AgrEvo USA Company; Pesticide Tolerance Petition Filing

Note: EPA no longer updates this information, but it may be useful as a reference or resource.
 [Federal Register: January 28, 1999 (Volume 64, Number 18)]
[Notices]               
[Page 4414-4418]
From the Federal Register Online via GPO Access [wais.access.gpo.gov]
[DOCID:fr28ja99-66]

-----------------------------------------------------------------------

ENVIRONMENTAL PROTECTION AGENCY

[PF-854; FRL-6056-3]

 
AgrEvo USA Company; Pesticide Tolerance Petition Filing

AGENCY: Environmental Protection Agency (EPA).

ACTION: Notice.

-----------------------------------------------------------------------

SUMMARY: This notice announces the initial filing of a pesticide 
petition proposing the establishment of regulations for residues of a 
certain pesticide chemical in or on various food commodities.

DATES: Comments, identified by the docket control number PF-854, must 
be received on or before March 1, 1999.

ADDRESSES: By mail submit written comments to: Information and Records 
Integrity Branch, Public Information 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 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. 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: Peg Perreault, Registration Support 
Branch, Registration Division (7505C), Office of Pesticide Programs, 
Environmental Protection Agency, 401 M St., SW,

[[Page 4415]]

Washington, DC 20460. Office location, telephone number, and e-mail 
address: Rm. 207, Crystal Mall #2, 1921 Jefferson Davis Highway, 
Arlington, VA 22202, (703) 305-5417; e-mail: 
perreault.peg@epamail.epa.gov.
SUPPLEMENTARY INFORMATION: EPA has received a pesticide petition as 
follows proposing the establishment and/or amendment of regulations for 
residues of certain pesticide chemical 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 this petition 
contains 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-854] (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:
    opp-docket@epamail.epa.gov


    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-854) 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: January 19, 1999.

James Jones,

Director, Registration Division, Office of Pesticide Programs.

Summary of Petition

    The petitioner summary of the pesticide petition is printed below 
as required by section 408(d)(3) of the FFDCA. The summary of the 
petition was prepared by the petitioner and represents the views of the 
petitioner. 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.

 AgrEvo USA Company

PP 9F3705 and 9H5572

    EPA has received pesticide petitions (PP 9F3705 and 9H5572) from 
AgrEvo USA Company, Little Falls Center One, 2711 Centerville Road, 
Wilmington, DE 19808, 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 clofentezine in or 
on the raw agricultural commodity apples at 0.5 parts per million 
(ppm), in the processed feed commodity wet apple pomace at 10 ppm, and 
in milk at 0.05 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 supports granting of 
the petition. Additional data may be needed before EPA rules on the 
petition.
    APOLLO<Register> SC Ovicide/Miticide (active ingredient 
clofentezine) is registered for use on apples (early season through 
tight cluster), pears, almonds, walnuts, apricots, cherries, 
nectarines, and peaches to control European red mites and several 
spider mite species. It is an environmentally-friendly, IPM-compatible 
product used at low dose rates, and only once per season. Clofentezine 
has been shown to be relatively non-toxic in studies conducted on 
mammals, fish, birds, aquatic invertebrates, predacious and other 
beneficial mites, bees, algae, and plants.
    On February 23, 1995, EPA conditionally approved the use of 
APOLLO<Register> SC on apples (early season through tight cluster) and 
established a permanent tolerance for clofentezine on fresh apples of 
0.01 ppm. The registration was made permanent February 19, 1998, 
following the completion of a successful analytical method try-out 
(MTO) by EPA (at the 0.01 ppm limit of quanitation (LOQ).
    The information summarized below was previously submitted in 
support of the requested label amendment for use on apples with a 45 
day pre-harvest interval. The studies on which this summary is based 
were thoroughly reviewed and approved by the Agency as part of previous 
regulatory actions. However, the accuracy of this summary has not been 
evaluated by the Agency.
    Upon re-examination of this tolerance petition, AgrEvo trusts that 
EPA will agree that the label amendment to allow the use of 
APOLLO<Register> SC (clofentezine) on apples through a 45 day pre-
harvest interval would not pose a significant risk to human health, 
including that of infants, and children, and is in compliance with the 
requirements of the Food Quality Protection Act (FQPA) of 1996.

A. Residue Chemistry

    1. Plant metabolism. The metabolism of clofentezine has been 
studied in three crops representative of the use pattern for 
APOLLO<Register> SC: apples (pome fruit), peaches (stone fruit), and 
grapes (vines/small fruit). In each case, unchanged clofentezine was 
the major extractable residue present. Non-extractable residues (fiber-
bound) were negligible. Minor amounts of 2-chlorobenzonitrile, the 
major photo-degradation product, were detected, predominantly on the 
fruit surface. Dissipation of this component may be a significant route 
in the degradation of clofentezine on the surface of these crops. The 
nature of the residue in apples, and in all the other registered crops, 
is therefore adequately understood. The residue of concern is the 
parent, clofentezine.
    2. Analytical method. EPA recently approved an analytical method 
for clofentezine on apples (MRID 43800801) at a LOQ of 0.01 ppm. In 
support of that effort, AgrEvo submitted an independent laboratory 
validation of the method (MRID 44038001) which involves organic 
extraction and then cleanup, followed by high-pressure liquid 
chromatography. This method is suitable for enforcement for the current 
registration of APOLLO<Register> SC ovicide/miticide on apples through 
the tight cluster timing.
    For the requested use on apples with a 45 day PHI, an analytical 
method similar to the above was previously approved during the review 
of the petition, PP 9F3705/9H5572. This method was deemed suitable for 
enforcement of the tolerances proposed

[[Page 4416]]

in the tolerance petition. Similar analytical methods suitable for 
enforcement purposes are available for all the other registered crops 
and relevant animal tissues/milk/fat.
    3. Magnitude of residues. Extensive field residue trials have been 
conducted with APOLLO<Register> SC on apples throughout the major 
apple-growing regions of the United States. Application through 45 days 
PHI at the maximum use rate resulted in residues of clofentezine on 
fresh apples of < 0.01 ppm to 0.44 ppm. In processing studies on apples 
which had been treated with APOLLO<Register> SC at the maximum use rate 
through 45 days PHI, residues in the processed commodity apple juice 
were lower than those in the raw agricultural commodity; residues in 
wet apple pomace ranged from < 0.01 ppm to 0.03 ppm. In tolerance 
petition PP 9F3705/9H5572 tolerances were proposed and approved 
(although not enacted) for apples (0.5ppm), and apple pomace, wet and 
dry (10 ppm).
    Residue trials were conducted for APOLLO<Register> SC on pears, 
apricots, cherries, nectarines, peaches, almonds, and walnuts at the 
maximum use rates and minimum pre-harvest intervals (PHIs) throughout 
the major growing regions of the United States. Residues in pears 
ranged from < 0.01 to 0.2 ppm. Residues in stone fruit ranged from < 
0.01 to 0.66 ppm. Residues on almond hulls ranged from 0.93 to 2.4 ppm, 
on almond nut meats from < 0.05 to 0.3 ppm, and on walnuts < 0.02 ppm. 
Tolerances were therefore established on pears (0.5 ppm); apricots, 
cherries, nectarines, and peaches (1.0 ppm); almond nutmeats (0.5 ppm); 
almond hulls (5.0 ppm); and walnuts (0.02 ppm).
    Ruminant feeding studies were conducted to determine the magnitude 
of the clofentezine-derived residues in the tissues and milk of cows. 
Four groups of three dairy cattle were fed technical clofentezine in 
the diet at dose levels of 0, 10, 30, and 100 ppm over a period of 28 
days. Daily milk samples were taken and at the termination of the 
study, the following organs were analyzed: liver, kidney, heart, 
muscle, peritoneal fat and subcutaneous fat. At the feeding level of 10 
ppm, residues were 0.3 ppm in liver and < 0.05 ppm in kidney, milk, and 
other tissues. EPA established tolerances for cattle, goats, hogs, 
horses, and sheep as follows: 0.05 ppm in meat, fat, and meat by-
products except liver; 0.4 ppm in liver; and 0.01 ppm in milk. The 
tolerances on meat, fat, meat by-products, and liver were also 
previously approved in tolerance petitions PP 9F3705/9H5572, the label 
amendment for use on apples through 45 days PHI. The tolerance for milk 
was approved (although not enacted) at 0.05 ppm in this tolerance 
petition.

B. Toxicological Profile

    The toxicology of clofentezine has been thoroughly evaluated by EPA 
as part of previous regulatory actions. The studies are considered to 
be valid, reliable and adequate for the purposes of evaluating 
potential health risks and for establishing tolerances. The primary 
studies submitted in support of the registration of clofentezine are 
summarized below. The conclusions presented are those determined by the 
Agency (as reported by the registrant).
    1. Acute toxicity. Technical grade clofentezine has a relatively 
low degree of acute toxicity and irritation potential. It is classified 
as Toxicity Category III for oral, dermal and inhalation toxicity, and 
Toxicity Category IV for eye and skin irritation. The acute oral 
LD<INF>50</INF> of clofentezine was determined to be >5,200 milligram/
kilogram (mg/kg) in rats and mice, >3,200 mg/kg in hamsters, and >2,000 
mg/kg in beagle dogs. The acute rat dermal LD<INF>50</INF> was >2,100 
mg/kg. Clofentezine is considered to be practically non-irritating to 
eyes and skin but is considered to be a weak skin sensitizer in the 
guinea pig maximization assay.
    APOLLO<Register> SC is classified as Toxicity Category IV for oral 
toxicity and skin irritation, and as Toxicity Category III for dermal 
toxicity and eye irritation. The acute oral LD<INF>50</INF> of 
APOLLO<Register> SC was determined to be > 5,000 mg/kg in rats; the 
acute dermal LD<INF>50</INF> in rats was > 2,400 mg/kg. 
APOLLO<Register> SC is considered slightly irritating to eyes and skin.
    2. Genotoxicty. No evidence of genotoxicity was noted in a battery 
of in vitro and in vivo studies. Studies submitted included Ames 
Salmonella and mouse lymphoma gene mutation assays, a mouse 
micronucleus assay, a rat dominant lethal assay, a gene conversion, and 
mitotic recombination assay in yeast.
    3. Reproductive and developmental toxicity. A multigeneration rat 
reproduction study was conducted at dietary concentrations of 0, 4, 40 
and 400 ppm. The parental no-observed adverse effect level (NOAEL) was 
40 ppm based on slightly reduced body weights, increased liver weights 
and hepatocellular hypertrophy at 400 ppm. No treatment related 
reproductive effects were noted at any dose level.
    In a rat developmental toxicity study, clofentezine was 
administered by gavage at dose levels of 0, 320, 1,280 and 3,200 mg/kg/
day during gestation days 6 to 20. Evidence of maternal toxicity was 
noted at 3,200 mg/kg/day and consisted of decreased weight gain, 
increased liver weights and centrilobular hepatocellular enlargement. 
No developmental effects were observed at any dose level.
    In a rabbit developmental toxicity study, clofentezine was 
administered by gavage at dose levels of 0, 250, 1,000 and 3,000 mg/kg/
day during gestation days 7 to 28. Slight maternal toxicity (decreased 
maternal food consumption and weight gain) and a slight decrease in 
fetal weight were noted at 3,000 mg/kg/day. Thus, the NOAEL was 
considered to be 1,000 mg/kg/day for both maternal and developmental 
effects.
    4. Subchronic toxicity. In a preliminary 90 day feeding study 
designed to select a suitable high dose level for a subsequent chronic 
rat study, clofentezine was administered to rats at dietary 
concentrations of 0, 3,000, 9,000 and 27,000 ppm. A significant 
reduction in weight gain was noted at 9,000 and 27,000 ppm. In 
addition, a marked, dose-related hepatomegaly and centrilobular 
hepatocyte enlargement was noted in all treatment groups. In a 
subsequent 90-day feeding study, clofentezine was administered to rats 
at dietary concentrations of 0, 40, 400 and 4,000 ppm. Slightly reduced 
weight gain, alterations in several clinical pathology parameters, 
increased liver, kidney and spleen weights, and centrilobular 
hepatocyte enlargement were noted at 400 and/or 4,000 ppm. Thus, 40 ppm 
(<difference>2.8 mg/kg/day) was considered to be the NOAEL for this 
study.
    Clofentezine was administered to beagle dogs for 90 days at dietary 
concentrations of 0, 3,200, 8,000 and 20,000 ppm. Increased liver 
weights were noted at all dose levels but no histopathological changes 
nor any other treatment-related effects were observed.
    5. Chronic toxicity. In a 12 month feeding study, clofentezine was 
administered to beagle dogs at dietary concentrations of 0, 50, 1,000 
and 20,000 ppm. An increase in adrenal and thyroid weights, as well as 
moderate hepatotoxicity consisting of minimal periportal hepatocyte 
enlargement with cytoplasmic eosinophilia, hepatomegaly and increased 
plasma cholesterol, triglycerides and alkaline phosphatase levels, were 
noted at 20,000 ppm. Evidence of slight hepatotoxicity was also noted 
at 1,000 ppm. Thus, the NOAEL for this study was considered to be 50 
ppm (<difference>1.25 mg/kg/day<SUP>1</SUP>).
    In a 27 month feeding study, clofentezine was administered to rats 
at dietary concentrations of 0, 10, 40 and 400 ppm. Effects noted at 
400 ppm were

[[Page 4417]]

limited to the liver and thyroid, primarily of males, and consisted of 
increased liver weights, a variety of microscopic liver lesions 
(centrilobular hepatocyte hypertrophy and vacuolation, focal cystic 
hepatocellular degeneration and diffuse distribution of fat deposits), 
increased serum thyroxine levels, and a slight but statistically 
significant increase in the incidence of thyroid follicular cell 
tumors. The NOAEL was considered to be 40 ppm (<difference>2 mg/kg/
day).
    Clofentezine was not oncogenic to mice when administered for 2 
years at dietary concentrations of 0, 50, 500 and 5,000 ppm. Decreased 
weight gain, increased liver weights, and increased mortality were 
noted at 5,000 ppm. An increased incidence of eosinophilic or 
basophilic hepatocytes was noted at 5,000 ppm, and possibly 500 ppm.
    6. Special studies. Numerous studies were conducted to investigate 
the mechanism for the increased incidence of male thyroid follicular 
tumors that was observed in the chronic rat study. These studies 
suggest that the tumors may have been caused by increased thyroid 
stimulating hormone (TSH) levels, which, in turn, resulted from 
clofentezine's liver toxicity.
    7. Animal metabolism. The metabolism, tissue distribution and 
excretion of clofentezine have been evaluated in a number of species. 
In all species, almost all of the administered dose was recovered 
within 24 to 48 hours after treatment, primarily via the feces. The 
major route of metabolism was found to be ring hydroxylation, sometimes 
preceded by the replacement of a chlorine atom with a methyl-thio 
group. Blood and tissue levels in the fetuses of pregnant rats that had 
been treated with clofentezine were much lower than the levels found in 
the mother, indicating that clofentezine does not readily pass across 
the placenta. In addition, less than 1% of the administered dose was 
absorbed through the skin of rats following a 10 hour exposure to a 50 
SC (50% suspension concentrate) formulation of clofentezine.
    Following oral dosing of a cow and three goats with <SUP>14</SUP>C- 
labeled clofentezine, the residue in milk was identified as a single 
metabolite, 4-hydroxyclofentezine. Similarly, 4-hydroxyclofentezine has 
been shown to be the only metabolite present in fat, liver, and kidney. 
No unchanged clofentezine or other metabolites were found. Therefore, 
the nature of the residue in animals is adequately understood. The 
residues of concern are the combined residues of the parent, 
clofentezine, and the 4-hydroxyclofentezine metabolite.
    8. Endocrine disruption. Except for the thyroid mechanistic studies 
mentioned above, no special studies have been conducted to investigate 
the potential of clofentezine to induce estrogenic or other endocrine 
effects. However, the standard battery of required toxicity studies has 
been completed. These studies include an evaluation of the potential 
effects on reproduction and development, and an evaluation of the 
pathology of the endocrine organs following repeated or long-term 
exposure. These studies are generally considered to be sufficient to 
detect any endocrine effects. However, with the exception of a slightly 
increased incidence of thyroid tumors in male rats, no such effects 
were noted in any of the studies with clofentezine. The male rat is 
known to be much more susceptible than humans to the carcinogenic 
effects resulting from thyroid hormone imbalance and/or increased 
levels of TSH. Therefore, the alterations in thyroid hormone and 
subsequent thyroid pathological changes, which have been noted 
following administration of high doses of clofentezine, are considered 
to be of minimal relevance to human risk assessment, particularly 
considering the low levels of clofentezine to which humans are likely 
to be exposed.

C. Aggregate Exposure

    Clofentezine is a miticide used on apples, pears, almonds, walnuts, 
apricots, cherries, peaches, and nectarines. Clofentezine has also been 
registered recently for use on ornamental plants, however, the product 
registered for use on ornamental plants (OVATION<Register> miticide/
insecticide) is not being marketed at this time. There are no other 
non-crop uses. Thus, potential sources of non-occupational exposure to 
clofentezine would consist only of any potential residues in food and 
drinking water. There are no acute toxicity concerns with clofentezine. 
Therefore, only chronic exposures are addressed here.
    1. Dietary exposure--Food. A worst case dietary exposure assessment 
was performed for clofentezine using the Exposure<Register> 1 software 
system (TAS, Inc.) and the 1977-78 USDA consumption data. This 
assessment assumed that 100% of all apples, pears, almonds, walnuts, 
apricots, cherries, nectarines, peaches, milk, and the fat, meat, and 
meat by-products of cattle, goats, horses, sheep, and hogs contained 
residues at the established and proposed tolerance levels. specify here 
or previously. A more realistic assessment was also conducted using 
estimates of market share.
    2. Drinking water. All EPA environmental fate data requirements 
have been satisfied. The potential for clofentezine to leach into 
groundwater was assessed in terrestrial field dissipation studies 
conducted in several locations and in varying soil types. Half-lives 
ranged from 32.4 to 83 days. No evidence of leaching of parent or 
degradation products was observed. Based upon these and other studies, 
EPA concluded that ``clofentezine is a relatively short-lived, non-
mobile compound which does not pose a risk to groundwater, and will not 
be expected to accumulate in rotational crops.'' Thus, the potential 
for finding significant clofentezine residues in drinking water is 
minimal and the contribution of any such residues to the total dietary 
intake of clofentezine will be negligible. No Maximum Contaminant Level 
for clofentezine has been established.

D. Cumulative Effects

    The primary effects observed in the toxicity studies conducted with 
clofentezine appear to be a result of its potency as an enzyme inducer. 
Although many other chemicals are also known to induce microsomal 
enzymes, insufficient information is available at this time to 
determine whether or not the potential toxic effects from these 
chemicals are cumulative. Furthermore, realistic estimates of potential 
non-occupational exposure to clofentezine indicate that such exposures 
are minimal and far below the levels that might be expected to produce 
any effects. Thus, any contribution of clofentezine to cumulative risk 
will not be significant. Therefore, only exposure from clofentezine is 
being addressed at this time.

E. Safety Determination

    1. U.S. population. The toxicity and residue data bases for 
clofentezine are considered to be valid, reliable and essentially 
complete. Although clofentezine has been classified by EPA as Category 
C for oncogenicity, quantitative oncogenic risk assessment was 
considered inappropriate for the following reasons:
    i. Evidence of tumors was limited to a single site in one sex of 
one species and occurred only at the high-dose level.
    ii. The increased incidence of thyroid follicular tumors was only 
marginally increased above both concurrent and historical control 
levels.

[[Page 4418]]

    iii. No evidence of genotoxicity has been observed.
    iv. Mechanistic data indicate that the thyroid tumors were likely a 
secondary, threshold-mediated effect associated with clofentezine's 
liver toxicity. Furthermore, humans are believed to be much less 
susceptible to this effect than rats. Therefore, no effect on the 
thyroid-pituitary axis or oncogenic response would be expected at 
exposure levels which did not affect #the liver.
    Thus, a standard margin of safety approach is considered 
appropriate to assess the potential for clofentezine to produce both 
oncogenic and non-oncogenic effects. Based on the previously described 
data, EPA has adopted an reference dose (RfD) value for clofentezine of 
0.0125 mg/kg/day, which was calculated using the NOAEL of 1.25 mg/kg/
day from the 1 year dog feeding study and a 100-fold safety factor.
    Using the worst-case assumptions of 100% of crop treated and that 
all crops and animal commodities contain residues of clofentezine at 
the current tolerance levels, the aggregate exposure of the general 
population to clofentezine from the established tolerances utilizes 
about 5% of the RfD. Using more realistic estimates of percent crop 
treated and adjusting for contribution from livestock diet, this 
decreases to less than 0.5% of the RfD. Repeating these assessments 
with the proposed tolerances, the percent RfD for the worst case is 
less than 10%, and for the more realistic case the percent RfD 
decreases to less than 1.2%. There is generally no concern for 
exposures which utilize less than 100% of the RfD because the RfD 
represents the level at or below which daily aggregate exposure over a 
lifetime would not pose significant risks to human health. Therefore, 
there is a reasonable certainty that no harm will result to the general 
population from aggregate exposure to clofentezine residues.
    2. Infants and children. Data from rat and rabbit developmental 
toxicity studies and rat multi generation reproduction studies are 
generally used to assess the potential for increased sensitivity of 
infants and children. The developmental toxicity studies are designed 
to evaluate adverse effects on the developing organism resulting from 
pesticide exposure during prenatal development. Reproduction studies 
provide information relating to reproductive and other effects on 
adults and offspring from prenatal and postnatal exposure to the 
pesticide.
    No indication of increased sensitivity to infants and children was 
noted in any of the studies with clofentezine. No developmental effects 
were noted in rats, even at a dose level (3,200 mg/kg/day) that 
exceeded the 1,000 mg/kg/day limit dose and produced maternal toxicity. 
In addition, no evidence of reproductive toxicity was noted in the rat 
multigeneration reproduction study. Slight developmental toxicity 
(decreased fetal weights) was noted in rabbits, but only at a dose 
level (3,000 mg/kg/day) that exceeded the EPA limit dose and also 
produced maternal toxicity.
    FFDCA Section 408 provides that EPA may apply an additional safety 
factor for infants and children to account for pre- and post-natal 
toxicity and the completeness of the data base. The toxicology database 
for clofentezine regarding potential pre- and post-natal effects in 
children is complete according to existing Agency data requirements and 
does not indicate any developmental or reproductive concerns. 
Furthermore, the existing RfD is based on a NOAEL of 1.25 mg/kg/day 
(from the 1 year dog study) which is already more than 800-fold lower 
than the NOAEL in the rabbit developmental toxicity study. Thus, the 
existing RfD of 0.0125 mg/kg/day is considered to be appropriate for 
assessing potential risks to infants and children and an additional 
uncertainty factor is not warranted.
    Using the conservative exposure assumptions described above 
(proposed tolerances, 100% crop treated, and no adjustments for percent 
contribution from livestock diet), aggregate exposure to residues of 
clofentezine are expected to utilize about 65% of the RfD in non-
nursing infants, 33% of the RfD in nursing infants, and 25% of the RfD 
in children aged 1 to 6 years old.
    Using more realistic estimates of percent crop treated and 
adjusting for the percent contribution from livestock diet, the percent 
of RfD utilized is less than 8% for these population subgroups. These 
numbers would be lowered further if anticipated residues were utilized 
rather than tolerance values. Therefore, there is a reasonable 
certainty that no harm will result to infants or children from 
aggregate exposure to clofentezine residues.

F. International Tolerances

    Codex tolerances have been established for clofentezine on a wide 
variety of crops, including apples. The following MRLs were adopted by 
the Codex Committee on Pesticide Residues (CCPR) in April, 1988, except 
as noted in parentheses:


------------------------------------------------------------------------
                 Commodity                           MRL (mg/kg)
------------------------------------------------------------------------
Cattle meat...............................  0.05
Cattle, edible offal,.....................  0.1
Cattle, milk..............................  0.01
1Citrus fruits............................  0.5 (1995)
Cucumber..................................  1.0 (1991)
Currants..................................  0.01 (1993)
Eggs (poultry)............................  0.05
Grapes....................................  1.0 (1995)
Pome fruits...............................  0.5
Poultry, edible offal.....................  0.05
Poultry meat..............................  0.05
Stone fruits..............................  0.2
Strawberry................................  2.0
------------------------------------------------------------------------

[FR Doc. 99-1904 Filed 1-27-99; 8:45 am]
BILLING CODE 6560-50-F
AgrEvo USA Company; Pesticide Tolerance Petition Filing

Local Navigation
