[Federal Register Volume 62, Number 107 (Wednesday, June 4, 1997)]
[Proposed Rules]
[Pages 30549-30554]
From the Federal Register Online via the Government Publishing Office [www.gpo.gov]
[FR Doc No: 97-14298]
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ENVIRONMENTAL PROTECTION AGENCY
40 CFR Parts 180 and 185
[OPP-300475; FRL-5600-6]
(S)-Hydroprene Biochemical Pest Control Agent; Pesticide
Tolerance
AGENCY: Environmental Protection Agency (EPA).
ACTION: Proposed Rule.
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SUMMARY: EPA proposes to expand the tolerance for residues of
hydroprene, [(S)-(Ethyl (2E,4E,7S)-3,7,11-trimethyl-2,4-
dodecadienoate)], an insect growth regulator, on all food items in
food-handling establishments to include perimeters and pantries, and
warehouses to the list of permissible food storage sites and ultra low
volume (ULV) fogging as a permissible treatment method under certain
precautions and conditions. The Agency also proposes permitting the use
of point source device treatments providing those devices do not come
into direct contact with food preparation surfaces and are kept a
minimum distance of 3 feet from exposed foods. The Agency is also
proposing to restrict the tolerance expression to residues of [(S)-
(Ethyl (2E,4E,7S)-3,7,11-trimethyl-2,4-dodecadienoate)], the S-racemer
of hydroprene since the R-racemer is no longer being supported in
reregistration. This regulation is proposed by the EPA at its own
initiative.
DATES: Comments identified by the docket control number [OPP-300475]
must be received on or before July 7, 1997.
ADDRESSES: Submit written comments by mail to: Public Information and
Records Integrity Branch, Information Resources and Services Division
(7506C), Office of Pesticide Programs, U.S. Environmental Protection
Agency, 401 M St., SW., Washington, DC 20460. In person, bring comments
to: Public Docket, Room 1132, Crystal Mall #2, 1921 Jefferson Davis
Highway, Arlington, VA 22202. Information submitted as a comment
concerning this document may be claimed confidential by marking any
part or all of that information as ``Confidential Business
Information'' (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.
Comments and data may also be submitted electronically by following
the instructions under Unit IV of this document. No Confidential
Business Information (CBI) should be submitted through e-mail.
FOR FURTHER INFORMATION CONTACT: By mail: Diana Horne, c/o Product
Manager (PM) 90, Biopesticides and Pollution Prevention Division
(7501W) Office of Pesticide Programs, Environmental Protection Agency,
401 M St. SW., Washington, DC 20460. Office location, telephone number
and e-mail address: Room 5-W38, 5th Floor, CS#1, 2800 Crystal Drive,
Arlington, VA 22202 (703) 308-8367; [email protected].
SUPPLEMENTARY INFORMATION: EPA proposes to amend 40 CFR parts 180 and
185 by removing Sec. 185.3625 and adding Sec. 180.501, and by adding
perimeters, pantries and warehouses to the list of permissible food
storage sites and ultra low volume (ULV) fogging as a permissible
treatment method under certain precautions and conditions. The Agency
is also permitting the use of point source device treatments providing
those devices do not come into direct contact with food preparation
surfaces and must be kept a minimum distance of 3 feet from exposed
foods. The Agency is also proposing to restrict the tolerance
expression to residues of [(S)-(Ethyl (2E,4E,7S)-3,7,11-trimethyl-2,4-
dodecadienoate)], the S-racemer of hydroprene. The R-racemer is being
removed from the tolerance expression since Sandoz Agro Inc., the
manufacturer, is supporting only the reregistration of (S)-hydroprene
and no longer manufacturers the R/S hydroprene racemic mixture.
I. Background and Statutory Authority
In the Federal Register of August 12, 1992 (57 FR 36005), EPA
promulgated a final rule which established a tolerance under sections
408 and 409 of the Federal Food, Drug and Cosmetic Act, 21 U.S.C. 346a
and 348, specifying a tolerance for (R)-hydroprene and (S)-hydroprene
racemic mixture residues of the insect growth regulator in or on food
commodities exposed during spot or crack and crevice treatment of food
handling establishments at 0.2 ppm. This was in response to a pesticide
tolerance petition (9H5573) filed by Zoecon Corporation.
The Food Quality Protection Act of 1996 (FQPA) (Pub. L. 104-170)
was signed into law August 3, 1996. FQPA amends both the Federal Food,
Drug and Cosmetic Act (FFDCA), 21 U.S.C. 301 et seq., and the Federal
Insecticide, Fungicide, and Rodenticide Act (FIFRA), 7 U.S.C, 136 at
seq. The FQPA amendments went into effect immediately. Among other
things, FQPA amends FFDCA to bring all EPA pesticide tolerance-setting
activities under a new section 408 with a new safety standard and new
procedures.
New section 408(b)(2)(A)(i) 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, 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....'' Section 408(b)(2)(D) specifies factors EPA is to consider
in establishing a tolerance. Section 408(b)(3) requires EPA to
determine that there is a practical method for detecting and measuring
levels of the pesticide chemical residue in or on food and that the
tolerance be set at a level at or above the limit of detection of the
designated method. Section 408(b)(4) requires EPA to determine whether
a maximum residue level has been established for the pesticide chemical
by the Codex Alimentarius Commission. If so, and EPA does not propose
to adopt that level, EPA must publish for public comment a notice
explaining the reasons for departing from the Codex level. Section 408
governs EPA's establishment of exemptions from the requirement for a
tolerance using the same safety standard as section 408(B)(2)(A) and
incorporating the provisions of section 408(b)(2)(C) and (D). Section
408(e) gives EPA general authority to establish tolerances and
exemptions from the requirement for a tolerance through notice and
comment rulemaking procedures upon EPA's initiative.
New section 408(c)(2)(A)(i) allows EPA to establish an exemption
from the
[[Page 30550]]
requirement of a tolerance only if EPA determines that the exemption is
``safe.'' Section 408(c)(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, but does not include occupational exposure. Section 408(c)(2)(B)
requires EPA to give special consideration to exposure of infants and
children to the pesticide chemical residue in establishing an exemption
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 ... `` and specifies factors EPA is to consider in
establishing an exemption. Section 408(c)(3)(B) provides for
circumstances when no need exists for a practical method for detecting
and measuring levels of pesticide chemical residue in or on food.
II. Risk Assessment and Statutory Findings
Consistent with section 408(b)(2)(A), EPA has reviewed the
available scientific data and other relevant information in support of
this action. The scientific data submitted in previous petitions and
other relevant material have been evaluated including toxicological and
residue chemistry data. EPA has assessed the toxicology data base for
(S)-hydroprene and has sufficient data to assess its hazards and to
make a determination on aggregate exposure.
A. Use Practices
1. Use practices. The biochemical pest control agent (S)-hydroprene
is presently used on walls, floors, ceilings, attics, basements, or
crawlspaces of apartment buildings, bakeries, bottling facilities,
breweries, boiler rooms, cafeterias, candy plants, grocery stores, day
care centers, hospitals, residential homes, office buildings, kitchens,
laboratories, cereal processing facilities, manufacturing plants,
mausoleums, meat and produce canneries, nursing homes, restaurants,
schools, locker rooms, stores, taverns, warehouses, as well as various
modes of transporation such as aircraft, buses, trucks, trailers, rail
cars, and marine vessels. It is also applied in food handling
establishments where food is held, prepared, processed or served
including areas where food is received, prepared, packaged and stored,
as well as enclosed food processing systems (mills, dairies, etc.) in
spot and crack and crevices, and small food storage areas. This
proposal would expand the permissible food storage sites to include
warehouses, pantries and perimeters and also ultra low volume (ULV)
fogging as a permissible treatment method.
2. Application rates. For general surface applications, one ounce
of product is applied to 1,500 square feet surface area (0.0015 gram
active ingredient/square foot) for surface spray/paint brush, spot and
crack crevice preparations. The product may be applied every 4 months
by spray/paint brush, hand pressurized or power operated sprayers,
foggers, mechanical misting sprayers, aerosol generators, Ultra Low
Volume (ULV) misters, or thermal foggers. For fogging, space spray/mist
applications, 1 ounce product/12,000 cubic feet (0.2 gram active
ingredient/1,000 cubic feet). Emissions from bait stations are at the
rate of 0.001 gram active ingredient/square feet over a 3-month period.
B. Product Identity/Residue Chemistry
1. Plant metabolism. (S)-hydroprene is not applied to living plants
or food and therefore plant metabolism studies have been waived. The
currently regulated residues are the racemic components of hydroprene,
namely [(R)-(Ethyl (2E,4E,)-3,7,11-trimethyl-2,4-- dodecadienoate)],
and [(S)-(Ethyl (2E,4E,)-3,7,11-trimethyl-2,4-dodecadienoate)] at 0.2
ppm. EPA proposes to keep the current tolerance limit of 0.2 ppm but to
limit the regulated residue to [(S)-(Ethyl (2E,4E,7E)-3,7,11-trimethyl-
2,4-dodecadienoate)]. The R-racemer is being removed from the tolerance
expression since Sandoz Agro Inc., the manufacturer, is supporting only
the reregistration of (S)-hydroprene and no longer manufacturers the R/
S hydroprene racemer mixture.
2. Analytical method. The Agency has reviewed scientific data
submitted by Zoecon Corporation and has determined that there is a
practical analytical method for detecting and measuring levels of (S-
)hydroprene in or on food with a limit of detection that allows
monitoring of food with residues at or above the levels set in these
tolerances. This method, Method No. 307, is an analytical method--Gas
chromatography/Flame Ionization Detector and Mass Specific Detector/
Selected Ion Monitoring (GC/FID and MD/SIM) with a limit of detection
of 0.01 ppm for most foods and 0.02 ppm for butter. The method will be
published in PAM II under Pesticide Reg. 40 CFR 185.3625. EPA has
provided information on this method to the Food and Drug
Administration. The method is available to anyone who is interested in
pesticide residue enforcement from: By mail, Calvin Furlow, Public
Information and Records Integrity Branch, Information Resoruces and
Services Division (7506C), Office of Pesticide Programs, Environmental
Protection Agency, 401 M St., SW., Washington, DC 20460. Office
location and telephone number: Crystal Mall #2, Rm. 1128, 1921
Jefferson Davis Highway, Arlington, VA 22202, (703) 305-5805.
3. Magnitude of residues. The Agency has also reviewed data for use
of (S)-hydroprene as a diluted spray for partial area treatment of
large food manufacturing/warehousing facilities. Residue studies of
food commodities exposed under simulated warehouse pantry conditions
for 24 hours indicate that the established tolerance of 0.2 ppm will
not be exceeded as long as label directions are followed. Residue
studies of food commodities exposed as a result of partial area
treatments of large food handling/warehousing facilities indicated that
food commodities exposed for up to 8 hours will not exceed the
established tolerance of 0.2 ppm. Residues resulting from ULV fogging
were also below the established tolerance of 0.2 ppm.
Also reviewed were exposure studies from the use of point source
devices. Submitted residue studies indicated that bait and/or stations
may be used in food handling establishments during food processing
without exceeding the established tolerance of 0.2 ppm under the
following conditions. The bait stations must not come into direct
contact with food preparation surfaces and must be a minimum of 3 feet
or more away from the exposed food.
C. Toxicological Profile
The toxicological findings include reviews/reassessments of a rat
chronic toxicity study, rat carcinogenicity study, rat reproductive
study, rat and rabbit developmental toxicity studies as well as an
Agency assessment of the reference dose (RfD). The test material for
all but one of the toxicology tests involved (S)-hydroprene which is
known to be the more biologically active hydroprene racemer. An R,S-
hydroprene racemic mixture was the test material in the rabbit
developmental study.
1. Acute toxicity. Based on the available acute toxicity data, EPA
has determined the (S)-hydroprene does not pose any acute dietary
risks. The following mammalian toxicity studies have been conducted in
support of the tolerance exemption for residues of technical (S)-
hydroprene except for the
[[Page 30551]]
acute inhalation test and the skin sensitizing test.
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Acute Toxicity Tests Results Rating
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(S)-hydroprene technical unless
otherwise stated.
Acute Oral.................... LD50 > 5,000 mg/kg/ Toxicity Category
day IV
Acute Dermal.................. LD50 > 5,000 mg/kg/ Toxicity Category
day, abraded skin III
Acute Inhalation.............. LC50 > 5.2 mg/L Toxicity Category
(actual) [65.7% III
formulation]
Primary Dermal Irritation Mild irritation at Toxicity Category
(Rat). 0 and 24 hours IV
Primary Eye Irritation Conjunctival Toxicity Category
(Rabbit). irritation only IV
after 24 hours
Dermal Sensitization (Guinea Sensitizing agent Toxicity Category
Pig). [65.7% IV
formulation]
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2. Genotoxicity. There is no evidence for the Agency to believe
that (S)-hydroprene, a biochemical, has genotoxic potential. Test
results were negative for the following mutagenicity tests: unscheduled
DNA synthesis in rat hepatocyte, micronucleus assay in mice, in vivo
cytogenicity in rat bone marrow cells, and the Ames assay.
3. Reproductive toxicity. Originally, the Agency determined a
parental toxicity no observed effect level (NOEL) of 300 ppm, lowest
observed effect level (LOEL) at 1,500 ppm, a reproductive toxicity NOEL
of 300 ppm and LOEL of 1,500 ppm (June 8, 1995 memo RfD/QA Peer Review
Committee). The Agency has now determined that the parental toxicity
NOEL is 1,500 ppm and the LOEL is 7,500 ppm for the rat reproductive
toxicity study. The conclusion is based on a review of additional data
indicating that: (a) Parental weight gain reductions of the low (300
ppm) and middle-dose (1,500 ppm) groups were sporadic and were not
considered to be of biological significance; this is supported by the
view of an FDA pathologist, (b) the mean parental body weight gains of
the 7,500 ppm group males and females decreased more than 10%
throughout the growth phase, when compared to the controls and appeared
to be treatment-related, (c) body weight reductions of F1 generation
males and females were inconsistent and did not exceed 10%; therefore
body weight gains of F1 generation progeny could not be used to
establish toxicological endpoints for setting the LOEL, (d) food
efficiency of F1 generation and mean body weights of pups at birth were
not affected by the treatment, (e) body weight gain reduction in pups
of F1 and F2 were significantly reduced on days 14 and 21 at 7500 ppm
when compared to controls, and (f) reduced conception rates in the F0
at the low- and high-dose levels were not treatment-related.
4. Developmental Toxicity. Following a reevaluation of the
submitted data, the Agency has altered its earlier conclusion
characterizing the post-implantation loss observed in the rabbit
developmental toxicity study as developmental toxicity. As a result,
the Agency is revising the developmental toxicity NOEL from 30 mg/kg/
day to 90 mg/kg/day, the highest dose tested in rabbits. The observed
developmental toxicity effects were maternal weight loss at the highest
dose tested, 90 mg/kg/day. While the test material involved a mixture
of R,S-hydroprene racemers, there were no adverse signs of development
toxicity at the highest dosage levels.
5. Subchronic toxicity. A 3-month feeding study in rats resulted in
a determination of lowest effect level (LEL) = 250 mg/kg/day and NOEL =
50 mg/kg/day. Vacuolated ovarian luteal cells were observed in females
as were microscopic findings of homogeneous cytoplasm in male and in
female hepatocytes. In a 28-day feeding study in rats, the LEL was 500
mg/kg/day and NOEL = 250 mg/kg/day. Observed was an increase in the
kidney to brain weight ration and an increase in absolute kidney
weight.
6. Chronic toxicity. In a previous review of the chronic toxicity
phase of the rat study, the overall NOEL was considered to be 100 ppm
(4.62 mg/kg/day in females), the lowest dose tested and was based on
the observance of cytoplasmic vacuolization in the ovaries. However,
the Agency now concludes that the cytoplasmic vacuolization observed in
the ovaries is a result of cellular overload of inert endogenous
products synthesized from hydroprene metabolites and thus constitutes
no toxicological significance. This explanation is supported by an FDA
pathologist (June 8, 1995 memo RfD/QA Peer Review Committee).
As a result of this finding (toxicological insignificance of the
ovarian changes), the NOEL and LOEL are now 1,000 and 10,000 ppm,
respectively, instead of 100 and 1,000 ppm. The NOEL and LOEL are based
on reduced body weight gains in males and females, pancreatic arteritis
in males, and increased incidence of syncytial macrophage aggregated in
cervical lymph nodes and deep cholesterol clefts and cortical fatty
vacuolization in the adrenals in females.
With respect to carcinogenicity, EPA used its Guidelines for
Carcinogen Risk Assessment published September 24, 1986 (51 FR 33992).
EPA has classified (S)-hydroprene as a Group ``D'' compound - not
classifiable as to human carcinogenicity. In a previous review of the
carcinogenicity phase of the rat study, the Agency noted that the
incidence of thyroid follicular cell adenomas appeared to be increased
in males of the highest dose group but never classified the compound
with regard to its human carcinogenicity potential. The Agency, in a
reconsideration of the findings, including the absence of a
carcinogenicity study involving a second species, and the equivocal
nature of the findings from the rat study, has now concluded that the
data set presented is only suggestive of a carcinogenic response. S-
hydroprene, therefore, should be classified as a ``Group D'' compound -
not classifiable as to human carcinogenicity. The conclusion, as drawn
from the rat study, is based on the following: (i) there was no
increase in the incidence of carcinomas; the incidence of carcinomas in
male groups were 6, 6, 2, 0 and 8%, respectively, in control group 1,
control group 2, 100 ppm, 1,000 ppm and 10,000 ppm groups, (ii) there
was no treatment-related increase in precancerous histopathological
changes such as hyperplasia, (iii) the compound was not associated with
a positive mutagenic response in several bioassay systems, (iv) the
compound is not structurally related to any known carcinogen, and (v)
the compound is a structural analog to methoprene, a pesticidal
compound that has been adequately tested and did not demonstrate
mutagenic or carcinogenic properties and has been found to be
extensively metabolized via beta oxidation and, almost totally
incorporated into components of the tricarboxylic acid cycle.
7. Reference dose. As a result of the recent findings, the Agency
is revising the RfD from 0.05 mg/kg/day to 0.1 mg/kg/day based on the
chronic toxicity in rats. Previously, in a February 2, 1994 meeting of
the RfD/QA Peer Review Committee, the Agency tentatively based the RfD
for this chemical on the two-generation reproduction study in rats with
a NOEL of 15 mg/kg/day for parental and reproductive toxicity (June
[[Page 30552]]
8, 1995 memo RfD/QA Peer Review Committee). Parental and reproductive
toxicity manifested as increased liver weight and increased incidence
of cytoplasmic vacuolization of the ovaries in the F1 were observed at
75 mg/kg/day and higher dose levels. The rat chronic toxicity study was
considered as a co-critical study with a NOEL of 4.62 mg/kg/day and a
lowest effect level of 45.7 mg/kg/day. Similar effects were observed in
this study. Although the chronic toxicity study in rats demonstrated a
slightly lower NOEL than the reproductive toxicity study, the Agency
considered the findings of the reproductive study to be more reliable.
An uncertainty factor (UF) of 100 was used to account for inter-species
extrapolation and intra-species variability. An additional UF of 3 was
used to account for the lack of chronic toxicity data on a non-rodent
species. On this basis, the RfD was calculated to be 0.05 mg/kg/day.
However, as a result of an April 20, 1995 reassessment meeting, the
Agency has now determined that the RfD should be based on the chronic
toxicity study in rats with a NOEL of 1,000 (36.2 and 45.7 mg/kg/day
for males and females, respectively) (June 8, 1995 memo RfD/QA Peer
Review Committee). Significantly decreased cumulative body weight gains
in males (18%) and females (20.6%) during growth phase (0 to 80 weeks),
syncytial macrophage aggregates in cervical lymph nodes, deep
cholesterol clefts and cortical fatty vacuolization in the adrenals of
females and pancreatic arteritis in males were observed at the next
higher dose level of 10,000 ppm (377 and 485 mg/kg/day for males and
females, respectively). A UF of 100 was used to account for inter-
species extrapolation and intra-species variability. An additional UF
of 3 was used to account for the lack of toxicity data on a non-rodent
species.
On the basis of the forementioned studies, the RfD is calculated to
be 0.1 mg/kg/day.
8. Animal metabolism. A rat metabolism study using a mixture of 2E/
4E and 2Z/4E isomers was submitted. About 13% is retained in the
carcasses of both males and female rats. Hydroprene concentration in
the plasma peaked at 5 to 7 hours. Elimination was biphasic. The half-
life of the second phase took place 2 to 10 days after dosing. In a 54
hour period, the highest residues were found after 6 hours, with
highest levels found in the liver, fat and adrenal glands. The Agency
has now classified (S)-hydroprene as a biochemical and therefore,
metabolism data are normally not required by the Agency due to the non-
toxic mode of action.
9. Metabolite toxicology. No metabolites have been identified for
(S)-hydroprene. No metabolite toxicity studies are required for this
pesticide which is presently classified as a biochemical.
D. Aggregate Exposure
In examining aggregate exposure, FQPA directs EPA to consider
available information concerning all routes of exposures from the
pesticide residue in the diet, including drinking water, and all other
non-occupational exposures. The primary non dietary routes of exposures
are exposure through pesticide use in gardens, lawns, or buildings
(residential and other indoor uses).
1. Dietary exposure-- a. Food. As indicated in earlier in this
document, reviewed data indicate that (S)-hydroprene residue levels are
below the tolerance level under worse-case scenarios.
b. Drinking water. Because the use pattern for (S)-hydroprene
involves only indoor uses, EPA does not anticipate any exposure to
result from residues of (S)-hydroprene in drinking water. Furthermore,
the chemical is not readily water-soluble.
2. Non-dietary exposure. With regard to non-dietary exposure, the
current registrations for (S)-hydroprene permits its use in cafeterias,
supermarkets, as well as kitchens in households. For general surface
treatments, the sprays must be allowed to dry before ventilation is
turned back on. Under these conditions, the risk from non-dietary
exposure to the general population is, thus, expected to be negligible.
E. Cumulative Exposure to Substances with Common Mechanism of Toxicity
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 and structurally 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).
F. Safety Determinations
1. U.S. population. In general, using conservative exposure
assumptions described earlier, and, based on the completeness and
reliability of the toxicity data, EPA has concluded that aggregate
exposure to (S)-hydroprene will utilize 6.8 percent of the RfD for the
U.S. population. It should be noted that there will be no exposure
issues for (S)-hydroprene residues in drinking water since this
biochemical pesticide is not used outdoors. EPA generally has no
concern for exposures below 100 percent of the RfD because the RfD
represents the level at or below which daily aggregate dietary exposure
over a lifetime will not pose appreciable risks to human health. EPA
concludes that there is a reasonable certainty that no harm will result
from aggregate exposure to S-hydroprene residues. There is no reason to
believe that (S)-hydroprene possesses any immunotoxic or estrogenic
properties at this time.
2. Infants and children. FFDCA section 408 provides that EPA shall
[[Page 30553]]
apply an additional tenfold margin of exposure (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 exposure (safety) will be safe
for infants and children. EPA believes that reliable data support using
the standard margin of exposure (usually 100X for combined inter- and
intra-species variability) and not the additional tenfold margin of
exposure 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 margin of exposure.
In assessing the potential for additional sensitivity of infants
and children to residues of (S)-hydroprene, EPA considered data from a
2-generation reproduction study in the rat and developmental toxicity
studies in the rat and rabbit.
Reproduction studies provide information relating to effects from
exposure to the pesticide on the reproductive capability of mating
animals and data on systemic toxicity. As detailed in a previous
paragraph in the toxicological profile section of this document, with
regard to the reproductive toxicity potential for (S)-hydroprene, the
Agency has concluded that the observed parental weight gain reductions
of the low (300 ppm) and middle-dose (1,500 ppm) groups were sporadic
and were not considered to be of biological significance. At the
highest dose tested, 7,500 ppm, there were no reproductive toxicity
effects other than a less than severe reduction in body weight gain in
pups of F1 and F2 on days 14 and 21.
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. As discussed in the
toxicology section, the Agency has set the developmental toxicity NOEL
at 90 mg/kg/day, the highest dose tested in rabbits. There was no
developmental effect on the pups observed at the highest dose tested in
the study.
Based on the current toxicological data requirements, the database
relative to pre- and post-natal effects for children is more than
adequate for this biochemical pesticide. The data from the reproductive
and developmental toxicity tests do not suggest additional sensitivity
for infants and children. Therefore, EPA concludes that an additional
uncertainty factor is not warranted for (S)-hydroprene. EPA concludes
that reliable data support the use of a 300-fold uncertainty factor as
providing an adequate margin of safety for infants and children. Using
the conservative exposure assumptions described above, EPA has
determined that the percent of the RfD that will be utilized by
aggregate exposure to residues of (S)-hydroprene ranges from 6.9
percent for nursing infants less than 1 year old to, 20.9 percent for
non-nursing infants less than 1 year old to 13.4 percent for children 7
to 12 years old. Therefore, based on the completeness and reliability
of the toxicity data and the conservative exposure assessment, EPA
concludes that there is a reasonable certainty that no harm will result
to infants and children from aggregate exposure to (S)-hydroprene
residues.
G. International Tolerances
There is no CODEX tolerance or any other international tolerance at
this time.
H. Other Considerations
The Agency does not conduct acute dietary risk analyses for
tolerances involving food handling establishments. It is the opinion of
the Science Advisory Panel and the Agency that the calculations would
result in a gross overestimation of acute dietary risk. In any case,
there are no acute endpoints of concern for (S)-hydroprene.
The proposed tolerance amendment has been jointly reviewed per a
Memorandum of Understanding between the California Environmental
Protection Agency (CalEPA) and the Agency. CalEPA has also concluded
that the proposed tolerance amendments present minimal toxicological
concern.
I. Conclusion
Consistent with section 408(b)(2)(D), EPA has reviewed the
available scientific data and other relevant information in support of
this action. Based on the information and data considered, the Agency
has determined that, in amending 40 CFR part 185, as proposed, there is
reasonable certainty that no harm to the general population will result
from aggregate exposure to the pesticide chemical residue.
IV. Public Docket
The official record for this rulemaking, as well as the public
version, has been established for this rulemaking under docket control
number [OPP-300475] (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''.
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 file format or ASCII
file format. All comments and data in electronic form must be
identified by the docket control number [OPP-300475]. Electronic
comments on this proposed rule may be filed online at many Federal
Depository Libraries.
V. Regulatory Assessment Requirements
This action proposes to establish a tolerance under section 408
ofthe FFDCA. 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, pursuant to 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 (46 FR 24950, May 4, 1981). In accordance
[[Page 30554]]
with Small Business Administration (SBA) policy, this determination
will be provided to the Chief Counsel for Advocacy of the SBA upon
request.
List of Subjects
40 CFR Part 180
Environmental protection, Administrative practice and procedure,
Agricultural commodities, Food additive, Pesticides and pests,
Reporting and recordkeeping requirements.
40 CFR Part 185
Environmental protection, Food additives, Pesticides and pests.
Dated: May 22, 1997.
Janet L. Andersen,
Director, Biopesticides and Pollution Prevention Division, Office of
Pesticide Programs.
Therefore, 40 CFR Chapter I is proposed to be amended as follows:
PART 180--[AMENDED]
In part 180:
a. The authority citation for part 180 continues to read as
follows:
Authority: 21 U.S.C. 346a and 348.
b. Section 180.501 is added to read as follows:
Sec. 180.501 Hydroprene; tolerances for residues.
A tolerance of 0.2 part per million is established for residues of
hydroprene [(S)-(Ethyl (2E,4E,7S)-3,7,11 trimethyl-2,4-
dodecadienoate)], (CAS Reg. NO. 65733-18-8)# on all food items in food-
handing establishments in accordance with the following prescribed
conditions:
(a) Application shall be limited to spot, crack and crevice,
perimeter and ultra low volume (ULV) fogging treatment in food storage
or food-handling establishments, including warehouses, food service,
manufacturing, and processing establishments such as restaurants,
cafeterias, supermarkets, bakeries, breweries, dairies, meat
slaughtering and packing plants, and canneries where food and food
products are held, processed, and served: Provided that the food is
removed or covered prior to such use, and food-processing surfaces are
covered during treatment or thoroughly cleaned before using, or in the
case of point-source device treatments, devices must not come into
direct contact with food preparation surfaces and must be in a minimum
distance of 3 feet from exposed foods.
(b) To assure safe use of the insect growth regulator, the label
and labeling shall conform to that registered by the U.S. Environmental
Protection Agency, and it shall be used in accordance with such label
and labeling.
PART 185--[AMENDED]
In part 185:
a. The authority citation for part 185 continues to read as
follows:
Authority: 21 U.S.C. 346a and 348.
Sec. 185.3625 [Removed]
b. Section 185.3625 is removed.
[FR Doc. 97-14298 Filed 6-3-97; 8:45 am]
BILLING CODE 6560-50-F