppm), yields 5.3 ppm 
as the maximum residue expected in raisins which is below the proposed 
tolerance of 6.0 ppm. The concentration factor was  0.25x in 
juice and  0.5x in wine grapes based on data from red and 
white wine grapes.

D. International Residue Limits

    There are no codex, Canadian or Mexican maximum residue limits 
established for this chemical. This petition was jointly reviewed with 
Canada's Pest Management and Regulatory Agency and the tolerances 
proposed have been harmonized with Canada.

E. Rotational Crop Restrictions

    The Agency concluded that a 30-day plantback interval is required 
for all crops without a fenhexamid tolerance.

IV. Conclusion

    Therefore, tolerances are established for residues of fenhexamid in 
or on grapes at 4.0 ppm, strawberries at 3.0 ppm, and raisins at 6.0 
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 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 July 27, 1999, 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 under the ``ADDRESSES'' section (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 
regulation. 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). EPA is authorized to waive any fee requirement 
``when in the judgement of the Administrator such a waiver or refund is 
equitable and not contrary to the purpose of this subsection.'' For 
additional information regarding tolerance objection fee waivers, 
contact James Tompkins, 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: Rm. 239, CM #2, 1921 Jefferson Davis Hwy., Arlington, VA, 
(703) 305-5697, [email protected]. Requests for waiver of tolerance 
objection fees should be sent to James Hollins, Information Resources 
and Services Division (7502C), Office of Pesticide Programs, 
Environmental Protection Agency, 401 M St., SW., Washington, DC 20460.
    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 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 regulation under docket 
control number [OPP-300866] (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 Rm. 119 of the Public Information and Records 
Integrity Branch, Information Resources and Services Division (7502C), 
Office of Pesticide Programs, Environmental Protection Agency, CM #2, 
1921 Jefferson Davis Hwy., Arlington, VA.
    Objections and hearing requests may be sent by e-mail directly to 
EPA at:

    [email protected]


    E-mailed objections and hearing requests must be submitted as an 
ASCII file avoiding the use of special characters and any form of 
encryption.
    The official record for this regulation, as well as the public 
version, as described in this unit 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 record which 
will also include all comments submitted directly in writing. The 
official 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 section 408(d) of the 
FFDCA 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 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 
tolerances 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 
previously assessed whether establishing tolerances, exemptions from 
tolerances,

[[Page 28924]]

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.

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 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 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: May 19, 1999.

Susan B. Hazen,

Acting Director, 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. 321(q), (346a) and 371.

    2. Section 180.553, is added to subpart C to read as follows:


Sec. 180.553  Fenhexamid; tolerances for residues.

    (a) General. Tolerances are established for the residues of the 
fungicide fenhexamid (N-2,3-dichloro-4-hydroxyphenyl)-1-methyl 
cyclohexanecarboxamide) in or on the following commodities:

 
------------------------------------------------------------------------
                   Commodity                        Parts per million
------------------------------------------------------------------------
Grapes.........................................                      4.0
Raisins........................................                      6.0
Strawberries...................................                      3.0
------------------------------------------------------------------------

    (b) Section 18 emergency exemptions. [Reserved]
    (c) Tolerances with regional registrations. [Reserved]
    (d) Indirect or inadvertent residues. [Reserved]

[FR Doc. 99-13656 Filed 5-27-99; 8:45 am]
BILLING CODE 6560-50-F