[Federal Register Volume 63, Number 97 (Wednesday, May 20, 1998)]
[Notices]
[Pages 27723-27727]
From the Federal Register Online via the Government Publishing Office [www.gpo.gov]
[FR Doc No: 98-13447]


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ENVIRONMENTAL PROTECTION AGENCY

[PF-793; FRL-5773-2]


Notice of Filing of Pesticide Petition

AGENCY: Environmental Protection Agency (EPA).

ACTION: Notice.

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SUMMARY: This notice announces the initial filing of a pesticide 
petition proposing the establishment of regulations for residues of the 
pesticide chemical pymetrozine, in or on various food commodities.
DATES: Comments, identified by the docket control number PF-793, must 
be received on or before June 19, 1998.
ADDRESSES: By mail submit written comments to: Public Information and 
Records Integrity Branch, Information Resources and Services Division 
(7506C), Office of Pesticides Programs, Environmental Protection 
Agency, 401 M St., SW., Washington, DC 20460. In person bring comments 
to: Rm. 1132, CM #2, 1921 Jefferson Davis Highway, Arlington, VA.
    Comments and data may also be submitted electronically by 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 inspection in Rm. 1132 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            telephone number          Address    
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Leonard Cole..................  Rm. 211, CM #2, 703-    1921 Jefferson  
                                 305-5412, e-            Davis Hwy,     
                                 mail:cole.l<a href="/cdn-cgi/l/email-protection" class="__cf_email__" data-cfemail="395c5657584b5d795c4958">[email protected]</a>   Arlington, VA  
                                 mail.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 food 
commodities under section 408 of the Federal Food, Drug, and Comestic 
Act (FFDCA), 21 U.S.C. 346a. EPA has determined that these petitions

[[Page 27724]]

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 granting of 
the petition. Additional data may be needed before EPA rules on the 
petition.
    The official record for this notice of filing, as well as the 
public version, has been established for this notice of filing under 
docket control number [PF-793] (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:
    <a href="/cdn-cgi/l/email-protection#d5baa5a5f8b1bab6beb0a195b0a5b4b8b4bcb9fbb0a5b4fbb2baa3"><span class="__cf_email__" data-cfemail="89e6f9f9a4ede6eae2ecfdc9ecf9e8e4e8e0e5a7ecf9e8a7eee6ff">[email protected]</span></a>

    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 number (insert docket number) and appropriate 
petition number. Electronic comments on this notice may be filed online 
at many Federal Depository Libraries.

List of Subjects

    Environmental protection, Agricultural commodities, Food additives, 
Feed additives, Pesticides and pests, Reporting and recordkeeping 
requirements.

    Dated: May 6, 1998.

James Jones,

Director, Registration Division, Office of Pesticide Programs.

Summaries of Petitions

    Petitioner summaries of the pesticide petitions are printed below 
as required by section 408(d)(3) of the FFDCA. The summaries of the 
petitions were prepared by the petitioners and represent the views of 
the petitioners. EPA is publishing the petition summaries verbatim 
without editing them in any way. 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.

Norvartis Crop Protection, Inc.

PP 8F4929

    EPA has received a pesticide petition (PP 8F4929) from Norvartis 
Crop Protection, Inc., P.O. Box 18300, Greensboro, NC 27419-8300 
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 by 
establishing a tolerance for residues of Pymetrozine in or on the raw 
agricultural commodity cucumbers, fruiting vegetables, potatoes, hops 
at 0.02, 0.05 parts per million. 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 
supports granting of the petition. Additional data may be needed before 
EPA rules on the petition.

A. Residue Chemistry

    1. Plant metabolism. The metabolism of CGA-215944 in plants is 
understood for the purposes of the proposed tolerance. Studies in rice, 
tomatoes, cotton and potatoes gave similar results. Identified 
metabolic pathways have demonstrated that pymetrozine is the residue of 
concern for tolerance setting purposes.
    2. Analytical method-- i. Crops. Novartis has submitted two 
analytical methods for the determination of pymetrozine and its major 
crop metabolite, in crop substrates. For both methods, the limit of 
detection (LOD) is 1.0 ng and the limit of quantitation (LOQ) is 0.02 
ppm. Samples are extracted using acetonitrile: 0.05M sodium borate and 
an aliquot is taken for each method. The aliquots were cleaned up with 
solid-phase and/or liquid-liquid partitions and analyzed by HPLC with 
column-switching and UV detection. Both methods have undergone 
independent laboratory validation. The pymetrozine Analytical Method is 
proposed as the tolerance enforcement method.
    ii. Livestock. Novartis has also submitted analytical methods for 
the determination of pymetrozine in eggs, milk and poultry, dairy and 
goat tissues, and for its major livestock metabolite in dairy and goat 
tissues and milk. This method also accounts for a phosphate conjugate, 
which is a significant metabolite found only in milk. The LOD for the 
analytical method is 1.0 ng and the LOQ is 0.01 ppm. Samples are 
extracted using acetonitrile: Water, cleaned up with solid-phase and 
liquid-liquid partitions, and analyzed for pymetrozine by HPLC with 
column switching and UV detection. The LOD for the metabolite method is 
1.5 ng and the is LOQ of 0.01 ppm. Samples are extracted using 
methanol: Water. Milk samples are heated to hydrolyze the phosphate 
conjugate, and all samples are cleaned up with solid-phase partitions 
and analyzed by HPLC with UV detection. The parent Analytical Method 
has successfully undergone independent laboratory validation.
    3. Magnitude of residues--i. Cucurbits. Twenty-two field trials 
were conducted in 13 states representing typical fruiting vegetables 
growing areas in the United States, including Arizona, California, 
Florida, Georgia, Indiana, Michigan, New York, North Carolina, Ohio, 
Oregon, South Carolina, and Texas. Cantaloupes, summer squash, and 
cucumbers were treated with two post foliar applications of pymetrozine 
50WG at 21 and 14 days prior to harvest of mature fruit using a 1X rate 
of 80 g a.i./A per application (160 g a.i. or 0.35 lb a.i.per a). 
Samples of summer squash and cucumbers from early harvest harvest 
intervals (pre-harvest interval (PHI) < 14 days) were collected to 
demonstrate decline of residues of pymetrozine.
     Residue data were generated for pymetrozine for tolerance setting 
and dietary exposure estimates. Data was generated for a major 
metabolite for dietary exposure purposes only as this metabolite does 
not need to be part of the tolerance expression. No pymetrozine 
residues were found in cantaloupes treated at the 1X rate and harvested 
at the target PHI of 14 days. Maximum GS-23199 residues of 0.02 ppm 
were found in only 1 of 16 cantaloupe samples. The maximum pymetrozine 
residues found in summer squash samples treated at the 1X rate were 
0.02 ppm in a sample harvested at 0-day PHI. No pymetrozine residues 
were found in any 3-day, 7-day, or 14-day sample of squash treated at 
the 1X rate. No metabolite residues were found in any summer squash 
sample at any PHI. No pymetrozine or metabolite residues were found in 
any sample of cucumbers treated at the 1X rate and harvested at 14 days 
PHI.
     No residues of pymetrozine are expected in cucurbits vegetables 
treated at the 1X rate and harvested 14 days after the last 
application.
    ii. Fruiting vegetables. Seventeen field trials were conducted in 
12 states representing typical fruiting vegetable growing areas in the 
United States, including California, Florida, Indiana, Maryland, 
Michigan, New Jersey, New Mexico, North Carolina, Ohio, Pennsylvania, 
Tennessee, and Texas. Tomatoes and peppers were treated

[[Page 27725]]

with two post foliar applications of pymetrozine 50 WP 21 and 14 days 
prior to harvest of mature fruit using a 1X rate of 80 g active 
ingredient/acre (a.i./A), a 2X rate of 160 g a.i./A, a 3X rate of 240 g 
a.i./A, and a 5X rate of 400 g a.i./A per application. Samples from 
early harvest intervals (pre-harvest interval < 14 days) were collected 
to demonstrate decline of residues of pymetrozine. Mature fruit from 
two tomato field trials were processed under simulated commercial 
practice.
    Residue data were generated for pymetrozine for tolerance setting 
and dietary exposure estimates. Data was generated for the major 
metabolite for dietary exposure purposes only as this metabolite does 
not need to be part of the tolerance expression. Pymetrozine residues 
were found in 0- and 3-day PHI samples of tomatoes treated at the 1X 
rate, but in none of the 7-day PHI 1X samples analyzed. No pymetrozine 
residues were found in tomatoes treated at the 1X rate and harvested at 
the target PHI of 14 days. No residues of the metabolite were found in 
samples harvested with 0-, 3-, or 7-day PHI, but metabolite residues of 
0.02 ppm were found in 1 of 22 1X tomato samples harvested with a 14-
day PHI.
    All analyzed tomato samples treated at exaggerated rates were 
harvested with a 14-day PHI. No pymetrozine residues were found in any 
2X tomato sample. The maximum pymetrozine residues found in 3X and 5X 
samples were 0.04 ppm and 0.10 ppm. The maximum residues found in 2X, 
3X, and 5X samples were 0.02 ppm, 0.08 ppm, and 0.10 ppm.
    All analyzed processed tomato fractions were from tomatoes 
harvested with a 14-day PHI. No residues of pymetrozine were found in 
any processed fraction from tomatoes treated at exaggerated rates. No 
1X processed tomato fraction samples were analyzed. The maximum 
residues of metabolite found in tomato processed fractions were 0.4 ppm 
in juice from tomatoes treated at the 5X rate.
    All pepper samples analyzed were treated at the 1X rate. 
Pymetrozine residues of 0.04 ppm were found in 1 of 20 pepper samples 
harvested at a 14-day PHI. Pymetrozine residues were found in all eight 
0-day PHI samples, but in none of the four 3-day or 7-day PHI samples 
analyzed. No metabolite residues were found in any pepper sample at any 
PHI.
    Little or no residues of pymetrozine are expected in fruiting 
vegetables treated at the 1X rate and harvested 14 days after the last 
application.
    Tuberous and corm vegetables. Sixteen field trials were conducted 
in 13 States representing typical potato growing areas in the United 
States, including Idaho, Washington, Oregon, California, Florida, North 
Dakota, Minnesota, North Carolina, Wisconsin, Colorado, Maine, New 
York, and Michigan. Potatoes were treated with two foliar applications 
of pymetrozine 50 WP made 21 and 14 days prior to first harvest using a 
1X rate of 40 g a.i./A, a 3X rate of 120 g a.i./A, and a 5X rate of 400 
g a.i./A per application. Samples from early harvest intervals (PHI < 
14 days) were collected to demonstrate decline of residues of 
pymetrozine.
    Residue data was generated for pymetrozine for tolerance setting 
and dietary exposure estimates. Data was generated for the major 
metabolite for dietary exposure purposes only as this metabolite does 
not need to be part of the tolerance expression. No residues of 
pymetrozine or GS-23199 were found in potatoes or processed fractions 
for any application rate at any PHI in this study.
    iii. Tobacco. Five field trials were conducted in five states 
representing typical tobacco growing areas in the United States, 
including North Carolina, South Carolina, Tennessee, Kentucky, and 
Virginia. Tobacco was treated with two post foliar applications of 
pymetrozine 50 WP 21 and 14 days prior to harvest of mature leaves. 
Rates of 20 g a.i./A and 40 g a.i./A per application were used. Samples 
from early harvest intervals (PHI < 14 days) were collected to 
demonstrate decline of residues of pymetrozine.
    The maximum residues of pymetrozine found in green leaves of 
tobacco harvested at 14 days after last application were 0.05 ppm. The 
maximum residues of metabolite found in green leaves harvested at 14 
days after last application were 0.04 ppm. The maximum Detectable 
residues of pymetrozine found in 23 of 24 samples of cured leaves of 
tobacco harvessted at 14 days after last application was 0.39 ppm. The 
maximum residues of metabolite found in cured leaves harvested at 14 
days after last application were 0.20 ppm.
     In decline studies, detectable residues of pymetrozine were found 
to decrease with increasing PHI in green leaves. Maximum average 
metabolite GS-23199 residues were found in 3- and 7- day samples with 
the lowest average residues in 14-day samples.
    iv. Hops. Data from eight field trials, conducted in Germany, were 
submitted August 6,1996. The residue data support a tolerance of 5.0 
ppm with a 14-day PHI.
    v. Livestock. A three-level dairy feeding study was conducted using 
pymetrozine as the test substance. Holstein dairy cows were dosed daily 
with pymetrozine at levels equivalent to 0 (Control), 1.0 ppm, 3.0 ppm 
and 10 ppm. These rates represents 8, 24 and 80 times the maximum 
expected contribution to the diet. This study was designed to provide 
data concerning the level of residues of pymetrozine, as pymetrozine 
and CGA-313124, in milk and tissues which could occur as a result of 
feeding crops treated with pymetrozine to dairy cows. The results are 
used to estimate the transfer of residues from the diet to the tissues 
and milk of livestock.
     No detectable residues of pymetrozine or CGA-313124 were observed 
in samples of liver, kidney, perirenal fat, omental fat, round muscle, 
or tenderloin muscle from cows dosed with 10 ppm (80X) pymetrozine. No 
detectable residues of pymetrozine were observed in samples of milk 
from cows dosed with 10 ppm (80X), 3 ppm (24X), or 1 ppm (8X) 
pymetrozine at any sampling interval. Detectable residues of CGA-313124 
occurred only in milk samples from 80X dosed cows at a maximum level of 
0.05 ppm. These results indicate that there is no need to establish a 
meat and milk tolerance.

B. Toxicological Profile

    1. Acute toxicity. Pymetrozine has low acute toxicity. The oral 
LD<INF>50</INF> in rats is > 5,820 milligrams per kilogram (mg/kg) for 
males and females, combined. The rat dermal LD<INF>50</INF> is > 2,000 
mg/kg and the rat inhalation LC<INF>50</INF> is > 1.8 mg/L air. 
Pymetrozine is not a skin sensitizer in guinea pigs and does not 
produce dermal irritation in rabbits. It produces minimal eye 
irritation in rabbits. End-use water-dispersible granule formulations 
of pymetrozine have similar low acute toxicity profiles.
    2. Genotoxicty. Pymetrozine did not induce point mutations in 
bacteria (Ames assay in Salmonella typhimurium and Escherichia coli) or 
in cultured mammalian cells (Chinese hamster V79) and was not genotoxic 
in an in vitro unscheduled DNA synthesis assay in rat hepatocytes. 
Chromosome aberrations were not observed in an in vitro test using 
Chinese hamster ovary cells and there were no clastogenic or aneugenic 
effects on mouse bone marrow cells in an in vivo mouse micronucleus 
test. These studies show that pymetrozine is not genotoxic.
    3. Reproductive and developmental toxicity. In a teratology study 
in rats, pymetrozine caused decreased body weights and food consumption 
in females given 100 and 300 mg/kg/day during gestation. This maternal 
toxicity was accompanied by fetal skeletal

[[Page 27726]]

anomalies and variations consistent with delayed ossification. The no-
observed-effect level (NOEL) for maternal and fetal effects in rats was 
30 mg/kg/day. A teratology in rabbits showed that pymetrozine caused 
maternal death and reduced body weight gain and food consumption at 125 
mg/kg/day (highest dose tested). Maternal toxicity was accompanied by 
embryo- and feto-toxicity (abortion in one female and total resorptions 
in two females). Body weight and food consumption decreases, early 
resorptions and postimplantation losses were also observed in maternal 
rabbits given 75 mg/kg/day. There was an increased incidence of fetal 
skeletal anomalies and variations at these maternally toxic doses. The 
NOEL for maternal and fetal effects in rabbits was 10 mg/kg/day. 
Pymetrozine is not teratogenic in rats or rabbits. In a two generation 
reproduction study in rats, parental body weights and food consumption 
were decreased, liver and spleen weights were reduced and 
histopathological changes in liver, spleen and pituitary were observed 
at 2,000 ppm (highest dose tested). Liver hypertrophy was observed in 
parental males at 200 ppm (approximately 10-40 mg/kg/day). Reproductive 
parameters were not affected by treatment with pymetrozine. The NOEL 
for reproductive toxicity is 2,000 ppm (approximately 110-440 mg/kg/
day). Offspring body weights were slightly reduced at 2,000 and 200 ppm 
and eye opening was slightly delayed in pups at 2,000 ppm. Effects on 
offspring were secondary to parental toxicity. The NOEL for toxicity to 
adults and pups is 20 ppm (approximately 1-4 mg/kg/day).
    4. Subchronic toxicity. Pymetrozine was evaluated in 13-week 
subchronic toxicity studies in rats, dogs and mice. Liver, kidneys, 
thymus and spleen were identified as target organs. The NOEL was 500 
ppm (33 mg/kg/day) in rats and 100 ppm (3 mg/kg/day) in dogs. In mice, 
increased liver weights and microscopical changes in the liver were 
observed at all doses tested. The NOEL in mice was < 1,000 ppm (198 mg/
kg/day). No dermal irritation or systemic toxicity occurred in a 28-day 
repeated dose dermal toxicity study with pymetrozine in rats given 
1,000 mg/kg/day. Minimum direct dermal absorption (1.1%) of pymetrozine 
was detected in rats over a 21 hour period of dermal exposure. Maximum 
radioactivity left on or in the skin at the application site and 
considered for potential absorption was 11.9%.
    5. Chronic toxicity. Based on chronic toxicity studies in the dog 
and rat, a reference dose (RfD) of 0.0057 mg/kg/day is proposed for 
pymetrozine. This RfD is based on a NOEL of 0.57 mg/kg/day established 
in the chronic dog study and an uncertainty factor of 100 to account 
for interspecies extrapolation and interspecies variability. Minor 
changes in blood chemistry parameters, including higher plasma 
cholesterol and phospholipid levels, were observed in the dog at the 
lowest-observed-effect level (LOEL) of 5.3 mg/kg/day. The NOEL 
established in the rat chronic toxicity study was 3.7 mg/kg/day, based 
on reduced body weight gain and food consumption, hematology and blood 
chemistry changes, liver pathology and biliary cysts.
    6. Animal metabolism. The metabolism of pymetrozine (CGA-215944) in 
the rat is well understood. Metabolism involves oxidation of the 5-
methylene group of the triazine ring yielding 4,5-dihydro-5-hydroxy-6-
methyl-4-[(3-pyridinylmethylene)amino]-1,2,4-triazin-3(2H)-one (CGA-
359009). Oxidation of the methyl substituent of the triazine ring led 
to 4,5-dihydro-6-(hydroxymethyl)-4-[(3-pyridinylmethylene)amino]-1,2,4-
triazin-3(2H)-one (CGA-313124) which was further oxidized to the 
corresponding carboxylic acid, 4,5-dihydro-6-carboxy-4-[(3-
pyridinylmethylene)amino]-1,2,4-triazin-3(2H)-one. Hydrolysis of the 
enamino bridge yielded 4-amino-6-methyl-1,2,4-triazin-3,5(2H,4H)-dione 
(CGA-294849). This was further degraded to 6-methyl-1,2,4-triazin-
3,5(2H,4H)-dione (METABOLITE). Hydrolysis of the enamino bridge of CGA-
215944 produced CGA-215525 which undergoes either acylation (CGA-
259168) or deamination yielding 4,5-dihydro-6-methyl-1,2,4-triazin-
3(2H)-one (CGA-249257). Hydrolysis of the enamino bridge also formed 3-
pyridinecarboxaldehyde (CGA-300407), nicotinic acid (CGA-180777), 
nicotinamide (CGA-180778), 3-pyridinemethanol (CGA-128632) and 1,6-
dihydro-1-methyl-6-oxo-3-pyridinecarboxamide. Identified metabolic 
pathways in animals and plants are similar.
    7. Metabolite toxicology. The residue of concern for tolerance 
setting purposes is the parent compound. Metabolites of pymetrozine are 
considered to be of equal or lesser toxicity than the parent.
    8. Endocrine disruption. Pymetrozine does not belong to a class of 
chemicals known or suspected of having adverse effects on the endocrine 
system. There is no evidence that pymetrozine has any effect on 
endocrine function in developmental and reproduction studies. 
Furthermore, histological investigation of endocrine organs in chronic 
dog, rat and mouse studies did not indicate that the endocrine system 
is targeted by pymetrozine.

C. Aggregate Exposure

    1. Food. For purposes of assessing the potential dietary exposure 
under the proposed tolerances, Novartis has estimated aggregate 
exposure based on exposure from residues of 0.05 ppm on fruiting 
vegetables, 0.02 ppm on cucurbits, 0.02 ppm on potatoes and 5 ppm on 
hops. A 100% market share was assumed.
    2. Drinking water. Another potential source of exposure of the 
general population to pymetrozine is via residues in drinking water. 
Pymetrozine is not expected to contaminate drinking water based on its 
environmental attributes and the low application rates applied. 
Pymetrozine breaks down relatively quickly in the environment by a wide 
variety of mechanisms and degradation pathways. Leaching studies showed 
that pymetrozine is tightly bound to soil and is unlikely to leach in 
the field. Field dissipation studies show little movement beyond the 
uppermost soil horizon.
    3. Non-dietary exposure. There are no other uses currently 
registered for pymetrozine. The proposed uses involve application of 
pymetrozine to crops grown in an agricultural environment. There are no 
proposed uses which would be expected to result in residential exposure 
of pymetrozine. Therefore, there is no potential for non-occupational 
exposure to the general population. is not expected to be significant.

D. Cumulative Effects

    The potential for cumulative effects of pymetrozine and other 
substances that have a common mechanism of toxicity has also been 
considered. Pymetrozine belongs to a new chemical class known as 
pyridine azomethines. It exhibits a unique mode of action which can be 
characterized as nervous system inhibition of feeding behavior. It does 
not have a general toxic or paralyzing effect on insects, but 
selectively interferes with normal feeding activities by affecting 
nervous system regulation of fluid intake. There is no reliable 
information to indicate that toxic effects produced by pymetrozine 
would be cumulative with those of any other chemical including another 
pesticide. Therefore, Novartis believes it is appropriate to consider 
only the potential risks of pymetrozine in an aggregate risk 
assessment.

[[Page 27727]]

E. Safety Determination

    1. U.S. population. Using the conservative exposure assumptions and 
the proposed RfD described above, the aggregate exposure to pymetrozine 
will utilize 3.78% 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 exposure over a 
lifetime will not pose appreciable risks to human health. Therefore, 
Novartis concludes that there is a reasonable certainty that no harm 
will result from aggregate exposure to pymetrozine residues.
    2. Infants and children. In assessing the potential for additional 
sensitivity of infants and children to residues of pymetrozine, data 
from developmental toxicity studies in the rat and rabbit and a two-
generation reproduction study in the rat have been considered.
    In a teratology study in rats, developmental toxicity anomalies and 
variations associated was observed only at maternally toxic doses. 
Similarly, in a rabbit teratology study, was observed only at 
maternally toxic doses. The NOELs in the rat and rabbit teratology 
studies were 30 and 10 mg/kg/day, respectively. In the two-generation 
reproduction study, there were no effects on reproductive parameters. 
Offspring body weights were slightly reduced and eye opening was 
slightly delayed at dose levels producing parental toxicity. The NOEL 
for parental and offspring toxicity was 20 ppm (approximately 1-4 mg/
kg/day).
    FFDCA section 408 provides that EPA may apply an additional safety 
factor for infants and children in the case of threshold effects to 
account for pre- and post-natal toxicity and the completeness of the 
database. Based on the current toxicological requirements, the database 
relative to pre- and post-natal effects for children is complete. 
Further, for pymetrozine, the NOEL of 0.57 from the chronic feeding 
study in dogs, which was used to calculate the RfD (0.0057 mg/kg/day), 
is already lower than the developmental NOELs (30 and 10 mg/kg/day) 
from the teratogenicity studies in rats and rabbits by a factor of more 
than tenfold. In the pymetrozine rat reproduction study, the mild 
nature of the effects observed (decreased body weight) at the systemic 
LOEL (10-40 mg/kg/day) and the fact that the effects were observed at a 
dose that is more than 10 times greater than the NOEL in the chronic 
dog study (0.57 mg/kg/day) suggest that there is no additional 
sensitivity for infants and children. Therefore, it is concluded that 
an additional uncertainty factor is not warranted to protect the health 
of infants and children and that an RfD of 0.0057 mg/kg/day based on 
the chronic dog study is appropriate for assessing aggregate risk to 
infants and children from pymetrozine.
    Using the exposure assumptions described above, the percent of the 
RfD that will be utilized by aggregate exposure to residues of 
pymetrozine is 0.43% for nursing infants less than 1 year old, 1.49% 
for non-nursing infants, 3.44% for children 1-6 years old and 2.72% for 
children 7-12 years old. Therefore, based on the completeness and 
reliability of the toxicity database, Novartis concludes that there is 
a reasonable certainty that no harm will result to infants and children 
from aggregate exposure to pymetrozine residues.

F. International Tolerances

     There are no Codex maximum levels established for residues of 
pymetrozine.

[FR Doc. 98-13447 Filed 5-19-98; 8:45 am]
BILLING CODE 6560-50-F


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