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lactofen (Cobra) Pesticide Tolerance Petition 12/96

Date: Fri, 13 Dec 1996 14:23:08 -0500
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Subject: Valent U.S.A. Corporation;Pesticide Tolerance
X-Comment: U.S. EPA FEDERAL REGISTER PESTICIDE documents
[Federal Register: December 12, 1996 (Volume 61, Number 240)]
[Notices]
[Page 65395-65400]
>From the Federal Register Online via GPO Access [wais.access.gpo.gov]
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ENVIRONMENTAL PROTECTION AGENCY
[PF-677; FRL-5576-1]
Valent U.S.A. Corporation; 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 to
renew a time-limited tolerance for residues of the herbicide lactofen,
1-(carboethoxy)ethyl 5-[2-chloro-4- (trifluoromethyl)phenoxy]-2-
nitrobenzoate, and its associated metabolites containing the diphenyl
ether linkage on the raw agricultural commodity (RAC) cottonseed at
0.05 part per million (ppm). This summary was prepared by the
petitioner, Valent U.S.A. Corporation (Valent).
DATES: Comments, identified by the docket number [PF-677], 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.,
[[Page 65396]]
Washington, DC 20460. In person, bring comments to Rm. 1132, CM #2,
1921 Jefferson Davis Highway, Arlington, VA. Comments and data may also
be submitted electronically by sending electronic mail (e-mail) to:
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. 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 docket number [PF-677].
Electronic comments on this notice 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. All written
comments will be available for public inspection in Rm. 1132 at the
address given above, from 8:30 a.m. to 4 p.m., Monday through Friday,
excluding legal holidays.
FOR FURTHER INFORMATION CONTACT: Joanne I. Miller, Product Manager (PM
23), Rm. 237, CM#2, 1921 Jefferson Davis Highway, Arlington, VA 22202;
(703) 305-6224. e-mail: miller.joanne@epamail.epa.gov.
SUPPLEMENTARY INFORMATION: In the Federal Register of June 14, 1990,
(55 FR 24084), EPA established a time-limited tolerance under section
408 of the Federal Food, Drug, and Cosmetic Act (21 U.S.C. 346a) for
residues of the herbicide lactofen, 1-(carboethoxy)ethyl 5-[2-chloro-4-
(trifluoromethyl)phenoxy]-2-nitrobenzoate, and its associated
metabolites containing the diphenyl ether linkage in or on the raw
agricultural commodity cottonseed at 0.05 ppm. The time-limited
tolerance expires on December 31, 1996. This tolerance was requested in
pesticide petition (PP) 9F3798 by Valent U.S.A. Corporation, 1333 N.
California Blvd., Walnut Creek, CA 94596, and establishes the maximum
permissible level for residues of the herbicide in or on this RAC. The
tolerance was issued as a time-limited tolerance because EPA required
additional residue chemistry data. The petitioner proposes to renew the
time-limited tolerance for a one-year period. Valent requested this
tolerance extension pursuant to the Federal Food, Drug, and Cosmetic
Act (FFDCA) as amended by the Food Quality Protection Act of 1996 (Pub.
L. 104-170). The request addresses the requirements of the new FFDCA
Section 408(d)(2). The time-limited tolerance would expire on December
31, 1997. The proposed analytical method is RM-28D, a gas
chromatography method.
    Pursuant to the Section 408(d)(2)(A)(i) of the FFDCA, as amended,
Valent has submitted the following summary of information, data and
arguments in support of their pesticide petition. This summary was
prepared by Valent 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. Valent Petition Summary
A.   Residue Chemistry
    1.   Plant metabolism. Lactofen is used to control broad leaved
weeds in crops by preemergent (soybean, peanut), or early postemergent
(soybean, cotton, peanut) applications with extended pre-harvest
intervals (45 to 70 days). Plant metabolism protocols (soybean, peanut,
and tomato) have been designed to mimic the field applications with
respect to timing, but have been applied at rates exceeding normal
application to facilitate identification of metabolites.
    The lactofen molecule is rapidly degraded in the environment and in
plants. Therefore, the consistent result of all plant metabolism
studies using lactofen has been: radiocarbon is distributed throughout
the plant; much of the radiocarbon is irreversibly bound; little
radiocarbon is found in the RAC (seeds, fruit); and very little
terminal residue is identified as finite metabolites due to extensive
degradation.
    To demonstrate plant metabolic pathways and to prove the analytical
methods can isolate, recover, and identify lactofen and its
metabolites, plant samples were analyzed soon after application and
well before normal harvest. It is from these early samples that the
definition of the residue has been obtained. The regulated residue is
defined as parent and four metabolites containing the diphenyl ether
moiety. Parent lactofen is identified as PPG-844 and the metabolites
are identified as PPG-847, PPG-947, PPG-1576, and PPG-2597. The
regulated residue as defined has never been found in a RAC sample
either from plant metabolism or from crop field studies. At maximum
treatment rates in crop field trials, only one soybean seed sample was
found to have residues of lactofen greater than the limit of detection,
but less than the limit of quantitation. Even at exaggerated rates in
metabolism or crop residue studies, residues are rarely above the limit
of detection for any analyte. In addition, more than analyte has never
been found above the limit of detection in a single RAC sample from
crop field trials. See further discussion in the Magnitude of Residue
section.
    2.   Analytical method. Adequate analytical methodology (gas
chromatography) is available for detecting and measuring levels of
lactofen and its metabolites in or on food with a limit of detection
that allows monitoring of food with residues at or above the level set
in the time-limited tolerance on cotton. The current method, RM-28D,
has been validated by an independent laboratory on both cottonseed and
peanuts and is still undergoing PMV trials at the EPA. In general, the
analytical method has a limit of detection of 0.005 ppm and limit of
quantitation of 0.01 ppm in crops.
    3.   Magnitude of residues. Lactofen is the active ingredient in
COBRA Herbicide (EPA Reg. No. 59639-34) and STELLAR Herbicide (EPA Reg.
No. 59639-92). Tolerances have been established for lactofen on cotton,
soybeans, and snap beans. A tolerance is also pending for peanuts.
Lactofen is a broad-spectrum broadleaf herbicide with the following use
patterns:
    Soybeans:   pre-emergence and/or post-emergence, broadcast
application with a PHI of 45 days.
    Cotton:   post-emergence, directed spray application with a PHI
of 70 days.
    Snap Beans:   pre-emergence, soil application with a PHI of 55
days.
    Peanuts:   (pending) pre-emergence and/or post-emergence,
broadcast application with a PHI of 70 days.
    Due to relatively long pre-harvest intervals and extensive
metabolism by plants, lactofen residues are rarely found in treated raw
agricultural or processed commodities. Consequently, tolerances have
been established based on the limit of quantitation for lactofen and
its metabolites containing the diphenyl ether linkage. To date,
tolerances have been established at 0.05 ppm based on a limit of
quantitation of 0.01 ppm for lactofen and four plant metabolites.
[[Page 65397]]
B. Toxicological Profile
    1.   Acute toxicity. Lactofen (PPG-844) Technical has been placed
in EPA Toxicity Category III for dermal toxicity and Category IV for
the other four acute toxicity tests. It has also been found to be a
weak skin sensitizer. Teratology and reproduction studies indicate that
adverse effects, including embryotoxicity, occur only at doses that are
also maternally toxic. This chemical therefore represents a minimal
acute toxicity risk.
    2.   Genotoxicity. Lactofen Technical has been tested and produced
negative results in a number of genotoxicity tests including
unscheduled DNA synthesis in rat hepatocytes, DNA covalent binding in
mouse liver, chromosomal aberration in CHO cells, and an Ames assay. In
a second Ames assay lactofen was positive without metabolic activation
at 5000 ug/plate and above. Overall lactofen is not considered a
genetic hazard.
    3.   Reproductive and developmental toxicity. Pregnant rats were
administered oral doses of 0, 15, 50 and 150 mg/kg/day Lactofen
Technical on days 6-19 of gestation. Maternal toxicity (death, abortion
and reduced body weight gain) was observed at 150 mg/kg/day.
Developmental toxicity (reduced fetal weight, slightly reduced
ossification, bent ribs and bent limb bones) was also observed at 150
mg/kg/day. The NOEL for this study was 50 mg/kg/day.
    Two developmental toxicity studies were conducted in rabbits with
Lactofen Technical. In the first study, pregnant rabbits were
administered oral doses of 0, 5, 15 or 50 mg/kg/day Lactofen Technical
on days 6-18 of gestation. Maternal toxicity (clinical signs and
reduced weight gain) and developmental effects (increased embryonic
death, decreased litter size and increased post-implantation loss) were
reported at 15 and 50 mg/kg, however EPA concluded that the data were
insufficient to establish a clear NOEL. The study was classified as
core-supplementary. In the second rabbit developmental toxicity study,
pregnant rabbits were exposed to 0, 1, 4 or 20 mg/kg/day oral doses on
days 6-18 of gestation. Maternal toxicity (reduced food consumption)
was observed at 20 mg/kg/day, while no developmental effects were
observed at any dose. Therefore, the maternal NOEL was 4 mg/kg/day and
the developmental NOEL was greater than 20 mg/kg/day.
    Groups of male and female rats were administered 0, 50, 500 or 2000
ppm of Lactofen Technical for two generations. Adult systemic toxicity
(mortality, reduced body weight, increased liver and spleen weight,
decreased kidney weight and histological changes in the liver and
testes) was observed at levels of 500 ppm and greater. Reproductive
toxicity (lower pup survival rates, reduced pup weight and pup organ
weight effects) was also observed at levels of 500 ppm and greater. The
NOEL for both systemic and reproductive toxicity was 50 ppm (2.5 mg/
kg).
    Since lactofen causes teratogenic and reproductive effects only at
levels which also produce systemic toxicity it is not considered a
reproductive hazard.
    4.   Subchronic toxicity. In a 4-week oral toxicity study of
Lactofen Technical in rats, a slight increase in spleen weight was the
basis for a LOEL of 200 ppm (lowest dose tested). At doses of 1000 ppm
or higher the following findings were reported: clinical signs of
toxicity; decreased RBC, hemoglobin, hematocrit, and increased WBC;
increased relative liver and spleen weights; and necrosis and
pigmentation of hepatocytes. At 10,000 ppm severe toxic signs were
observed by day 7 and all animals were dead or killed in extremis by
day 11. Hypocellularity of the spleen, thymus and bone marrow was also
observed in animals exposed to 10,000 ppm.
    Histopathological changes in the liver and significant changes in
clinical chemistry associated with the liver were observed in rats
exposed to 1000 ppm Lactofen Technical in the diet for 90 days.
Decreased RBC, hemoglobin and hematocrit values were also observed at
1000 ppm. The NOEL in this study was 200 ppm.
    In a 90-day study in mice, the LOEL for Lactofen Technical was 200
ppm based on: increased WBC; decreased hematocrit, hemoglobin and RBC;
increased alkaline phosphatase, SGOT, SGPT, cholesterol and total serum
protein levels; increased weights or enlargement of the spleen, liver,
adrenals, heart and kidney; histopathological changes of the liver,
kidney, thymus, spleen, ovaries and testes observed at 1000 ppm.
    Butler et al (1988) studied the effects of lactofen on peroxisome
proliferation in mice exposed for seven weeks to dietary concentrations
of 2, 10, 50 and 250 ppm. Liver-weight to body-weight ratio, liver
catalase, liver acyl-CoA oxidase, liver cell cytoplasmic eosinophilia,
nuclear and cellular size, and peroxisomal staining were increased by
the tumorigenic dose of lactofen, i.e. 250 ppm. Lower doses of lactofen
had little to no effect on these parameters. Thus, this study indicates
that lactofen induces peroxisome proliferation and further, that 50
ppm, a dose which is not tumorigenic, would be considered a threshold
dose for peroxisome proliferation produced by lactofen.
    As noted in the study by Butler et al (1989), the NOEL for
peroxisome proliferation in mice following a seven week exposure period
is 50 ppm (7 mg/kg/day) and the LOEL is 250 ppm (36 mg/kg/day). A
subchronic study conducted in chimpanzees (Couch and Erickson, 1986),
indicated no effect on clinical chemistry or histological endpoints
that would suggest liver toxicity or peroxisome proliferation at doses
up to 75 mg/kg/day administered for 93 days. Therefore, Valent believes
that 75 mg/kg/day is a clear NOEL for peroxisome proliferation observed
in a species closely related to man.
    5.   Chronic toxicity. In an 18-month oncogenicity study in mice at
doses of 10, 50 and 250 ppm Lactofen Technical, an increase in liver
adenomas and carcinomas, cataracts and liver pigmentation was observed
at 250 ppm. The lowest dose, 10 ppm, was the LOEL based on increased
liver weight and hepatocytomegaly.
    In a 2-year chronic feeding/oncogenicity study of Lactofen
Technical in rats at doses of 500, 1000 or 2000 ppm in the diet, an
increase in liver neoplastic nodules and foci of cellular alteration
was observed in both sexes at 2000 ppm. The NOEL for systemic toxicity
is 500 ppm based on kidney and liver pigmentation.
    In a 1-year study in dogs exposed to 40, 200, or 1000(wk1-17)/3000
ppm(wk 18-52) ppm of Lactofen Technical, the NOEL was determined to be
200 ppm based on renal dysfunction and decreased RBC, hemoglobin
hematocrit and cholesterol observed at 1000/3000 ppm.
    Lactofen (PPG-844) Technical causes adverse health effects when
administered to animals for extended periods of time. The effects
include proliferative changes in the liver, spleen, and kidney;
hematological changes; and blood biochemistry changes. Based on the
Lowest Effect Level (LEL) of 1.5 mg/kg/day in the 18-month mouse
feeding study and an uncertainty factor of 1000, a reference dose (RfD)
of 0.002 mg/kg/day has been established for lactofen. An uncertainty
factor of 1000 was used since a NOEL was not be established.
    The Toxicology Branch Peer Review Committee in EPA's Office of
Pesticide Programs has determined that lactofen meets the criterion for
a B2 (possible human) carcinogen since it caused an increase in liver
tumors (adenomas and/or carcinomas) in two species. Based on
[[Page 65398]]
the mouse oncogenicity study, a human upper-bound potency estimate
(Q1*) was calculated as 0.17 (mg/kg/day)-1.
    The calculated human Q1* was based on the standard interspecies
scaling factor of BW0.67 and recent EPA guidance indicates that BW0.75
is a more appropriate factor for general use. This change alone would
result in a reduction of the calculated human potency factor and a
reduction in the calculated carcinogenic risk by about 20%. In
addition, evidence suggests that carcinogenic effects caused by
lactofen in rodent livers may be due to peroxisomal proliferation as
opposed to a direct genotoxic effect. This mechanism of action would
more appropriately be regulated as a threshold effect (similar to RfD
comparisons) as opposed to a non-threshold effect with a quantitative
potency factor derived from low dose extrapolations. These changes in
the hazard assessment process for lactofen would have a profound effect
on the exposure and risk assessments for this chemical.
    6.   Animal metabolism. Rat metabolism studies have been conducted
for lactofen and demonstrate that lactofen is almost completely
eliminated (>95%) in excreta within three days of oral dosing.
Generally about 60% of orally administered radioactivity (14C-lactofen)
is found in the feces with lactofen itself being the major component.
About 40% of radioactivity is recovered in urine and PPG-847
(hydrolyzed side chain) is the major metabolite. Other metabolites
include PPG-947, PPG-1576, and PPG-2053.
C.   Aggregate Exposure
    Complete information to perform an aggregate exposure assessment
may be available to the Agency, but is not available to Valent, and an
extension of the lactofen cotton tolerance has been requested by Valent
in order to allow EPA time to perform a complete aggregate exposure
assessment. As discussed below, lactofen contributes insignificant
chronic toxicity and carcinogenic risks as compared to the other
diphenyl ethers.
    1.   Dietary exposure. (a)   Food.   Lactofen is approved for use
in the production of commercial agricultural crops including soybeans,
cotton, snap beans, and pine seedlings. Dietary exposures are expected
to represent the major route of exposure to the public.
    A chronic dietary assessment for lactofen has been conducted by the
registrant using Anticipated Residue Contributions (ARC) for existing
and proposed uses of lactofen. Since crop field trial data indicate
that quantifiable residues of lactofen are rarely found in raw
agricultural and processed commodities , ARCs were estimated based on
the analytical method limit of detection (LOD) for each commodity. When
available, analytical results for control samples were used to
determine the method LOD for lactofen and its related metabolites. When
all control samples contained no detectable residues, the limit of
detection was determined to be 0.005 ppm. Mean anticipated residues
were determined based on the sum of residues found above the LOD, or
when no detectable residues were present for lactofen or any
metabolite, one-half the greatest LOD for any analyte was used as the
anticipated residue level. Anticipated residue levels also considered
the percent of crop treated with lactofen as follows: 5% of soybeans,
2.5% of cotton, 4.5% of snap beans, and 5% of peanuts. The soybean and
cotton values are based on 1995 marketing research data (Maritz) and
the snap bean and peanut values are estimates for the future from the
registrant. Note that a lactofen peanut tolerance is still pending at
the Agency and no lactofen is used on this crop even though peanuts are
included in the dietary exposure assessment. The assessment results are
summarized below in the Safety Determination section.
    EPA has performed chronic dietary exposure assessments for the
related diphenyl ethers mentioned above in conjunction with tolerance
approvals. For acifluorfen and fomesafen, recent assessments were
performed with anticipated residues, but did not consider percent of
crop treated. For oxyfluorfen, anticipated residues were considered for
only some crops and the same is true for percent of crop treated. And
for diclofop, neither anticipated residues nor percent of crop treated
were considered. Therefore, the current dietary assessments performed
by EPA are highly conservative, but not worst case. Additional time is
necessary for the Agency to perform a consistent and integrated dietary
exposure assessment for these related chemicals. The assessment results
are summarized below in the Safety Determination section.
    (b)   Drinking water.   Since lactofen is applied outdoors to
growing agricultural crops, the potential exists for lactofen or its
metabolites to leach into groundwater. Drinking water, therefore
represents a potential route of exposure for lactofen and should be
considered in an aggregate exposure assessment.
    Based on available lactofen studies used in EPA's assessment of
environmental risk, EPA required a prospective groundwater study for
lactofen. Valent conducted a study using the maximum application rate
applied to a site which was extremely vulnerable to leaching to a
shallow aquifer. The water table was at a depth of 6 to 9 feet, the top
two feet of soil were classified as loamy sand (78 - 82% sand), and the
deeper soil was classified as sand (88 - 94% sand).
    A final report was submitted in 1994 which indicates that lactofen
degrades rapidly without downward movement in soil and will not
contaminate even shallow groundwater beneath light, sandy soils. There
were no reported or possible detections of lactofen (< 1 ppb) in
lysimeter or monitoring well water samples with the exception of
apparent detections (1.4 - 1.6 ppb) in two well water samples which
were determined to be due to matrix interferences. Reanalysis to
resolve the interference problem indicated that lactofen was not
present at the 1 ppb level. Lactofen degrades to acifluorfen, which was
also monitored in the study. Although acifluorfen was found to degrade
somewhat more slowly than lactofen, it did not leach to groundwater
during the study. Since acifluorfen results from lactofen degradation,
but is not the only degradation product, concentrations are expected to
be lower for acifluorfen than for lactofen. In fact, there were no
reported or possible detections of acifluorfen (< 1 ppb) in lysimeter
or monitoring well samples. This report has been placed in review at
EPA, but a review has not been completed.
    There is no established Maximum Concentration Level for residues of
lactofen in drinking water under the Safe Drinking Water Act.
    Based on this information, lactofen appears to represent an
insignificant risk for exposure through drinking water.
    2.   Non-dietary exposure. Lactofen is currently approved only for
the commercial production of agricultural crops including cotton,
soybeans, snap beans, and pine seedlings. The potential for non-
occupational exposure to the general public, other than through the
diet or drinking water, is therefore insignificant.
D.   Cumulative Effects.
    There are several other pesticide compounds which are structurally
related and may have similar effects on animals. Specifically,
lactofen, acifluorfen, fomesafen, oxyfluorfen, and diclofop methyl are
all diphenyl ethers which have caused liver tumors in
[[Page 65399]]
rodents. These chemicals are approved for food uses in the U.S. and
could be considered in an aggregate exposure assessment. Dietary
exposures to these other diphenyl ethers are expected to represent the
major route of exposure to the public. It is premature to add the risk
from these chemicals since exposure considerations as well as endpoint,
pharmacokinetic, and pharmacodynamic considerations may indicate that
it is inappropriate to add the risks. However, to meet the requirements
of the FQPA of 1996, it is prudent to consider if it is likely that
these chemicals violate the provisions of the new law. The information
presented below indicates that while more study is necessary, it is
unlikely that these materials violate the provisions of the act.
    Summaries of the established reference doses, quantitative cancer
potency factors, and cancer sites in animals for these structurally
related chemicals are presented below.
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                                        Reference Dose (mg/kg/   Cancer
Potency Factor
               Chemical                          day)
(mg/kg/day)<SUP>-1             Cancer Site
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------------------------------------
Lactofen                               0.002                    0.17
Liver
Acifluorfen                            0.013                    0.107
Liver, Stomach
 Fomesafen                             0.0025                   0.19
Liver
Oxyfluorfen                            0.003                    0.13
Liver
Diclofop Methyl                        0.002                    0.231
Liver
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------------------------------------
    This comparison indicates that reference doses determined from
chronic toxicity studies and cancer potency factors for these related
chemicals are on the same order of magnitude as for lactofen.
    It should be noted that these related chemicals would benefit from
the use of the EPA's new interspecies scaling factor as well as
lactofen, and that the rodent liver tumor effects may also be due to
peroxisome proliferation which would more appropriately be regulated as
a threshold effect. The carcinogenic risk assessments performed to date
are, therefore, highly conservative.
E.   Safety Determination
    1.   U.S. population. Using the dietary exposure assessment
procedures described above (and performed by Valent) for lactofen, and
recent EPA assessments for related chemicals, chronic dietary exposures
resulting from existing and proposed uses of lactofen and related
chemicals were compared to the reference dose (RfD) for each chemical.
The following contributions to the RfD were found for the U.S.
Population and all of the subpopulations for which dietary consumption
data are available:
    Lactofen:  less than 0.1% for all subpopulations.
    Acifluorfen:  less than 1% for all subpopulations.
    Fomesafen:  less than 1% for all subpopulations.
    Oxyfluorfen:  less than 1% for all subpopulations.
    Diclofop:  not available to Valent.
    EPA generally has no concern for exposures below 100 percent of the
RfD because the RfD represents the level at or below which daily
aggregate dietary exposure over a lifetime will not pose appreciable
risks to human health. The current and proposed uses of these
chemicals, even when considered collectively, represent a minimal
chronic toxicological risk to the general public.
    Carcinogenic risks were calculated by Valent using a potency factor
(Q1*) for lactofen of 0.17 (mg/kg/day)<SUP>-1. The dietary carcinogenic
risk resulting from existing and proposed uses of lactofen is
calculated at 1.54 X 10<SUP>-8 or less for several lifetime population
groups. This is approximately 65 times lower than the acceptable level
of one-in-a-million additional lifetime cancers. It should be noted
that the proposed use on peanuts, which is not being considered in the
current action, accounts for more than a third of the exposure
contributing to the calculated carcinogenic risk. Therefore, these
estimates of carcinogenic risk are conservative and are well within
acceptable levels.
    EPA has performed dietary carcinogenic risk assessments for the
related diphenyl ethers mentioned above in conjunction with tolerance
approvals. The following table summarizes the dietary risk assessment
made by Valent for lactofen and the most recent dietary risk
assessments performed by EPA for related chemicals.
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------------------------------------
               Chemical                      Data Source
Date              Carcinogenic Risk
----------------------------------------------------------------------------
------------------------------------
Lactofen                               Valent Report            8/20/96
1.54 X 10<SUP>-8
Acifluorfen                            61 FR 16740              4/17/96
5.8 X 10<SUP>-7
Fomesafen                              61 FR 31057              6/19/96
1.56 X 10<SUP>-6
Oxyfluorfen                            60 FR 49816              9/27/95
1.8 X 10<SUP>-6
Diclofop methyl                        51 FR 19176              5/28/86
1 X 10<SUP>-5
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------------------------------------
    Regarding drinking water exposures, groundwater monitoring studies
have been required for acifluorfen, fomesafen, and diclofop methyl as
well as for lactofen. Detections in groundwater have been reported for
acifluorfen and fomesafen. Complete information may be available to the
Agency, but is not to available to Valent, and additional time is
requested to allow time for EPA to adequately address the drinking
water exposure issue. However, based on the lactofen groundwater study,
lactofen exposures to the public through drinking water are expected to
be insignificant compared to these other chemicals.
    Regarding non-dietary exposures, the other diphenyl ethers are also
used primarily for commercial agricultural production. However, some of
these chemicals may involve some uses around the home which could lead
to non-occupational exposure. Information about this small potential
exposure is not available to Valent, but if a significant potential
exists for non-occupational exposure, is should be considered in an
aggregate risk assessment by EPA. Some exposures to residential
pesticides are being evaluated by an industry task force, the Outdoor
Residential Exposure Task Force (ORETF), of which Valent is a member.
    In summary, this comparison shows that lactofen's contribution to
aggregate cancer risk is insignificant compared to the other diphenyl
ethers, based on
[[Page 65400]]
current registrant and EPA assessments. In addition, the conservative
risks calculated by EPA for fomesafen and oxyfluorfen are slightly
above the new standard set by FQPA and for diclofop methyl is
significantly above the new standard. Valent believes that when these
other diphenyl ethers are evaluated using anticipated residues, percent
of crop treated, revised cancer potency factors, and up-to-date
exposure methodology the projected risks will be much lower than 1 X
10<SUP>-6 for all of these chemicals. Industry and EPA are also
developing methodology for determining whether or not multiple
exposures will occur and with what frequency for these and other
chemicals. If multiple exposures do not occur, or occur with a low
frequency, it is not appropriate to add risks. For these reasons,
additional time will be necessary for the Agency to address the
aggregate risk to the U.S. population for this group of related
chemicals.
    2.   Infants and children. As stated above, dietary exposure
assessments utilize less than 1% of the RfD for all subpopulations
including infants and children. Reproduction and developmental effects
have been found in toxicology studies for lactofen, however, the
adverse effects were seen at levels that were also maternally toxic.
This indicates that developing animals are not more sensitive than
adults. FQPA requires an additional safety factor of up to 10 for
chemicals which present special risks to infants or children. Lactofen
does not meet the criterion for application of an additional safety
factor for infants and children.
    Information on the reproduction and developmental effects caused by
the other diphenyl ethers is not available to Valent. Additional time
is necessary for the Agency to evaluate the need for an additional
safety factor related to these other chemicals. However, even if an
additional safety factor were deemed necessary, the dietary exposures
are still expected to be well below the established reference doses.
F.   International Tolerances
    There are no Codex Maximum Residue Limits (MRL) established for
lactofen on cotton commodities, so there is not conflict between this
proposed action and international residue limits.
II.   Administrative Matters
    Interested persons are invited to submit comments on this notice of
filing. Comments must bear a notation indicating the document control
number, [PF-677]. All written comments filed in response to this
petition will be available in the Public Response and Program Resources
Branch, at the address give above from 8:30 a.m. to 4 p.m., Monday
through Friday, except legal holidays.
    A record has been established for this notice under docket number
[PF-677] 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 public
record is located in Rm. 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-Docket@epamail.epa.gov
    Electronic comments must be submitted as ASCII file avoiding the
use of special characters and any form of encryption.
    The official record for this rulemaking, as well as the public
version, as described above will be kept in paper form. Accordingly,
EPA will transfer all comments received electronically into printed,
paper form as they are received and will place the paper copies in the
official rulemaking record which will also include all comments
submitted directly in writing. The official rulemaking record is the
paper record maintained at the 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. 96-31556 Filed 12-11-96; 8:45 am]
BILLING CODE 6560-50-F