[Federal Register Volume 63, Number 176 (Friday, September 11, 1998)]
[Rules and Regulations]
[Pages 48579-48586]
From the Federal Register Online via the Government Publishing Office [www.gpo.gov]
[FR Doc No: 98-24472]
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ENVIRONMENTAL PROTECTION AGENCY
40 CFR Part 180
[OPP-300706; FRL-6025-6]
RIN 2070-AB78
Cypermethrin; Pesticide Tolerance
AGENCY: Environmental Protection Agency (EPA).
ACTION: Final rule.
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SUMMARY: This regulation establishes a tolerance for residues of
cypermethrin () alpha-cyano-(3-phenoxyphenyl)methyl
() cis, trans-3(2,2-dichloroethyenyl)-2,2-
dimethylcyclopropane carboxylate in or on the commodity green onion at
6.0 parts per million (ppm). The Interregional Research Project Number
4 (IR-4) requested this tolerance under the Federal Food, Drug and
Cosmetic Act (FFDCA), as amended by the Food Quality Protection Act of
1996.
DATES: This regulation is effective September 11, 1998. Objections and
requests for hearings must be received by EPA on or before November 10,
1998.
ADDRESSES: Written objections and hearing requests, identified by the
docket control number, [OPP-300706], must be submitted to: Hearing
Clerk (1900), Environmental Protection Agency, Rm. M3708, 401 M St.,
SW., Washington, DC 20460. Fees accompanying objections and hearing
requests shall be labeled ``Tolerance Petition Fees'' and forwarded to:
EPA Headquarters Accounting Operations Branch, OPP (Tolerance Fees),
P.O. Box 360277M, Pittsburgh, PA 15251. A copy of any objections and
hearing requests filed with the Hearing Clerk identified by the docket
control number, [OPP-300706], must also be submitted 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,
bring a copy of objections and hearing requests to Rm. 119, CM #2, 1921
Jefferson Davis Hwy., Arlington, VA.
A copy of objections and hearing requests filed with the Hearing
Clerk may also be submitted electronically by sending electronic mail
(e-mail) to: [email protected]. Copies of objections and
hearing requests must be submitted as an ASCII file avoiding the use of
special characters and any form of encryption. Copies of objections and
hearing requests will also be accepted on disks in WordPerfect 5.1/6.1
file format or ASCII file format. All copies
[[Page 48580]]
of objections and hearing requests in electronic form must be
identified by the docket control number [OPP-300706]. No Confidential
Business Information (CBI) should be submitted through e-mail.
Electronic copies of objections and hearing requests on this rule may
be filed online at many Federal Depository Libraries.
FOR FURTHER INFORMATION CONTACT: By mail: Sidney Jackson, 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) 305-7610, e-mail:
[email protected].
SUPPLEMENTARY INFORMATION: In the Federal Register of March 19, 1998
(63 FR 13404) (FRL-5776-6), EPA, issued a notice pursuant to section
408 of the Federal Food, Drug, and Cosmetic Act (FFDCA), 21 U.S.C.
346a(e), announcing the filing of a pesticide petition (PP 5E4463) for
tolerance by the Interregional Research Project (IR-4). This notice
included a summary of the petition prepared by FMC Corporation, 1735
Market St., Philadelphia, PA 19103, the registrant. There were no
comments received in response to the notice of filing.
The petition requested that 40 CFR 180.418 be amended by
establishing a tolerance for residues of the insecticide cypermethrin
() alpha-cyano-(3-phenoxyphenyl)methyl () cis,
trans-3(2,2-dichloroethyenyl)-2,2-dimethylcyclopropane carboxylate in
or on the commodity green onion at 6.0 ppm.
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) 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) 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% 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
100-fold MOE is based on the same rationale as the 100-fold 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
[[Page 48581]]
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.)
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.
Percent of crop treated estimates are derived from federal and
private market survey data. Typically, a range of estimates are
supplied and the upper end of this range is assumed for the exposure
assessment. By using this upper end estimate of percent of crop
treated, the Agency is reasonably certain that exposure is not
understated for any significant subpopulation group. Further, regional
consumption information is taken into account through EPA's computer-
based model for evaluating the exposure of significant subpopulations
including several regional groups, to pesticide residues. For this
pesticide, the most highly exposed population subgroup was not
regionally based.
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
this action, EPA has sufficient data to assess the hazards of
cypermethrin and to make a determination on aggregate exposure,
consistent with section 408(b)(2), for a tolerance for residues of
cypermethrin on green onions at 6.0 ppm. EPA's assessment of the
dietary exposures and risks associated with establishing the tolerance
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 cypermethrin are
discussed below.
1. Acute toxicity. The required battery of acute toxicity studies
has been submitted and found adequate. The findings were as follows:
oral toxicity, lethal dose (LD)50 > 263 milligram/kilogram
(mg/kg); dermal toxicity, LD50 > 2,460 mg/kg; inhalation
toxicity lethal concentration (LC)50, 2.5 mg/liter (L);
primary eye irritation--Toxicity Category III; primary dermal
irritation --Toxicity Category IV. Cypermethrin is considered to be a
dermal sensitizer.
2. Genotoxicity. The Agency has reviewed several mutagenicity
studies. Types include an Ames mutagenicity assay; a dominant lethal
study, a mouse lymphoma mutagenicity assay, a Chinese hamster ovary/
hypoxanthine quanine phosphoribose transferase (CHO/HGPRT) assay, and a
bone marrow cytogenic study. The data base for mutagenicity is
considered to be adequate. Based on the available mutagenicity studies,
there are no concerns for mutagenicity.
3. Reproductive and developmental toxicity-- i. Developmental
toxicity study in the rat. Cypermethrin was administered by gavage to
rats at dose levels of 0, 17.5, 35, or 70 mg/kg/day on days 6-15 of
gestation. The maternal lowest-observed effect level (LOEL) is 35 mg/
kg/day, based on bodyweight. The maternal NOEL is 17.5 mg/kg/day. The
developmental LOEL was > 70 mg/kg/day. The developmental NOEL is > 70
mg/kg/day.
ii. Developmental toxicity study in the rabbit. Cypermethrin was
administered to 20 New Zealand White rabbits per dose group by gavage
at dose levels of 0, 100, 450, or 700 mg/kg/day from days 7 through 19
of gestation. The test animals were sacrificed on day 29 of gestation.
The maternal LOEL was 450 mg/kg/day, based on bodyweight gain. The
maternal NOEL was 100 mg/kg/day. There were no indications of
developmental toxicity. The NOEL and LOEL for developmental toxicity
was > 700 mg/kg/day.
iii. Three-generation reproduction study in rats. Cypermethrin was
administered to rats at dose levels of 0, 50, 150, or 1,000/750 ppm
(reduced to 750 ppm after 12 weeks because of severe neurological
symptoms). These dose levels correspond to 2.5, 7.5, or 50/37.5 mg/kg/
day. Three successive generations were produced, each consisting of two
separate breedings to produce six sets of litters. The LOEL is 150 ppm
(7.5 mg/kg/day) based on consistent decreased bodyweight gain in both
sexes. The NOEL was 50 ppm (2.5 mg/kg/day).
4. Subchronic toxicity. The data base for subchronic toxicity is
considered to be complete except for a series 82-4 subchronic
inhalation toxicity study of 90-days duration. This study is required
if inhalation exposure is for periods greater than 21-days.
i. A 21-day dermal study in the rabbit. Cypermethrin was applied at
dose levels of control, 2, 20, or 200 mg/kg/day applied in 20% weight/
weight (w/w) basis PEG 300 with daily applications
[[Page 48582]]
for 3 weeks for a total of 15 applications. The LOEL is 200 mg/kg/day
based on liver effects. The NOEL is 20 mg/kg/day.
ii. A 21-day inhalation study in the rat. Cypermethrin was
administered to rats by nose only exposure at concentrations of 0,
0.01, 0.05, or 0.25 mg/L for 6 hours per day, 5 days per week for total
of 15 exposures. The LOEL was 0.05 mg/L based mainly on bodyweight
decrease. The NOEL was 0.01 mg/L.
5. Chronic toxicity/carcinogenicity-- i. Chronic oral study in the
dog. Cypermethrin was administered to beagle dogs at dose levels of 0,
1, 5, or 15 mg/kg/day for 52 weeks. The LOEL was 5 mg/kg/day based on
gastrointestinal effects. The NOEL is 1 mg/kg/day.
ii. Carcinogenicity study in the mouse. Cypermethrin was
administered to mice at dose levels of control-1, control-2, 100, 400,
and 1,600 ppm (corresponding to 0, 0, 14, 57, or 229 mg/kg/day) for 97
weeks for males and 101 weeks for females. The LOEL was 400 ppm (57 mg/
kg/day) based on liver weight. The NOEL was 100 ppm (14 mg/kg/day).
This study was determined to be positive for induction of benign
alveologenic neoplasms.
iii. Chronic feeding/carcinogenicity study in the rat. Cypermethrin
was administered to rats at dose levels of control-1, control-2, 20,
150, or 1,500 ppm (corresponding to 0, 1, 7.5, or 75 mg/kg/day) for 2
years. The LOEL is 1,500 ppm (75 mg/kg/day) based on body weight. The
NOEL was 150 ppm (7.5 mg/kg/day). Cypermethrin was not considered to be
oncogenic in this study. A possible association with increased
testicular interstitial tumors was not considered definite.
6. Metabolism. Studies in rats, dogs, and mice are available to
support the requirement of metabolism in mammals. Studies show that
cypermethrin is readily absorbed from the gastrointestinal tract and
extensively metabolized. It is mostly excreted in the urine. No
additional data are required.
7. Neurotoxicity. Additional data considered by the Agency included
an acute delayed type neurotoxicity in hens, an acute neurotoxicity
screening study in rats with a NOEL of 30 mg/kg and a LOEL of 100 mg/
kg, and a subchronic neurotoxicity screening study in rats with a NOEL
of 31 mg/kg/day and a LOEL of 77 mg/kg/day. Additional data will be
required under a special Data Call-In (DCI) letter pursuant to section
3(c)(2)(B) of FIFRA. Although these data are lacking EPA has a
sufficient toxicity data base to support these tolerances and these
additional studies are not expected to significantly change its risk
assessment.
B. Toxicological Endpoints
1. Acute toxicity. To assess risk from acute dietary exposure, the
Agency used a NOEL of 1.0 mg/kg/day based on increased incidence of
passage of liquid stools at 5 mg/kg/day and above starting the first
weeks of dosing in a chronic-dog study. A MOE of 100 is required
2. Short - and intermediate - term toxicity. To assess risk from
(non-food) short- and intermediate-term dermal exposure, the Agency
used a NOEL of 5 mg/kg/day from the chronic-dog study, incorporating
25% dermal absorption. A dermal absorption rate of 25% was derived
based on the weight-of-evidence available for structurally related
pyrethroids. For exposure via inhalation, the Agency used a NOEL of
0.01 mg/L from the 21-day inhalation study in rats.
3. Chronic toxicity. EPA has established the RfD for cypermethrin
at 0.01 mg/kg/day. This RfD is based on a NOEL of 1.0 mg/kg/day from
the chronic-dog study with an uncertainty factor of 100.
4. Carcinogenicity. Using its Guidelines for Carcinogen Risk
Assessment published September 24, 1986 (51 FR 33992) the
Carcinogenicity Peer Review Committee (CPRC) has classified
cypermethrin as a Group C chemical, possible human carcinogen, based on
increased incidence of lung adenomas in female mice, but did not
recommend assignment of a cancer potency factor (Q*1) for a linear
quantitative cancer risk assessment. Instead, the CPRC recommended the
RfD approach. Based on the CPRC's recommendation that the RfD approach
be used to assess dietary cancer risk, a quantitative linear dietary
cancer risk assessment was not performed. Human health risk concerns
due to long-term consumption of cypermethrin residues are adequately
addressed by the dietary risk evaluation chronic exposure analysis
using the RfD.
C. Exposures and Risks
1. From food and feed uses. Tolerances have been established (40
CFR 180.418) for residues of cypermethrin in or on a variety of raw
agricultural commodities. Tolerances currently exist for residues of
cypermethrin on cottonseed; pecans; lettuce, head; onions, bulb;
cabbage; Brassica, head and stem; Brassica, leafy and livestock
commodities of cattle, goats, hogs, horses, and sheep as well as this
pending tolerance for green onions. For the purposes of dietary risk
assessment, residue data generated from residue field trials conducted
at maximum application rates and minimum preharvest intervals were
used. To assess secondary exposure from edible animal commodities,
animal dietary burdens were calculated using mean field trial residue,
adjusted for percent crop treated and applying appropriate processing
factors for all feed items. Risk assessments were conducted by EPA to
assess dietary exposures and risks from cypermethrin 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 one day or single exposure. The acute dietary exposure assessment
used Monte Carlo modeling (in accordance with Tier 3 of EPA June
1996``Acute Dietary Exposure Assessment'' guidance document)
incorporating anticipated residues and percent crop treated refinement.
The acute exposure via dietary intake for the U.S. Population is
estimated at 0.004438 mg/kg/day. The acute dietary risk estimated by
MOE at the 99.9th percentile for the U.S. population is 225. The acute
dietary exposure for children is 0.005465 mg/kg/day with a resulting
MOE of 183. EPA concludes that there is a reasonable certainty of no
harm for MOEs of 100 or greater.
ii. Chronic exposure and risk. The chronic dietary exposure
assessment incorporated anticipated residues, tolerance values, FDA and
PDP monitoring data, and percent crop treated information. The RfD used
was 0.01 mg/kg/day. For the U.S. population, the exposure was estimated
at 0.000025 mg/kg/day. The risk assessment resulted in use of 0.3% of
the RfD. For children, the exposure was estimated at 0.000042 mg/kg/
day, which uses 0.4% of the RfD.
Section 408(b)(2)(E) of the FFDCA authorizes EPA to consider
available data and information on the anticipated residue levels of
pesticides 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 five 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. Section
408(b)(2)(F) allows the Agency to use data on the actual percent of
crop treated when establishing a tolerance only where the Agency can
make the following
[[Page 48583]]
findings: (a) that the data used are reliable and provide a valid basis
for showing the percentage of food derived from a crop that is likely
to contain residues; (b) that the exposure estimate does not
underestimate the exposure for any significant subpopulation and; (c)
where data on regional pesticide use and food consumption are
available, that the exposure estimate does not understate exposure for
any regional population. In addition, the Agency must provide for
periodic evaluation of any estimates used.
The percent of crop treated estimates for cypermethrin were derived
from federal and market survey data. EPA considers these data reliable.
A range of estimates are supplied by these data and the upper end of
this range was used for the exposure assessment. By using this upper
end estimate of percent crop treated, the Agency is reasonably certain
that exposure is not underestimated for any significant subpopulation.
Further, regional consumption information is taken into account through
EPA's computer based model for evaluating exposure of significant
subpopulations including several regional groups. Review of this
regional data allows the Agency to be reasonably certain that no
regional population is exposed to residue levels higher than those
estimated by the Agency. To meet the requirement for data on
anticipated residues, EPA will issue a Data Call-In (DCI) notice
pursuant to section 408(f) of the FFDCA requiring submission of data on
anticipated residues in conjunction with approval of the registration
under FIFRA.
2. From drinking water. Studies show that cypermethrin is immobile
in soil and does not leach into ground water. Drinking water residue
levels were estimated using the PRZM1/EXAMS computer models in 1993 for
comparative ecological risk assessment.
i. Acute exposure and risk. For the U.S. population, acute exposure
is estimated at 0.000126 mg/kg/day (MOE = 7,965). For non-nursing
infants < 1 year old, exposure is estimated at 0.000242 mg/kg/day (MOE=
4,138).
ii. Chronic exposure and risk. For the U.S. population, chronic
exposure is estimated at 0.000005 mg/kg/day, or essentially 0% of the
RfD. For non-nursing infants < 1 year old, exposure is estimated at
0.000021 mg/kg/day, or 0.2% of the RfD.
3. From non-dietary exposure. Cypermethrin is currently registered
for use on the following residential non-food sites: lawns and carpet.
Non-occupational exposure to cypermethrin may occur as a result of
inhalation or contact from indoor residential, indoor commercial, and
outdoor residential uses. Using surrogate data and conservative
exposure scenarios, the Agency has estimated combined inhalation,
dermal, and oral non-dietary exposure.
4. Short- and intermediate-term exposure and risk. For the U.S.
population, exposure is estimated at 0.0000515 mg/kg/day. For infants
less than 1 year old, the exposure is estimated at 0.00259 mg/kg/day.
It should be noted that carpet uses are considered short and
intermediate term exposures because available data indicate that
cypermethrin dissipates over time and is thus unavailable to contribute
as chronic exposure and risk.
5. Cumulative exposure to substances with 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.'' 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).
Four members of the insecticide class pyrethroids produce a common
metabolite known as DCVA (3-(2,2-dichloroethenyl)-2,2-
dimethylcyclopropane carboxylic acid). These insecticides are
cyfluthrin, cypermethrin, zeta-cypermethrin and permethrin. Although
the residues of DCVA can be estimated, no toxicology data on the
compound per se are available to directly conduct a hazard evaluation
and thereby establish an appropriate endpoint for use in a joint risk
assessment. To date, for the purpose of assessing the risk of the
parent compound the toxicity of DCVA has been assumed to be equivalent
to the parent compound. However, due to the different toxicological
profiles of cyfluthrin, cypermethrin, permethrin, and zeta-
cypermethrin, EPA does not believe that it would be appropriate to
cumulate DCVA for these pesticides, or DCVA residues from one of these
pesticides with the parent of another of these pesticides, in
conducting the risk assessment for these pesticides. Accordingly, for
the purposes of this tolerance action, EPA has not assumed that
cypermethrin has a common mechanism of toxicity with other substances.
D. Aggregate Risks and Determination of Safety for U.S. Population
The Agency has determined that an aggregate systemic oral and
dermal exposure risk assessment is not appropriate due to difference in
the toxicity endpoints observed between the oral (neurotoxicity) and
dermal (hepatotoxicity) routes. An aggregate oral and inhalation risk
assessment is appropriate due to the similarity of toxicity
(neurotoxicity) observed in rats via these routes.
1. Acute risk. Aggregate acute risk represents the sum of acute
food and acute drinking water exposure. For cypermethrin, the aggregate
acute exposure is estimated at 0.004564 mg/kg/day, with a resulting MOE
of 219 for the adult U.S. population. EPA generally has no concern for
acute risk when the MOE is greater than 100.
[[Page 48584]]
2. Chronic risk. Aggregate chronic exposure is the sum of chronic
exposure from food and drinking water. Using the exposure assumptions
described above, EPA has concluded that aggregate exposure to
cypermethrin from food and water will utilize 0.3% of the RfD for the
U.S. population. 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.
3. Short- and intermediate-term risk. Short- and intermediate-term
aggregate exposure takes into account chronic dietary food and water
(considered to be a background exposure level) plus indoor and outdoor
residential exposure. For cypermethrin, exposure is estimated at
0.000082 mg/kg/day, with a resulting MOE of 61,000 for the U.S.
population. EPA generally has no concern for short-term risks if MOEs
are shown to be over 100.
E. Aggregate Cancer Risk for U.S. Population
Cypermethrin is classified as a weak Group C carcinogen based on
the increased incidence of lung adenomas in female mice. An RfD
approach was recommended for human risk assessment purposes. Therefore,
a quantitative dietary cancer risk assessment was not performed.
Dietary risk concerns due to long-term consumption of cypermethrin are
adequately addressed in the chronic exposure analysis. For the U.S.
population, less than 1% of the RfD is occupied by aggregate chronic
food and water exposure.
F. Conclusion
EPA concludes that there is a reasonable certainty that no harm
will result from aggregate exposure to cypermethrin residues.
G. Aggregate Risks and Determination of Safety for Infants and Children
1. Safety factor for infants and children-- i. In general. In
assessing the potential for additional sensitivity of infants and
children to residues of cypermethrin, EPA considered data from
developmental toxicity studies in the rat and rabbit and a 2-generation
reproduction study in the rat. The developmental toxicity studies are
designed to evaluate adverse effects on the developing organism
resulting from maternal pesticide exposure gestation. 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 ten-
fold 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 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.
ii. Developmental toxicity studies. In the pre-natal developmental
toxicity studies in rats and rabbits, there was no evidence of
developmental toxicity at the highest dose tested (70 mg/kg/day in rats
and 700 mg/kg/day in rabbits).
iii. Reproductive toxicity study. An acceptable 3-generation
reproduction study in rats has been submitted. Offspring toxicity was
observed only at the highest dietary level tested, (700/1,000 ppm; 50/
37.5 mg/kg/day), while toxicity in parental animals was observed at the
lower treatment levels. The parental systemic NOEL was 50 ppm (2.5 mg/
kg/day) and the parental systemic LOEL was 150 ppm (7.5 mg/kg/day).
iv. Pre- and post-natal sensitivity. The developmental and
reproductive toxicity data demonstrated no indications of increased
pre- and post-natal sensitivity.
v. Conclusion. From available adequate data, there is no indication
that the developing fetus or neonate is more sensitive than adult
animals. No developmental neurotoxicity studies are being required at
this time. A developmental neurotoxicity data requirement is an upper
tier study and required only if effects observed in the acute and 90-
day neurotoxicity studies indicate concerns for frank neuropathy or
alterations seen in fetal nervous system in the developmental or
reproductive toxicology studies. The FQPA conditional requirement of an
additional tenfold margin of safety for pesticide residues be applied
for infants and children to take into account potential pre-and post-
natal toxicity was not imposed in this case. The Agency believes that
reliable data support the use of the standard 100-fold uncertainty
factor, and that a ten-fold (10x) uncertainty factor is not needed to
protect the safety of infants and children.
2. Acute risk. For children 1 to 6 years old, (most highly exposed
subgroup), the aggregate acute exposure is estimated at 0.005572 mg/kg/
day, with a resulting MOE of 179. EPA generally has no concern for MOEs
over 100.
3. Chronic exposure and risk. Using the conservative exposure
assumptions, EPA has concluded that aggregate exposure to cypermethrin
from food and water is estimated at 0.000044 mg/kg/day for children 1
to 6 years old (the highly exposed subgroup) will utilize 0.4% of the
RfD for infants and children. 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.
4. Short- or intermediate-term risk. Short- and intermediate-term
aggregate exposure takes into account chronic dietary food and water
(considered to be a background exposure level) plus short-term and
intermediate-term residential exposure. The MOE for non-nursing infants
< 1 year old (most highly exposed subgroup) is estimated at 1,900, well
above MOE values of a MOE less than 100 which the Agency finds
unacceptable.
Therefore, EPA concludes that there is reasonable certainty that no
harm will result to infants and children from aggregate exposure to
cypermethrin residues.
5. Special docket. The complete acute and chronic exposure analyses
(including dietary, non-dietary, drinking water, and residential
exposure, and analysis of exposure to infants and children) used for
risk assessment purposes can be found in the Special Docket for the
FQPA under the title ``Risk Assessment for Extension of Tolerances for
Synthetic Pyrethroids.'' Further explanation regarding EPA's decision
regarding the additional safety factor can also be found in the Special
Docket.
H. Endocrine Disrupter Effects
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
[[Page 48585]]
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 the program. Congress has allowed 3 years from
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 disruption effects.
III. Other Considerations
A. Metabolism In Plants and Animals
The metabolism of cypermethrin in plants and animals is adequately
understood. Studies have been conducted to delineate the metabolism of
radiolabelled cypermethrin in various crops all showing similar
results. The residue that is regulated is the parent compound,
cypermethrin.
B. Analytical Enforcement Methodology
Adequate enforcement methodology Gas Chromatography with Electron
Capture Detection (GC/ECD) is available in PAM II for enforcement of
the tolerance.
C. Magnitude of Residues
Residue data from field trial and the FDA monitoring program (1992-
1995) and the PDP monitoring program (1994) were used to estimate
chronic dietary exposure. For the chronic analyses, mean residues from
FDA monitoring were used for letttuce and onions (dry bulbs). Residue
field trial data were used for broccoli, cabbage, cotton, green onions,
mustard greens, and pecans. For acute dietary exposure analysis, field
trial residue data, along with percent crop treated were used in the
Monte Carlo analysis.
D. International Residue Limits
There are no Codex Maximum Residue Limits (MRL) for cypermethrin on
green onions.
IV. Conclusion
Therefore, the tolerance is established for residues of
cypermethrin () alpha-cyano(3-phenoxyphenyl)methyl
() cis, trans 3-(2,2-dichloroethenyl)-2,2-
dimethylcyclopropanecarboxylate) in or on the raw agricultural
commodity green onions at 6.0 ppm.
V. Objections and Hearing Requests
The new FFDCA section 408(g) provides essentially the same process
for persons to ``object'' to a tolerance regulation issued by EPA under
new section 408(e) and (l)(6) as was provided in the old section 408
and in section 409. However, the period for filing objections is 60
days, rather than 30 days. EPA currently has procedural regulations
which govern the submission of objections and hearing requests. These
regulations will require some modification to reflect the new law.
However, until those modifications can be made, EPA will continue to
use those procedural regulations with appropriate adjustments to
reflect the new law.
Any person may, by November 10, 1998, file written objections to
any aspect of this regulation and may also request a hearing on those
objections. Objections and hearing requests must be filed with the
Hearing Clerk, at the address given above (40 CFR 178.20). A copy of
the objections and/or hearing requests filed with the Hearing Clerk
should be submitted to the OPP docket for this rulemaking. The
objections submitted must specify the provisions of the regulation
deemed objectionable and the grounds for the objections (40 CFR
178.25). Each objection must be accompanied by the fee prescribed by 40
CFR 180.33(i). If a hearing is requested, the objections must include a
statement of the factual issues on which a hearing is requested, the
requestor's contentions on such issues, and a summary of any evidence
relied upon by the requestor (40 CFR 178.27). A request for a hearing
will be granted if the Administrator determines that the material
submitted shows the following: There is 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 in the manner sought by the requestor would be adequate
to justify the action requested (40 CFR 178.32). 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.
VI. Public Record and Electronic Submissions
EPA has established a record for this rulemaking under docket
control number [OPP-300706] (including any comments and data submitted
electronically). A public version of this record, including printed,
paper versions of electronic comments, which does not include any
information claimed as CBI, is available for inspection from 8:30 a.m.
to 4 p.m., Monday through Friday, excluding legal holidays. The public
record is located in Room 119 of the Public Information and Records
Integrity Branch, Information Resources and Services Division (7502C),
Office of Pesticide Programs, Environmental Protection Agency, Crystal
Mall #2, 1921 Jefferson Davis Highway, Arlington, VA.
Electronic comments may 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.
The official record for this rulemaking, as well as the public
version, as described above will be kept in paper form. Accordingly,
EPA will transfer any copies of objections and hearing requests
received electronically into printed, paper form as they are received
and will place the paper copies in the official rulemaking record which
will also include all comments submitted directly in writing. The
official rulemaking record is the paper record maintained at the
Virginia address in ``ADDRESSES'' at the beginning of this document.
VII. Regulatory Assessment Requirements
A. Certain Acts and Executive Orders
This final rule establishes a tolerance under FFDCA section 408(d)
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). 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) (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
[[Page 48586]]
Populations (59 FR 7629, February 16, 1994), or require 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).
B. Executive Order 12875
Under Executive Order 12875, entitled Enhancing Intergovernmental
Partnerships (58 FR 58093, October 28, 1993), EPA may not issue a
regulation that is not required by statute and that creates a mandate
upon a State, local or tribal government, unless the Federal government
provides the funds necessary to pay the direct compliance costs
incurred by those governments. If the mandate is unfunded, EPA must
provide to the Office of Management and Budget (OMB) a description of
the extent of EPA's prior consultation with representatives of affected
State, local and tribal governments, the nature of their concerns,
copies of any written communications from the governments, and a
statement supporting the need to issue the regulation. In addition,
Executive Order 12875 requires EPA to develop an effective process
permitting elected officials and other representatives of State, local
and tribal governments ``to provide meaningful and timely input in the
development of regulatory proposals containing significant unfunded
mandates.''
Today's rule does not create an unfunded federal mandate on State,
local or tribal governments. The rule does not impose any enforceable
duties on these entities. Accordingly, the requirements of section 1(a)
of Executive Order 12875 do not apply to this rule.
C. Executive Order 13084
Under Executive Order 13084, entitled Consultation and Coordination
with Indian Tribal Governments (63 FR 27655, May 19,1998), EPA may not
issue a regulation that is not required by statute, that significantly
or uniquely affects the communities of Indian tribal governments, and
that imposes substantial direct compliance costs on those communities,
unless the Federal government provides the funds necessary to pay the
direct compliance costs incurred by the tribal governments. If the
mandate is unfunded, EPA must provide OMB, in a separately identified
section of the preamble to the rule, a description of the extent of
EPA's prior consultation with representatives of affected tribal
governments, a summary of the nature of their concerns, and a statement
supporting the need to issue the regulation. In addition, Executive
Order 13084 requires EPA to develop an effective process permitting
elected and other representatives of Indian tribal governments ``to
provide meaningful and timely input in the development of regulatory
policies on matters that significantly or uniquely affect their
communities.''
Today's rule does not significantly or uniquely affect the
communities of Indian tribal governments. This action does not involve
or impose any requirements that affect Indian Tribes. Accordingly, the
requirements of section 3(b) of Executive Order 13084 do not apply to
this rule.
In addition, since these tolerances and exemptions that are
established on the basis of a petition under FFDCA section 408(d), 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. Nevertheless, the Agency has
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.
VIII. Submission to Congress and the Comptroller General
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 the rule in the Federal Register. This 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
recordkeeping requirements.
Dated: August 31, 1998.
James Jones,
Director, Registration Division, Office of Pesticide Programs.
Therefore, 40 CFR chapter I is 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. 180.418, the table in paragraph (a)(1) is amended by
alphabetically adding the commodity to read as follows:
Sec. 180.418 Cypermethrin; tolerances for residues.
(a)(1)* * *
------------------------------------------------------------------------
Commodity Parts per million
------------------------------------------------------------------------
* * * * *
Onions, green............................. 6.0
* * * * *
------------------------------------------------------------------------
* * * * *
[FR Doc. 98-24472 Filed 9-10-98; 8:45 am]
BILLING CODE 6560-50-F