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Lactofen (Valent). September 24, 2004. Pesticide Tolerance. Final Rule. Federal Register.
Docket identification (ID) number OPP-2004-0293
[Federal Register: September 24, 2004 (Volume 69, Number 185)]
[Rules and Regulations]
From the Federal Register Online via GPO Access [wais.access.gpo.gov]
ENVIRONMENTAL PROTECTION AGENCY
40 CFR Part 180
Lactofen; Pesticide Tolerance
AGENCY: Environmental Protection Agency (EPA).
ACTION: Final rule.
SUMMARY: This regulation establishes tolerances for residues of
lactofen in or on cotton undelinted seed, cotton gin byproducts, and
peanut. Valent U.S.A. Corporation requested this tolerance under the
Federal Food, Drug, and Cosmetic Act (FFDCA), as amended by the Food
Quality Protection Act of 1996 (FQPA).
DATES: This regulation is effective September 24, 2004. Objections and
requests for hearings must be received on or before November 23, 2004.
ADDRESSES: To submit a written objection or hearing request follow the
detailed instructions as provided in Unit VI. of the SUPPLEMENTARY
INFORMATION. EPA has established a docket for this action under Docket
identification (ID) number OPP-2004-0293. All documents in the docket
are listed in the EDOCKET index at http://www.epa.gov/edocket/.
Although listed in the index, some information is not publicly
available, i.e., CBI or other information whose disclosure is
restricted by statute. Certain other material, such as copyrighted
is not placed on the Internet and will be publicly available only in
hard copy form. Publicly available docket materials are available
either electronically in EDOCKET or in hard copy at the Public
Information and Records Integrity Branch (PIRIB), Rm. 119, Crystal Mall
#2, 1801 S. Bell St., Arlington, VA. This docket facility is
open from 8:30 a.m. to 4 p.m., Monday through Friday, excluding legal
holidays. The docket telephone number is (703) 305-5805.
FOR FURTHER INFORMATION CONTACT: Joanne I. Miller, Registration
Division (7505C), Office of Pesticide Programs, Environmental
Protection Agency, 1200 Pennsylvania Ave., NW., Washington, DC 20460-
0001; telephone number: (703) 305-6224; e-mail address:
I. General Information
A. Does this Action Apply to Me?
You may be potentially affected by this action if you are an
agricultural producer, food manufacturer, or pesticide manufacturer.
Potentially affected entities may include, but are not limited to:
• Crop production (NAICS 111), e.g., agricultural workers;
greenhouse, nursery, and floriculture workers; farmers.
• Animal production (NAICS 112), e.g., cattle ranchers and
farmers, dairy cattle farmers, livestock farmers.
• Food manufacturing (NAICS 311), e.g., agricultural
workers; farmers; greenhouse, nursery, and floriculture workers;
ranchers; pesticide applicators.
• Pesticide manufacturing (NAICS 32532), e.g., agricultural
workers; commercial applicators; farmers; greenhouse, nursery, and
floriculture workers; residential users.
This listing is not intended to be exhaustive, but rather provides
a guide for readers regarding entities likely to be affected by this
action. Other types of entities not listed in this unit could also be
affected. The North American Industrial Classification System (NAICS)
codes have been provided to assist you and others in determining
whether this action might apply to certain entities. If you have any
questions regarding the applicability of this action to a particular
entity, consult the person listed under FOR FURTHER INFORMATION CONTACT.
B. How Can I Access Electronic Copies of this Document and Other
In addition to using EDOCKET (http://www.epa.gov/edocket/), you may
access this Federal Register document electronically through the EPA
Internet under the ``Federal Register'' listings at http://www.epa.gov/
fedrgstr/. A frequently updated electronic version of 40 CFR part 180
is available on E-CFR Beta Site Two at http://www.gpoaccess.gov/ecfr/.
To access the OPPTS Harmonized Guidelines referenced in this
document, go directly to the guidelines at
II. Background and Statutory Findings
In the Federal Register of January 29, 2003 (68 FR 4475) (FRL-7287-
6), EPA issued a notice pursuant to section 408(d)(3) of FFDCA, 21
U.S.C. 346a(d)(3), announcing the filing of pesticide petitions (PP
8F3591 and 9F3798) by Valent U.S.A. Corporation, 1333 North California
Blvd., Suite 600, Walnut Creek, CA 94596-8025. The petitions requested
that 40 CFR 180.432 be amended by establishing tolerances for residues
of the herbicide lactofen, 1-(carboethoxy)ethyl 5-[2-chloro-4-
(trifluoromethyl)phenoxy]-2-nitrobenzoate, in or on cottonseed at 0.01
part per million (ppm), cotton gin byproducts at 0.02 ppm (PP 9F3798),
and peanut nutmeats at 0.01 ppm (PP 8F3591). That notice included a
summary of the petitions prepared by Valent U.S.A. Corporation, the
registrant. There were no comments received in response to the notice
The proposed and established tolerances are corrected to conform to
the Food and Feed Commodity Vocabulary Database (http://www.epa.gov/
pesticides/foodfeed/) and to lower the established tolerances for snap
bean and soybean to 0.01 ppm as required by the Lactofen Tolerance
to read as follows: Tolerances for residues of the herbicide lactofen,
nitrobenzoate, in or on beans, snap, succulent (excluding limas) at
0.01 ppm; cotton, undelinted seed at 0.01 ppm; cotton, gin byproducts
at 0.02 ppm; peanut at 0.01 ppm; and soybean, seed at 0.01 ppm.
Section 408(b)(2)(A)(i) of FFDCA allows EPA to establish a
tolerance (the legal limit for a pesticide chemical residue in or on a
food) only if EPA determines that the tolerance is ``safe.'' Section
408(b)(2)(A)(ii) of FFDCA defines ``safe'' to mean that ``there is a
reasonable certainty that no harm will result from aggregate exposure
to the pesticide chemical residue, including all anticipated dietary
exposures and all other exposures for which there is reliable
information.'' This includes exposure through drinking water and in
residential settings, but does not include occupational exposure.
Section 408(b)(2)(C) of FFDCA requires EPA to give special
consideration to exposure of infants and children to the pesticide
chemical residue in establishing a tolerance and to ``ensure that there
is a reasonable certainty that no harm will result to infants and
children from aggregate exposure to the pesticide chemical residue....''
EPA performs a number of analyses to determine the risks from
aggregate exposure to pesticide residues. For further discussion of the
regulatory requirements of section 408 of FFDCA and a complete
description of the risk assessment process, see the final rule on
Bifenthrin Pesticide Tolerances (62 FR 62961, November 26, 1997) (FRL-
III. Aggregate Risk Assessment and Determination of Safety
Consistent with section 408(b)(2)(D) of FFDCA, EPA has reviewed the
available scientific data and other relevant information in support of
this action. EPA has sufficient data to assess the hazards of and to
make a determination on aggregate exposure, consistent with section
408(b)(2) of FFDCA, for tolerances for residues of lactofen on cotton,
undelinted seed at 0.01 ppm; cotton, gin byproducts at 0.02 ppm; and
peanut at 0.01 ppm ppm. EPA's assessment of exposures and risks
associated with establishing the tolerances follows.
A. Toxicological Profile
EPA has evaluated the available toxicity data and considered its
validity, completeness, and reliability as well as the relationship of
the results of the studies to human risk. EPA has also considered
available information concerning the variability of the sensitivities
of major identifiable subgroups of consumers, including infants and
children. The nature of the toxic effects caused by lactofen are
discussed in Table 1 of this unit as well as the no observed adverse
effect level (NOAEL) and the lowest observed adverse effect level
(LOAEL) from the toxicity studies reviewed.
Table 1.--Subchronic, Chronic, and Other Toxicity
Study Type Results 870.3100 13-Week oral toxicity-- rodents (rat) NOAEL = 14.1 milligrams/kilogram/day (mg/kg/ day).
LOAEL = 73.7 mg/kg/day based on decreased body weight, increased incidence of anemia, increased levels of serum enzymes and bilirubin, decreased levels of glucose, increased liver weights, and increased incidence of microscopic liver lesions.
870.3100 90-Day oral toxicity-- rodents (mouse) NOAEL = not established.
LOAEL = 28.6 mg/kg/day based on changes clinical chemistry parameters, increases in organ weight, and histopathological findings.
870.3700 Prenatal developmental-- rodents (rat) Maternal NOAEL = 50 mg/kg/day.
Maternal LOAEL = 150 mg/kg/day based on signs of toxicity (excessive salivation, lethargy, dried red material around the nares and inguinal regions) and statistically significant decreases in body weight gain.
Developmental NOAEL = 50 mg/kg/day.
Developmental LOAEL = 150 mg/kg/day based on decreased fetal weight and skeletal abnormalities (increased incidence of bent ribs and/or limb bones) and reduced ossification of vertebral arches.
870.3700 Prenatal developmental- - nonrodents (rabbit) Maternal NOAEL >= 20 mg/kg/day.
Maternal LOAEL > 20 mg/kg/day Highest Dose Tested (HDT).
Developmental NOAEL >= 20 mg/kg/day.
Developmental LOAEL > 20 mg/kg/day HDT.
870.3800 Reproduction and fertility effects Parental/Systemic NOAEL = 2.6 mg/kg/day.
Parental/Systemic LOAEL = 26.2 mg/kg/day based on mortality and decreased male fertility.
Reproductive NOAEL = 2.6 mg/kg/day.
Reproductive LOAEL = 26.2 mg/kg/day based on decreased male fertility.
Offspring NOAEL = 2.6 mg/kg/day.
Offspring LOAEL = 26.2 mg/kg/day based on reduced pup body weigh and decreases in the absolute and relative spleen weight.
870.4100 Chronic toxicity--dogs NOAEL = 0.79 mg/kg/day.
LOAEL = 3.96 mg/kg/day based on increased incidence of proteinaceous casts in the kidneys, and statistically significant increases in the absolute weights of the thyroid and adrenal glands in males.
870.4300 Combined Chronic toxicity Carcinogenicity--rats NOAEL = 2 mg/kg/day.
LOAEL = 19 mg/kg/day based on statistically significant increases in the incidence of mottled or discolored livers and changes in clinical chemistry.
No evidence of carcinogenicity.
870.4300 Carcinogenicity--mice NOAEL = not established.
LOAEL = 1.4 mg/kg/day Lowest Dose Tested (LDT) based on hepatocytomegaly, increased liver weight, and increased sinusoidal cell pigmentation. Likely to be carcinogenic to humans at high enough doses to cause these biochemical and histopathological effects (peroxisome proliferation) in the livers of rodents but unlikely to be carcinogenic at doses below those causing these changes.
870.5100 Gene mutation in S. typhimurium/ mammalian microsome mutagenicity assay. No cytotoxicity evident at 50 [mu]g (gram)/
plate in the absence or presence of
metabolic activation. PPG-844 induced a
dose-related increase in revertant colonies
of strain TA1538 in the absence of S9
activation; however, no effect seen in strain TA98 (derived from TA1538).
870.5100 Gene mutation in S. typhimurium/mammalian microsome mutagenicity assay Cytotoxicity was not evident for any strain
up to the limit dose (5,000Fg/plate). No
evidence of PPG-844 induced mutagenic
870.5375 In vitro cytogenetic assay with Chinese Hamster Ovary (CHO) cells No evidence of clastogenic effect in the
presence or absence of S9 activation.
870.5375 Mammalian cells in culture gene mutation in CHO cells No evidence of cytotoxicity at any dose
tested. No clear indication of mutagenic
effect in the presence or absence of S9
870.5550 Unscheduled DNA Synthesis No unscheduled DNA synthesis. - In vivo DNA covalent binding in mouse liver In vivo DNA covalent A covalent binding index of 1.4 ± 0.6 was determined for lactofen.
This suggests a low binding to mouse
hepatic DNA may occur. This finding could
not be attributed solely to DNA binding
since some protein-binding of the parent
compound and/or metabolite could be
- Analysis of biochemical and microscopic parameters in Chimpanzee liver Aryl CoA oxidase, catalase, and carnitine acetlytransferase activities not affected by treatment. No nuclear enlargement, cytoplasmic eosinophilia, or hepertrophy observed in liver biopsies after 0, 1, and 3 months of treatment. Slight + response for peroxisomal staining (brown stippling). - Results of the analysis of biochemical parameters in mouse and rat liver Following Exposure to PPG-844. Catalase and CN-insensitive palmiloyl CoA
oxidase increased. Rats (2,000 ppm) and
mice (50 ppm) showed increased nuclear
enlargement, cytoplasmic eosinophilia,
hypertrophy, and peroxisomes in number of
The NOAEL for this study was established at 0.3 mg/kg/day, based on increased
activities of liver enzymes and increased
incidence of liver histopathological
findings at the LOAEL of 1.5 mg/kg/day.
- Measurement of peroxisome proliferation in primary rat hepatocytes induced by PPG-844 and five of its metabolites Concentration-dependent increase in CN-
insensitive palmitoyl CoA oxidase
activities with each of the metabolites.
EM: Lactofen (0.01 millimole (mM))
increased number of peroxisomes and
glycogen aggregates. Other metabolites
showed occasional peroxisomes.
B. Toxicological Endpoints
The dose at which no adverse effects are observed (the NOAEL) from
the toxicology study identified as appropriate for use in risk
assessment is used to estimate the toxicological level of concern
(LOC). However, the lowest dose at which adverse effects of concern are
identified (the LOAEL) is sometimes used for risk assessment if no
NOAEL was achieved in the toxicology study selected. An uncertainty
factor (UF) is applied to reflect uncertainties inherent in the
extrapolation from laboratory animal data to humans and in the
variations in sensitivity among members of the human population as well
as other unknowns. An UF of 100 is routinely used, 10X to account for
interspecies differences and 10X for intraspecies differences.
Three other types of safety or uncertainty factors may be used:
``Traditional uncertainty factors;'' the ``special FQPA safety
factor;'' and the ``default FQPA safety factor.'' By the term
``traditional uncertainty factor,'' EPA is referring to those
additional uncertainty factors used prior to FQPA passage to account
for database deficiencies. These traditional uncertainty factors have
been incorporated by the FQPA into the additional safety factor for the
protection of infants and children. The term ``special FQPA safety
factor'' refers to those safety factors that are deemed necessary for
the protection of infants and children primarily as a result of the
FQPA. The ``default FQPA safety factor'' is the additional 10X safety
factor that is mandated by the statute unless it is decided that there
are reliable data to choose a different additional factor (potentially
a traditional uncertainty factor or a special FQPA safety factor).
For dietary risk assessment (other than cancer) the Agency uses the
UF to calculate an acute or chronic reference dose (acute RfD or
chronic RfD) where the RfD is equal to the NOAEL divided by an UF of
100 to account for interspecies and intraspecies differences and any
traditional uncertainty factors deemed appropriate (RfD = NOAEL/UF).
Where a special FQPA safety factor or the default FQPA safety factor is
used, this additional factor is applied to the RfD by dividing the RfD
by such additional factor. The acute or chronic Population Adjusted
Dose (aPAD or cPAD) is a modification of the RfD to accommodate this
type of safety factor.
For non-dietary risk assessments (other than cancer) the UF is used
to determine the LOC. For example, when 100 is the appropriate UF (10X
to account for interspecies differences and 10X for intraspecies
differences) the LOC is 100. To estimate risk, a ratio of the NOAEL to
exposures (margin of exposure (MOE) = NOAEL/exposure) is calculated and
compared to the LOC.
The linear default risk methodology (Q*) is the primary method
currently used by the Agency to quantify carcinogenic risk. The Q*
approach assumes that any amount of exposure will lead to some degree
of cancer risk. A Q* is calculated and used to estimate risk which
represents a probability of occurrence of additional cancer cases
(e.g., risk). An example of how such a probability risk is expressed
would be to describe the risk as one in one hundred thousand (1 X
10-\5\), one in a million (1 X 10-\6\), or one in
ten million (1 X 10-\7\). Under certain specific
circumstances, MOE calculations will be used for the carcinogenic risk
assessment. In this non-linear approach, a ``point of departure'' is
identified below which carcinogenic effects are not expected. The point
of departure is typically a NOAEL based on an endpoint related to
cancer effects though it may be a different value derived from the dose
response curve. To estimate risk, a ratio of the point of departure to
exposure (MOEcancer = point of departure/exposures) is
A summary of the toxicological endpoints for lactofen used for
human risk assessment is shown in Table 2 of this unit:
Table 2.--Summary of Toxicological Dose and Endpoints for lactofen for Use in Human Risk Assessment Exposure Scenario Dose Used in Risk
Assessment, Interspecies and Intraspecies and any Traditional UF
Special FQPA SF and Level of Concern for Risk Assessment Study and Toxicological Effects Acute Dietary (Females 13-50 years of age) NOAEL = 50 mg/kg/day UF
= 100 Acute RfD = 0.5 mg/kg/day
Special FQPA SF = 3 aPAD = acute RfD/ Special FQPA SF = 0.17 mg/kg/day Rat Developmental Toxicity Study
LOAEL = 150 mg/kg/day based on decreased fetal weight and skeletal
Acute Dietary (General population including infants and children). An endpoint attributable to a single dose (exposure) was not identified from the available studies, including the developmental toxicity studies in rats and rabbits. Chronic Dietary (All populations) NOAEL = 0.79 mg/kg/day
UF = 100 Chronic RfD = 0.008 mg/kg/day
Special FQPA SF = 1 cPAD = chronic RfD/ Special FQPA SF = 0.008 mg/kg/day Dog chronic toxicity LOAEL = 3.96 mg/kg/day based on increased incidence of
proteinaceous casts in
the kidneys, and
statistically significant increases in the absolute weights of the thyroid and adrenal glands in males.
Cancer (Oral, dermal, inhalation) Lactofen acts via a peroxisome proliferation mechanism of action. Likely to be carcinogenic to humans at high enough doses to cause these biochemical and histopathological effects (peroxisome proliferation) in the livers of rodents but unlikely to be carcinogenic at doses below those causing these changes. Lactofen is considered to be a threshold carcinogen. NOAEL = 0.3 mg/kg/day based on increased activities of liver enzymes and increased incidence of liver histopathological findings at the LOAEL of 1.5 mg/kg/day.
C. Exposure Assessment
1. Dietary exposure from food and feed uses. Tolerances have been
established (40 CFR 180.432) for the residues of lactofen in or on
succulent snap bean and soybeans. Risk assessments were conducted by
EPA to assess dietary exposures from lactofen in food as follows:
i. Acute exposure. Acute dietary risk assessments are performed for
a food-use pesticide, if a toxicological study has indicated the
possibility of an effect of concern occurring as a result of a 1-day or
The Dietary Exposure Evaluation Model (DEEM\TM\) analysis evaluated
the individual food consumption as reported by respondents in the USDA
1989-1992 Nationwide Continuing Surveys of Food Intake by Individuals
(CSFII) and accumulated exposure to the chemical for each commodity.
The following assumptions were made for the acute exposure assessments:
The acute dietary analysis uses average food residue values from field
trial studies and percent crop treated (PCT) information.
ii. Chronic exposure. In conducting this chronic dietary risk
assessment, the DEEM\TM\ analysis evaluated the individual food
consumption as reported by respondents in the USDA 1989-1992 CSFII and
accumulated exposure to the chemical for each commodity. The following
assumptions were made for the chronic exposure assessments: The chronic
dietary analysis utilized average residue values based on field trial
studies, concentration factors from processing studies, and PCT
iii. Cancer. In conducting this cancer dietary risk assessment, the
DEEM\TM\ analysis evaluated the individual food consumption as reported
by respondents in the USDA 1989-1992 CSFII and accumulated exposure to
the chemical for each commodity. The following assumptions were made
for the chronic exposure assessments: The chronic dietary analysis
utilized the average consumption values for food and average residue
values for those foods over a 70-year lifetime.
iv. Anticipated residue and PCT information. Section 408(b)(2)(E)
of FFDCA authorizes EPA to use available data and information on the
anticipated residue levels of pesticide residues in food and the actual
levels of pesticide chemicals that have been measured in food. If EPA
relies on such information, EPA must require that data be provided 5
years after the tolerance is established, modified, or left in effect,
demonstrating that the levels in food are not above the levels
anticipated. Following the initial data submission, EPA is authorized
to require similar data on a time frame it deems appropriate. As
required by section 408(b)(2)(E) of FFDCA, EPA will issue a data call-
in for information relating to anticipated residues to be submitted no
later than 5 years from the date of issuance of this tolerance.
Section 408(b)(2)(F) of FFDCA states that the Agency may use data
on the actual percent of food treated for assessing chronic dietary
risk only if the Agency can make the following findings:
Condition 1, that the data used are reliable and provide a valid
basis to show what percentage of the food derived from such crop is
likely to contain such pesticide residue.
Condition 2, that the exposure estimate does not underestimate
exposure for any significant subpopulation group
Condition 3, if data are available on pesticide use and food
consumption in a particular area, the exposure estimate does not
understate exposure for the population in such area.
In addition, the Agency must provide for periodic evaluation of any
estimates used. To provide for the periodic evaluation of the estimate
of PCT as required by section 408(b)(2)(F) of FFDCA, EPA may require
registrants to submit data on PCT.
The Agency used PCT information as follows:
Table 3.--PCT for Registered Lactofen Uses Crop PCT Cotton 5 Succulent snap beans
5 Soybeans 5
The Agency believes that the three conditions listed in this unit
have been met. With respect to Condition 1, PCT estimates are derived
from Federal and private market survey data, which are
reliable and have a valid basis. EPA uses a weighted average PCT for
chronic dietary exposure estimates. This weighted average PCT figure is
derived by averaging State-level data for a period of up to 10 years,
and weighting for the more robust and recent data. A weighted average
of the PCT reasonably represents a person's dietary exposure over a
lifetime, and is unlikely to underestimate exposure to an individual
because of the fact that pesticide use patterns (both regionally and
nationally) tend to change continuously over time, such that an
individual is unlikely to be exposed to more than the average PCT over
a lifetime. For acute dietary exposure estimates, EPA uses an estimated
maximum PCT. The exposure estimates resulting from this approach
reasonably represent the highest levels to which an individual could be
exposed, and are unlikely to underestimate an individual's acute
dietary exposure. The Agency is reasonably certain that the percentage
of the food treated is not likely to be an underestimation. As to
Conditions 2 and 3, regional consumption information and consumption
information for significant subpopulations is taken into account
through EPA's computer-based model for evaluating the exposure of
significant subpopulations including several regional groups. Use of
this consumption information in EPA's risk assessment process ensures
that EPA's exposure estimate does not understate exposure for any
significant subpopulation group and allows the Agency to be reasonably
certain that no regional population is exposed to residue levels higher
than those estimated by the Agency. Other than the data available
through national food consumption surveys, EPA does not have available
information on the regional consumption of food to which lactofen may
be applied in a particular area.
2. Dietary exposure from drinking water. The Agency lacks
sufficient monitoring exposure data to complete a comprehensive dietary
exposure analysis and risk assessment for lactofen in drinking water.
Because the Agency does not have comprehensive monitoring data,
drinking water concentration estimates are made by reliance on
simulation or modeling taking into account data on the physical
characteristics of lactofen.
The Agency uses the Generic Estimated Environmental Concentration
(GENEEC) or the Pesticide Root Zone Model/Exposure Analysis Modeling
System (PRZM/EXAMS) to estimate pesticide concentrations in surface
water and Screening Concentration in Ground Water (SCI-GROW), which
predicts pesticide concentrations in ground water. In general, EPA will
use GENEEC (a tier 1 model) before using PRZM/EXAMS (a tier 2 model)
for a screening-level assessment for surface water. The GENEEC model is
a subset of the PRZM/EXAMS model that uses a specific high-end runoff
scenario for pesticides. GENEEC incorporates a farm pond scenario,
while PRZM/EXAMS incorporate an index reservoir environment in place of
the previous pond scenario. The PRZM/EXAMS model includes a percent
crop area factor as an adjustment to account for the maximum percent
crop coverage within a watershed or drainage basin.
None of these models include consideration of the impact processing
(mixing, dilution, or treatment) of raw water for distribution as
drinking water would likely have on the removal of pesticides from the
source water. The primary use of these models by the Agency at this
stage is to provide a screen for sorting out pesticides for which it is
unlikely that drinking water concentrations would exceed human health
levels of concern.
Since the models used are considered to be screening tools in the
risk assessment process, the Agency does not use estimated
environmental concentrations (EECs), which are the model estimates of a
pesticide's concentration in water. EECs derived from these models are
used to quantify drinking water exposure and risk as a %RfD or %PAD.
Instead drinking water levels of comparison (DWLOCs) are calculated and
used as a point of comparison against the model estimates of a
pesticide's concentration in water. DWLOCs are theoretical upper limits
on a pesticide's concentration in drinking water in light of total
aggregate exposure to a pesticide in food, and from residential uses.
Since DWLOCs address total aggregate exposure to lactofen they are
further discussed in the aggregate risk sections in Unit III.E.
Based on the PRZM/EXAMS and SCI-GROW models, the EECs of lactofen
for acute exposures are estimated to be 0.39 parts per billion (ppb)
for surface water and 0.006 ppb for ground water. The EECs for chronic
exposures are estimated to be 0.008 ppb for surface water and 0.006 ppb
for ground water.
3. From non-dietary exposure. The term ``residential exposure'' is
used in this document to refer to non-occupational, non-dietary
exposure (e.g., for lawn and garden pest control, indoor pest control,
termiticides, and flea and tick control on pets).
Lactofen is not registered for use on any sites that would result
in residential exposure.
4. Cumulative effects from substances with a common mechanism of
toxicity. Section 408(b)(2)(D)(v) of FFDCA requires that, when
considering whether to establish, modify, or revoke a tolerance, the
Agency consider ``available information'' concerning the cumulative
effects of a particular pesticide's residues and ``other substances
that have a common mechanism of toxicity.''
Lactofen is a member of the diphenyl ether group of herbicides,
which includes acifluorfen (lactofen's major metabolite), nitrofen,
oxyfluorfen, and fomefasen. In addition, lactofen degrades to
acifluorfen in the environment. The Agency has evidence that these
compounds induce similar toxic effects but has not yet determined
whether these compounds exhibit a common mechanism of toxicity. The
Agency defers the cumulative risk assessment of lactofen and the other
diphenyl ethers to a later date. For the purposes of this tolerance
action, therefore, EPA has not assumed that lactofen has a common
mechanism of toxicity with other substances. For information regarding
EPA's efforts to determine which chemicals have a common mechanism of
toxicity and to evaluate the cumulative effects of such chemicals, see
the policy statements released by EPA's OPP concerning common mechanism
determinations and procedures for cumulating effects from substances
found to have a common mechanism on EPA's web site at
D. Safety Factor for Infants and Children
1. In general. Section 408 of FFDCA provides that EPA shall apply
an additional tenfold margin of safety for infants and children in the
case of threshold effects to account for prenatal and postnatal
toxicity and the completeness of the data base on toxicity and exposure
unless EPA determines based on reliable data that a different margin of
safety will be safe for infants and children. Margins of safety are
incorporated into EPA risk assessments either directly through use of a
MOE analysis or through using uncertainty (safety) factors in
calculating a dose level that poses no appreciable risk to humans. In
applying this provision, EPA either retains the default value of 10X
when reliable data do not support the choice of a different factor, or,
if reliable data are available, EPA uses a different additional safety
factor value based on the use of traditional uncertainty factors and/or
special FQPA safety factors, as appropriate.
2. Prenatal and postnatal sensitivity. The toxicology database for
lactofen is complete for FQPA purposes except for a developmental
toxicity study in rabbits. Based on the quality of the exposure data,
EPA determined that the 10X SF to protect infants and children should
be reduced to 3X and still be protective for any possible toxicity to
infants and children which might be observed in the missing rabbit
developmental study. The FQPA factor was reduced based on the following:
i. The available data provide no indication of quantitative or
qualitative increased susceptibility from in utero and/or postnatal
exposure to lactofen in rats.
ii. The available rabbit developmental toxicity study was
considered unacceptable because dosing was not done at a high enough
level to observe significant toxicity. However, the study provides
sufficient information to indicate that the NOAEL for both maternal and
developmental effects will be 20 mg/kg/day (the HDT that elicited no
significant toxicity) or higher. The acute dietary risk assessment for
which the missing rabbit developmental study could potentially be used
currently uses a NOAEL = 50 mg/kg/day from the rat developmental study.
Risk estimates using a new developmental rabbit study could increase at
most by a factor of 2.5X (50/20 mg/kg/day); therefore, a 3X UF is
protective for any toxicity which might be observed in the outstanding
rabbit developmental study.
iii. Endpoints for other risk assessments (chronic and cancer)
utilize NOAELs significantly lower than 20mg/kg/day; therefore the
developmental rabbit study will not affect these assessments. Based on
mechanistic studies with transgenic mice, lactofen has been classified
as a non-genotoxic hepatocarcinogen in rodents with peroxisome
proliferation being a plausible mode of action. Lactofen is currently
classified as likely to be carcinogenic to humans at high enough doses
to cause the biochemical and histopathological changes in the liver of
rodents, but unlikely to be carcinogenic to humans below those doses
causing these changes. A non-linear methodology (MOE) was applied for
the estimation of human cancer risk using a NOAEL of 0.3 mg/kg/day.
Generally, for threshold cancer effects where the mode of action is
well understood, the general margin of exposure that indicates a
reasonable certainty of no harm would be 100 (10X for intraspecies
extrapolation and 10X for interspecies variation). Given that the %
cPAD (Food) is < 0.1 % and the cancer MOE is 300,000 for the U.S.
population, a 100 fold safety factor would be protective for chronic
and cancer toxicity.
iv. Adequate actual data, surrogate data, and/or modeling outputs
are available to satisfactorily assess food exposure and to provide a
screening level drinking water exposure assessment (there are currently
no residential uses). Since there is uncertainty associated with the
data gap for a developmental toxicity study in rabbits with lactofen
the safety factor is reduced to 3X.
3. Conclusion. There is a complete toxicity data base for lactofen
except for a developmental toxicity study in rabbits and exposure data
are complete or are estimated based on data that reasonably accounts
for potential exposures.
E. Aggregate Risks and Determination of Safety
To estimate total aggregate exposure to a pesticide from food,
drinking water, and residential uses, the Agency calculates DWLOCs
which are used as a point of comparison against EECs. DWLOC values are
not regulatory standards for drinking water. DWLOCs are theoretical
upper limits on a pesticide's concentration in drinking water in light
of total aggregate exposure to a pesticide in food and residential
uses. In calculating a DWLOC, the Agency determines how much of the
acceptable exposure (i.e., the PAD) is available for exposure through
drinking water [e.g., allowable chronic water exposure (mg/kg/day) =
cPAD - (average food + residential exposure)]. This allowable exposure
through drinking water is used to calculate a DWLOC.
A DWLOC will vary depending on the toxic endpoint, drinking water
consumption, and body weights. Default body weights and consumption
values as used by the EPA's Office of Water are used to calculate
DWLOCs: 2 liter (L)/70 kg (adult male), 2L/60 kg (adult female), and
1L/10 kg (child). Default body weights and drinking water consumption
values vary on an individual basis. This variation will be taken into
account in more refined screening-level and quantitative drinking water
exposure assessments. Different populations will have different DWLOCs.
Generally, a DWLOC is calculated for each type of risk assessment used:
Acute, short-term, intermediate-term, chronic, and cancer.
When EECs for surface water and ground water are less than the
calculated DWLOCs, OPP concludes with reasonable certainty that
exposures to the pesticide in drinking water (when considered along
with other sources of exposure for which OPP has reliable data) would
not result in unacceptable levels of aggregate human health risk at
this time. Because OPP considers the aggregate risk resulting from
multiple exposure pathways associated with a pesticide's uses, levels
of comparison in drinking water may vary as those uses change. If new
uses are added in the future, OPP will reassess the potential impacts
of residues of the pesticide in drinking water as a part of the
aggregate risk assessment process.
1. Acute risk. Using the exposure assumptions discussed in this
unit for acute exposure, the acute dietary exposure from food to
lactofen will occupy < 0.1% of the aPAD for females 13 years and older.
In addition, there is potential for acute dietary exposure to lactofen
in drinking water. After calculating DWLOCs and comparing them to the
EECs for surface and ground water, EPA does not expect the aggregate
exposure to exceed 100% of the aPAD, as shown in Table 4 of this unit:
Table 4.--Aggregate Risk Assessment for Acute Exposure to Lactofen Population Subgroup - Females 13 years and older aPAD (mg/kg) 0.17 % aPAD (Food) < 0.1% Surface Water EEC (ppb) 0.39 Ground Water EEC (ppb) 0.006 Acute DWLOC (ppb) 5,100
2. Chronic risk. Using the exposure assumptions described in this
unit for chronic exposure, EPA has concluded that exposure to lactofen
from food will utilize < 0.1% of the cPAD for the U.S. population, < 0.1
% of the cPAD for children 1-6, and < 0.1% of the cPAD for Females 13
years and older. There are no residential uses for lactofen that
result in chronic residential exposure to lactofen. In addition, there
is potential for chronic dietary exposure to lactofen in drinking
water. After calculating DWLOCs and comparing them to the EECs for
surface and ground water, EPA does not expect the aggregate exposure to
exceed 100% of the cPAD, as shown in Table 5 of this unit:
Table 5.--Aggregate Risk Assessment for Chronic (Non-Cancer) Exposure to Lactofen Population Subgroup
cPAD mg/kg/day 0.08 % cPAD (Food) < 0.1% Surface Water EEC (ppb) 0.008 Ground Water EEC (ppb) 0.006 Chronic DWLOC (ppb) 80
cPAD mg/kg/day 0.08 % cPAD (Food) < 0.1% Surface Water EEC (ppb) 0.008 Ground Water EEC (ppb) 0.006 Chronic DWLOC (ppb) 80
cPAD mg/kg/day 0.08 % cPAD (Food) < 0.1% Surface Water EEC (ppb) 0.008 Ground Water EEC (ppb) 0.006 Chronic DWLOC (ppb) 80
3. Short-term risk. Short-term aggregate exposure takes into
account residential exposure plus chronic exposure to food and water
(considered to be a background exposure level).
Lactofen is not registered for use on any sites that would result
in residential exposure. Therefore, the aggregate risk is the sum of
the risk from food and water, which do not exceed the Agency's level of
4. Aggregate cancer risk for U.S. population. Lactofen is
considered to be a threshold carcinogen. Because lactofen is considered
to be unlikely to be carcinogenic at low doses, the chronic exposure
value is compared with a NOAEL to determine the cancer risk estimate.
DWLOCs were calculated based on NOAEL of 0.3 mg/kg/day from a special
7-week rodent study which evaluated peroxisome proliferation in the
liver of rats and mice. The aggregate cancer risk is presented in Table
6 of this unit.
Table 6.--Aggregate Risk Assessment for Cancer From Exposure to Lactofen Population Subgroup U.S. Population Cancer MOE from food alone 300,000 Surface Water EEC (ppb) 0.005 Ground Water EEC (ppb) 0.006 Cancer DWLOC (ppb) 105
5. The Agency also conducted an aggregate chronic and cancer risk
assessment for acifluorfen, derived from the use of the herbicides
lactofen and sodium acifluorfen, by comparing the total acifluorfen
surface water and groundwater EECs with the corresponding DWLOCs. As
indicated in Table 7 of this unit, the EECs for all exposures were less
than the corresponding DWLOCs; therefore, the Agency has no concern for
the aggregate risk of the acifluorfen degradate from both lactofen and
Table 7.--Aggregate Chronic and Cancer Risk Assessments From Exposure to Total Aciflurofen Degradate From all Sources Population Subgroup U.S. Population Surface Water EEC (ppb) (Chronic) 2.43 Surface Water EEC (ppb) (Cancer) 1.34 Ground Water EEC (ppb) 3.71 Chronic DWLOC (ppb) 80 Cancer DWLOC (ppb) 105
6. Determination of safety. Based on these risk assessments, EPA
concludes that there is a reasonable certainty that no harm will result
to the general population, and to infants and children from aggregate
exposure to lactofen residues.
IV. Other Considerations
A. Analytical Enforcement Methodology
Adequate enforcement methodology (example--gas chromotography) is
available to enforce the tolerance expression. The method may be
requested from: Chief, Analytical Chemistry Branch, Environmental
Science Center, 701 Mapes Rd., Ft. Meade, MD 20755-5350; telephone
number: (410) 305-2905; e-mail address: email@example.com.
B. International Residue Limits
No maximum residue limits (MRLs) for lactofen have been established
or proposed by Codex, Canada, or Mexico for any agricultural commodity;
therefore, no compatibility questions exist with respect to U.S.
The following data must be submitted: Developmental toxicity study
Therefore, the tolerance is established for residues of lactofen,
nitrobenzoate, in or on cotton, undelinted seed at 0.01 ppm; cotton,
gin byproducts at 0.02 ppm, and peanut at 0.01 ppm.
In addition, this regulatory action is part of the tolerance
reassessment requirements of section 408(q) of FFDCA, 21 U.S.C.
346a(q), as amended by FQPA. By law, EPA is required to reassess all
tolerances in existence on August 2, 1996 by August 2006. This
regulatory action will count for two reassessments toward the August
VI. Objections and Hearing Requests
Under section 408(g) of FFDCA, as amended by FQPA, any person may
file an objection to any aspect of this regulation and may also request
a hearing on those objections. The EPA procedural regulations which
submission of objections and requests for hearings appear in 40 CFR
part 178. Although the procedures in those regulations require some
modification to reflect the amendments made to FFDCA by FQPA, EPA will
continue to use those procedures, with appropriate adjustments, until
the necessary modifications can be made. The new section 408(g) of
FFDCA provides essentially the same process for persons to ``object''
to a regulation for an exemption from the requirement of a tolerance
issued by EPA under new section 408(d) of FFDCA, as was provided in the
old sections 408 and 409 of FFDCA. However, the period for filing
objections is now 60 days, rather than 30 days.
A. What Do I Need to Do to File an Objection or Request a Hearing?
You must file your objection or request a hearing on this
regulation in accordance with the instructions provided in this unit
and in 40 CFR part 178. To ensure proper receipt by EPA, you must
identify docket ID number OPP-2004-0293 in the subject line on the
first page of your submission. All requests must be in writing, and
must be mailed or delivered to the Hearing Clerk on or before November
1. Filing the request. Your objection must specify the specific
provisions in the regulation that you object to, and the grounds for
the objections (40 CFR 178.25). If a hearing is requested, the
objections must include a statement of the factual issues(s) on which a
hearing is requested, the requestor's contentions on such issues, and a
summary of any evidence relied upon by the objector (40 CFR 178.27).
Information submitted in connection with an objection or hearing
request may be claimed confidential by marking any part or all of that
information as CBI. Information so marked will not be disclosed except
in accordance with procedures set forth in 40 CFR part 2. A copy of the
information that does not contain CBI must be submitted for inclusion
in the public record. Information not marked confidential may be
disclosed publicly by EPA without prior notice.
Mail your written request to: Office of the Hearing Clerk (1900L),
Environmental Protection Agency, 1200 Pennsylvania Ave., NW.,
Washington, DC 20460--0001. You may also deliver your request to the
Office of the Hearing Clerk in Suite 350, 1099 14\th\ St., NW.,
Washington, DC 20005. The Office of the Hearing Clerk is open from 8
a.m. to 4 p.m., Monday through Friday, excluding legal holidays. The
telephone number for the Office of the Hearing Clerk is (202) 564-6255.
2. Copies for the Docket. In addition to filing an objection or
hearing request with the Hearing Clerk as described in Unit VI.A., you
should also send a copy of your request to the PIRIB for its inclusion
in the official record that is described in ADDRESSES. Mail your
copies, identified by docket ID number OPP-2004-0293, to: Public
Information and Records Integrity Branch, Information Resources and
Services Division (7502C), Office of Pesticide Programs, Environmental
Protection Agency, 1200 Pennsylvania Ave., NW., Washington, DC 20460-
0001. In person or by courier, bring a copy to the location of the
PIRIB described in ADDRESSES. You may also send an electronic copy of
your request via e-mail to: firstname.lastname@example.org. Please use an ASCII
file format and avoid the use of special characters and any form of
encryption. Copies of electronic objections and hearing requests will
also be accepted on disks in WordPerfect 6.1/8.0 or ASCII file format.
Do not include any CBI in your electronic copy. You may also submit an
electronic copy of your request at many Federal Depository Libraries.
B. When Will the Agency Grant a Request for a Hearing?
A request for a hearing will be granted if the Administrator
determines that the material submitted shows the following: There is a
genuine and substantial issue of fact; there is a reasonable
possibility that available evidence identified by the requestor would,
if established resolve one or more of such issues in favor of the
requestor, taking into account uncontested claims or facts to the
contrary; and resolution of the factual issues(s) in the manner sought
by the requestor would be adequate to justify the action requested (40
VII. Statutory and Executive Order Reviews
This final rule establishes a tolerance under section 408(d) of
FFDCA in response to a petition submitted to the Agency. The Office of
Management and Budget (OMB) has exempted these types of actions from
review under Executive Order 12866, entitled Regulatory Planning and
Review (58 FR 51735, October 4, 1993). Because this rule has been
exempted from review under Executive Order 12866 due to its lack of
significance, this rule is not subject to Executive Order 13211,
entitled Actions Concerning Regulations That Significantly Affect
Energy Supply, Distribution, or Use (66 FR 28355, May 22, 2001). This
final rule does not contain any information collections subject to OMB
approval under the Paperwork Reduction Act (PRA), 44 U.S.C. 3501 et
seq., or impose any enforceable duty or contain any unfunded mandate as
described under Title II of the Unfunded Mandates Reform Act of 1995
(UMRA) (Public Law 104-4). Nor does it require any special
considerations under Executive Order 12898, entitled Federal Actions to
Address Environmental Justice in Minority Populations and Low-Income
Populations (59 FR 7629, February 16, 1994); or OMB review or any
Agency action under Executive Order 13045, entitled Protection of
Children from Environmental Health Risks and Safety Risks (62 FR 19885,
April 23, 1997). This action does not involve any technical standards
that would require Agency consideration of voluntary consensus
standards pursuant to section 12(d) of the National Technology Transfer
and Advancement Act of 1995 (NTTAA), Public Law 104-113, section 12(d)
(15 U.S.C. 272 note). Since tolerances and exemptions that are
established on the basis of a petition under section 408(d) of FFDCA,
such as the tolerance in this final rule, do not require the issuance
of a proposed rule, the requirements of the Regulatory Flexibility Act
(RFA) (5 U.S.C. 601 et seq.) do not apply. In addition, the Agency has
determined that this action will not have a substantial direct effect
on States, on the relationship between the national government and the
States, or on the distribution of power and responsibilities among the
various levels of government, as specified in Executive Order 13132,
entitled Federalism(64 FR 43255, August 10, 1999). Executive Order
13132 requires EPA to develop an accountable process to ensure
``meaningful and timely input by State and local officials in the
development of regulatory policies that have federalism implications.''
``Policies that have federalism implications'' is defined in the
Executive order to include regulations that have ``substantial direct
effects on the States, on the relationship between the national
government and the States, or on the distribution of power and
responsibilities among the various levels of government.'' This final
rule directly regulates growers, food processors, food handlers and
food retailers, not States. This action does not alter the
relationships or distribution of power and responsibilities established
by Congress in the preemption provisions of section 408(n)(4) of FFDCA.
For these same reasons, the Agency has determined that this rule does
not have any ``tribal implications'' as described in Executive Order
entitled Consultation and Coordination with Indian Tribal Governments
(59 FR 22951, November 6, 2000). Executive Order 13175, requires EPA to
develop an accountable process to ensure ``meaningful and timely input
by tribal officials in the development of regulatory policies that have
tribal implications.'' ``Policies that have tribal implications'' is
defined in the Executive order to include regulations that have
``substantial direct effects on one or more Indian tribes, on the
relationship between the Federal Government and the Indian tribes, or
on the distribution of power and responsibilities between the Federal
Government and Indian tribes.'' This rule will not have substantial
direct effects on tribal governments, on the relationship between the
Federal Government and Indian tribes, or on the distribution of power
and responsibilities between the Federal Government and Indian tribes,
as specified in Executive Order 13175. Thus, Executive Order 13175 does
not apply to this rule.
VIII. Congressional Review Act
The Congressional Review Act, 5 U.S.C. 801 et seq., as added by the
Small Business Regulatory Enforcement Fairness Act of 1996, generally
provides that before a rule may take effect, the agency promulgating
the rule must submit a rule report, which includes a copy of the rule,
to each House of the Congress and to the Comptroller General of the
United States. EPA will submit a report containing this rule and other
required information to the U.S. Senate, the U.S. House of
Representatives, and the Comptroller General of the United States prior
to publication of this final rule in the Federal Register. This final
rule is not a ``major rule'' as defined by 5 U.S.C. 804(2).
List of Subjects in 40 CFR Part 180
Environmental protection, Administrative practice and procedure,
Agricultural commodities, Pesticides and pests, Reporting and
Dated: September 16, 2004.
Director, Registration Division, Office of Pesticide Programs.
Therefore, 40 CFR chapter I is amended as follows:
1. The authority citation for part 180 continues to read as follows:
Authority: 21 U.S.C. 321(q), 346a and 371.
2. Section 180.432 is revised to read as follows:
Sec. 180.432 Lactofen; tolerances for residues.
(a) Tolerances are established for residues of the herbicide
lactofen, 1-(carboethoxy)ethyl 5-[2-chloro-4-(trifluoromethyl)phenoxy]-
2- nitrobenzoate, in or on the following raw agricultural commodities:
Commodity Parts per million Beans, snap, succulent (excluding limas) 0.01 Cotton, gin byproducts 0.02 Cotton, undelinted seed 0.01 Peanut 0.01 Soybean, seed 0.01
(b) Section 18 emergency exemptions. [Reserved]
(c) Tolerances with regional registrations. [Reserved]
(d) Indirect or inadvertent residues. [Reserved]
[FR Doc. 04-21500 Filed 9-23-04; 8:45 am]
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