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Lactofen (Valent). December
12, 1996. Renewal of Time-Limited Tolerance
for residues on cottonseed at 0.05 ppm. Federal Register.
http://www.epa.gov/docs/fedrgstr/EPA-PEST/1996/December/Day-12/pr-927DIR/pr-927.html
[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]
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.
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
- 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.
- 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.
- 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
- 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.
- 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.
- 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.
- 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.
- 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.
- 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.
- 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 nonoccupational
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.
Reference Dose (mg/kg/ Cancer Potency Factor
Chemical day) (mg/kg/day)<SUP>-1 Cancer Site
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
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
- 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.
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
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