PMEP Home Page --> Pesticide Active Ingredient Information --> Fungicides and Nematicides --> famoxadone to sulfur (Kolospray) --> fenhexamid --> fenhexamid Pesticide Petition Filing 11/98

fenhexamid Pesticide Petition Filing 11/98


[Federal Register: November 20, 1998 (Volume 63, Number 224)]
[Notices]               
[Page 64498-64502]
>From the Federal Register Online via GPO Access [wais.access.gpo.gov]
[DOCID:fr20no98-53]


[[Page 64498]]

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

ENVIRONMENTAL PROTECTION AGENCY

[PF-842; FRL-6042-1]

 
Notice of Filing of Pesticide Tolerance Petitions

AGENCY: Environmental Protection Agency (EPA).

ACTION: Notice.

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

SUMMARY: This notice announces the initial filing of pesticide 
petitions proposing the establishment of regulations for residues of 
certain pesticide chemicals in or on various food commodities.
DATES: Comments, identified by the docket control number PF-842, must 
be received on or before December 21, 1998.
ADDRESSES: By mail submit written comments to: Information and Records 
Integrity Branch, Public Information and Services Divison (7502C), 
Office of Pesticides Programs, Environmental Protection Agency, 401 M 
St., SW., Washington, DC 20460. In person bring comments to: Rm. 119, 
CM #2, 1921 Jefferson Davis Highway, Arlington, VA.
    Comments and data may also be submitted electronically by following 
the instructions under ``SUPPLEMENTARY INFORMATION.'' No confidential 
business information should be submitted through e-mail.
    Information submitted as a comment concerning this document may be 
claimed confidential by marking any part or all of that information as 
``Confidential Business Information'' (CBI). CBI should not be 
submitted through e-mail. Information marked as CBI will not be 
disclosed except in accordance with procedures set forth in 40 CFR part 
2. A copy of the comment 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. All written 
comments will be available for public inspection in Rm. 119 at the 
address given above, from 8:30 a.m. to 4 p.m., Monday through Friday, 
excluding legal holidays.

FOR FURTHER INFORMATION CONTACT: Mary L. Waller, Registration Support 
Branch, Registration Division (7505W), Office of Pesticide Programs, 
Environmental Protection Agency, 401 M St., SW, Washington, DC 20460. 
Office location, telephone number, and e-mail address: Rm. 247, Crystal 
Mall #2, 1921 Jefferson Davis Highway, Arlington, VA 22202, (703) 308-
9354; e-mail: waller.mary@epamail.epa.gov.
SUPPLEMENTARY INFORMATION: EPA has received pesticide petitions as 
follows proposing the establishment and/or amendment of regulations for 
residues of certain pesticide chemicals in or on various food 
commodities under section 408 of the Federal Food, Drug, and Cosmetic 
Act (FFDCA), 21 U.S.C. 346a. EPA has determined that this petition 
contains data or information regarding the elements set forth in 
section 408(d)(2); however, EPA has not fully evaluated the sufficiency 
of the submitted data at this time or whether the data supports 
granting of the petition. Additional data may be needed before EPA 
rules on the petition.
    The official record for this notice of filing, as well as the 
public version, has been established for this notice of filing under 
docket control number [PF-842] (including comments and data submitted 
electronically as described below). 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 official record is located at the address in 
``ADDRESSES'' at the beginning of this document.
    Electronic comments can be sent directly to EPA at:
    opp-docket@epamail.epa.gov


    Electronic comments must be submitted as an ASCII file avoiding the 
use of special characters and any form of encryption. Comment and data 
will also be accepted on disks in Wordperfect 5.1/6.1 file format or 
ASCII file format. All comments and data in electronic form must be 
identified by the docket control number (PF-842) and appropriate 
petition number. Electronic comments on this notice may be filed online 
at many Federal Depository Libraries.

List of Subjects

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

    Dated: November 10, 1998.

James Jones,

Director, Registration Division, Office of Pesticide Programs.

Summary of Petition

    Petitioner summaries of the pesticide petitions are printed below 
as required by section 408(d)(3) of the FFDCA. The summaries of the 
petitions were prepared by the petitioners and represent the views of 
the petitioners. EPA is publishing the petition summaries verbatim 
without editing them in any way. The petition summaries announce the 
availability of a description of the analytical methods available to 
EPA for the detection and measurement of the pesticide chemical 
residues or an explanation of why no such method is needed.

2. Tomen Agro, Inc. and Bayer Corporation, Agriculture Division

PP 7F4890

    EPA has received a pesticide petition (PP 7F4890) from the TM-402 
Fungicide Task Force comprised of Tomen Agro, Inc., 100 First Street, 
Suite 1610, San Francisco, CA 94105 and Bayer Corporation, Agriculture 
Division, 8400 Hawthorn Road, P.O. Box 4913, Kansas City, MO 64120-
0013, proposing pursuant to section 408(d) of the Federal Food, Drug, 
and Cosmetic Act, 21 U.S.C. 346a(d), to amend 40 CFR part 180 by 
establishing a tolerance for residues of N-(2,3-dichloro-4-
hydroxyphenyl)-1-

[[Page 64501]]

methyl-cyclohexanecarboxamide (TM-402 or Fenhexamid) in or on the raw 
agricultural commodities grapes and strawberries at 3.0 parts per 
million (ppm) and in raisens at 6.0 ppm. EPA has determined that the 
petition contains data or information regarding the elements set forth 
in section 408(d)(2) of the FFDCA; however, EPA has not fully evaluated 
the sufficiency of the submitted data at this time or whether the data 
supports granting of the petition. Additional data may be needed before 
EPA rules on the petition.

A. Residue Chemistry

    1. Analytical method. An adequate method for purposes of 
enforcement of the proposed TM-402 tolerances in plant commodities is 
available. Bayer AG Analytical Method No. 00362 was used by Bayer AG to 
determine magnitude of TM-402 residues in fresh and processed grapes. 
This method has been independently validated. The limits of 
quantitation (LOQ) were determined to be 0.02 ppm for grapes, wine, and 
juice, and 0.05 ppm for strawberries, and raisins.
    2. Magnitude of residues. The maximum TM-402 residues in fresh 
grapes, grape juice, raisins or wine permitted by the proposed label is 
2.9 ppm. The maximum TM-402 calculated residue for grape juice is 1.7 
ppm. For raisins the calculated residue value is 5.2 ppm, and for wine 
the value is 1.2 ppm. The maximum TM-402 residue for fresh strawberries 
permitted by the proposed label is 2.3 ppm. The average TM-402 residues 
for fresh grapes, grape juice, raisins and wine resulting from the 
treatment of grapes permitted by the proposed label are 1.3 ppm. The 
average TM-402 calculated residue for grape juice is 0.8 ppm. For 
raisins the average calculated residue value was 2.3 ppm, and for wine 
the values are 0.52 ppm. The average TM-402 residue for fresh 
strawberries permitted by the proposed label is 1.2 ppm. Since 
strawberries, grapes and processed grape commodities are not 
significant livestock feeds, a nature-of-the-residue discussion in 
livestock is not required. Additionally, since no aquatic uses are 
proposed, magnitude of the residue data in fish and irrigated crops are 
not required.

B. Toxicological Profile

    1. Acute toxicity. Data from a complete battery of acute toxicity 
studies for TM-402 technical are available. The acute oral toxicity 
study resulted in an LD<INF>50</INF> of >5,000 milligrams/kilogram (mg/
kg) for both sexes. The acute dermal toxicity in rats resulted in an 
LD<INF>50</INF> of > 5,000 mg/kg for both sexes. The acute inhalation 
was investigated in two studies in rats. Inhalation by aerosol at the 
maximum technically possible concentration of 0.322 mg/l resulted in no 
deaths or symptoms (LC<INF>50</INF> >0.322 mg/l). A dust inhalation 
study resulted in an LC<INF>50</INF> >5.057 mg/l. TM-402 was not 
irritating to the skin or eyes after a 4 hour exposure period. The 
Buehler dermal sensitization study in guinea pigs indicated that TM-402 
is not a sensitizer. Based on these results TM-402 technical is placed 
in toxicity Category IV and does not pose any acute dietary risks.
    2. Genotoxicty. The potential for genetic toxicity of TM-402 was 
evaluated in six assays including two Ames tests, an HGPRT forward 
mutation assay, a UDS assay, an in vitro chromosomal aberration assay 
in CHO cells, and a micronucleus test in mice. The compound was found 
to be devoid of any mutagenic activity in each of these assays 
including those tests that investigated the absence or presence of 
metabolic activating systems. The weight of evidence indicates that TM-
402 technical does not pose a risk of mutagenicity or genotoxicity.
    3. Reproductive and developmental toxicity. TM-402 has been tested 
for reproductive toxicity in rats and developmental toxicity in both 
rats and rabbits.
    i. In a 2-generation reproduction study (one mating per 
generation), 30 Sprague-Dawley rats per sex per dose were administered 
0, 100, 500, 5,000, or 20,000 ppm of TM-402 in the diet. The 
reproductive toxicity no observed adverse effect level (NOAEL) was 
20,000 ppm. The neonatal NOAEL was 500 ppm, and the lowest abserved 
effect level (LOAEL) was 5,000 ppm based on decreased pup body weight. 
The parental toxicity NOAEL was 500 ppm based on lower adult pre-mating 
body weights at 5,000 and 20,000 ppm, lower gestation body weights at 
20,000 ppm, lower lactation body weights at 5,000 and 20,000 ppm, and 
statistically significant changes in clinical chemistry parameters, 
terminal body weights, and organ weights at 5,000 and 20,000 ppm. Based 
on this study, it is clear that the only toxic effects in the neonates 
occurred at parentally toxic doses.
    ii. In rats. TM-402 was administered by gavage at doses of 0 or 
1,000 mg/kg for gestation days 6-15. No maternal toxicity, 
embryotoxicity, fetotoxicity, or teratogenic effects were observed at 
the limit dose of 1,000 mg/kg/day. Therefore, the NOAEL for maternal 
and developmental toxicity was 1,000 mg/kg/day.
    iii. In rabbits. TM-402 was administered by gavage at doses of 0, 
100, 300, and 1,000 mg/kg for gestation days 6-18. Body weight gain and 
feed consumption of the dams were reduced at the two top doses. One 
abortion occurred in each of the top two dose groups and two total 
resorptions occurred in the top dose group. The placental weights were 
slightly decreased at 300 mg/kg/day and above. In the 1,000 mg/kg/day 
group slightly decreased fetal weights and a slightly retarded skeletal 
ossification were observed. All other parameters investigated in the 
study were unaffected. Therefore, the NOAELs for maternal and 
developmental toxicity were 100 mg/kg/day in this study.
    Based on the 2-generation reproduction study in rats, TM-402 is not 
considered a reproductive toxicant and shows no evidence of endocrine 
effects. The data from the developmental toxicity studies on TM-402 
show no evidence of a potential for developmental effects 
(malformations or variations) at doses that are not maternally toxic. 
The NOAEL for both maternal and developmental toxicity in rats was 
1,000 mg/kg/day and for rabbits the NOAEL for both maternal and 
developmental toxicity was 100 mg/kg/day.
    4. Subchronic toxicity. The subchronic toxicity of TM-402 has been 
evaluated in rats, mice, and dogs.
    i. TM-402 was administered in the diet to rats for 13 weeks at 
doses of 0, 2,500, 5,000, 10,000 and 20,000 ppm. The NOAEL was 5,000 
ppm (415 mg/kg/day in males and 549 mg/kg/day in females). Reversible 
liver effects were observed at 10,000 ppm.
    ii. TM-402 was administered in the diet to mice for approximately 
14 weeks at doses of 0, 100, 1,000 and 10,000 ppm. The NOAEL was 1,000 
ppm (266.6 mg/kg/day in males and 453.9 mg/kg/day in females). 
Increased feed and water consumption and kidney and liver effects were 
observed at 10,000 ppm.
    iii. TM-402 was administered in the diet to beagle dogs for 13 
weeks at doses of 0, 1,000, 7,000 and 50,000 ppm. The NOAEL was 1,000 
ppm (33.9 mg/kg/day in males and 37.0 mg/kg/day in females. Increased 
Heinz bodies were observed at 7,000 ppm.
    5. Chronic toxicity. The chronic toxicity of TM-402 has been 
evaluated in a 1 year dog study and a 2 year chronic toxicity/
oncogenicity study in rats.
    i. TM-402 was administered in the feed at doses of 0, 500, 3,500, 
or 25,000 ppm to 4 male and 4 female beagle dogs per group for 52 
weeks. A systemic

[[Page 64502]]

NOAEL of 500 ppm (an average dose of 17.4 mg/kg/day over the course of 
the study) was observed based on decreased food consumption and 
decreased body weight gain at 25,000 ppm, decreased erythrocyte, 
hemoglobin and hematocrit values at 25,000 ppm, increased Heinz bodies 
at 3,500 ppm and above, and a dose-dependent increase of alkaline 
phosphatase at 3,500 ppm and above. There were no treatment related 
effects on either macroscopic or histologic pathology.
    ii. A combined chronic/oncogenicity study was performed in Wistar 
rats. Fifty animals/sex/dose were administered doses of 0, 500, 5,000, 
or 20,000 ppm for 24 months in the feed. A further 10 animals/sex/group 
received the same doses and were sacrificed after 52 weeks. The doses 
administered relative to body weight were 0, 28, 292, or 1,280 mg/kg/
day for males and 0, 40, 415, or 2067 mg/kg/day for females. The NOAEL 
in the study was 500 ppm (28 mg/kg/day for males and 40 mg/kg/day for 
females) based on body weight decreases in females at 5,000 ppm and 
above, changes in biochemical liver parameters in the absence of 
morphological changes in both sexes at 5,000 ppm and above, and caecal 
mucosal hyperplasia evident at 5,000 ppm and above.
    The NOAEL in the chronic dog study was 17.4 mg/kg/day based on body 
weight, hematology and clinical chemistry effects. The lowest NOAEL in 
the 2 year rat study was determined to be 28 mg/kg/day based on body 
weight, clinical chemistry parameters in the liver, and caecal mucosal 
hyperplasia.
    6. Oncogenicity. The oncogenic potential of TM-402 has been in a 2 
year oncogenicity study in mice and a 2 year chronic toxicity/
oncogenicity study in rats.
    i. Mouse. TM-402 was administered to 50 B6C3F1 mice/sex/group in 
their feed at concentrations of 0, 800 ,2,400 , or 7,000 ppm for 24 
months. These concentrations resulted in a compound intake of 
247.4,807.4 or 2354.8 mg,kg,day in males and 364.5, 1054.5 and 3178.2 
mg/kg/day in females. A further 10 mice/sex/group received the same 
concentrations and were sacrificed after 12 months. There was no 
treatment effect on mortality, feed consumption,the hematological 
system or on the liver. Water consumption was increased in both sexes, 
and body weights were 8% lower in males at the highest dose of 7,000 
ppm. At 7,000 ppm, elevated plasma creatinine concentrations, decreased 
kidney weights, and an increased occurrence of morphological lesions 
indicated a nephrotoxic effect of the compound. There was no shift in 
the tumor spectrum with treatment, and therefore, TM-402 was not 
oncogenic in this study.
    ii. Rat. In the 2 year rat chronic/oncogenicity study described 
above, there was no indication of an oncogenic response. There was no 
indication of an oncogenic response in the 2 year rat and mouse studies 
on TM-402.
    7. Neurotoxicity. The possibility for acute neurotoxicity of TM-402 
was investigated. TM-402 was administered by gavage ina single dose to 
12 Wistar rats/sex/group at doses of 0, 200, 630, 2,000 mg/kg. There 
was no evidence of neurotoxicity at any level tested.
    8. Endocrine disruption. TM-402 has no endocrine-modulation 
characteristics as demonstrated by the lack of endocrine effects in 
developmental, reproductive, subchronic, and chronic studies.

C. Aggregate Exposure

    1. Dietary exposure. Sources of dietary exposure to TM-402 are 
limited to the crops in the current submission. The following are the 
proposed tolerances: grapes - 3.0 ppm and strawberries - 3.0 ppm. A 
food additive tolerance of 6.0 ppm in raisins is also being proposed.
    2. Drinking water. Review of the environmental fate data indicates 
the TM-402 is relatively immobile and rapidly degrades in the soil and 
water. TM-402 dissipates in the environment via several processes. 
Therefore, a significant contribution to aggregate risk from drinking 
water is unlikely.
    3. Non-dietary exposure. There is no significant potential for non-
occupational exposure to the general public. The proposed uses are 
limited to agricultural and horticultural use.

D. Cumulative Effects

    Consideration of a common mechanism of toxicity is not appropriate 
at this time since there is no significant toxicity observed for TM-
402. Even at toxicology limit doses, only minimal toxicity is observed 
for TM-402. Therefore, only the potential risks of TM-402 are 
considered in the exposure assessment.

E. Safety Determination

    1. U.S. population. Based on the most sensitive species, Tomen Agro 
has calculated an appropriate Reference Dose (RfD) for TM-402. Using 
the NOAEL of 17.4 mg/kg/day in the 1 year dog study and an uncertainty 
factor (UF) of 100 to account for inter- and intra-species variability, 
an RfD of 0.177 mg/kg/day is recommended.
    A chronic dietary risk assessment which included all proposed 
tolerances was conducted on TM-402 using U.S. EPA's Dietary Risk 
Evaluation System (DRES). The theoretical maximum residue contribution 
(TMRC) for the U.S. population (48 States) is 0.00125 mg/kg/day and 
this represents 0.71% of the propoed RfD. The most highly exposed 
subgroup was children (1- 6 years old) where the TMRC was 0.00382 mg/
kg/day, representing only 2.15% of the proposed RfD. For non-nursing 
infants (>1 year old) the TMRC was 0.00101 mg/kg/day (0.57% of the RfD) 
and for children 7-12 years old the TMRC is 0.00156 mg/kg/day (0.88% of 
the RfD). If these calculations consider the average of anticipated 
residue values instead of assuming ``tolerance level'' residues, the 
values are reduced to approximately one-third of those listed above. 
Even under the most conservative assumptions, the estimates of dietary 
exposure clearly demonstrate adequate safety margins of all segments of 
the population.
    2. Infants and children. In assessing the potential for additional 
sensitivity of infants and children to residues of TM-402, the 
available developmental toxicity and reproductive toxicity studies and 
the potential for endocrine modulation by TM-402 were considered. 
Developmental toxicity studies in two species indicate that TM-402 does 
not impose additional risks to developing fetuses and is not a 
teratogen. The 2-generation reproduction study in rats demonstrated 
that there were no adverse effects on reproductive performance, 
fertility, fecundity, pup survival, or pup development at non-
maternally toxic levels. Maternal and developmental NOAELs and LOAELs 
were comparable, indicating no increase in susceptibility of developing 
organisms. No evidence of endocrine effects were noted in any study. It 
is therefore concluded that TM-402 poses no additional risk for infants 
and children and no additional uncertainty factor is warranted.


[FR Doc. 98-31069 Filed 11-19-98; 8:45 am]
BILLING CODE 6560-50-F