[Federal Register Volume 63, Number 53 (Thursday, March 19, 1998)]
[Notices]
[Pages 13404-13409]
From the Federal Register Online via the Government Publishing Office [www.gpo.gov]
[FR Doc No: 98-7140]
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ENVIRONMENTAL PROTECTION AGENCY
[PF-796; FRL-5776-6]
Notice of Filing of Pesticide Petitions
AGENCY: Environmental Protection Agency (EPA).
ACTION: Notice.
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SUMMARY: This notice announces the initial filing of pesticide
petitions proposing the establishment of regulations for residues of
certain pesticide chemicals in or on various agricultural commodities.
DATES: Comments, identified by the docket control number PF-796, must
be received on or before April 20, 1998.
ADDRESSES: By mail submit written comments to: Public Information and
Records Integrity Branch, Information Resources and Services Divison
(7502C), Office of Pesticides Programs, Environmental Protection
Agency, 401 M St., SW., Washington, DC 20460. In person bring comments
to: Rm. 119, CM #2, 1921 Jefferson Davis Highway, Arlington, VA.
Comments and data may also be submitted electronically to: opp-
[email protected]. Following the instructions under
``SUPPLEMENTARY INFORMATION.'' No confidential business information
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
``Confidential Business Information'' (CBI). CBI should not be
submitted through e-mail. Information marked as CBI will not be
disclosed except in accordance with procedures set forth in 40 CFR part
2. A copy of the comment that does not contain CBI must be submitted
for inclusion in the public record. Information not marked confidential
may be disclosed publicly by EPA without prior notice. All written
comments will be available for public
[[Page 13405]]
inspection in Rm. 119 at the address given above, from 8:30 a.m. to 4
p.m., Monday through Friday, excluding legal holidays.
FOR FURTHER INFORMATION CONTACT: The product manager listed in the
table below:
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Office location/
Product Manager/Petition No. telephone number/e- Address
mail address
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Bipin Gandhi (PM 5); (PP Rm. 4W53, Crystal 2800 Crystal
7E4918). Station, 703-308- Dr., Arlington,
8380, e-mail: VA
gandhi.bipin@epamail.
epa.gov.
Sidney Jackson (PM 5); (PP Rm. 233, CM #2, 703- 1921 Jefferson
5E4463). 305-7610, e-mail: Davis Hwy,
jackson.sidney@epamai Arlington, VA
l.epa.gov.
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SUPPLEMENTARY INFORMATION: EPA has received pesticide petitions as
follows proposing the establishment and/or amendment of regulations for
residues of certain pesticide chemicals in or on various raw
agricultural commodities under section 408 of the Federal Food, Drug,
and Comestic Act (FFDCA), 21 U.S.C. 346a. EPA has determined that these
petitions contain data or information regarding the elements set forth
in section 408(d)(2); however, EPA has not fully evaluated the
sufficiency of the submitted data at this time or whether the data
supports grantinig of the petition. Additional data may be needed
before EPA rules on the petition.
The official record for this notice, as well as the public version,
has been established for this notice of filing under docket control
number PF-796 (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 record is located at the 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 file format or
ASCII file format. All comments and data in electronic form must be
identified by the docket control number PF-796 and appropriate petition
number. Electronic comments on this notice may be filed online at many
Federal Depository Libraries.
Authority: 21 U.S.C. 346a.
List of Subjects
Environmental protection, Agricultural commodities, Food additives,
Feed additives, Pesticides and pests, Reporting and recordkeeping
requirements.
Dated: March 5, 1998.
James Jones,
Director, Registration Division, Office of Pesticide Programs.
Summaries of Petitions
Below summaries of the pesticide petitions are printed. The
summaries of the petitions were prepared by the petitioners. The
petition summary announces the availability of a description of the
analytical methods available to EPA for the detection and measurement
of the pesticide chemical residues or an explanation of why no such
method is needed.
1. Hercon Environmental Corporation
PP 7E4918
EPA has received a pesticide petition (PP 7E4918) from Hercon
Environmental Corporation, Aberdeen Road, P.O. box 467, Emigsville, PA
17318-0467, proposing pursuant to section 408(d) of the Federal Food,
Drug and Cosmetic Act, 21 U.S.C. 346a(d), to amend 40 CFR part 180 to
establish an exemption from the requirement of a tolerance for Trioctyl
Trimellitate (TOTM) as an inert ingredient under 40 CFR 180.1001(c).
A. Product Identity/Chemistry
Tris(2-ethylhexyl)1,2,4-benzenetricarboxylate, the chemical name
for TOTM, CAS # [3319-31-1], has a molecular formula of C33
H45 O6, and a molecular weight of 546.8.
TOTM is a primary plasticizer used in applications requiring good
elongation retention such as high-temperature PVC wire coatings. Its
excellent resistance to soapy water extraction also makes it attractive
for use in vinyl film and vinyl-coated fabrics. Its stereochemical
properties make it especially attractive in pheromone formulations as a
control-release agent, and its extremely low vapor pressure (0.7 x
10-7 mm Hg), assures its retention in the formulation to
perform its intended purpose.
B. Residue Chemistry
No residue chemistry data are available. However, arguments
provided above relative to modes of exposure, support the lack of
potential for any residues of TOTM to be present in raw agricultural
product of the foods from them.
Since this petition requests an exemption from the requirement of a
tolerance, Hercon believes that an analytical method for the detection
and measurement of TOTM residues is not necessary. The low rate of
application and the fact that it is encapsulated in the product leads
to the conclusion that TOTM will not migrate into a food from the
treatment of crops to any degree that would be detectable.
C. Toxicological Profile
Hercon has submitted to the EPA acute toxicological information and
studies of chronic toxicology which exhibit the low toxicity of TOTM.
In addition, it was determined from a manufacturer that no reports have
been submitted on TOTM under TSCA 8(e) Substantial Risk Notification
requirements.
1. Acute toxicity. Acute toxicology studies conducted with the
``neat'' material show:
Acute Toxicity: At most only slightly toxic. Slight skin
irritant. LD50 >3200 mg/kg.
Skin Absorption and Irritation: No evidence of skin
absorption. LD50 >20 mg/kg
Skin Sensitization: Sensitized 0/5 guinea pigs in drop-on
test.
Inhalation: At lowest exposure of 0.23 mg/l, no mortality was
experienced.
Eye Irritation: In unwashed eye, there was an initial moderate
effect after 1 hour, but the effect disappeared after 48 hours. No
effects reported in the washed eye.
2. Genotoxicty. -- a. TOTM evaluation in the CHO/HGPRT forward
mutation assay. TOTM was considered to be inactive under the conditions
of testing in this assay. The test material did not induce dose-related
increases in the mutant frequency at the HGPRT locus in CHO cell
cultures. TOTM was not toxic to CHO cells at concentrations up to 5,000
nl/ml either with or without S9 metabolic activation. Mutation assays
were performed in duplicate both with
[[Page 13406]]
a nd without S9 metabolic activation using 6 concentrations of TOTM
ranging from 10.0 nl/ml to 200 nl/ml.
b. Evaluation of TOTM in the rat primary hepatocyte unscheduled DNA
synthesis assay. The test material did not induce significant changes
in the nuclear labeling of primary rat hepatocytes for an applied
concentration range of 5000 nl/ml to 250 nl/ml. Little or no toxicity
was observed (88.4% to 102.2% survival) but higher concentrations could
not be assayed because of the insoluble nature of TOTM in medium. None
of the criteria used to indicate UDS were approached by the treatments,
and no dose-related response was observed. Therefore, the test material
was evaluated as inactive in the Primary Rat Hepatocyte UDS Assay.
3. Subchronic toxicity. Twenty-eight Day Toxicity Study with TOTM
in the Rat: The results of this study demonstrates that TOTM caused
slight peroxisome proliferation but was less potent than DEHP [di(2-
ethylhexyl) phthalate], with 2.0% TOTM producing less effects than
0.67% DEHP. There was no effect of feeding TOTM on the body weight or
food intakes of the male rats. The females fed 2.0% TOTM showed an
initial rejection of the diet which did not have any marked effect on
their weight gain.
4. Chronic toxicity. Chronic Toxicity of TOTM to Daphnia magna
Under Flow-Through Test Conditions: The daphnid lengths in all TOTM
mean measured concentrations after 21 days of testing were not
significantly different (a = 0.05) from the control. Statistical
analysis of survival for Daphnia magna after a 21 days exposure to TOTM
indicated that survival rates in all the mean measured test
concentrations were not significantly different from the control. The
mean young/adult/reproduction day after 21 days was not significantly
affected in a deleterious manner in all mean measured test
concentrations of TOTM. Based on the statistical analysis of adult mean
length, survival and young/adult/reproduction day from the 21 day
Daphnia magna dynamic life cycle study, the MATC (Maximum Acceptable
Toxicant Concentration) limits were estimated to be greater than the
TOTM mean measured concentration of 82 g/l.
5. Metabolite toxicology. Study No. 4: Absorption and Metabolism of
[Hexyl-2-14C] TOTM: TOTM is called TEHT in this study. These studies
show that TEHT was hydrolyzed to a limited extent in the
gastrointestinal tract and was largely excreted unchanged in the feces.
Sixteen percent was excreted in the urine as metabolites and 1.9% was
expired as CO2.
D. Aggregate Exposure
Hercon's pheromone formulations containing TOTM will not result in
an application rate of product in which more than 25 grams/acre of TOTM
on food related crops will result. Depending on an extended or delayed
infestation of target pests, no more than 3 applications per crop
should be necessary.
It must be remembered that this amount of TOTM is contained in the
formulated device, a 0.05 square inch laminated PVC flake, and
therefore the TOTM itself does not come into direct contact with the
plants or crops treated. At the maximum application rate, there are
approximately 0.26 flakes per square foot. This equates to
approximately 0.5 mg TOTM / sq.ft. At the lowest recommended
application rate, this amount is halved.
To present a worst case scenario for dietary exposure to humans,
Hercon has selected applications to a sugar cane crop. This worst case
scenario hypothetically presumes that all available TOTM in the product
is finally present in the processed sugar.
At an application rate corresponding to 0.5 mg TOTM/sq.ft, and a
harvest resulting in 3.3 tons of sugar per acre, the available
concentration of TOTM in the sugar would calculate to be 8.4 mg TOTM /
Kg of sugar.
The assumption of an intake of 20 gms of sugar per day, would
equate to a daily intake of 0.168 mg of TOTM. This hypothetical intake
is much lower than the NOEL from a 28 day Chronic oral study in the
male rat of 185 mg/kg/day noted in the MSDS.
Actually, it is expected that since the TOTM is contained in the
formulated devise, that no detectable TOTM would be found in the sugar.
Exposure to drinking water will be minimal. Hercon's products
containing TOTM are not sprayed on lawns or gardens, around swimming
pools, etc., and due to the low rates of application, even drift from
an agricultural application to lakes or waterways, will not affect
drinking water.
Data, calculations, low exposure potential and low toxicity
discussed and presented in this petition request, precludes a concern
for significant dietary or non-dietary exposure to infants and
children.
Non-dietary exposure to TOTM will be mitigated through the use of
personal protective equipment which is described on the label of
products for personnel which may be around or in a treated field.
E. Cumulative Exposure
No cumulative mode of exposure is expected. Again, the application
rate is extremely low, and encapsulation of the TOTM in the product
prevents direct exposure.
Normal use patterns will not lead to accumulation of TOTM in the
environment.
F. Safety Determinations
Hercon believes that the use of pheromone products containing TOTM,
which is of low toxicity and which is used in such low concentrations,
is compatible with EPA's objectives to register reduced risk
pesticides.
In an absorption and metabolism study on rats, which is included in
this package, 75% of the dose was excreted in the feces, 16% in the
urine, and 1.9% was expired as CO2. Less than 0.6% remained in the
tissues.
At an acute oral LD50 toxicity level of >3200 mg/kg in
the rat and mouse, TOTM is a low level toxin with at most a class III
toxicity rating. A 28 day Chronic Oral toxicity study resulted in a
NOEL of 184 mg/kg/day.
Mutagenicity and Genotoxicity data showed negative results in
Salmonella typhimurium assay, DHO/HGPRT assay and the Unscheduled DNA
synthesis assay.
Because of the low toxcicity of TOTM and the low rate of
application, and encapsulation in the product, and more importantly
because no residue is expected in the final food product, a
determination can be made that there is little or no exposure to the
general population or to children and infants.
G. List of International Tolerances
The petitioner understands that therte are no current or known
established residue levels for TOTM.
H. Environmental Fate Summary
This summary is taken directly from the Material Safety Data Sheet
from Eastman Chemical Co.
``Data for this material have been used to estimate its
environmental impact. It has the following properties: a low
biochemical oxygen demand and little potential to cause oxygen
depletion in aqueous systems, a low potential to affect aquatic
organisms, a low potential to biodegrade (high persistence) with
acclimated microorganisms from activated sludge, a low potential to
bio-concentrate. After dilution with a large amount of water,
followed by secondary waste treatment, this material is not expected
to cause adverse environmental effects.''
[[Page 13407]]
2. IR-4 Project
PP 5E4463
EPA has received a pesticide petition (PP 5E4463) from the
Interregional Research Project Number 4 (IR-4), proposing pursuant to
section 408(d) of the Federal Food, Drug and Cosmetic Act (FFDCA), 21
U.S.C. 346a(d), to amend 40 CFR Part 180 by establishing a tolerance
for residues of the insecticide 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 parts per million (ppm). EPA has
determined that the petition contains data or information regarding the
elements set forth in section 408(d)(2) of the FFDCA; however, EPA has
not fully evaluated the sufficiency of the submitted data at this time
or whether the data support granting of the petition. Additional data
may be needed before EPA rules on the petition. This notice contains a
summary of the petition submitted by FMC Corporation, the registrant.
A. Residue Chemistry
1. Plant metabolism. The metabolism of cypermethrin in plants is
adequately understood. Studies have been conducted to delineate the
metabolism of radiolabelled cypermethrin in various crops all showing
similar results. The residue of concern is the parent compound only.
2. Analytical method. There is a practical analytical method for
detecting and measuring levels of cypermethrin 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. The analytical method is Gas
Chromatography with Electron Capture Detection (GC/ECD).
3. Magnitude of residues. Field residue trials meeting EPA study
requirements have been conducted at the maximum label rate for the crop
green onions. Results from these trials demonstrate that the proposed
cypermethrin tolerance on green onions at 6.0 ppm will not be exceeded
when the product is applied following the proposed use directions.
These data have previously been reviewed and classified by the Agency
as supportive of this tolerance.
B. Toxicological Profile
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 of 263 milligram (mg) per
kilogram (kg); dermal toxicity, LD50 2,460 mg/kg; inhalation
toxicity lethal concentration LC50 2.5 mg/liter (L); primary
eye irritation is Toxicity Category III; primary dermal irritation is
Toxicity Category IV. Cypermethrin is considered to be a dermal
sensitizer.
2. Genotoxicity. All reported results from the following
genotoxicity tests were all negative: gene mutation (Ames); chromosome
aberration in Chinese hamster bone marrow cells; host mediated assay in
mice; dominant lethal assay in mice.
3. Reproductive and developmental toxicity. No evidence of
additional sensitivity to young rats or rabbits was reported following
pre- or postnatal exposure to cypermethrin.
a. A 3-generation reproductive toxicity study in rats demonstrated
a no observed effect level (NOEL) of 2.5 mg/kg/day and a lowest
observed effect level (LOEL) of 7.5 mg/kg/day for parental/systemic
toxicity based on decreased body weight gain in both sexes. There were
no adverse effects in reproductive performance. The NOEL for
reproductive toxicity was considered to be 37.5 mg/kg/day, the highest
dose level tested.
b. A developmental study in rats demonstrated a maternal NOEL of
17.5 mg/kg/day and a LOEL of 35 mg/kg/day based on decreased body
weight gain. There were no signs of developmental toxicity at 70 mg/kg/
day, the highest dose level tested.
c. A developmental study in rabbits demonstrated a maternal NOEL of
100 mg/kg/day and a LOEL of 450 mg/kg/day based on decreased body
weight gain. There were no signs of developmental toxicity at 700 mg/
kg/day, the highest dose level tested.
4. Subchronic toxicity. The systemic NOEL of 5.0 mg/kg/day from the
chronic toxicity study in dogs is also used for short- and
intermediate-term margin of exposure (MOE) calculations (as well as
acute toxicity, discussed in (1) above). This NOEL was based on
neurotoxic clinical signs observed in the first week of treatment of
the study.
5. Chronic toxicity. The Reference Dose (RfD) has been established
at 0.010 mg/kg/day. This RfD is based on a chronic toxicity study in
dogs with a NOEL of 1.0 mg/kg/day, based on gastrointestinal
disturbances observed at the LOEL of 5.0 mg/kg/day during the first
week of the study; an uncertainty factor of 100 is used.
Cypermethrin is classified as a Group C chemical (possible human
carcinogen with limited evidence of carcinogenicity in animals) based
upon limited evidence for carcinogenicity in female mice; assignment of
a Q* has not been recommended.
6. Animal metabolism. The metabolism of cypermethrin in animals is
adequately understood. Cypermethrin has been shown to be rapidly
absorbed, distributed, and excreted in rats when administered orally.
Cypermethrin is metabolized by hydrolysis and oxidation.
7. Metabolite toxicology. The Agency has previously determined that
the metabolites of cypermethrin are not of toxicological concern and
need not be included in the tolerance expression.
8. Endocrine disruption. No evidence of potential estrogenic or
other endocrine effects of cypermethrin were reported in the standard
battery of required toxicology studies which have been completed and
found acceptable. Based on these studies, there is no evidence to
suggest that cypermethrin has an adverse effect on the endocrine
system.
C. Aggregate Exposure
1. Dietary exposure. a. Food. Tolerances have been established for
the residues of cypermethrin, in or on a variety of raw agricultural
commodities. Tolerances, in support of registrations, 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
assessing the potential dietary exposure for these existing and pending
tolerances, FMC has utilized available information on anticipated
residues, monitoring data and percent crop treated as follows:
i. Acute exposure and risk. Acute dietary exposure 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. For the purposes of assessing acute
dietary risk for cypermethrin, the maternal NOEL of 1.0 mg/kg/day from
the chronic toxicity study in dogs was used. The LOEL of this study of
5.0 mg/kg/day was based on gastrointestinal disturbances observed in
the first week of the study. This acute dietary endpoint was used to
determine acute dietary risks to all population subgroups. Available
information on anticipated residues, monitoring data and percent crop
treated was incorporated into a Tier 3 analysis, using Monte Carlo
modeling for commodities that may be consumed in a single serving.
These assessments show that the MOEs are significantly greater than the
EPA standard of 100 for all subpopulations. The 95th percentile
[[Page 13408]]
of exposure for the overall U. S. population was estimated to be
0.000488 mg/kg/day (MOE of 2,047); 99th percentile 0.002014 mg/kg/day
(MOE of 496); and 99.9th percentile 0.004438 mg/kg/day (MOE of 225).
The 95th percentile of exposure for all infants < one year old was
estimated to be 0.00007 mg/kg/day (MOE of 14,240); 99th percentile
0.000345 mg/kg/day (MOE of 2,902); and 99.9th percentile 0.000997 mg/
kg/day (MOE of 1,003). The 95th percentile of exposure for nursing
infants < one year old was estimated to be 0.000033 mg/kg/day (MOE of
30,026 ); 99th percentile 0.000241 mg/kg/day (MOE of 4,144); and 99.9th
percentile 0.001400 mg/kg/day (MOE of 714). The 95th percentile of
exposure for non-nursing infants < one year old was estimated to be
0.000075 mg/kg/day (MOE of 13,331); 99th percentile 0.000375 mg/kg/day
(MOE of 2,667); and 99.9th percentile 0.000748 mg/kg/day (MOE of
1,337). The 95th percentile of exposure for children 1 to 6 years old
(the most highly exposed population subgroup) was estimated to be
0.000361 mg/kg/day (MOE of 2,767); 99th percentile 0.002088 mg/kg/day
(MOE of 479); and 99.9th percentile 0.005465 mg/kg/day (MOE of 183).
Therefore, FMC concludes that the acute dietary risk of cypermethrin,
as estimated by the dietary risk assessment, does not appear to be of
concern.
ii. Chronic exposure and risk. The acceptable RfD is based on a
NOEL of 1.0 mg/kg/day from the chronic dog study and an uncertainty
factor of 100 is 0.010 mg/kg/day. The endpoint effect of concern was
based on gastrointestinal disturbances observed in the first week of
the study at the LOEL of 5.0 mg/kg/day. A chronic dietary exposure/risk
assessment has been performed for cypermethrin using the above RfD.
Available information on anticipated residues, monitoring data and
percent crop treated was incorporated into the analysis to estimate the
anticipated residue contribution (ARC). The ARC is generally considered
a more realistic estimate than an estimate based on tolerance level
residues. The ARC is estimated to be 0.000025 mg/kg body weight (bwt)/
day and utilize 0.3 percent of the RfD for the overall U. S.
population. The ARCs for non-nursing infants (<1 year) and children 1-6
years old (subgroups most highly exposed) are estimated to be 0.000014
mg/kg bwt/day and 0.000042 mg/kg bwt/day and utilizes 0.1 percent and
0.4 percent of the RfD, respectively. Generally speaking, the EPA has
no cause for concern if the total dietary exposure from residues for
uses for which there are published and proposed tolerances is less than
100 percent of the RfD. Therefore, FMC concludes that the chronic
dietary risk of cypermethrin, as estimated by the dietary risk
assessment, does not appear to be of concern.
b. Drinking water. Laboratory and field data have demonstrated that
cypermethrin is immobile in soil and will not leach into groundwater.
Other data show that cypermethrin is virtually insoluble in water and
extremely lipophilic. As a result, FMC concludes that residues reaching
surface waters from field runoff will quickly adsorb to sediment
particles and be partitioned from the water column. Further, a
screening evaluation of leaching potential of a typical pyrethroid was
conducted using EPA's Pesticide Root Zone Model (PRZM3). Based on this
screening assessment, the potential concentrations of a pyrethroid in
groundwater at depths of 1 and 2 meters are essentially zero (<<0.001
parts per billion). Surface water concentrations for pyrethroids were
estimated using PRZM3 and Exposure Analysis Modeling System (EXAMS)
using standard EPA cotton runoff and Mississippi pond scenarios. The
maximum concentration predicted in the simulated pond was 0.052 parts
per billion(ppb). Concentrations in actual drinking water would be much
lower than the levels predicted in the hypothetical, small, stagnant
farm pond model since drinking water derived from surface water would
normally be treated before consumption. Based on these analyses, FMC
believes that the contribution of water to the dietary risk estimate is
negligible. Therefore, FMC concludes that together these data indicate
that residues of cypermethrin are not expected to occur in drinking
water.
2. Non-dietary exposure. Analyses were conducted which included an
evaluation of potential non-dietary (residential) applicator, post-
application and chronic dietary aggregate exposures associated with
cypermethrin products used for residential flea infestation control and
agricultural/commercial applications. The aggregate analysis
conservatively assumes that a person is concurrently exposed to the
same active ingredient via the use of consumer or professional flea
infestation control products and to chronic level residues in the diet.
In the case of potential non-dietary health risks, conservative
point estimates of non-dietary exposures, expressed as total systemic
absorbed dose for each product use category (indoor total release
fogger and lawn care) and exposed population group (adults, children 1-
6 years, and infants < 1 year) are compared to the systemic absorbed
dose NOEL for cypermethrin to provide estimates of the MOEs. Based on
the toxicity endpoints selected by EPA for cypermethrin, inhalation and
incidental oral ingestion absorbed doses were combined and compared to
the relevant systemic NOEL for estimating MOEs.
In the case of potential aggregate health risks, the above
mentioned conservative point estimates of non-dietary exposure
(expressed as systemic absorbed dose) are combined with estimates
(arithmetic mean values) of chronic average dietary (oral) absorbed
doses. These aggregate absorbed dose estimates are also provided for
adults, children 1 - 6 years and infants < 1 year. The combined or
aggregated absorbed dose estimates (summed across non-dietary and
chronic dietary) are then compared with the systemic absorbed dose NOEL
to provide estimates of aggregate MOEs.
The total non-dietary MOEs (combined across all product use
categories) for the inhalation plus incidental oral routes are 97,000
for adults, 2,100 for children 1-6 years old, and 1,900 for infants (<
1 year). The aggregate MOE (inhalation + incidental oral + chronic
dietary, summed across all product use categories) was estimated to be
65,000 for adults, 2,000 for children 1-6 years old and 1,900 for
infants (<1 year). FMC concludes that the potential non-dietary and
aggregate (non-dietary + chronic dietary) exposures for cypermethrin
are associated with substantial margins of safety.
D. Cumulative Effects
In consideration of potential cumulative effects of cypermethrin
and other substances that may have a common mechanism of toxicity, to
our knowledge there are currently no available data or other reliable
information indicating that any toxic effects produced by cypermethrin
would be cumulative with those of other chemical compounds; thus only
the potential risks of cypermethrin have been considered in this
assessment of its aggregate exposure. FMC intends to submit information
for the EPA to consider concerning potential cumulative effects of
cypermethrin consistent with the schedule established by EPA at in the
Federal Register of August 4, 1997, (62 FR 42020), and other EPA
publications pursuant to the Food Quality Protection Act.
[[Page 13409]]
E. Safety Determination
1. U.S. population. Based on a complete and reliable toxicology
database, the acceptable reference dose RfD is 0.010 mg/kg/day, based
on a LOEL of 5.0 mg/kg/day from the chronic dog study and an
uncertainty factor of 100. Available information on anticipated
residues, monitoring data and percent crop treated was incorporated
into an analysis to estimate the Anticipated Residue Contribution (ARC)
for 26 population subgroups. The ARC is generally considered a more
realistic estimate than an estimate based on tolerance level residues.
The ARC are estimated to be 0.000025 mg/kg body weight (bwt)/day and
utilize 0.3 percent of the RfD for the overall U. S. population. The
ARC for non-nursing infants (<1 year) and children 1-6 years old
(subgroups most highly exposed) are estimated to be 0.000014 mg/kg bwt/
day and 0.000042 mg/kg bwt/day and utilizes 0.1 percent and 0.4 percent
of the RfD, respectively. Generally speaking, the EPA has no cause for
concern if the total dietary exposure from residues for uses for which
there are published and proposed tolerances is less than 100 percent of
the RfD. Therefore, FMC concludes that the chronic dietary risk of
cypermethrin, as estimated by the aggregate risk assessment, does not
appear to pose significant risk.
For the overall U.S. population, the calculated margins of exposure
(MOE) at the 95th percentile was estimated to be 2,047; 496 at the 99th
percentile; and 225 at the 99.9th percentile. For all infants < one
year old, the calculated MOE at the 95th percentile was estimated to be
14,240; 2,902 at the 99th percentile; and 1,003 at the 99.9th
percentile. For nursing infants < one year old, the calculated margins
of exposure (MOE) at the 95th percentile was estimated to be 30,026;
4,144 at the 99th percentile; and 714 at the 99.9th percentile. For
non-nursing infants < one year old, the calculated margins of exposure
(MOE) at the 95th percentile was estimated to be 13,331; 2,667 at the
99th percentile; and 1,337 at the 99.9th percentile. For the most
highly exposed population subgroup, children 1 - 6 years old, the
calculated MOE at the 95th percentile was estimated to be 2,767 ; 479
at the 99th percentile; and 183 at the 99.9th percentile. Therefore,
FMC concludes that there is reasonable certainty that no harm will
result from acute exposure to cypermethrin.
2. Infants and children. --a. General. In assessing the potential
for additional sensitivity of infants and children to residues of
cypermethrin, FMC considered data from developmental toxicity studies
in the rat and rabbit, and a three-generation reproductive study in the
rat. The data demonstrated no indication of increased sensitivity of
rats or rabbits to in utero and/or postnatal exposure to cypermethrin.
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 may apply an
additional 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.
b. Developmental toxicity studies. In the prenatal developmental
toxicity studies in rats and rabbits, there was no evidence of
developmental toxicity at the highest doses tested (70 mg/kg/day in
rats and 700 mg/kg/day in rabbits). Decreased body weight gain was
observed at the maternal LOEL in each study; the maternal NOEL was
established at 17.5 mg/kg/day in rats and 100 mg/kg/day in rabbits.
c. Reproductive toxicity study. In the 3-generation reproduction
study in rats, offspring toxicity (reduced mean litter weight gain) was
observed only at the highest dietary level tested (37.5 mg/kg/day),
while toxicity in the parental animals was observed at the lower
treatment levels. The parental systemic NOEL was 2.5 mg/kg/day and the
parental systemic LOEL was 7.5 mg/kg/day. There were no developmental
(pup) or reproductive effects up to 37.5 mg/kg/day (highest dose
tested).
d. Pre- and post-natal sensitivity. --i. Pre-natal. There was no
evidence of developmental toxicity in the studies at the highest doses
tested in the rat (70 mg/kg/day) or in the rabbit (700 mg/kg/day).
Therefore, there is no evidence of a special dietary risk (either acute
or chronic) for infants and children which would require an additional
safety factor.
ii. Post-natal. Based on the absence of pup toxicity up to dose
levels which produced toxicity in the parental animals, there is no
evidence of special post-natal sensitivity to infants and children in
the rat reproduction study.
Based on the above, FMC concludes that reliable data support use of
the standard 100-fold uncertainty factor, and that an additional
uncertainty factor is not needed to protect the safety of infants and
children. As stated above, aggregate exposure assessments utilized
significantly less than 1 percent of the RfD for either the entire U.
S. population or any of the 26 population subgroups including infants
and children. Therefore, FMC concludes that there is reasonable
certainty that no harm will result to infants and children from
aggregate exposure to cypermethrin residues.
F. International Tolerances
There are no codex, Canadian, or Mexican residue limits for
residues of cypermethrin in or on green onions.
[FR Doc. 98-7140 Filed 3-18-98; 8:45 am]
BILLING CODE 6560-50-F