[Federal Register Volume 63, Number 144 (Tuesday, July 28, 1998)]
[Notices]
[Pages 40273-40279]
From the Federal Register Online via the Government Publishing Office [www.gpo.gov]
[FR Doc No: 98-20145]


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ENVIRONMENTAL PROTECTION AGENCY

[PF-816; FRL-5799-3]


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 food commodities.
DATES: Comments, identified by the docket control number PF-816, must 
be received on or before August 27, 1998.
ADDRESSES: By mail submit written comments to: Public Information and 
Records Integrity Branch, Information Resources and Services Division 
(7502C), 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 to: <a href="/cdn-cgi/l/email-protection#d6b9a6a6fbdcb2b9b5bdb3a296b3a6b7bbb7bfbaf8b3a6b7f8b1b9a0">opp-
<span class="__cf_email__" data-cfemail="c1a5aea2aaa4b581a4b1a0aca0a8adefa4b1a0efa6aeb7">[email protected]</span></a>. Follow 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:

------------------------------------------------------------------------
                                   Office location/                     
        Product Manager            telephone number          Address    
------------------------------------------------------------------------
Bipin Gandhi (PM 21)..........  Rm. 707A, CM #2, 703-   1921 Jefferson  
                                 308-8380, e-            Davis Hwy,     
                                 mail:gandhi.bipin@epa   Arlington, VA. 
                                 mail.epa.gov.                          
Cynthia Giles-Parker (PM 22)..  Rm. 247, CM #2, 703-    1921 Jefferson  
                                 305-7740, e-            Davis          
                                 mail:giles-             Hwy.,Arlington,
                                 <a href="/cdn-cgi/l/email-protection" class="__cf_email__" data-cfemail="becedfccd5dbccfedbcedfd3dfd7d290dbcedf90d9d1">[email protected]</a>   VA.            
                                 v.                                     
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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 
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-816] (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#375847471a5358545c5243775247565a565e5b1952475619505841"><span class="__cf_email__" data-cfemail="7d120d0d5019121e1618093d180d1c101c141153180d1c531a120b">[email protected]</span></a>


    Electronic comments must be submitted as an ASCII file avoiding the 
use of special characters and any form of encryption. Comments and data 
will also be accepted on disks in Wordperfect 5.1 file format or ASCII 
file format. All comments and data in electronic form must be 
identified by the docket number (insert docket number) and appropriate 
petition number. Electronic comments on 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:July 9, 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

[[Page 40274]]

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.

1. Fleming Laboratories, Inc.

PP 4G4276

    EPA has received a pesticide petition (PP 4G4276) from Fleming 
Laboratories, Inc., P.O.Box 34384, Charlotte, NC 28234 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 (4-methylphenyl)arsonic acid in or on the raw 
agricultural commodity fresh market grapefruit grown only in Florida at 
0.5 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 
supports granting of the petition. Additional data may be needed before 
EPA rules on the petition.

A. Residue Chemistry

    1. Plant metabolism. A plant metabolism study is being conducted at 
the proposed use rate of 6.22 lbs active ingredient (6.25 lbs product) 
per acre and has revealed approximately 0.46 ppm total radioactive 
residue (TRR) in whole fruit, of which 0.13 ppm or 29.2% of the TRR was 
parent compound. Four of the 11 metabolites isolated from whole fruit 
exceed 10% of the TRR. Metabolite characterization and identification 
is still in progress.
    2. Analytical method. A High Performance Liquid Chromatography 
(HPLC) method is available to verify the certified limits of arsanilic 
acid in the end-use product.
    Currently there is no validated method for determining any of the 
residues of arsanilic acid in/on grapefruit. However, method 
development is partially complete for an analytical method to determine 
residues of (4-aminophenyl)arsonic acid, per se, the active ingredient 
of Pro-Gen(r), in or on whole grapefruit. In principle, a 50 gram 
sample of grapefruit is extracted by homogenization with water. The 
extract is centrifuged, filtered, concentrated by rotary evaporation, 
cleaned up on a florisil column, buffered to pH 4.5, then derivatized 
with methyl thioglycolate. The derivative is partitioned into toluene, 
which is analyzed by gas chromatography (GC) and an electron capture 
detector (ECD). The anticipated Limit of Quantitation (LOQ) is 0.05 
ppm. Method development for the metabolite residues will ensue as the 
metabolites are identified.
    3. Magnitude of residues. Field residue trials are currently in 
progress at several sites in Florida. Mature grapefruit samples have 
been harvested from trees treated with 6.25 lbs Pro-Gen(r) per acre and 
are being stored until residue analytical method development is 
complete. However, based on the data from the plant metabolism study, 
total residues of arsanilic acid in grapefruit are expected to be less 
than 0.5 ppm.

B. Toxicological Profile

    1. Acute toxicity. Pro-Gen(r)/arsanilic acid is only moderately 
acutely toxic to mammals. The rat acute oral LD<INF>50</INF> values 
were 1,411 mg/kg for males, 976 (646-2883) mg/kg for females and 1,461 
mg/kg for males and females combined. A study with New Zealand white 
rabbits established acute dermal LD<INF>50</INF> values of 922 mg/kg 
for males, 909 (445-1972) mg/kg for females and 921 (577-1402) mg/kg 
for males and females combined. Arsanilic acid has caused minimal signs 
of toxicity in rats following a 4 hour inhalation exposure to a 
measured atmospheric concentration of 5.35 mg/l. The acute inhalation 
LC<INF>50</INF> is greater than 5.35 mg/l. Arsanilic acid is slightly 
irritant to rabbit eyes and is not irritant to rabbit skin.
    Arsanilic acid is not considered a skin sensitizer. Arsanilic acid 
does not cause sensitization in guinea pigs. Additionally, arsanilic 
acid has been manufactured and used since the 1940's as a medicinal 
feed additive for poultry and swine with no reported incidents of 
hypersensitivity among workers.
    2. Genotoxicty. Arsanilic acid is not mutagenic to five strains of 
Salmonella typhimurium. In the mouse micronucleus test, arsanilic acid 
(99.6% purity) was devoid of micronucleus inducing potential in the 
bone marrow of male and female CD-1 mice when tested to maximum 
tolerated doses. Arsanilic acid was determined to be weakly mutagenic 
in mouse lymphoma L51178Y cells in the presence of S9 mix, when tested 
at concentrations extending into the toxic range. However, evidence of 
mutagenicity in the absence of S9 mix was inconclusive.
    3. Reproductive and developmental toxicity. A review of three 
studies detailing the effects of arsanilic acid on reproduction in 
swine found no adverse effects on the fertility, fecundity, or health 
and survival of swine dams and their offspring at an arsanilic acid 
feed concentration of 100 ppm. Furthermore, at the 100 ppm arsanilic 
acid feeding level, no gross abnormalities or adverse effects were 
found on organ weights or pathology. To the contrary, arsanilic acid in 
the diet improved the overall health, improved weight gain, and 
increased survival of swine.
    No developmental effects were found in rats exposed in utero to 
arsanilic acid at levels up to and including that which produced overt 
maternal toxicity. Arsanilic acid was administered orally by gavage to 
pregnant rats at nominal dose levels of up to 60 mg/kg/day. Reduced 
body weight gains early in the treatment period, reduced food 
consumption, and the presence clinical signs (60 mg/kg/day group) were 
considered evidence of maternal toxicity. No developmental toxicity was 
apparent at any dose level. A no observable effect level (NOEL) for 
maternal effects (reduced food consumption) was considered to be less 
than 6 mg/kg/day (based on a 60.0% of target concentration analysis of 
the 10 mg/kg/day formulation used during the first 5 days of dose 
administration). The NOEL for maternal clinical signs was 30 mg/kg/day. 
The NOEL for developmental toxicity of rats was 60 mg/kg/day.
    No developmental effects were noted in rabbits exposed in utero to 
arsanilic acid (100%) at levels up to and including that which produced 
overt maternal toxicity. Arsanilic acid (Pro-Gen(r)) was administered 
orally by gavage to pregnant rabbits at nominal dose levels up to 6 mg/
kg/day. Maternal effects were observed only in the 6 mg/kg/day dosed 
dams and were limited to reductions in mean body weight gain and food 
consumption. No maternal effects were apparent at dose levels of 1 and 
3 mg/kg/day. No developmental toxicity was expressed at any dose level. 
The NOEL for maternal effects was 3 mg/kg/day. The NOEL for 
developmental toxicity was 6 mg/kg/day.
    4. Subchronic toxicity. No mortality occurred during a 91-day 
feeding study in which male and female rats were fed nominal 
concentrations of up to 750 ppm arsanilic acid in the diet. Some signs 
of toxicity (behavior, locomotion and excreta) were observed at feeding 
levels of 375 ppm and above. No definite treatment effects were 
observed in animals receiving 50 ppm arsanilic acid in the diet. The 
NOEL was determined to be 50 ppm (3.77 mg/kg/day for males and 4.76 mg/
kg/day for females).

[[Page 40275]]

    No mortality occurred during a 90-day feeding study in which male 
and female beagles were fed arsanilic acid at up to 200 ppm in diet. No 
ophthalmoscopic abnormalities were observed at any level. Clinical 
signs of toxicity were observed in some dogs receiving 200 ppm 
arsanilic acid in diet. While there was no observable indication of 
toxicity in animals receiving up to 100 ppm arsanilic acid in the diet, 
microscopic evaluation of the kidneys revealed dose-related 
abnormalities. The NOEL for female beagle dogs was 50 ppm (1.7 mg/kg/
day). The NOEL for male beagle dogs was 25 ppm (0.7 mg/kg/day).
    5. Chronic toxicity. Arsanilic acid is not carcinogenic to rats. 
Arsanilic acid is approved by the FDA for use as a medicinal feed 
supplement for swine and poultry at concentrations up to 0.01% of the 
ration and has been extensively used in commercial rations since the 
1940's.
    Arsanilic acid was fed to rats (two separate studies) at 
concentration levels of 100, 500 and 1,000 ppm in the diet for 106 to 
116-weeks. In both studies, the presence of arsanilic acid in the diet 
was reported to have caused no gross abnormalities or adverse effects 
on organ weights, pathology, incidence of tumors or health of rats.
    Long term feeding of 0.01% arsanilic acid in pig feed for up to 51 
months during a multigeneration study resulted in increased survival 
and overall improved health of arsanilic acid-treated pigs.
    6. Animal metabolism. Arsanilic acid uniformly labeled with 
<SUP>14</SUP>C in the benzene ring was used to determine the metabolic 
fate of arsanilic acid fed to pigs and chickens. Arsanilic acid was 
well absorbed by both species. Urine was the predominant route of 
excretion. The bile was a minor (<5% of the dose) route of excretion in 
pigs (was not measured in chickens). Arsanilic acid and two other 
metabolites, N-acetylarsanilic acid and (4-
acetamidophenyl)dimethylarsine oxide, were identified in the pig urine. 
In pigs, somewhere between 17-39% of the urinary <SUP>14</SUP>C 
metabolites was excreted as arsanilic acid, 15-29% as N-acetylarsanilic 
acid and <5% as (4-acetamidophenyl)dimethylarsine oxide. Only 2-5% of 
the radio-labeled arsanilic acid dose remained in the carcass or liver 
of pigs while less than 1% remained in the chicken carcasses (liver 
included). There was no evidence of any biotransformation of arsanilic 
acid in chickens. The study authors also note that the results of this 
study corroborate earlier research showing that chickens rapidly 
excrete arsanilic acid with no biotransformation.
    7. Metabolite toxicology. There is no known information about the 
toxicity of any of the currently identified metabolites of arsanilic 
acid.
    8. Endocrine disruption. Arsanilic acid is not considered to be an 
endocrine disruptor. Several studies in which different species were 
administered high levels of arsanilic acid have shown no effect on the 
time-to-mating or on mating and fertility indices. Radiolabelled 
[<SUP>14</SUP>C]-arsanilic acid fed to chickens (laying hens) had no 
effect on the ability of the hens to produce eggs. Multigeneration 
reproduction studies in swine, developmental toxicity studies in rats 
and rabbits, chronic studies in rats plus long term medicinal use in 
animal husbandry amply demonstrates that arsanilic acid does not affect 
the estrous cycle, mating behavior, male or female fertility, or male 
or female reproductive tracts.

C. Aggregate Exposure

    1. Dietary exposure--Food-- i. From medicinal feed additive use. 
Arsanilic acid has been utilized under FDA approval as a medicinal feed 
additive in pig, chicken and turkey feeds since the 1940's. However, 
the feed additive tolerances established by the FDA are expressed in 
terms of total residues of combined arsenic (calculated as As) instead 
of as arsanilic acid (21 CFR 558.62 and 556.60). Because arsanilic acid 
may be the sole dietary contributor that necessitates the feed additive 
tolerances for arsenic, these tolerances can be converted to total 
arsanilic acid equivalents by using a conversion factor of 2.9, the 
ratio of the molecular weight of arsanilic acid (217.04) to that of its 
arsenic content (74.92).

----------------------------------------------------------------------------------------------------------------
                                                           Total Residues as                                    
             Total Residues as Arsenic (ppm)                 Arsanilic Acid                Commodity            
                                                                 (ppm)                                          
----------------------------------------------------------------------------------------------------------------
0.5......................................................               1.45                       eggs, chicken
0.5......................................................               1.45                     muscle, chicken
2.0......................................................                5.8         edible by-products, chicken
0.5......................................................               1.45                        eggs, turkey
0.5......................................................               1.45                      muscle, turkey
2.0......................................................                5.8          edible by-products, turkey
2.0......................................................                5.8                        liver, swine
2.0......................................................                5,8                       kidney, swine
0.5......................................................               1.45                       muscle, swine
0.5......................................................               1.45                  by-products, swine
----------------------------------------------------------------------------------------------------------------

    ii. From proposed use on fresh market grapefruit grown only in 
Florida. In the amended petition for a Saleable Experimental Use 
Permit, the following temporary tolerance is proposed for total 
residues of arsanilic acid expressed as arsanilic acid, per se, in or 
on fresh market grapefruit.
     0.5 ppm in/on grapefruit (whole fruit)
    Because the treated fruit are prohibited from being processed under 
the amended Experimental Use Permit, no dietary exposure is anticipated 
from the processed commodities nor are any temporary tolerances 
proposed for the processed commodities, grapefruit juice, dried 
grapefruit pulp or grapefruit citrus oil.
    iii. From livestock consumption of treated grapefruit and/or 
processed products. Under the amended petition for Experimental Use 
Permits (EUP), treated fruit may not be fed to livestock. The amended 
EUP also restricts livestock grazing or consumption of forage or hay 
from Pro-Gen(r) treated orchards. Therefore, no dietary exposure to 
arsanilic acid is anticipated from livestock consumption of Pro-Gen(r) 
under the auspices of the proposed EUP.
    2. Drinking water. No exposure to arsanilic acid is expected from 
consumption of drinking water. Arsanilic acid is not proposed for 
application to sources of drinking water. Additionally, hydrolysis, 
soil metabolism and soil adsorption/desorption studies have shown that 
arsanilic acid is stable to environmental degradation and binds tightly 
and irreversibly to the organic and mineral fractions of soils. Any 
arsanilic acid that

[[Page 40276]]

might be excreted by poultry or swine administered arsanilic acid for 
medicinal purposes will be tightly bound to soil if incorporated in to 
the soil as a fertilizer. Consequently, potential exposure of surface 
and/or ground water to arsanilic acid will be minimized.
    3. Non-dietary exposure. There are no known sources of non-dietary 
exposure to arsanilic acid, outside of occupational exposure in the 
manufacturing and packaging of Pro-Gen(r)/arsanilic acid in its current 
usage in animal husbandry, or in its proposed use in Florida fresh 
market grapefruit production. There is little concern that children 
would be exposed to non-dietary sources of arsanilic acid.

D. Cumulative Effects

    For cumulative exposure considerations, Fleming Laboratories 
believes it is appropriate to consider only the potential risks of 
arsanilic acid noted in the discussion of aggregate exposure (above), 
based on the current approaches used by the FDA and EPA for regulating 
organic arsenical compounds in animal husbandry and crop production.
    Arsanilic acid is an organic arsenical compound. FDA regulations 
have established feed additive tolerances, expressed as ppm total 
combined arsenic, for the following medicinal organoarsenical 
compounds, arsanilic acid, arsanilate sodium, nitarsone, carbarsone, 
and roxarsone.
    Although FDA has authorized the use of these compounds as medicinal 
feed additives, only one of these organoarsenicals may be used at a 
time as the sole source of organic arsenic in the feed. Therefore, 
there is no exposure from multiple organic arsenicals in animal feeds.
    With regards to crop protection, the only known organic arsenicals 
registered in the U.S. are the herbicides: cacodylic acid, a cotton 
defoliant; and disodium or monosodium methanearsonic acid, contact 
herbicides used in cotton and citrus production. With regard to residue 
tolerances for these herbicides, residues of cacodylic acid are 
regulated discretely for that compound under 40 CFR 180.311. While, 
residues of disodium and monosodium methanearsonic acid are regulated 
simultaneously as methanearsonic acid under 40 CFR 180.289. Since these 
compounds are regulated discretely, it can be assumed that EPA 
considers them to have distinct metabolic pathways and modes of action.
    Since arsanilic acid has a considerably different chemical 
structure (containing a phenyl ring) from these other straight-chained 
organic arsenical herbicides, it is reasonable to assume that arsanilic 
acid will have a unique mode of action compared to the straight chain 
herbicides. The proposed use of arsanilic acid as a plant growth 
regulator further illustrates the differences when comparing arsanilic 
acid to these herbicides.
    Therefore, for cumulative exposure considerations, Fleming 
Laboratories believes it is appropriate to consider only the potential 
risks of arsanilic acid noted in the discussion of aggregate exposure 
(above).

E. Safety Determination

    U.S. population. The Acceptable Daily Intake (ADI) is the amount of 
pesticide residue that can be ``safely'' ingested by humans and still 
be protective of the health of all segments of the population. An ADI 
must be established for any pesticide that results in a residue on 
crops used for human consumption. The ADI, sometimes referred to as the 
Reference Dose (RfD), is a mathematically derived figure based on the 
NOEL of a chronic or subchronic toxicity study and safety or 
uncertainty factors. Uncertainty factors are used to compensate for 
inter- and intra-species differences, type of study, etc. when 
extrapolating from toxicity data (animal or human) to human risk 
assessments.
    For arsanilic acid, the ADI will be based on the results of the dog 
subchronic feeding study. The ADI is equal to the NOEL times a safety 
or uncertainty factor (UF). It is customary to use a UF of 100 fold 
(100x) to account for the species differences from dog to human, as 
well as for extrapolating from a subchronic study to chronic exposure 
of humans. Assuming that EPA concurs with an uncertainty factor of 
100x, the ADI based on the most sensitive NOEL can be calculated as 
follows:
     NOEL = 25 ppm arsanilic acid in diet of dogs = 0.75 mg/kg/day
     Then the ADI or RfD = 0.75 mg/kg/day x (1/100) = 0.0075 mg/kg/day
    Based on EPA's total diet survey, sensitive populations, such as 
infants, have little or no intake of grapefruit or grapefruit juice. 
Therefore the ADI is based on consumption of grapefruit and grapefruit 
juice by 70 kg adult humans. Therefore, if the ADI is 0.0075 mg/kg/day, 
a 70 kg adult could safely consume 0.525 mg arsanilic acid /day (0.0075 
mg/kg/day x 70 kg).

F. Dietary Risk Assessment

    The dietary risk assessment evaluates how much of the ADI would be 
``used up'' when residue tolerances are proposed for pesticide-bearing 
crop or animal commodities that may be consumed by humans. To conduct 
the risk assessment for arsanilic acid under the tenets of the proposed 
amended Experimental Use Permit for Florida-grown, fresh market fruit 
only, one needs to know how much grapefruit would typically be consumed 
by humans and the amount of arsanilic acid residues in or on the fruit. 
Additionally, human exposure from consumption of swine and poultry 
products from medicinally treated animals must be considered.
    For estimating grapefruit dietary consumption, EPA's Total Diet 
Study, which is used to calculate exposure and dietary risk for 
pesticides, reveals that 25-30 year-old men have the highest 
consumption of grapefruit compared to all other age and sex groupings. 
Consumption rates in this group are listed as 4.3 grams of grapefruit 
per day. Consumption of whole grapefruit (4.3 grams/day) contributes to 
less than 0.08% of the total diet in this age and sex category.
    Dietary exposure from grapefruit consumption will be reduced by the 
limited use of Pro-Gen(r) to grapefruit grown in Florida. According to 
the Florida Citrus Summary 1993-94, Florida produced 816,800 tons of 
grapefruit in 1993-1994, which was 66.10% of the total U.S. production 
of grapefruit. This means that grapefruit grown in Florida would 
contribute to less than 0.053% (i.e. 0.08% of diet x 66.1% of 
grapefruit = 0.053%) of the total diet for the highest consumers of 
grapefruit, 25-30 year-old men.
    For estimating the dietary consumption of swine and poultry 
products, EPA's Total Diet Study reveals that 25-30 year-old men have 
the highest consumption of pork (39.5 grams/day) and poultry (chicken 
plus turkey; 28.7 grams/day). (Gram servings of pork, chicken and 
turkey kidneys and livers were not included). While 60-65 year old men 
have the highest consumption of eggs, the 25-30 year-old men have the 
second highest consumption rate (31 grams/day). Total consumption of 
pork, poultry and eggs accounts for 3.23% of the diet of 25-20 year-old 
men. In comparison, the same commodities comprise 3.1% of the diet of 2 
year-old children, 2.7 % for females 14-16 years-old, 2.9% for males 
14-16 years-old and 2.8% for 25-30 year-old women.
    For conducting a dietary risk assessment and to provide 
conservative estimates: (1) the total consumption of fruit has been 
adjusted up from an estimated 4.3 grams to 5 grams grapefruit consumed 
per day (2); total

[[Page 40277]]

residues of arsanilic acid in or on whole fruit are considered to be 
0.5 ppm, based on the proposed temporary tolerance for total residues 
of Pro-Gen(r) in or on treated grapefruit (3); the total consumption of 
pork, poultry and eggs has been adjusted from the estimated 39.5 grams/
day to 40 grams/day; and (4) total FDA allowed residues of arsanilic 
acid in pork or poultry products (with the exception of kidneys and 
liver) is 1.45 ppm. Since the estimated gram quantities of pork and 
poultry organ meats (kidneys and livers) were not provided using the 
estimated daily consumption of 2.8 g beef liver provides an extremely 
conservative estimate for pork and poultry livers with FDA allowed 
arsanilic acid residues of 5.8 ppm.
    If it is assumed that all grapefruit in Florida are treated with 
Pro-Gen(r), which results in total arsanilic acid residue levels of 0.5 
ppm in fruit, and a 70 kg adult consumes 5 grams of grapefruit per day 
of which 66.1% is from Florida, then the total dietary intake per day 
can be calculated as follows:
    5 grams/day grapefruit consumed = 0.005 kg/day grapefruit consumed
    0.005 kg/day grapefruit x 0.661 = 0.00331 kg/day Florida fresh 
market grapefruit consumed
    Total residues of 0.5 ppm arsanilic acid = 0.5 mg total arsanilic 
acid residues /kg food
    (Amount of Florida fruit consumed) x (residue level) = 0.00331 kg 
fruit/day x 0.5 mg total arsanilic acid residues /kg fruit = 0.00166 mg 
total arsanilic acid/day in grapefruit
    If it is assumed that all swine and poultry received arsanilic 
acid-treated, then the total dietary intake per day of arsanilic acid 
from pork and poultry products except organ meats, can be calculated as 
follows:
    40 grams/day pork, poultry and eggs consumed = 0.04 kg/day animal 
products consumed
    X total residues of 1.45 ppm arsanilic acid = 1.45 mg total 
arsanilic acid residues /kg food
    (Amount of pork, poultry and eggs consumed) x (residue level) = 
0.04 kg/day x 1.45 mg total arsanilic acid residues /kg food = 0.058 mg 
total arsanilic acid/day in pork, poultry and eggs.
    If it is assumed that all swine and poultry received arsanilic 
acid-treated, then the total dietary intake per day of arsanilic acid 
from pork and poultry kidneys and liver can be calculated as follows:
    2.8 grams/day pork and poultry organs consumed = 0.0028 kg/day 
organs consumed
    Total residues of 5.8 ppm arsanilic acid = 5.8 mg total arsanilic 
acid residues /kg food
    (Amount of kidneys and liver consumed) x (residue level) = 0.0028 
kg total arsanilic acid /day x 5.8 mg/kg = 0.016 mg total arsanilic 
acid/day in pork and poultry kidneys and liver.
    Total dietary intake of total arsanilic acid = 0.00166 + 0.058 + 
0.016 = 0.07566 mg total arsanilic acid residues per day
    This estimate of total dietary intake represents only 14% of the 
allowable daily consumption of 0.525 mg arsanilic acid/day for a 70 kg 
adult, established by a NOEL of 25 ppm and an ADI of 0.0075 mg/kg/day. 
The estimated dietary intake of total arsanilic acid residues from Pro-
Gen(r)-treated fresh market grapefruit is only 0.03% of the ADI of 
0.0075 mg/kg/day.
     Infants and children. Based on EPA's total diet survey, sensitive 
populations, such as infants, have little or no intake of grapefruit or 
grapefruit juice. Therefore, the proposed use of Pro-Gen(r) on Florida 
grapefruit will pose no additional risk of adverse effects to infants 
or children beyond that which already exists from consumption of 
poultry and swine products from animals medicinally treated with 
arsanilic acid. Even so, it is appropriate to consider the results of 
the developmental, reproductive, and chronic studies. The available 
data clearly show that there is no increased risk to neonates or young 
when arsanilic acid is ingested. Therefore, Fleming Laboratories 
concludes that
     An additional safety factor for the protection of infants and 
children is not needed and
     The ADI or RfD of 0.0075 mg/kg/day is appropriate for assessing 
arsanilic acid risks to infants and children.

G. International Tolerances

    The Applicant is not aware of any international tolerances or Codes 
Maximum Residue Limits (MRLs) for arsanilic acid on any crop or 
livestock commodities. (Cynthia Giles-Parker)

2. ICI Surfactants

PP 8E4965

    EPA has received a pesticide petition (PP 8E4965) from ICI 
Surfactants, 3411 Silverside Road, Wilmington, DE, proposing pursuant 
to section 408(d) of the Federal Food, Drug, and Cosmetic Act, 21 
U.S.C. 346a(d), to amend 40 CFR 180.1001(c) and (e) to establish an 
exemption from the requirement of a tolerance for oxirane, methyl-, 
polymer with oxirane, mono[2-(2-butoxyethoxy)ethyl]ether (CAS Registry 
No. 85637-75-8) when used as an inert ingredient in pesticide 
formulations applied to growing crops or to raw agricultural 
commodities after harvest or to animals. 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

     Magnitude of residues. No residue chemistry data or environmental 
fate data are presented in the petition as the Agency does not 
generally require some or all of the listed studies to rule on the 
exemption from the requirement of a tolerance for an inert ingredient.

B. Toxicological Profile

    1. Acute toxicity. ICI believes sufficient information was 
submitted in the petition to assess the hazards of oxirane, methyl-
,polymer with oxirane, mono[2-(2-butoxyethoxy)ethyl]ether. No 
toxicology data were presented in the petition as the Agency does not 
generally require some or all of the listed studies to rule on the 
exemption from the requirement of a tolerance for an inert ingredient. 
Based on this polymer conforming to the definition of a polymer and 
meeting the criteria of a polymer under 40 CFR 723.250 ICI believes 
there are no concerns for risks associated with toxicity.
    2. Endocrine disruption. ICI has no information to suggest that 
oxirane, methyl-, polymer with oxirane, mono[2-(2- 
butoxyethoxy)ethyl]ether will have an effect on the immune and 
endocrine systems. EPA is not requiring information on the endocrine 
effects of this substance at this time; Congress has allowed 3-years 
after August 3, 1996, for the Agency to implement a screening program 
with respect to endocrine effects.

C. Cumulative Effects

    ICI believes sufficient information was submitted in the petition 
to assess the hazards of oxirane, methyl-,polymer with oxirane, mono[2-
(2-butoxyethoxy)ethyl]ether. Based on this polymer conforming to the 
definition of a polymer and meeting the criteria of a polymer under 40 
CFR 723.250 ICI believes there are no concerns for risks associated 
with cumulative effects.

D. Safety Determination

    1. U.S. population. ICI believes sufficient information was 
submitted in

[[Page 40278]]

the petition to assess the hazards of oxirane, methyl-,polymer with 
oxirane, mono[2-(2-butoxyethoxy)ethyl]ether. Based on this polymer 
conforming to the definition of a polymer and meeting the criteria of a 
polymer under 40 CFR 723.250 ICI believes there are no concerns for 
risks associated with any potential exposure to adults.
    2. Infants and children. ICI believes sufficient information was 
submitted in the petition to assess the hazards of oxirane, methyl-
,polymer with oxirane, mono[2-(2-butoxyethoxy)ethyl]ether. Based on 
this polymer conforming to the definition of a polymer and meeting the 
criteria of a polymer under 40 CFR 723.250 ICI believes there are no 
concerns for risks associated with any potential exposure to infants 
and children. (Bipin Gandhi)

3. KIM-C1, LLC

PP 7G4906

    EPA has received a pesticide petition (PP 7G4906) from KIM-C1, LLC, 
6333 East Liberty Avenue, Fresno, CA 93727 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 N-(2-chloro-4-pyridinyl)-N-phenylurea in or on the raw 
agricultural commodities grape, kiwi, almond, apple, blueberries, 
cranberries, figs, plums, pears, and olives at 0.01 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 supports granting of 
the petition. Additional data may be needed before EPA rules on the 
petition.

A. Residue Chemistry

    1. Plant metabolism. The qualitative nature of the residues of CPPU 
in almonds, apples, blueberries, cranberries, figs, grapes, kiwis, 
olives, pears and plums are adequately understood. Three <SUP>14</SUP>C 
radiolabeled plant metabolism studies conducted in apples, grapes and 
kiwis shows CPPU leaves the same residue pattern in all three crops, 
representing three unrelated botanical species. These studies show that 
the residue is in the low parts per billion (ppb) range at harvest and 
that the residue is primarily associated with the skin. CPPU does not 
translocate any significant distance in the plant, not moving from the 
leaves to the fruit nor from the fruit to the leaves. The use level of 
10 to 20 grams of CPPU per acre assures that only low residues will 
occur. Residue analysis on grapes and kiwis confirm the radiolabel 
findings. In grapes and kiwis the residue level was below the level of 
quantification (LOQ) in all cases and generally below the level of 
validated detection. The LOQ in whole grape was 0.01 ppm; the level of 
detection (LOD) was 0.003 ppm. In grape juice, the LOQ was 0.002 ppm 
and the LOD was 0.0007 ppm (0.7 ppb). In raisins the LOQ was 0.01 ppm 
and the LOD was 0.003 ppm.
    2. Analytical method. The analytical method extracted the parent 
material and analyzed it using HPLC analysis with UV fluorescence at 
wavelength 265 nm.
    3. Magnitude of residues. The magnitude of the residues in the 
crops are anticipated to be below the level of quantification which, 
based on whole fruit, will be 0.01 ppm.

B. Toxicological Profile

    1. Acute toxicity. Based on EPA criteria, CPPU would be placed in 
EPA toxicity Category III generally, while the dermal irritation 
results would be placed in EPA Category IV.

------------------------------------------------------------------------
                                                                        
------------------------------------------------------------------------
Acute Oral                                81-1  LD<INF>50 4.9 gr/kg          
Acute Dermal                              81-2  LD<INF>50 >2000 mg/kg        
Acute Inhalation                          81-3  LC<INF>50 >3.0 mg/l (the     
                                                 higest conc achievable)
Eye Irritation                            81-4  Mildly irritating; No   
                                                 corneal or iridial     
                                                 irritation noted       
Dermal Irritation                         81-5  Non-irritating          
Skin Sensitization                        81-6  Non-sensitizing         
------------------------------------------------------------------------

    2. Genotoxicity. The results from a battery of three genetic 
toxicity tests with CPPU show that this compound is not mutagenic or 
genotoxic.
    Gene mutation - Ames: Slightly Positive
    In-vivo structural chromosomal aberration assay: Negative
    In-vivo micronucleus aberration assay: Negative
    3. Reproductive and developmental toxicity. Results of these 
studies indicate that CPPU is not a reproductive toxicant, 
developmental toxicant, or a teratogen.
    Teratology in rats: NOAEL (maternal) = 100 mg/kg/day; no observed 
adverse effect level (NOAEL) (fetal/development) = 200 mg/kg/day
    Teratology in rabbits: NOAEL (maternal) = 25 mg/kg/day; NOAEL 
(fetal/development) = 100 mg/kg/day
    2-Generation reproduction in rats: NOAEL (parental) = 150 ppm; 
NOAEL (reproductive) = 2,000 ppm (115 mg/kg/day - males) (205 mg/kg/day 
- females).
    4. Subchronic toxicity. No treatment-related adverse effects were 
noted in subchronic toxicity studies at the highest doses tested.
    28 - Day dietary in rats: NOEL 1,000 ppm
    13 - Week dietary in rats: NOEL 200 ppm
    28 - Day dietary in dogs: NOEL 2,500 ppm
    13 - Week Dietary in dogs: NOAEL 500 ppm 13 - Week dietary in mice: 
NOAEL 3,500 ppm.
    5. Chronic toxicity 1-year chronic toxicity in dogs: not required 
for EUP; Test initiated.
    18 -month chronic toxicity and carconogeniscity in mice: not 
required for EUP will be initiated section 3 reg.
    24-month chronic toxicity and carcinogenicity in rats: NOAEL 150 
ppm (8 mg/kg/day); NOAEL 7,500 ppm (435 mg/kg/day). #
    6. Animal metabolism. Study will be completed prior to section 3 
registration requirement. (Not required for an Experiment Use Permit.)
    7. Metabolite toxicology. Metabolites occur at levels below 0.1 ppm 
and therefore are below levels required to be assayed in animal 
testing. The <SUP>14</SUP>C radiolabel plant studies show metabolites 
to be glucosides of the parent material.
    8. Endocrine disruption. Collective weights and histopathological 
findings from the 2-generation rat reproductive study, as well as from 
the subchronic

[[Page 40279]]

and chronic toxicity studies in two or more animal species, demonstrate 
no apparent effects on the endocrine system. There is no information 
available which suggests that CPPU would be associated with endocrine 
effects.

C. Aggregate Exposure

    1. Dietary exposure--Food. A reference dose (RfD) was calculated 
using the most sensitive species data available from the toxicological 
testing. This RfD 0.08 mg/kg/day/based on a temporary tolerance of 0.01 
ppm, was used to calculate the impact of the estimated residue levels 
with results from treatment of the indicated crops. The table below 
shows the Theoretical Maximum Residue Concentrations (TMRC) of CPPU on 
or in the listed crops requested in this EUP request.
     Theoretical Maximum Residue Concentrations for CPPU for the crops 
listed in the EUP request.

----------------------------------------------------------------------------------------------------------------
                                                                                       Total Exposure           
                                          All-Apples         All+Apples    -------------------------------------
                                                                            mg/kg body wt/day    Percent of RfD 
----------------------------------------------------------------------------------------------------------------
General U.S. Populations, all                                                                                   
 seasons............................           0.000005           0.000011           0.000016               0.02
Non-nursing infants.................           0.000029           0.000064           0.000093               0.12
Children 1 to 6-years of age........           0.000010           0.000048           0.000058               0.07
Children 7 to 12-years of age.......           0.000005           0.000017           0.000022               0.03
----------------------------------------------------------------------------------------------------------------

    The anticipated use rate of 17 grams of CPPU per acre applied once 
per year yielding residue levels in the very low ppb range indicates 
that less than 1% of the reference dose would be consumed in aggregate 
with all of these crops. The crop contributing greatest to the percent 
of the reference dose related to the most sensitive of the population 
i.e. all nursing infants (less than 1-year old), non-nursing infants 
(less than 1-year old), children (1 to 6 years old) would represent 1/
10th of 1% of the reference dose. Making the same risk exposure 
calculations, it is shown that no significant impact on reducing the 
RfD by using blueberries, cranberries, cranberry juice, grapes-raisins, 
pears, pears dried, cherries, cherries dried, cherry juice, plums 
(Damsons), plums as prunes (dried), plum/prune juice, figs, kiwifruit, 
grapes-wine and sherry, cranberry juice concentrate, pear nectar in 
aggregate. Combining the RfD consumption from the large group of crops 
with that of the apples would exceed 1% of the reference dose only 
slightly if the total acreage of all of these crops were treated. The 
intention of this experimental use permit is not to treat all of the 
various crops listed; the table below shows the requested acreage of 
each crop.

------------------------------------------------------------------------
                                                  Acreage      % Total  
                     Crop                        Requested     Acreage  
------------------------------------------------------------------------
Grape                                                 3,500         0.53
Kiwi                                                  1,000        14.08
Almond                                                   50         0.01
Apple                                                    50         0.14
Blueberries                                              50             
Cranberries                                              50             
Figs                                                     50         0.40
Plums                                                    50         0.03
Pears                                                    50         0.15
Olives                                                   50         0.05
------------------------------------------------------------------------

    This program would permit development of requisite data to assure 
safe and efficacious use and, yet, not subject any segment of the 
public to a health risk.
    2. Dietary exposure - drinking water. The very low use rate of CPPU 
i.e. 17 grams or less per acre, if used constantly for 20-years, would 
apply only 3/4 of a pound of CPPU per acre during that 20-year period. 
Computer modeling, using the conservative pesticide root zone model 
(PRZM) means of analysis has shown that no CPPU would reach ground 
water, even in sandy loam soils. The results of this risk analysis 
supported an unambiguous conclusion of ``essentially zero risk to 
ground water'' even under reasonable worst case assumptions. 
Concentrations are not predicted to exceed 15 to 20 ppb of CPPU in the 
soil in the upper soil horizons, even following yearly applications for 
as long as 30 years. No secondary exposure is anticipated as a result 
of contamination of drinking water.
    3. Non-dietary exposure. No non-dietary exposure is expected since 
CPPU is not anticipated to be found in the drinking water. It does not 
translocate in plants and thus secondary exposure through plants 
growing in soil receiving CPPU is not anticipated. The extremely low 
application rates will not result in significant buildup in the 
environment.

D. Cumulative Effects

    There are no cumulative effects expected since CPPU is not taken up 
by plants from the soil. It slowly degrades to mineral end points. Its 
low use rate is not conducive to buildup in the environment.

E. Safety Determination

    1. U.S. population. As pointed out above in dietary exposure-food 
the percentage of the reference dose consumed by treating the subject 
crops represents only slightly more than 1% of the estimated safe level 
for the most sensitive segment of the population, non-nursing infants.
    2. Infants and children. No developmental, reproductive or 
fetotoxic effects have been associated with CPPU. The calculation of 
safety margins with respect to these segments of the population were 
taken into consideration in the TMRC estimates with respect to the risk 
associated with the percentage of the reference dose being consumed.

F. International Tolerances

    There is no Codex maximum residue level established for CPPU. 
However, CPPU is registered for use on grapes and other crops in Japan, 
Chile, Mexico, and South Africa. (Cynthia Giles-Parker)
[FR Doc. 98-20145 Filed 7-27-98; 8:45 am]
BILLING CODE 6560-50-F


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