[Federal Register Volume 61, Number 240 (Thursday, December 12, 1996)]
[Notices]
[Pages 65392-65395]
From the Federal Register Online via the Government Publishing Office [www.gpo.gov]
[FR Doc No: 96-31555]


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ENVIRONMENTAL PROTECTION AGENCY
[PF-678; FRL-5576-2]


Clofencet; Pesticide Tolerance Petition Filing

AGENCY: Environmental Protection Agency (EPA).

ACTION: Notice of Filing.

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SUMMARY: This notice is a summary of a pesticide petition proposing the 
establishment of a regulation for residues of clofencet, [MON 21200], 
in or on wheat as a primary application; in or on the cereal grains 
group (excluding rice, wild rice and sweet corn) and soybeans as 
rotational crops; and in animal products. This summary was prepared by 
the petitioner, Monsanto Company.

DATES: Comments, identified by docket number [PF-678], must be received 
on or before January 13, 1997.


ADDRESSES By mail, submit written comments to Public Response and 
Program Resources Branch, Field Operations Division (7506C), Office of 
Pesticide Programs, Environmental Protection Agency, 401 M St., SW., 
Washington, DC 20460. In person, bring comments to: Rm. 1132 CM #2, 
1921 Jefferson Davis Highway, Arlington, VA 22202.
    Comments and data may also be submitted electronically by sending 
electronic mail (e-mail) to: [email protected]. Electronic 
comments must be submitted as an ASCII file avoiding the use of special 
characters and any form of encryption. Comments and data will also be 
accepted on disks in WordPerfect 5.1 file format or ASCII file format. 
All comments and data in electronic form must be identified by the 
docket number [PF-678]. Electronic comments on this proposed rule may 
be filed online at many Federal Depository Libraries. Additional 
information on electronic submissions can be found below in this 
document.
    Information submitted as comments 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.

FOR FURTHER INFORMATION CONTACT: By mail: Robert J. Taylor, Product 
Manager (PM) 25, Registration Division, (7505C), Office of Pesticide 
Programs, Environmental Protection Agency, 401 M St., SW., Washington, 
DC 20460. Office location and telephone number: Rm. 241, CM #2, 1921 
Jefferson Davis Highway, Arlington, VA 22202, 703-305-6027, e-mail: 
[email protected].

SUPPLEMENTARY INFORMATION: EPA has received a pesticide petition (PP 
4F4346) from the Monsanto Company, 700 14th St., NW., Suite 1100, 
Washington, DC 20005 proposing pursuant to section 408(d) of the 
Federal Food, Drug and Cosmetic Act (FFDCA), 21 U.S.C. 346a(d), to 
amend 40 CFR part 180 by establishing tolerances for residues of the 
plant growth regulator (hybridizing agent) clofencet, [MON 21200], 2-
(4-chlorophenyl)-3-ethyl-2,5- dihydro-5-oxo-4-pyridazinecarboxylic 
acid, potassium salt in or on the raw agricultural commodities from 
direct treatment with clofencet: wheat grain at 250 parts per million 
(ppm), wheat hay at 40 ppm, wheat straw at 50 ppm and wheat forage at 
10 ppm. Secondary residues in the animal product commodities of cattle, 
goats, hogs, horses and sheep: fat at 0.04 ppm, kidney at 10 ppm, meat 
at 0.15 ppm, meat by-products (except kidney) at 0.5 ppm and milk at 
0.02 ppm. Secondary residues in the animal product commodities of 
poultry: eggs at 1 ppm, fat at 0.04 ppm, meat at 0.15 ppm, and meat by-
products at 0.2 ppm. Rotational crop tolerances in the raw agricultural 
commodities: soybeans at 30 ppm, soybean hay at 10 ppm and soybean 
forage at 10 ppm. The cereal grain crop group (except rice, wild rice 
and sweet corn) grown as rotational crops: grain at 20 ppm, straw at 4 
ppm, forage at 4 ppm, stover (fodder) at 1 ppm and hay at 15 ppm. The 
proposed analytical method for primary and rotational crops includes 
derivatization of clofencet to its methyl ester followed by analysis 
via gas chromatography with electron

[[Page 65393]]

capture detection. For rotational crops, it is necessary to first 
hydrolyze clofencet-sugar conjugates to clofencet before proceeding 
with derivatization. The proposed method for animal tissues includes 
derivatization of clofencet to its methyl ester followed by analysis 
via HPLC with UV detection. For milk and eggs, analysis is achieved by 
extraction, concentration and direct analysis via HPLC with UV 
detection.
    Pursuant to the section 408(d)(2)(A)(i) of the FFDCA, as amended, 
Monsanto has submitted the following summary of information, data and 
arguments in support of their pesticide petition. This summary was 
prepared by Monsanto and EPA has not fully evaluated the merits of the 
petition. EPA edited the summary to clarify that the conclusions and 
arguments were the petitioner's and not necessarily EPA's and to remove 
certain extraneous material.

I. Monsanto Petition Summary

    1. Clofencet uses. Clofencet is the active ingredient in Genesis 
Chemical Hybridizing Agent (CHA), which is used in the production of 
hybrid wheat seed. Clofencet prevents normal pollen development in 
wheat without affecting female fertility. This allows for efficient 
cross-pollination of the treated female line by an untreated male 
pollinator line grown in close proximity, to produce hybrid wheat seed. 
By using this technique, hybrid wheat with greater yield potential, 
drought resistance and disease resistance may be produced. It is 
important to note that clofencet will not be sold directly to the wheat 
grower; rather it will be a tool utilized by specially trained seed 
company personnel to produce hybrid wheat seed which will ultimately be 
purchased by the wheat grower for planting.
    The proposed use pattern of Genesis is a single postemergent 
application at the appropriate stage of growth, namely stages 7 to 9 
(Feekes scale) or stages 32 to 39 (Zadoks scale). The maximum proposed 
application rate in the United States is 10 pounds active ingredient 
per acre. Due to seed production considerations, Genesis will not be 
applied to the same site in successive years. The maximum market 
penetration for Genesis will not exceed 0.2 to 1 percent of the total 
wheat acreage in the United States.
    Genesis has been effective across a wide range of germplasm in all 
market classes of wheat. It has a wide crop-safety margin and the seed 
produced from treated females is of high quality. Wheat is the only 
crop for which Genesis is known to be commercially efficacious.
    2. Clofencet safety. Monsanto has submitted over 40 separate 
mammalian and ecological toxicology studies in support of tolerances 
for clofencet. The following mammalian toxicity studies on clofencet 
(technical grade active ingredient (TGAI)) have been conducted: A rat 
acute oral toxicity study with an LD50 of 3,306 mg/kg/day.
    A rat dermal toxicity study with an LD50 of >500 mg/kg/day.
    A rat acute inhalation study with an LC50 of >3.8 mg/l (MON 
21233 manufacturing use product).
    A primary eye irritation study in the rabbit which showed moderate 
irritation.
    A primary dermal irritation study in the rabbit which showed 
essentially no irritation.
    A primary dermal sensitization study in guinea pigs which showed no 
sensitization.
    An acute neurotoxicity study in the rat which showed no neurotoxic 
effects at any dose.
    A subchronic (90-day) neurotoxicity study in the rat which showed 
no neurotoxic effects at any dose.
    A 21-day dermal toxicity study in the rat which showed no toxic 
effects at any dose tested with a NOEL of 1,000 mg/kg/day.
    A 90-day feeding study in dogs with a NOEL of 50 mg/kg/day based on 
histological findings in the thymus and testes.
    A 90-day feeding study in the rat with a NOEL of 5,000 ppm in the 
diet based on decreased cumulative weight gain and slightly increased 
kidney weights.
    A 24-month chronic feeding/oncogenicity study in the rat with a 
systemic NOEL of 1,000 ppm (47 and 58 mg/kg/day in males and females, 
respectively) based on hematology effects and histological findings in 
the lung and kidney. There was an equivocal oncogenic response in the 
liver and thyroid at 20,000 ppm, the highest dose tested.
    An 18-month oncogenicity study in the mouse with a systemic NOEL of 
3,000 ppm (453 and 642 mg/kg/day for males and females, respectively) 
based on decreased survival in the high dose group. A slightly 
increased incidence of histiocytic sarcomas were observed in female 
mice at 7,000 ppm, the highest dose tested.
    A 12-month feeding study in the dog with a NOEL of 5 mg/kg/day 
based on histological changes in the testes/epididymis and thymus.
    A teratology study in the rat with a maternal and developmental 
NOEL of 1,000 mg/kg/day, the highest dose level tested.
    A teratology study in the rabbit with a maternal and developmental 
NOEL of 150 mg/kg/day based on excessive maternal toxicity (including 
mortality, abortions and excessive weight loss) and slight 
developmental effects including slight decreases in fetal weight and 
slight, non-statistically significant increased incidences in 
hydrocephaly and delayed ossification.
    A two-generation reproduction study in the rat with a NOEL of 500 
ppm (38 and 52 mg/kg/day for males and females, respectively) based on 
a decrease in pup viability during the first four days of lactation.
    Several mutagenicity studies: Ames Salmonella Assay; CHO/HGPRT 
Point Mutation Assay; In Vitro Cytogenetics Assay in Human Lymphocytes; 
Mouse Micronucleus Assay; and In Vivo/In Vitro Hepatocyte DNA Repair 
Assay; all negative.
    3. Threshold effects -- chronic effects. Based on the available 
chronic toxicity data, EPA has established the Reference Dose (RfD) for 
clofencet at 0.005 milligrams (mg)/ kilogram (kg)/day. The RfD for 
clofencet is based on a 1-year feeding study in dogs with a No 
Observable Effect Level (NOEL) of 0.5 mg/kg/day and an uncertainty 
factor of 100.
    Acute toxicity. Based on the available acute toxicity data, EPA has 
determined that clofencet does not pose any acute dietary risks.
    4. Non threshold effects--carcinogenicity. Using the Guidelines for 
Carcinogenic Risk Assessment published September 24, 1986 (51 FR 
33992), EPA has classified clofencet as Group ``C'' for carcinogenicity 
(possible human carcinogen - limited evidence of carcinogenicity in the 
absence of human data) based on the results of carcinogenicity studies 
in two species.
    In a 24-month feeding study in rats, statistically significant 
increases in thyroid C-cell adenomas and combined adenoma/carcinoma 
were observed in male rats at the highest dose tested (20,000 ppm). 
There was also a statistically significant positive trend for these 
tumors, but the incidences were within or only slightly above that 
reported for historical controls. In addition, the tumors were mostly 
benign and occurred only at an excessive dose. The highest dose in this 
study was considered to be excessive in males, and adequate in female 
rats.
    In an 18-month feeding study in mice, statistically significant 
increases in histiocytic sarcomas were observed in female mice at the 
highest dose tested (7,000 ppm) with a statistically significant 
positive trend. The incidence of these tumors also exceeded historical

[[Page 65394]]

controls. In male mice there were no statistically significant 
increases in tumors at any dose. The highest dose tested in both sexes 
was determined to have been adequate for assessing the carcinogenic 
potential of clofencet, without excessive toxicity.
    The classification of Group ``C'' was based on the increase in 
histiocytic sarcomas in female mice. The thyroid C-cell tumors in male 
rats were considered to have occurred only at an excessive dose. There 
were no apparent genotoxicity concerns and little additional support 
for carcinogenicity based on SAR analysis; therefore, EPA's 
Carcinogenicity Peer Review Committee (CPRC) recommended that the RfD 
approach be used for quantitation of human risk.
    5. Aggregate exposure. For purposes of assessing the potential 
dietary exposure under these tolerances, the EPA has estimated 
aggregate exposure based on the anticipated residue for clofencet on 
primary crop (PC) wheat grain at 96.8 ppm, rotational crop (RC) 
soybeans at 8.87 ppm, RC corn at 0.92 ppm, RC sorghum at 2.05 ppm and 
other RC cereal grains (except rice, wild rice and sweet corn) at 6.7 
ppm. In addition, aggregate exposure from animal products were 
estimated from tolerance values of 0.02 ppm for milk, 0.15 ppm for 
meat, 0.04 ppm for fat, 10.0 ppm for kidney, 0.5 ppm for meat by-
products (except kidney), 0.15 ppm for poultry meat, 0.2 ppm for 
poultry meat by-products, 0.04 ppm for poultry fat and 1.0 ppm for 
eggs. Estimated exposure is obtained by multiplying the anticipated 
residue or tolerance level residue by the consumption data which 
estimates the amount of food products consumed for each of the above 
commodities by various population subgroups. There are no other 
established (permanent) U.S. tolerances for clofencet, and there are no 
registered uses (section 3) for clofencet on food or feed crops in the 
United States.
    In conducting this exposure assessment, the EPA has made very 
conservative assumptions. First, the reasonable assumption is made that 
1 percent of the total wheat acreage will be sprayed with clofencet, 
but it is further assumed that all of this clofencet treated wheat - 
which is only intended for seed production - will enter the food chain. 
Monsanto estimates that a maximum of 10 percent of this seed will enter 
the food chain. Second, it is assumed that 100 percent of all labeled 
rotational crops will be planted on clofencet treated fields - even 
though only 1 percent of wheat fields will be treated with clofencet 
and, further, it is not possible to plant multiple crops on the same 
field. Third, full tolerance values are used for animal products rather 
than anticipated residues. These factors result in an overestimate of 
human exposure which should be taken in consideration when reviewing 
the calculated human dietary exposure values.
    Other potential sources of exposure of the general population to 
residues of pesticides are residues in drinking water and exposure from 
non-occupational sources. Based on the available studies used in EPA's 
assessment of environmental risk, the mitigation measures volunteered 
by Monsanto and requested by the EPA and the unique and restricted use 
characteristics of the chemical, Monsanto does not anticipate exposure 
to residues of clofencet in drinking water. There are no established 
Maximum Concentration Level (MCL) for residues of clofencet in drinking 
water. Monsanto has not estimated non-occupational exposure for 
clofencet since the proposed registration for clofencet is limited to 
wheat seed production by certified hybrid seed technicians only. It 
will be a restricted use registration. Thus, the non-occupational 
exposure to the general population is expected to be negligible.
    Monsanto also considered the potential for cumulative effects of 
clofencet and other substances that have a common mechanism of 
toxicity. Monsanto concluded that consideration of a common mechanism 
of toxicity is not appropriate at this time. First, clofencet is only 
one of two chemical hybridizing agents currently registered on wheat 
and the other one is owned by this petitioner and is not currently 
available commercially. Second, Monsanto does not have reliable 
information to indicate that toxic effects produced by clofencet would 
be cumulative with those of any other chemical compounds. Thus, 
Monsanto is considering only the potential risks of clofencet in its 
aggregate exposure assessment.
    6. Determination of safety for U.S. population-- reference dose. 
Using the conservative exposure assumptions described above and based 
on the completeness and reliability of the toxicity data, EPA has 
concluded that aggregate exposure to clofencet will utilize 7.6 percent 
of the RfD for the U.S. population. EPA generally has no concern for 
exposures below 100 percent of the RfD for the U.S. population 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. Monsanto concludes that there is a reasonable certainty that no 
harm will result from aggregate exposure to clofencet residues.
    7. Safety determination for infants and children. In assessing the 
potential for additional sensitivity of infants and children to 
residues of clofencet, Monsanto 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 the potential for adverse effects on the developing organism 
resulting from exposure during prenatal development to the female 
parent. Reproduction studies provide information relating to effects 
from exposure to the chemical on the reproductive capability of both 
(mating) parents and on systemic toxicity.
    In a developmental toxicity study in the rat, no developmental or 
maternal toxicity were observed up to a dosage of 1,000 mg/kg/day, the 
highest dose level tested and the limit dose for this species as 
specified in the Pesticide Assessment Guidelines. The NOEL was 
considered to be 1,000 mg/kg/day.
    In a developmental toxicity study in the rabbit, severe maternal 
toxicity (mortality, abortion, decreased body weight gain and decreased 
food consumption) and equivocal developmental toxicity (possible lower 
fetal body weights, marginal increased incidence of fetal 
hydroencephalus and delayed ossification) were observed at 500 mg/kg/
day, the highest dose level tested. The NOEL for both maternal and 
developmental toxicity was considered to be 150 mg/kg/day. The 
developmental effects observed in this study were considered to be 
secondary to the severe maternal stress.
    In a 2-generation reproduction study in rats, pups from the 5,000 
and 20,000 ppm dose levels had an increased incidence of pup mortality 
in both matings of the F1 generation during lactation days 1 to 4. The 
NOEL was considered to be 500 ppm (38 and 52 mg/kg/day for males and 
females, respectively). Although the increased incidence of pup 
mortality was significantly increased when compared to concurrent 
controls, the laboratory at which the study was conducted reports that 
their historical control incidence of pup survivability is less than is 
seen at other laboratories. A viral infection in the colony was 
suspected, but nothing was definitely proven. No effects on fertility 
were observed.
    FFDCA Section 408 provides that EPA may apply an additional safety 
factor (up to 10) in the case of threshold effects for infants and 
children to account for pre- and post-natal toxicity and the 
completeness of the database. Based on

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current toxicological data requirements, the database relative to pre- 
and post-natal effects in children is complete. Further, in the 
developmental toxicity study in the rabbit and the 2-generation 
reproduction study in the rat, the NOEL's are already an additional 30X 
and an average (male/female) of 9X, respectively, above the NOEL on 
which the RfD was established (5.0 mg/kg/day from a one-year feeding 
study in dogs). Based on all the above information, Monsanto concludes 
that an additional uncertainty factor is not warranted and that the RfD 
of 0.05 mg/kg/day is appropriate for assessing risk to infants and 
children.
    Using the conservative dietary exposure assumptions described 
above, EPA has concluded that the percent of the RfD that will be 
utilized by aggregate exposure to residues of clofencet by children 
aged <1 (nursing) to age 12, ranges from 10.5 percent for children 7 to 
12 years old up to 22.7 percent for non-nursing infants (<1 year old). 
Therefore, based on the completeness and reliability of the toxicity 
data and the conservative exposure assessment, Monsanto concludes that 
there is a reasonable certainty that no harm will result to infants and 
children from aggregate exposure to clofencet residues.
    8. Estrogenic effects. No specific tests have been conducted with 
clofencet to determine whether the chemical may have an effect in 
humans that is similar to an effect produced by a naturally occuring 
estrogen or other endocrine effects. However, there were no significant 
findings in other relevant toxicity tests, i.e., teratology and multi-
generation reproduction studies, which would suggest that clofencet 
produces these kinds of effects.
    9. Chemical residue. The metabolism of clofencet in plants and 
animals is adequately understood for the purposes of these tolerances. 
There are no Codex maximum residues levels established for residues of 
clofencet on wheat or indicated rotational crops. There is a practical 
analytical method for detecting and measuring levels of clofencet in or 
on food with a limit of detection that allows monitoring of food with 
residues at or above the levels set in these tolerances. EPA will 
provide information on this method to the Food and Drug Administration 
(FDA). The method is available to anyone who is interested in pesticide 
residue enforcement from: By mail: Calvin Furlow, Public Response and 
Program Resources Branch, Field Operations Division (7506C), Office of 
Pesticide Programs, Environmental Protection Agency, 401 M St., SW., 
Washington, DC 20460. Office location and telephone number: Crystal 
Mall #2, Rm. 1128, 1921 Jefferson Davis Hwy., Arlington, VA 22202, 
(703) 305-5805.
    Residues of clofencet have been found to concentrate slightly 
(<2 x ) in wheat shorts and bran, and in soybean hulls and meal. The 
EPA examined all relevant data and after consideration of the 
restricted use of the chemical for seed production only, the limited 
opportunity for this seed to enter commerce as grain and the dilution 
factors involved in making all of the above processed fractions (with 
the exception of wheat bran) ``ready to eat'', the EPA determined that 
no additional tolerances were necessary to cover these processed 
fractions. All of the proposed tolerance levels are adequate to cover 
residues likely to be present from the proposed use of clofencet. 
Therefore, no special processing to reduce the residues will be 
necessary
    10. Environmental fate. Laboratory studies indicate that clofencet 
has the potential to persist in soil and be mobile. However, the 
results of field dissipation studies indicate that downward movement of 
clofencet is limited. In addition, the limited use of clofencet for 
hybrid wheat seed production only, the current practice of never using 
the same seed production field in two consecutive years and label 
mitigation measures agreed upon by Monsanto and the EPA, will further 
reduce the likelihood of clofencet appearing in ground or surface 
water.

II. Administrative Matters

    Interested persons are invited to submit written comments on this 
notice of filing. Comments must bear a notation indicating the document 
control number, [PF-678]. All written comments filed in response to 
this petition will be available, in the Public Response and Program 
Resources Branch, at the address given above from 8:30 a.m. to 4:00 
p.m., Monday through Friday, except legal holidays.
    A record has been established for this notice of filing under 
docket number [PF-678] (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 4:00 p.m., Monday through Friday, excluding legal 
holidays. The public record is located in Room 1132 of the Public 
Response and Program Resources Branch, Field Operations Division 
(7506C), Office of Pesticide Programs, Environmental Protection Agency, 
Crystal Mall #2, 1921 Jefferson Davis Highway, Arlington, VA.
    Electronic comments can be sent directly to EPA at:
    opp=D[email protected]


    Electronic comments must be submitted as as ASCII file avoiding the 
use of special characters and any form of encryption.
    The official record for this filing of notice, as well as the 
public version, as described above will be kept in paper form. 
Accordingly, EPA will transfer all comments 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 rulemaking record is the 
paper record maintained at the address in ``ADDRESSES'' at the 
beginning of this document.

List of Subjects

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

    Dated: December 4, 1996.

Stephen L. Johnson,

Director, Registration Division, Office of Pesticide Programs.

[FR Doc. 96-31555 Filed 12-11-96; 8:45 am]
BILLING CODE 6560-50-F