[Federal Register Volume 63, Number 144 (Tuesday, July 28, 1998)]
[Proposed Rules]
[Pages 40239-40247]
From the Federal Register Online via the Government Publishing Office [www.gpo.gov]
[FR Doc No: 98-20286]
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ENVIRONMENTAL PROTECTION AGENCY
40 CFR Part 180
[OPP-300693; FRL-6020-6]
RIN 2070-AC18
Spinosad; Time-Limited Pesticide Tolerance
AGENCY: Environmental Protection Agency (EPA).
ACTION: Proposed rule.
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SUMMARY: EPA proposes to establish a time-limited tolerance for
residues of spinosad in or on coffee at 0.02 parts per million (ppm).
This action is being initiated by EPA under the Federal Food, Drug and
Cosmetic Act (FFDCA), as amended by the Food Quality Protection Act of
1996 (Pub. L. 104-170). The United States Department of Agriculture/
Agricultural Research Service (USDA/ARS) has requested that EPA
establish a time-limited tolerance on coffee in order for USDA/ARS to
conduct efficacy testing of spinosad to control the Mediterranean Fruit
Fly. This testing will be conducted on 80 acres in Hawaii under an
Experimental Use Permit (EUP).
DATES: Comments, identified by the docket conrol number [OPP-300693],
must be received by EPA on or before August 11, 1998.
ADDRESSES: By mail, submit written comments to: Public Information and
Records Integrity Branch, Information Resources and Services Division
(7502C), Office of Pesticide Programs, Environmental Protection Agency,
401 M St., SW., Washington, DC 20460. In person, deliver comments to:
Rm. 119, CM #2, 1921 Jefferson Davis Highway, Arlington, VA.
Comments and data may also be submitted electronically to: opp-
[email protected]. Follow the instructions under Unit VI of this
document. No Confidential Business Information (CBI) should be
submitted through e-mail.
Information submitted as a comment concerning this document may be
claimed confidential by marking any part or all of that information as
CBI. Information so marked 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 will be included in the
public docket by EPA without prior notice. The public docket is
available for public inspection in Rm. 119 at the Virginia address
given above, from 8:30 a.m. to 4 p.m., Monday through Friday, excluding
legal holidays.
FOR FURTHER INFORMATION CONTACT: By mail: Susan Lewis, Registration
Division [7505C], Office of Pesticide Programs, Environmental
Protection Agency, 401 M St., SW., Washington, DC 20460. Office
location, telephone number, and e-mail address: Crystal Mall #2, 1921
Jefferson Davis Hwy., Arlington, VA, (703) 305-7448, e-mail:
[email protected].
SUPPLEMENTARY INFORMATION: In the Federal Register of April 15, 1998
(63 FR 18329)(FRL-5785-7), EPA established permanent tolerances by
removing the time limitation for the tolerance for residues of the
insecticide spinosad in or on cottonseed at 0.02 ppm and by
establishing tolerances in or on almonds at 0.02 ppm; almond hulls at
2.0 ppm; apples at 0.2 ppm; apple pomace, wet at 0.5 ppm; citrus fruits
group at 0.3 ppm; dried citrus pulp at 0.5 ppm; citrus oil at 3.0 ppm;
cotton gin byproducts at 1.5 ppm; fruiting vegetables (except
cucurbits) group at 0.4 ppm; leafy vegetables (except Brassica
vegetables) group at 8.0 ppm; Brassica (cole), leafy vegetables, head
and stem subgroup at 2.0 ppm; Brassica (cole), leafy vegetables, greens
subgroup at 15.0 ppm; fat of cattle, goats, hogs, horses, and sheep at
0.7 ppm; meat of cattle, goats, hogs, horses, and sheep at 0.04 ppm;
meat byproducts of cattle, goats, hogs, horses, and sheep at 0.2
[[Page 40240]]
ppm; milk fat at 0.5 ppm; and whole milk at 0.04 ppm.
The USDA has requested that EPA establish a time-limited tolerance
for residues of spinosad in or on coffee. This tolerance will expire on
August 28, 2000. USDA has requested this tolerance in order to conduct
efficacy testing of spinosad for control of the Mediterranean Fruit
Fly. This testing will be conducted on 80 acres in Hawaii under an
Experimental Use Permit (EUP).
The Agency has concluded that a tolerance of 0.02 ppm (which is the
Limit of Quantitation (LOQ) for the analytical method) is adequate for
coffee. This is based on a very low application rate and the fact that
the hull of the coffee bean is removed. No residues are expected to be
found on the coffee beans.
I. Risk Assessment and Statutory Findings
New section 408(b)(2)(A)(i) of the 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) 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)
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. First, EPA determines the
toxicity of pesticides based primarily on toxicological studies using
laboratory animals. These studies address many adverse health effects,
including (but not limited to) reproductive effects, developmental
toxicity, toxicity to the nervous system, and carcinogenicity. Second,
EPA examines exposure to the pesticide through the diet (e.g., food and
drinking water) and through exposures that occur as a result of
pesticide use in residential settings.
A. Toxicity
1. Threshold and non-threshold effects. For many animal studies, a
dose response relationship can be determined, which provides a dose
that causes adverse effects (threshold effects) and doses causing no
observed effects (the ``no-observed effect level'' or ``NOEL'').
Once a study has been evaluated and the observed effects have been
determined to be threshold effects, EPA generally divides the NOEL from
the study with the lowest NOEL by an uncertainty factor (usually 100 or
more) to determine the Reference Dose (RfD). The RfD is a level at or
below which daily aggregate exposure over a lifetime will not pose
appreciable risks to human health. An uncertainty factor (sometimes
called a ``safety factor'') of 100 is commonly used since it is assumed
that people may be up to 10 times more sensitive to pesticides than the
test animals, and that one person or subgroup of the population (such
as infants and children) could be up to 10 times more sensitive to a
pesticide than another. In addition, EPA assesses the potential risks
to infants and children based on the weight of the evidence of the
toxicology studies and determines whether an additional uncertainty
factor is warranted. Thus, an aggregate daily exposure to a pesticide
residue at or below the RfD (expressed as 100 percent or less of the
RfD) is generally considered acceptable by EPA. EPA generally uses the
RfD to evaluate the chronic risks posed by pesticide exposure. For
shorter term risks, EPA calculates a margin of exposure (MOE) by
dividing the estimated human exposure into the NOEL from the
appropriate animal study. Commonly, EPA finds MOEs lower than 100 to be
unacceptable. This hundredfold MOE is based on the same rationale as
the hundredfold uncertainty factor.
Lifetime feeding studies in two species of laboratory animals are
conducted to screen pesticides for cancer effects. When evidence of
increased cancer is noted in these studies, the Agency conducts a
weight of the evidence review of all relevant toxicological data
including short-term and mutagenicity studies and structure activity
relationship. Once a pesticide has been classified as a potential human
carcinogen, different types of risk assessments (e.g., linear low dose
extrapolations or MOE calculation based on the appropriate NOEL) will
be carried out based on the nature of the carcinogenic response and the
Agency's knowledge of its mode of action.
2. Differences in toxic effect due to exposure duration. The
toxicological effects of a pesticide can vary with different exposure
durations. EPA considers the entire toxicity data base, and based on
the effects seen for different durations and routes of exposure,
determines which risk assessments should be done to assure that the
public is adequately protected from any pesticide exposure scenario.
Both short and long durations of exposure are always considered.
Typically, risk assessments include ``acute,'' ``short-term,''
``intermediate term,'' and ``chronic'' risks. These assessments are
defined by the Agency as follows.
Acute risk, by the Agency's definition, results from 1-day
consumption of food and water, and reflects toxicity which could be
expressed following a single oral exposure to the pesticide residues.
High end exposure to food and water residues are typically assumed.
Short-term risk results from exposure to the pesticide for a period
of 1-7 days, and therefore overlaps with the acute risk assessment.
Historically, this risk assessment was intended to address primarily
dermal and inhalation exposure which could result, for example, from
residential pesticide applications. However, since enaction of FQPA,
this assessment has been expanded to include both dietary and non-
dietary sources of exposure, and will typically consider exposure from
food, water, and residential uses when reliable data are available. In
this assessment, risks from average food and water exposure, and high-
end residential exposure, are aggregated. High-end exposures from all
three sources are not typically added because of the very low
probability of this occurring in most cases, and because the other
conservative assumptions built into the assessment assure adequate
protection of public health. However, for cases in which high-end
exposure can reasonably be expected from multiple sources (e.g.
frequent and widespread homeowner use in a specific geographical area),
multiple high-end risks will be aggregated and presented as part of the
comprehensive risk assessment/characterization. Since the toxicological
endpoint considered in this assessment reflects exposure over a period
of at least 7 days, an additional degree of conservatism is built into
the assessment; i.e., the risk assessment nominally covers 1-7 days
exposure, and the toxicological endpoint/NOEL is selected to be
adequate for at least 7 days of exposure. (Toxicity results at lower
levels when the dosing duration is increased.)
[[Page 40241]]
Intermediate-term risk results from exposure for 7 days to several
months. This assessment is handled in a manner similar to the short-
term risk assessment.
Chronic risk assessment describes risk which could result from
several months to a lifetime of exposure. For this assessment, risks
are aggregated considering average exposure from all sources for
representative population subgroups including infants and children.
B. Aggregate Exposure
In examining aggregate exposure, FFDCA section 408 requires that
EPA take into account available and reliable information concerning
exposure from the pesticide residue in the food in question, residues
in other foods for which there are tolerances, residues in groundwater
or surface water that is consumed as drinking water, and other non-
occupational exposures through pesticide use in gardens, lawns, or
buildings (residential and other indoor uses). Dietary exposure to
residues of a pesticide in a food commodity are estimated by
multiplying the average daily consumption of the food forms of that
commodity by the tolerance level or the anticipated pesticide residue
level. The Theoretical Maximum Residue Contribution (TMRC) is an
estimate of the level of residues consumed daily if each food item
contained pesticide residues equal to the tolerance. In evaluating food
exposures, EPA takes into account varying consumption patterns of major
identifiable subgroups of consumers, including infants and children.
The TMRC is a ``worst case'' estimate since it is based on the
assumptions that food contains pesticide residues at the tolerance
level and that 100% of the crop is treated by pesticides that have
established tolerances. If the TMRC exceeds the RfD or poses a lifetime
cancer risk that is greater than approximately one in a million, EPA
attempts to derive a more accurate exposure estimate for the pesticide
by evaluating additional types of information (anticipated residue data
and/or percent of crop treated data) which show, generally, that
pesticide residues in most foods when they are eaten are well below
established tolerances.
II. Aggregate Risk Assessment and Determination of Safety
Consistent with section 408(b)(2)(D), EPA has reviewed the
available scientific data and other relevant information in support of
the existing uses of spinosad. EPA had sufficient data to assess the
hazards of spinosad and to make a determination on aggregate exposure,
consistent with section 408(b)(2), for tolerances for residues of
spinosad for those uses. EPA's assessment of the dietary exposures and
risks associated with establishing the existing 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 spinosad are
discussed below.
1. Acute toxicity studies with technical spinosad (88% - 90.4%):
Oral LD50 in the rat is > 5,000 milligram/kilogram (mg/kg)
for males and females - Toxicity Category IV; dermal LD50 in
the rat is > 2,800 mg/kg for males and females - Toxicity Category III;
inhalation LC50 in the rat is > 5.18 mg/L - Toxicity
Category IV; primary eye irritation in the rabbit (slight conjunctival
irritation) - Toxicity Category IV; primary dermal irritation in the
rabbit (no erythema and edema) - Toxicity Category IV. Spinosad is not
a sensitizer.
2. Acute toxicity studies with the end-use (44% formulation)
product for spinosad: Oral LD50 in the rat is > 5,000 mg/kg
for males and females - Toxicity Category IV; dermal LD50 in
the rat is > 2,800 mg/kg for males and females - Toxicity Category III;
inhalation LC50 in the rat is > 5 mg/L - Toxicity Category
IV; primary eye irritation in the rabbit (slight conjunctival
irritation) - Toxicity Category IV; primary dermal irritation in the
rabbit (slight transient erythema and edema) - Toxicity Category IV;
not a sensitizer.
3. In a subchronic feeding study in rats, the no-observed adverse
effect level (NOAEL) was 33.9 and 38.8 mg/kg/day for males and females,
respectively. The lowest observed effect level (LOEL) was 68.5 and 78.1
mg/kg/day for males and females, respectively based on decreased body
weight gain, anemia, and vacuolation in multiple organs (kidney, liver,
heart, spleen, adrenals, and thyroid).
4. In a subchronic feeding study in mice, the no observed effect
level (NOEL) was 7.5 mg/kg/day and the LOEL was 22.5 mg/kg/day based on
cytoplasmic vacuolation in multiple organs (kidney, liver, heart,
stomach, lymphoid organs, and ovary).
5. In a subchronic feeding study in dogs, the NOEL was 4.89 and
5.38 mg/kg/day for males and females, respectively. The LOEL was 9.73
mg/kg/day and 10.5 mg/kg/day based on decreased mean body weights and
food consumption, and anemia.
6. In a 21-day dermal study in rats, the NOEL for systemic effects
was > 1,000 mg/kg/day (limit dose). No systemic toxicity was observed
at any dose tested.
7. In a chronic feeding study in dogs, the NOEL was 2.68 mg/kg/day.
The LOEL was 8.22 mg/kg/day based on increased liver enzymes (ALT,
AST), triglycerides; vacuolated cells (parathyroid), and arteritis.
8. In an carcinogenicity study in mice, the NOEL was 11.4 mg/kg/
day. The LOEL was 50.9 mg/kg/day based on decreased body weight gains,
increased mortality, hematologic effects, increased thickening of the
gastric mucosa, and histologic changes in the stomach of males.
9. In a chronic feeding/carcinogenicity/neurotoxicity study in
rats, the NOEL (systemic) was 9.5 and 12.0 mg/kg/day for males and
females, respectively. The LOEL (systemic) was 24.1 and 30.3 mg/kg/day
for males and females, respectively based on vacuolation of epithelial
follicular cells of the thyroid. The neurological NOEL was 46 and 57
mg/kg/day for males and females, respectively. The neurological LOEL
was not determined.
10. In a developmental study in rabbits, the maternal NOEL was
50 mg/kg/day. The maternal LOEL was not established. The
developmental NOEL was 50 mg/kg/day. The developmental LOEL
was not established.
11. In a developmental study in rats, the maternal NOEL was > 200
mg/kg/day. The maternal LOEL was not established. The developmental
NOEL was > 200 mg/kg/day. The developmental LOEL was not established.
12. In a two-generation reproduction toxicity study in rats, the
systemic NOEL was 10 mg/kg/day. The systemic LOEL was 100 mg/kg/day
based on increased organ weights (heart, liver, kidney, spleen,
thyroid), histopath lesions in the lungs and mesenteric lymph nodes,
stomach (F), and prostate. The reproductive NOEL was 10 mg/kg/day. The
reproductive LOEL was 100 mg/kg/day based on decreased litter size,
decreased pup survival, decreased body weight, increased incidence of
dystocia and/or vaginal bleeding post-partum with associated increased
mortality of dams.
[[Page 40242]]
13. Studies on gene mutation and other genotoxic effects: In a Gene
Mutation Assay (mouse forward mutation) there was no forward mutation
induction in mouse lymphoma L5178Y Tk +/- cells at concentrations of 0,
1, 5, 10, 15, 20, or 25 g/ml without metabolic activation or
at concentrations of 15 through 50 g/ml with metabolic
activation. In a Structural Chromosomal Aberration Assay In vitro there
was no increase in the number of CHO (chinese hamster ovary) cells with
chromosomal aberrations at concentrations from 20 to 35 g/ml
(without activation) or concentrations from 100 to 500 g/ml
(with activation). In a Micronucleus Test in mice, there was no
increase in the frequencey of micronuclei in bone marrow cells from
mice treated at concentrations from 500 to 2,000 g/ml for 2
days. In Other Genotoxicity Assays, unscheduled DNA synthesis was not
induced in adult rat hepatocytes in vitro at concentrations of 0.01 to
5 g/ml tested.
14. The results of three metabolism studies are as follows: i.
Approximately 95% of technical spinosad was eliminated by 24 hours
mainly in the urine (34%), bile (36%), and tissues and carcass (21%).
Metabolites include the glutathione conjugates of the unchanged form as
well as N- and O-demethylated forms of XDE-105 (Factor D).
ii. At 100 mg/kg/dose, the radiolabeled XDE-105 (Factor D) was
primarily excreted in the feces (68%) after 24-hours. The absorption,
distribution, and elimination of 14C-XDE-105 (Factor A) demonstrated no
appreciable differences based on dose or repeated dosing.
iii. At high (100 mg/kg) doses, there are no major differences in
the bioavailability, routes or rates of excretion or metabolism of 14C-
XDE-105 (Factor A) following oral administration.
15. In an acute neurotoxicity study, groups of Fischer 334 rats
(10/sex/dose) received a single oral (gavage) administration of
spinosad (87.9%) at dose levels of 0, 200, 630, or 2,000 mg/kg. There
were no effects on neurobehavioral endpoints or histopathology of the
nervous system. For neurotoxicity, the NOEL was 2,000 mg/
kg/day (HDT). A LOEL was not established.
16. In a subchronic neurotoxicity study, groups of Fischer 344 rats
(10/sex/dose) were administered diets containing spinosad at levels of
0, 0.003, 0.006, 0.012, or 0.06% (0, 2.2, 4.3, 8.6, or 42.7 mg/kg/day
for males and 2.6, 5.2, 10.4, or 52.1 mg/kg/day for females,
respectively). There were no effects on neurobehavior endpoints or
histopathology of the nervous system. For neurotoxicity, the NOEL was
42.7 and 52.1 mg/kg/day in males and females,
respectively (HDT).
17. In the 2-year chronic neurotoxicity study, groups of Fischer
344 rats (65/sex/dose) received diets containing spinosad at dose
levels of 0, 0.005, 0.02, 0.05, or 0.1% (0, 2.4, 9.5, 24.1, or 49.4 mg/
kg/day for males and 0, 3.0, 12.0, 30.3, or 62.2 mg/kg/day for females,
respectively). Neurobehavioral testing performed at 3, 6, 9, and 12
months of study was negative, and histopathological evaluation of
perfused tissues at study termination did not identify pathology of the
central or peripheral nervous system. There was no evidence of
neurotoxicity. For neuropathology, the NOEL was 0.1% ( 46
mg/kg/day for males and 57 mg/kg/day for females (HDT).
B. Toxicological Endpoints
1. Acute toxicity. EPA did not select a dose and endpoint for an
acute dietary risk assessment due to the lack of toxicological effects
attributable to a single exposure (dose) in studies available in the
data base including oral developmental toxicity studies in rats and
rabbits. In the acute neurotoxicity study the NOEL was
2,000 mg/kg/day.
2. Short - (1 day to 7 days), intermediate- (1 week to several
months), and chronic - term occupational and residential dermal and
inhalation toxicity. EPA did not select a dose or endpoint for short-,
intermediate and long-term dermal risk assessments because (i) lack of
appropriate endpoints; (ii) the combination of molecular structure and
size as well as the lack of dermal or systemic toxicity at 2,000 mg/kg/
day in a 21-day dermal toxicity study in rats which indicates the lack
of dermal absorption; and (iii) the lack of long-term exposure based on
the current use pattern. Therefore, a dermal risk assessment is not
required. EPA also determined that based on the current use pattern and
exposure scenario, and inhalation risk assessment is not required.
3. Chronic toxicity. EPA has established the RfD for spinosad at
0.027 mg/kg/day. This RfD is based on a chronic toxicity study in dogs
using a NOEL of 2.68 mg/kg/day. The LOEL was 8.46 mg/kg/day based on
vacuolation in glandular cells (parathyroid) and lymphatic tissues,
arteritis and increases in serum enzymes such as alanine
aminotransferase, and aspartate aminotransferase, and triglyceride
levels in dogs fed spinosad in the diet at dose levels of 1.44, 2.68,
or 8.46 mg/kg/day for 52 weeks. A hundredfold uncertainty factor (UF)
was applied to the NOEL of 2.68 mg/kg/day to account for inter- and
intra-species variation.
EPA determined that the 10X factor to account for enhanced
sensitivity of infants and children (as required by FQPA) should be
removed. Thus, an uncertainty factor of 100 is adequate and the RfD
remains at 0.027 mg/kg/day. The FQPA factor is removed because: (i) the
data provided no indication of increased susceptibility of rats or
rabbits to in utero and/or post-natal exposure to spinosad. In the
prenatal developmental toxicity studies in rats and rabbits and the
two-generation reproduction study in rats, effects in the offspring
were observed only at or below treatment levels which resulted in
evidence of parental toxicity. (ii) No neurotoxic signs have been
observed in any of the standard required studies conducted. (iii) The
toxicology data base is complete and there are no data gaps.
4. Carcinogenicity. There is no evidence of carcinogenicity in
studies in either the mouse or rat.
C. Exposures and Risks
1. From food and feed uses. Tolerances have been established (40
CFR 180.495) for the residues of spinosad in or on almonds at 0.02 ppm;
almond hulls at 2.0 ppm; apples at 0.2 ppm; apple pomace, wet at 0.5
ppm; citrus fruits group at 0.3 ppm; dried citrus pulp at 0.5 ppm;
citrus oil at 3.0 ppm; cottonseed at 0.02 ppm; cotton gin byproducts at
1.5 ppm; fruiting vegetables (except cucurbits) group at 0.4 ppm; leafy
vegetables (except Brassica vegetables) group at 8.0 ppm; Brassica
(cole), leafy vegetables, head and stem subgroup at 2.0 ppm; Brassica
(cole), leafy vegetables, greens subgroup at 15.0 ppm; fat of cattle,
goats, hogs, horses, and sheep at 0.7 ppm; meat of cattle, goats, hogs,
horses, and sheep at 0.04 ppm; meat byproducts of cattle, goats, hogs,
horses, and sheep at 0.2 ppm; milk fat at 0.5 ppm; and whole milk at
0.04 ppm.
For the existing uses referred to above, risk assessments were
conducted by EPA to assess dietary exposures and risks from spinosad as
follows:
i. Acute exposure and risk. 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 single exposure. No acute toxicological endpoints were
identified for spinosad due to the lack of toxicological effects
attributable to a single exposure (dose). Therefore, the
[[Page 40243]]
Agency concludes that there is a reasonable certainty of no harm from
acute dietary exposure.
ii. Chronic exposure and risk. The RfD used for the chronic dietary
analysis is 0.027 mg/kg/day. In conducting this chronic dietary risk
assessment, EPA made very conservative assumptions: 100% of citrus,
almonds, apples, fruiting (except cucurbit) vegetables, Brassica leafy
vegetables, leafy vegetables, cottonseed, and ruminant commodities
having spinosad tolerances will contain spinosad residues and those
residues will be at the level of the established tolerance. This
results in an overestimate of human dietary exposure. This chronic
dietary risk assessment used 10 ppm tolerances for the leafy vegetables
(except Brassica vegetables) crop group and for the Brassica leafy
vegetables head and stem subgroup from section 18 tolerances that were
established last year. For the section 3 registrations on these groups,
EPA has recommended tolerances of 8 ppm (leafy vegetables) and 2 ppm
(Brassica head and stem leafy vegetables). The use pattern for these
section 18 registrations is identical to the section 3 registrations
proposed in this risk assessment, but due to an incomplete data base at
the time the section 18 registrations were reviewed, the tolerances
were set high which resulted in a conservative risk assessment. With
this action, these section 18 tolerances are replaced by the new
section 3 tolerances. Thus, in making a safety determination for this
tolerance, EPA is taking into account this conservative exposure
assessment.
The existing spinosad tolerances resulted in a Theoretical Maximum
Residue Contribution (TMRC) that is equivalent to the following
percentages of the RfD: U.S. population (24% of RfD); nursing infants
(< 1 year old)( 8% of RfD); non-nursing infants (< 1 year old) (24% of
RfD); children (1-6 years old) (34% of RfD); children (7-12 years old)
(29% of RfD); Northeast Region (25% of RfD); Western Region (27% of
RfD); Non-Hispanic Blacks (27% of RfD); Non-Hispanic others (37% of
RfD); females 13+ years, nursing (27% of RfD).
The Agency believes that the addition of a 0.02 ppm tolerance for
spinosad on coffee will only change the percent of the RfD used for any
of the categories listed above by less than 1%. This is based on the
fact that the use will be limited to 80 acres in Hawaii for
experimental purposes for period of time not to exceed 2 years.
2. From drinking water. The Agency has determined that spinosyns
Factor A and Factor D are immobile in soil and will not leach into
ground water. Based on structure/activity relationships, the Agency
concluded that the spinosad metabolites/fermentation impurities
(spinosyns Factor B, Factor B of D, Factor K, and other related
Factors) were of no more toxicological concern than the two parent
compounds (spinosyns Factor A and Factor D) and therefore, only these
were considered in the drinking water assessment. EPA used the
``Interim Approach for Addressing Drinking Water Exposure in Tolerance
Decision Making'' issued on 11/17/97. Thus, the PRZM/EXAMS Models were
run to produce estimates of spinosad in surface water. The primary use
of these models is to provide a screen for sorting out pesticides for
which OPP has a high degree of confidence that the true levels of the
pesticide in drinking water will be less than the human health drinking
water levels of concern (DWLOCs). A human health DWLOC is the
concentration of a pesticide in drinking water which would result in
acceptable aggregate risk, after having already factored in all food
exposures and other non-occupational exposures for which OPP has
reliable data. PRZM/EXAMS was used to conduct a Tier 2 surface water
analysis. The Tier 2 estimated drinking water concentration (EEC) of
spinosad from surface water sources is not likely to exceed 0.059
g/l from use on apples, 0.092 g/l from use on
Brassica vegetables, 0.065 g/l from use on cotton, and 0.075
g/l from use on citrus.
i. Acute exposure and risk. Because no acute dietary endpoint was
determined, the Agency concludes that there is a reasonable certainty
of no harm from acute exposure from drinking water.
ii. Chronic exposure and risk. Based on the chronic dietary (food)
exposure and using default body weights and water consumption figures,
chronic drinking water levels of concern (DWLOC) were calculated. The
chronic drinking water exposure and risk estimates are 0.019890 mg/kg/
day (690 g/l DWLOC) for the overall U.S. population; 0.01896
mg/kg/day (570 g/l DWLOC) for females 13+ years, nursing; and
0.016865 mg/kg/day (170 g/l DWLOC) for children age 1-6 years.
3. From non-dietary exposure. There are no current residential uses
for spinosad. However, the proposed use of a 0.5% spinosad product on
structural lumber may have residential uses. This product is injected
into drilled holes and then sealed after treatment. Due to the lack of
toxicity endpoints (hazard) and minimal contact with the active
ingredient during and after application, exposure to residential
occupants is not expected.
4. Cumulative exposure to substances with common mechanism of
toxicity. Spinosad has not yet been grouped with any other insecticides
into a class.
Section 408(b)(2)(D)(v) 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.'' The Agency believes that ``available
information'' in this context might include not only toxicity,
chemistry, and exposure data, but also scientific policies and
methodologies for understanding common mechanisms of toxicity and
conducting cumulative risk assessments. For most pesticides, although
the Agency has some information in its files that may turn out to be
helpful in eventually determining whether a pesticide shares a common
mechanism of toxicity with any other substances, EPA does not at this
time have the methodologies to resolve the complex scientific issues
concerning common mechanism of toxicity in a meaningful way. EPA has
begun a pilot process to study this issue further through the
examination of particular classes of pesticides. The Agency hopes that
the results of this pilot process will increase the Agency's scientific
understanding of this question such that EPA will be able to develop
and apply scientific principles for better determining which chemicals
have a common mechanism of toxicity and evaluating the cumulative
effects of such chemicals. The Agency anticipates, however, that even
as its understanding of the science of common mechanisms increases,
decisions on specific classes of chemicals will be heavily dependent on
chemical specific data, much of which may not be presently available.
Although at present the Agency does not know how to apply the
information in its files concerning common mechanism issues to most
risk assessments, there are pesticides as to which the common mechanism
issues can be resolved. These pesticides include pesticides that are
toxicologically dissimilar to existing chemical substances (in which
case the Agency can conclude that it is unlikely that a pesticide
shares a common mechanism of activity with other substances) and
pesticides that produce a common toxic metabolite (in which case common
mechanism of activity will be assumed).
EPA does not have, at this time, available data to determine
whether
[[Page 40244]]
spinosad has a common mechanism of toxicity with other substances or
how to include this pesticide in a cumulative risk assessment. Unlike
other pesticides for which EPA has followed a cumulative risk approach
based on a common mechanism of toxicity, spinosad does not appear to
produce a toxic metabolite produced by other substances. For the
purposes of these tolerance actions, therefore, EPA has not assumed
that spinosad has a common mechanism of toxicity with other substances.
D. Aggregate Risks and Determination of Safety for U.S. Population
Chronic risk. The following information is based on the review of
the existing uses of spinosad: Using the TMRC exposure assumptions
described above, EPA has concluded that aggregate exposure to spinosad
from food will utilize 24% of the RfD for the U.S. population. For the
most highly exposed populations subgroup, children (1-6 years old),
chronic dietary (food only) exposure occupies 34% of the RfD. This is a
conservative risk estimate for reasons described above. EPA generally
has no concern for exposures below 100% 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
chronic DWLOC for the infants and children subgroup is 170 parts per
billion (ppb). The chronic modeling estimates (EECs) for spinosad
residues in surface water are as high as 0.092 ppb from use on Brassica
leafy vegetables. The maximum estimated concentrations of spinosad in
surface water are less than EPA's levels of concern for spinosad in
drinking water as a contribution to chronic aggregate exposure. Taking
into account present uses and uses proposed in this risk assessment,
EPA concludes with reasonable certainty that residues of spinosad in
drinking water (when considered along with other sources of exposure
for which EPA has reliable data ) would not result in unacceptable
levels of aggregate human health risk at this time. Therefore, the
Agency concludes that there is a reasonable certainty that no harm will
result from chronic aggregate exposure to spinosad residues from food
and water.
No dermal or inhalation endpoints were identified. Due to the
nature of the non-dietary use, EPA believes that the use of spinosad in
treating structural lumber will not result in any exposure through the
oral route. Therefore, the chronic aggregate risk is the sum of food
and water.
Based on the above information, the Agency concludes that there is
a reasonable certainty that no harm will result from chronic aggregate
exposure to spinosad from food and water resulting from the addition of
the time-limited experimental use on coffee as described above.
E. Aggregate Cancer Risk for U.S. Population
The RfD Committee determined that there is no evidence of
carcinogenicity in studies in either the mouse or rat. Therefore, a
carcinogenic risk assessment is not required.
F. Aggregate Risks and Determination of Safety for Infants and Children
1. Safety factor for infants and children-- a. In general. In
assessing the potential for additional sensitivity of infants and
children to residues of spinosad, EPA considered data from
developmental toxicity studies in the rat and rabbit and a two-
generation reproduction study in the rat. The developmental toxicity
studies are designed to evaluate adverse effects on the developing
organism resulting from pesticide exposure during prenatal development
to one or both parents. Reproduction studies provide information
relating to effects from exposure to the pesticide on the reproductive
capability of mating animals and data on systemic toxicity.
FFDCA section 408 provides that EPA shall apply an additional
tenfold margin of safety for infants and children in the case of
threshold effects to account for pre-and post-natal toxicity and the
completeness of the database unless EPA determines 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. EPA believes that reliable data support using the standard MOE
and uncertainty factor (usually 100 for combined inter- and intra-
species variability) and not the additional tenfold MOE/uncertainty
factor when EPA has a complete data base under existing guidelines and
when the severity of the effect in infants or children or the potency
or unusual toxic properties of a compound do not raise concerns
regarding the adequacy of the standard MOE/safety factor.
b. Developmental toxicity studies. i. In a prenatal developmental
toxicity study, groups of pregnant Sprague-Dawley rats (30/group)
received oral (gavage) administration of spinosad (88.6%) in aqueous
0.5% methycellulose at dose levels of 0, 10, 50, 200 mg/kg/day during
gestation days 6 through 17. For maternal toxicity, the NOEL was
200 mg/kg/day (HDT); a LOEL was not established. Marginal
maternal toxicity was reported at this dose level (decreased body
weight gain). Based upon the results of a range-finding study, which
showed maternal toxicity (body weight and food consumption decreases at
100 and 300 mg/kg/day), the dose level of 200 mg/kg/day in the main
study was considered adequate. For developmental toxicity, the NOEL was
> 200 mg/kg/day; a LOEL was not established. In the range-finding
study, fetal body weight decrements occurred at 300 mg/kg/day.
ii. In a prenatal developmental toxicity study, groups of pregnant
New Zealand White rabbits (20/group) received oral (gavage)
administration of spinosad (88.6%) in 0.5% aqueous methyl cellulose at
doses of 0, 2.5, 10, or 50 mg/kg/day during gestation days 7 through
19. For maternal toxicity, the NOEL was 50 mg/kg/day (HDT);
a LOEL was not established. At this dose, slight body weight loss was
observed in the first few days of dosing, but this finding was not
supported by other signs. In the range-finding study, inanition was
observed at doses of 100, 200, and 400 mg/kg/day, with significant
decreases in body weight gain during dosing. All does at these dose
levels were sacrificed prior to scheduled termination; no fetal data
were available. No evidence of developmental toxicity was noted. For
developmental toxicity, the NOEL was 50 mg/kg/day; a LOEL
was not established. (No fetal effects were noted for fetuses of the
range-finding study at doses up to 50 mg/kg/day).
c. Reproductive toxicity study. In a two-generation reproduction
study, groups of Sprague-Dawley rats (30/sex/group) received diets
containing spinosad (88%) at dose levels of 0, 0.005, 0.02, or 0.2% (3,
10, or 10 mg/kg/day, respectively) for two successive generations. For
parental systemic toxicity, the NOEL was 0.02% (10 mg/kg/day) and the
LOEL was 0.2% (100 mg/kg/day), based on increased heart, kidney, liver,
spleen, and thyroid weights (both sexes), histopathology in the spleen
and thyroid (both sexes), heart and kidney (males), and histopathologic
lesions in the lungs and mesenteric lymph nodes (both sexes), stomach
(females), and prostate. For offspring toxicity, the NOEL was 0.02% (10
mg/kg/day) and the LOEL was 0.2% (100 mg/kg/day) based on decreased
litter size, survival (F2), and body weights. Reproductive effects at
that
[[Page 40245]]
dose level included increased incidence of dystocia and/or vaginal
bleeding after parturition with associated increase in mortality of
dams.
d. Neurotoxicity. i. In an acute neurotoxicity study, groups of
Fischer 344 rats (10/sex/dose) received a single oral (gavage)
administration of spinosad (87.9%) at dose levels of 0, 200, 630, or
2,000 mg/kg. There were no effects on neurobehavioral endpoints or
histopathology of the nervous system. For neurotoxicity, the NOEL was >
2,000 mg/kg (HDT); a LOEL was not established.
ii. In a subchronic neurotoxicity study, groups of Fisher 344 rats
(10/sex/dose) were administered diets containing spinosad at levels of
0, 0.003, 0.006, 0.012, or 0.06% (0, 2.2, 4.3, 8.6, or 42.7 mg/kg/day
for males and 2.6, 5.2, 10.4, or 52.1 mg/kg/day for females,
respectively). There were no effects on neurobehavioral endpoints or
histopathology of the nervous system. For neurotoxicity, the NOEL was
42.7 for males and 52.1 mg/kg/day for females
(HDT).
iii. In the 2-year chronic toxicity study, groups of Fischer 344
rats (65/sex/dose) received diets containing spinosad at dose levels of
0, 0.005, 0.02, 0.05, or 0.1% (0, 2.4, 9.5, 24.1, or 49.4 mg/kg/day for
males and 0, 3.0, 12.0, 30.3, or 62.2 mg/kg/day for females,
respectively). Neurobehavioral testing performed at 3, 6, 9, and 12
months of study was negative, and histopathological evaluation of
perfused tissues at study termination did not identify pathology of the
central or peripheral nervous system. There was no evidence of
neurotoxicity. For neuropathology, the NOEL was 0.1% (> 49.4 mg/kg/day
for males and 62.8 mg/kg/day for females).
e. Pre- and post-natal sensitivity. There was no increased
susceptibility to rats or rabbits following in utero and/or postnatal
exposure to spinosad.
f. Conclusion. The data provided no indication of increased
susceptibility of rats or rabbits to in utero and/or postnatal exposure
to spinosad. In the prenatal developmental toxicity studies in rats and
rabbits and the two-generation reproduction study in rats, effects in
the offspring were observed only at or below treatment levels which
resulted in evidence of parental toxicity. In addition, all
neurotoxicity studies were negative for effects on the central or
peripheral nervous system.
EPA determined that the 10X factor to account for enhanced
sensitivity of infants and children (as required by FQPA) should be
removed. The FQPA factor is removed because (i) the data provided no
indication of increased susceptibility of rats or rabbits to in utero
and/or post natal exposure to spinosad. In the prenatal developmental
toxicity studies in rats and rabbits and the two-generation
reproduction study in rats, effects in the offspring were observed only
at or below treatment levels which resulted in evidence of parental
toxicity. (ii) No neurotoxic signs have been observed in any of the
standard required studies conducted. (iii) The toxicology data base is
complete and there are no data gaps.
2. Acute risk. An acute risk assessment is not required because no
acute toxicological endpoints were identified for spinosad.
3. Chronic risk. Using the conservative exposure assumptions
described above, EPA has concluded that aggregate exposure to spinosad
from food will utilize 34% of the RfD for children age 1-6 years old.
EPA generally has no concern for exposures below 100% 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. EPA concludes that there is a reasonable certainty that
no harm will result to infants and children from aggregate exposure to
spinosad residues.
Based on the above information, EPA concludes that there is a
resonable certainty that no harm will result to infants and children
from aggregate exposure to spinosad residues as a result of the use on
coffee in an experimental use program in Hawaii.
G. Endocrine Disruption
EPA is required to develop a screening program to determine whether
certain substances (including all pesticides and inerts) ``may have an
effect in humans that is similar to an effect produced by a naturally
occurring estrogen, or such other endocrine effect...'' The Agency is
currently working with interested stakeholders, including other
government agencies, public interest groups, industry and research
scientists in developing a screening and testing program and a priority
setting scheme to implement this program. Congress has allowed 3 years
from the passage of FQPA (August 3, 1999) to implement this program. At
that time, EPA may require further testing of this active ingredient
and end use products for endocrine disrupter effects.
III. Other Considerations
A. Metabolism In Plants and Animals
EPA has reviewed the results of plant metabolism studies (apples,
cabbage, cotton, tomatoes, turnips) and livestock metabolism studies
(goat and hen). The metabolism of spinosad in plants and animals is
adequately understood for the purposes of these tolerances. Based on
structure/activity relationships, EPA concluded that the spinosad
metabolites/fermentation impurities (spinosyns Factor B, Factor B or D,
Factor K, and other related Factors) were of no more toxicological
concern than the two parent compounds (spinosyns Factor A and Factor
D).
EPA focused on the following data/information: the overall low
toxicity of spinosad; the low levels of metabolites/fermentation
impurities present; and that spinosad appears to photodegrade rapidly
and become incorporated into the general carbon pool. EPA concluded
that only 2 parent compounds (spinosyns Factor A and Factor D) need to
be included in the tolerance expression and used for dietary risk
assessment purposes.
B. Analytical Enforcement Methodology
Method GRM 94.02 (method for determination of spinosad residues in
cottonseed and related commodities using HPLC/UV) underwent successful
independent lab validation and EPA lab validation and has been
submitted to FDA for inclusion in PAM II as Method I. Additional
methods have been submitted for other crop matrices (leafy vegetables -
GRM 95.17; citrus - GRM 96.09; tree nuts - GRM 96.14; fruiting
vegetables - GRM 95.04; and cotton gin byproducts - GRM 94.02.S1). All
of these methods are essentially similar to GRM 94.02 and have been
submitted to FDA for inclusion in PAM II as letter methods. These
methods are adequate for regulation of the tolerance expression.
Method RES 94094 (method for determination of spinosad residues in
ruminant commodities using HPLC/UV) underwent successful independent
lab validation and EPA lab validation and has been submitted to FDA for
inclusion in PAM II as Method I. This method is adequate for regulation
of the tolerance expression.
Method RES 95114 (method for determination of spinosad residues in
ruminant commodities using immunoassay) underwent successful
independent lab validation and EPA lab validation and has been
submitted to FDA for inclusion in PAM II as Method I. This method is
adequate for regulation of the tolerance expression.
C. International Residue Limits
No CODEX, Canadian, or Mexican MRLs have been established for
residues of spinosad on any crops.
[[Page 40246]]
IV. Conclusion
A time-limited tolerance is being proposed for residues of spinosad
in coffee at 0.02 ppm.
V. Public Comment Procedures
EPA invites interested persons to submit written comments,
information, or data in response to this proposed rule. After
consideration of comments, EPA will issue a final rule. Such rule will
be subject to objections. Failure to file an objection within the
appointed period will constitute waiver of the right to raise in future
proceedings issues resolved in the final rule.
The period for comments on this proposed rule has been shortened to
14 days because the Agency believes that it is in the public interest
to do so. The purpose of this temporary tolerance is to allow for
efficacy testing to determine whether this reduced risk chemical will
control the Mediterranean Fruit Fly. This quarantine insect is a
serious economic pest which is threatening continental U.S. borders.
The USDA/ARS needs to begin their experimental use program in Hawaii no
later than August 15, 1998 and therefore, the Agency is allowing a 14
day public comment period to accommodate this need.
VI. Public Docket and Submission of Electronic Comments
The official record for this rulemaking, as well as the public
version, has been established for this rulemaking under docket control
number [OPP-300693] (including comments and data submitted
electronically as described below). A public version of this record,
including printed, paper versions of electronic comments, which does
not include any information claimed as CBI, is available for inspection
from 8:30 a.m. to 4 p.m., Monday through Friday, excluding legal
holidays. The official rulemaking record is located at the Virginia
address in ``ADDRESSES'' at the beginning of this document.
Electronic comments can be sent directly to EPA at:
[email protected]
Electronic comments must be submitted as an ASCII file avoiding the
use of special characters and any form of encryption. Comment and data
will also be accepted on disks in Wordperfect 5.1/6.1 or ASCII file
format. All comments and data in electronic form must be identified by
the docket control number [OPP-300693]. Electronic comments on this
proposed rule may be filed online at many Federal Depository Libraries.
VIII. Regulatory Assessment Requirements
This action proposes a time-limited tolerance under FFDCA section
408(e). 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). In
addition, this proposed 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) (Pub. L. 104-4). Nor does
it require any prior consultation as specified by Executive Order
12875, entitled Enhancing the Intergovernmental Partnership (58 FR
58093, October 28, 1993), or special considerations as required by
Executive Order 12898, entitled Federal Actions to Address
Environmental Justice in Minority Populations and Low-Income
Populations (59 FR 7629, February 16, 1994), or require special OMB
review in accordance with Executive Order 13045, entitled Protection of
Children from Environmental Health Risks and Safety Risks (62 FR 19885,
April 23, 1997).
In addition, under the Regulatory Flexibility Act (RFA) (5 U.S.C.
601 et seq.), the Agency previously assessed whether establishing
tolerances, exemptions from tolerances, raising tolerance levels or
expanding exemptions might adversely impact small entities and
concluded, as a generic matter, that there is no adverse economic
impact. The factual basis for the Agency's generic certification for
tolerance actions published on May 4, 1981 (46 FR 24950), and was
provided to the Chief Counsel for Advocacy of the Small Business
Administration.
List of Subjects in 40 CFR Part 180
Environmental protection, Administrative practice and procedure,
Agricultural commodities, Pesticides and pests, Reporting and
recordkeeping requirements.
Dated: July 23, 1998.
James Jones,
Director, Registration Division, Office of Pesticide Programs.
Therefore, it is proposed that 40 CFR part 180 be amended as
follows:
PART 180--[AMENDED]
1. The authority citation for part 180 continues to read as
follows:
Authority: 21 U.S.C. 346a and 371.
2. In Sec. 180.495, by revising paragraph (a) to read as follows:
Sec. 180.495 Spinosad; tolerances for residues.
(a) General . Tolerances are established for residues of the
insecticide Spinosad. Factor A is 2-[(6-deoxy-2,3,4-tri-O-methyl-
-L-manno-pyranosyl)oxy]-13-[[5-(dimethylamino)-tetrahydro-6-
methyl-2H-pyran-2-yl]oxy]-9-ethyl-
2,3,3a,5a,5b,6,9,10,11,12,13,14,16a,6b-tetradecahydro-14-methyl-1H-as-
Indaceno[3,2-d]oxacyclododecin-7,15-dione. Factor D is 2-[(6-deoxy-
2,3,4-tri-O-methyl--L-manno-pyranosyl)oxy]-13-[[5-
(dimethylamino)-tetrahydri-6-methyl-2H-pyran-2-yl]oxy]-9-ethyl-
2,3,3a,5a,5b,6,9,10,11,12,13,14,16a,16b-tetradecahydro-4,14-dimethyl-
1H-as-Indaceno[3,2-d]oxacyclododecin-7,15-dione.
------------------------------------------------------------------------
Expiration/Revocation
Commodity Parts per million Date
------------------------------------------------------------------------
Almonds..................... 0.02 None
Almond hulls................ 2.0 None
Apples...................... 0.2 None
Apple pomace, wet........... 0.5 None
Brassica (cole), leafy
vegetables, greens subgroup 10.0 None
Brassica (cole), leafy
vegetables, head and stem
subgroup................... 2.0 None
Cattle, fat................. 0.6 None
Cattle, meat................ 0.04 None
Cattle, meat byproducts..... 0.2 None
[[Page 40247]]
Citrus fruits group......... 0.3 None
Citrus oil.................. 3.0 None
Citrus pulp, dried.......... 0.5 None
Coffee...................... 0.02 8/28/00
Cotton gin byproducts....... 1.5 None
Cottonseed.................. 0.02 None
Fruiting vegetables (except
cucurbits) group........... 0.4 None
Goat, fat................... 0.6 None
Goat, meat.................. 0.04 None
Goat, meat byproducts....... 0.2 None
Hogs, fat................... 0.6 None
Hogs, meat.................. 0.04 None
Hogs, meat byproducts....... 0.2 None
Horses, fat................. 0.6 None
Horses, meat................ 0.04 None
Horses, meat byproducts..... 0.2 None
Leafy vegetables (except
Brassica vegetables) group. 8.0 None
Milk, fat................... 0.5 None
Milk, whole................. 0.04 None
Sheep, fat.................. 0.6 None
Sheep, meat................. 0.04 None
Sheep, meat byproducts...... 0.2 None
------------------------------------------------------------------------
* * * * *
[FR Doc. 98-20286 Filed 7-27-98; 8:45 am]
BILLING CODE 6560-50-F